Proceedings from the 2015 NIEHS/EPA Children's Centers Annual Meeting: Protecting Children's Health for a Lifetime U.S. Environmental Protection Agency National Institute of Environmental Health Sciences Washington, D.C. October 29-30, 2015 JELCDA 85£5SMfMm» rtetoal \/tl #1 loo-ncv iBalUr tnoromwm. VtwrHoaHn mIJhui S(mJ> jYb ------- ------- Disclaimer This document has been reviewed in accordance with U.S. Environmental Protection Agency (EPA) policy and approved for publication. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. The National Center for Environmental Research (NCER), Office of Research and Development was responsible for the preparation of this meeting report. Nica Louie served as the Task Assignment Manager, providing overall direction and technical assistance, and is a contributing author/reviewer. The proceedings were prepared by ICF International under contract with the U.S. EPA (contract number EP-C-14-001). The document serves as a general record of presentations and discussions during the meeting and captures the main points while highlighting discussions. It is not a complete record of all details discussed, nor does it interpret or elaborate upon matters that were incomplete or unclear. Statements represent the individual views of the workshop participants; except as specifically noted, none of the statements represent analyses by or positions of EPA. Reference herein to any specific commercial products, process or service by trade name, trademark, manufacturer or otherwise, does not necessarily constitute or imply its endorsement, recommendation or favoring by the U.S. Government. The views and opinions of authors expressed herein do not necessarily state or reflect those of the U.S. Government, and shall not be used for advertising or product endorsement purposes. ------- ------- UNITED STATES ENVIRONMENTAL PROTECTION AGENCY NATIONAL INSTITUTES OF HEALTH WASHINGTON, D.C. National Institute of Environmental Health Sciences OFFICE OF RESEARCH AND DEVELOPMENT DIVISION OF EXTRAMUARAL RESEARCH AND TRAINING October 29, 2015 Dear Conference Participants: It is our pleasure to welcome each of you to the 2015 NIEHS/EPA Children's Centers Annual Meeting. We want you to know that it brings us much joy that children's environmental health advocates are convening during children's health month. We are confident that your discourse will benefit children in communities across the United States and beyond. We are also inspired by the continued accomplishments from the Children's Centers program. Their high-quality research findings have been instrumental in safeguarding children and reducing their health risks from environmental exposures. We are delighted that this year's meeting builds on previous partnerships with clinicians from the Pediatric Environmental Health Specialty Units. We have high expectations that this meeting will further foster collaboration and lead to a greater understanding of research successes and needs. As we embark on 17 years of outstanding interagency collaboration, we recognize that we will all gain strength and momentum by working together to protect the most vulnerable population - our children. So once again, welcome and hope you enjoy the really exciting agenda that we have prepared for you! Sincerely, James H. Johnson. Jr., Ph.D. Director National Center for Environmental Research, EPA Gwen W. Collman, Ph.D. Director Division of Extramural Research & Training, NIEHS ------- ------- Table of Contents Meeting Summary 11 Session I - Welcome and Introduction 11 The Role of NIEHS in Supporting Children's Environmental Health - Linda Birnbaum 11 CDC/ATSDR's Role in Children's Environmental Health - Patrick Breysse 12 Children's Environmental Health: From Knowledge to Action - Ruth Etzel 13 Session I Questions, Answers, and Comments 14 Session 2 - Keynote 16 America Healing: A 21st Century Imperative - Gail Christopher 16 Session 2 Questions, Answers, and Comments 19 Session 3 20 Protecting Children's Health in the Future: Adapting to a Changing World - Thomas Burke 20 Session 4 - Social Determinants of Health 22 Asthma Disparities and the Indoor Environment - Greg Diette 23 Psychological Stress & Perinatal Programming of Chronic Disease - Rosalind Wright 25 Students Break the Cycle of Environmental Health Disparities - Leslie Rubin 27 CalEnviroScreen and Potentially Preventable Childhood Morbidity in California's Central Valley - Emanuel Alcala 28 Session 4 Questions, Answers, and Comments 29 Session 5 - Lifestage Approach to Prematurity 31 The Life Course Perspective and Children's Environmental Health - Michael Lu 31 Session 5 Questions, Answers, and Comments 34 Session 6 - Neurodevelopmental Disorders 35 Lessons Learned From the New Bedford Cohort Study -Susan Korrick 35 The Long-Term, Brain-Based Effects of Prenatal Exposure to Two Environmental Neurotoxicants - Bradley Peterson 37 It's about 4 Million Brains a Year - Toxic Chemicals and the In Utero Environment - Tracey Woodruff 40 From Science to Policy: Targeting Environment and Neuro-Developmental Risks (Project TENDR) - Irva Hertz-Picciotto 42 Session 6 Questions, Answers, and Comments 43 Session 7a - Obesity 45 The Contribution of Environmental Exposures to Childhood Obesity - Rob McConnell 45 Early Toxicant Exposures and Development of Child Obesity: Evidence and Gaps from Recent Research - Karen Peterson 47 Environmental Health and Childhood Obesity: From Research to Action - Maida Galvez 49 ------- Session 7a Questions, Answers, and Comments 51 Session 7b - Exposome 52 Using a Risk Assessment Framework to Integrate Epigenetic Outcomes with Exposome Assessment for Neurodevelopment - Elaine Faustman 52 High-Resolution Metabolomics for Sequencing the Exposome - Dean Jones 54 Environmental Exposures in Early Life Influence Childhood Leukemia - Stephen Rappaport 55 Session 7b Questions, Answers, and Comments 57 Session 7c - Reproductive Health 58 Updates on Environmental Effects on Reproductive Health - Marya Zlatnik 58 Impacts of Early-life Exposure to Endocrine Disrupting Chemicals on Puberty -John Meeker 59 The Pros and Cons of Testing Patients for Toxin Exposures -Susan Buchanan 60 Session 7c Questions, Answers, and Comments 62 Session 8 - Keynote 63 Little Things Matter: The Impact of Toxins on Children's Health - Bruce Lanphear 63 Session 8 Questions, Answers, and Comments 65 Session 9 - Community Outreach and Research Translation 67 Environmental Health Perspectives (EHP): Your Partner in Research Translation-Sally Darney 67 Why Are Doctors Talking Toxics? - Patrice Sutton 68 Do No Environmental Health Harm - An Updated Oath - Jennifer Lowry 69 Simplifying the Complicated: Leveraging Digital Media for More Effective Community Engagement and Research Translation - Carolyn Murray 70 Build It and Will They Come? Lessons Learned from A Story of Health e-Book - Mark Miller 72 #duetoepigenetics #whatdoesthatmean #mustbevoodooscience - Susan Murphy 73 Session 9 Questions, Answers, and Comments 74 Session 10-The Pediatric Environmental Health Specialty Units Present: Emerging Topics in Children's Health 77 A Blueprint for Protecting Children's Environmental Health: An Urgent Call to Action - Nsedu Witherspoon 77 Potential Health Hazards of Increasing Cell Phone Use - Laura Anderko 78 Studies of Children's Exposure to Chemicals on Artificial Turf Fields - Gary Ginsberg 79 Not So Pretty - Endocrine Disrupting Chemicals in Cosmetics and Perfumes - Katie Huffling 81 Maternal Exposure to High Levels of Electromagnetic Fields (EMFs) During Pregnancy and the Long- Term Health Impact on Their Offspring - De-Kun Li 82 Trends in Consumption of Artificial Sweeteners and their Metabolic Effects - Allison Sylvetsky 83 Children's Health Impacts of Climate Change - Perry Sheffield 84 Global Children's Environmental Health - Kathleen Alexander 85 Session 10 Questions, Answers, and Comments 86 ------- Session 11 - Next Steps for Collaboration between the Children's Environmental Health Centers and the Pediatric Environmental Health Specialty Units 87 Overview of Pediatric Environmental Health Specialty Units- Ruth Etzel 87 How Pediatric Environmental Health Speciality Units and Children's Environmental Health Centers Can Inform Children's Environmental Health Policy - Sheela Sathyanarayana 88 Preventing Childhood Leukemia: A Fruitful Partnership for Action - Catherine Metayer 90 Session 11 Questions, Answers, and Comments 91 Session 12 - Keynote 92 Adam Smith and the Business Case for Children's Environmental Health - Leonardo Trasande 92 Session 12 Questions, Answers, and Comments 97 Conclusions 98 Appendix A - Agenda 99 Appendix B - Speaker Biographies 105 Appendix C - Poster Session Abstracts 127 Appendix D - Participant List 151 ------- 10 ------- 2015 NIEHS/EPA Children's Centers Annual Meeting October 29-30, 2015 Meeting Suaaaaary Session I - Welcome and Introduction The Role of NIEHS in Supporting Children's Environmental Health Linda Birnbaum, Ph.D. | Director, National Institutes for Environmental Health Sciences (NIEHS) Dr. Linda Birnbaum kicked off the 2015 NIEHS/EPA Children's Centers Annual Meeting and welcomed the participants. She explained that the mission of NIEHS is to understand how the environment impacts human health in order to promote healthier lives. Specifically, for children, it is important to give them the healthiest start possible and the tools to maintain a healthy lifestyle throughout their lifetime. Dr. Birnbaum provided an overview of the NIEHS budget for children's environmental health and identified the priority research areas. In fiscal year (FY) 2014, the most recent year for which budget data are available, NIEHS gave over $115 million in grants for research to explore children's environmental health in the following 15 areas: neurological/cognitive outcomes, birth outcomes, cardiovascular outcomes, respiratory outcomes, metabolic outcomes, cancer outcomes, reproductive outcomes, immune outcomes, liver outcomes, thyroid dysfunction, skin, morbidity/mortality, musculoskeletal outcomes, and microbiome outcomes. Dr. Birnbaum went on to outline the goals of the NIEHS/EPA Children's Centers, which are to better understand the factors that influence children's environmental health; promote multi-disciplinary interactions by including clinical, public health, and basic science research; turn research into real-world treatments and interactions; establish a national network of children's environmental health experts; and provide community outreach and translation. Dr. Birnbaum discussed the path forward for NIEHS and EPA collaboration on children's environmental health, which includes five new Children's Centers that will be announced in December 2015. She noted that NIEHS is also responsible for redistributing the funds intended for the now-defunct National Children's Study. These funds will be used to achieve three main goals: develop tools to measure environmental exposures in children's health research, enhance the understanding of in-utero and postnatal development, and leverage existing programs. Dr. Birnbaum discussed the development of tools to measure environmental exposures in detail, using the Children's Health Exposure Analysis Resource (CHEAR) as an example. CHEAR aims to expand the number of studies with environmental exposure analysis, implement the exposome concept in children's health studies, create a public resource of children's exposures across the country, and develop data and metadata standards for the environmental health sciences community. CHEAR is comprised of a National Exposure Assessment Laboratory Network where the actual exposure analyses are conducted. The Network will focus on conducting both targeted 11 ------- and untargeted exposure analyses, measuring biological response indicators, and developing and validating new exposure characterization methods. CHEAR is also comprised of a Data Repository, Analysis, and Science Center, which will store exposure data and provide analytical support to exposure scientists. The CHEAR Coordinating Center will deliver overall administrative management. Dr. Birnbaum discussed NIEHS-funded extramural environmental epidemiology resources, noting that in FYs 2013 and 2014 alone, this involved 58 studies. Specifically, this includes 50 cohort studies, six case control studies, and two cross-sectional studies. The cohort studies included assessment of 20 birth cohorts, 15 child/adolescent cohorts, and three reproductive health cohorts. She also pointed out that individual studies have a project details page that is publicly available through the NIEHS website. As for next steps, Dr. Birnbaum highlighted the Agency's intentions to enhance the inventory of existing birth cohorts with additional detail and linked grants; promote the use of CHEAR; implement the exposome concept in children's health research; and create a program to maintain environmental health cohorts and promote the use and sharing of extant data. The latter will be implemented through the new Environmental Influence on Child Health Outcomes (ECHO), a program being established by NIH. CDC/ATSDR's Role in Children's Environmental Health Patrick Breysse, Ph.ID. || Director; National Center for Environmental Health/Agency for Toxic Substances and Disease Registry (ATSDR), Centers for Disease Control (CDC) Dr. Patrick Breysse presented on the role of the CDC/ATSDR in children's environmental health. He explained that the mission of NCEH/ATSDR is to "protect people's health from environmental hazards that can be present in the air we breathe, the water we drink, and the world that sustains us" by investigating the relationship between environmental factors and health, developing guidance, and building partnerships to support healthy decision making. He highlighted the NCEH/ATSDR priorities, which include reducing asthma morbidity and mortality; protecting children from the health risks of harmful exposures and conditions; ensuring safe drinking water; and using innovative laboratory methods to detect, diagnose, and prevent environmental disease. Specifically, NCEH/ATSDR works to protect children from the health risks of harmful exposures by: • Implementing a national strategy to protect children from harmful exposures related to daycare and early learning centers; • Implementing a nationwide education campaign to protect children from exposures to mercury and promote recovery of mercury from schools, homes, and abandoned facilities; • Using laboratory testing, modeling, and data systems to collect and analyze data describing children's exposure; • Preventing children's exposure to environmental health concerns such as lead, vapor intrusion, and carbon monoxide; • Building the skills of health care providers and emergency responders regarding children's vulnerabilities to harmful exposures; and • Ensuring that children are considered in land-use and transportation health impact assessments (HIAs). 12 ------- Dr. Breysse discussed in detail several NCEH/ATSDR programs intended to protect children against the harms of environmental exposures: Childhood Lead Poisoning Prevention Program. He noted that four million U.S. households have children that are exposed to high levels of lead and approximately half a million children ages one to five years have blood lead levels above the CDC's reference value of five ng/dL. Dr. Breysse stated that the program will fund the reestablishment of blood lead surveillance efforts on the state and local level, which will involve collecting and analyzing data to identify the highest risk areas. The program will continue to help reduce childhood lead poisoning, reduce associated health care costs, and improve academic achievement and later-life success for at-risk children. National Biomonitoring Program. The National Biomonitoring Program, which functions as part of the National Health and Nutrition Examination Survey (NHANES), samples a subset of the NHANES study population to assess exposure to priority environmental chemicals. The broader goal of the program is to provide the laboratory science that improves the diagnosis, treatment, and prevention of disease resulting from exposure. He displayed results of an analysis of NHANES data that shows the decrease of certain phthalates overtime. He noted that this highlights the shifting practices of the chemical industry that may imply the need for updating research hypotheses or changing the focus of funding. National Asthma Control Program. The program promotes collaboration between the health care industry and public health communities relative to asthma focusing on infrastructure, services, and health systems. National Environmental Public Health Tracking Network. This network is an online system of exposure and response data and information intended to enable public health officials to respond quickly to specific inquiries about risks. Data specific to children include asthma, biomonitoring, childhood cancers, lead poisoning, developmental disabilities, heat vulnerabilities, and pesticide exposures. To illustrate the capabilities of the National Environmental Public Health Tracking Network, he displayed maps of asthma hospitalizations by county in the state of Florida for two age groups and a map showing the incidence of childhood leukemia by state. The data can be used for descriptive or analytical purposes. Pediatric Environmental Health Specialty Units (PEHSUs). The PEHSUs advise pediatricians and families on treating and protecting children potentially exposed to harmful chemicals and address the health risks children face from environmental hazards like lead, mercury, mold, plastics, and pesticides. He noted that these programs are key in protecting and promoting children's health. Children's Environmental Health: From Knowledge to Action Ruth Etzel, M.D., Ph.D. || Director, Office of Children's Health Protection, U.S. EPA Dr. Ruth Etzel discussed how EPA implements children's environmental health science data in the regulatory context. She began by noting the annual presidential proclamation on children's health during Children's Health Month. This year, President Obama explicitly included the implications of climate change on children's health and the importance of coordinating action at the national and international levels. Dr. Etzel also highlighted several of EPA's Children's Health Month events, which included a meeting 13 ------- hosted by the newest PEHSU in El Paso, Texas to discuss environmental health issues for children living along the United States/Mexico border; an EPA open house showcasing the Agency's accomplishments during the 20 years since the implementation of the 1995 Policy on Evaluating Health Risks to Children; and a meeting of the President's Task Force on Environmental Health Risks and Safety Risks to Children, which includes 17 Federal Agencies, Office and Departments. During the President's Task Force meeting, Co-Chairs U.S. EPA Administrator Gina McCarthy and Department of Health and Human Services (HHS) Secretary Sylvia Mathews Burwell reviewed the Task Force's actions addressing children's environmental health issues such as asthma disparities, healthy homes, chemical exposures, and climate change. A recent success in children's health protection is the updated Agricultural Worker Protection Standard, which includes provisions that protect children. Specifically, it requires that pesticide handlers and early- entry workers must be at least 18 years old, whereas there was no minimum age prior to the 2015 update. Progress on preventing pesticide poisonings has been supported by health effects research results from cohort studies conducted at three NIEHS/EPA Children's Centers: the Center for Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort, the Columbia University cohort, and the Mount Sinai cohort. Another success in promoting children's health that Dr. Etzel discussed was the new air quality standard for ground-level ozone. She noted that the National Ambient Air Quality Standards (NAAQS) for ground- level ozone have been strengthened to 70 parts per billion (ppb), which is estimated to translate to between $2.9-5.9 billion in health benefits in 2025. Of particular note, the new standard will avoid an estimated 230,000 childhood asthma attacks, 160,000 missed school days, and 340 cases of acute bronchitis among children. Session I Questions, Answers, and Comments1 Jennifer Lowry, Region 7 PEHSU, stated that she was involved in the REACH program at University of California, San Francisco (UCSF). One project within the REACH program is focused on integrating environmental data sets with those at EPA. She recognized that this would be a complicated, but worthwhile, effort. Patrick Breysse agreed, saying that he, Tom, and Ruth have discussed how to better integrate information across data systems. They are being told by Congress that each of their agencies must be more efficient in their data gathering efforts in order to reduce the burden on states and local governments. They are planning to talk further about this effort. Tom Burke added that there is a big push to make this happen as it is a natural potential marriage of the analytic tools and community-based tools. In the era of HIAs and tracking, there is huge incentive to move that forward. Patrick Breysse agreed, saying they need to identify the things that are best suited for integration and move forward. Natalie Grant, U.S. HHS, inquired about how they might be able to utilize these integrated data sets to inform and support post disaster community decision-making (when funding is available) where multiple environments and exposures to hazards exist. She wondered how to apply the best available data to 1 Due to last minute changes to the agenda, Dr. Tom Burke presented as part of Session 1, and participated in the panel discussion. Please see Session 3 (pg 18) for a summary of his presentation. 14 ------- community-level planning processes in a way that local residents can easily understand, recognizing that there is limited capacity to have those analytics done. Linda Birnbaum mentioned that NIEHS with colleagues from EPA and CDC developed a program called the Disaster Research Response Project (DR2). She added that when there is an emergency, steps need to be taken to protect public health and often research must be conducted to identify what the community needs. This can be very difficult to do, and it can be challenging to get into the field rapidly. On the HHS website, there is a lot of information on what needs to be done when responding to emergencies; approved protocols for collecting data are also available on the National Library of Medicine website. Sue Kiridly, Cohen Children's Hospitalsaid her son had a rare tumor in his lungs, and what she discovered during that process was that our country does not have a cohesive children's rare tumor registry, which was mind-boggling to her because other countries (e.g., the UK, Germany, and South Africa) do have one. In the United States, some institutions are obligated to report rare tumors, and some are not. Sue stated that she thinks that the most important thing for children's cancer research as well as research for other environmental health concerns is to develop a process for getting the correct numbers. She asked, "How can we move forward without numbers that encompass everyone?" Ruth Etzel agreed, acknowledging the huge gap that needs to be addressed in order to put prevention into place. She stated that there are no reliable data on rare childhood cancers—which we know probably have environmental influences— and that this is something on which federal agencies can collaborate. Linda Birnbaum commented that NIH does a lot of work related to rare tumor research and that it is currently instituting a very stringent policy related to reporting of clinical trials. Negative findings are often not reported or they are not reported in a timely manner. She believes this issue is related to medical practice that is changing where results—whatever they may be—will be broadly available online. An individual from EPA Office of Solid Waste and Emergency Response asked whether the panel had any specific resources regarding children's health for offices like Superfund that primarily deal with regulations and guidance. Tom Burke said that, from an EPA perspective, Superfund has done great things, but they need to work on their formulaic approach to understanding community risk by looking at a broader range of exposures, pathways, and impacts. Patrick Breysse said that on the ATSDR website, they are challenged to provide community education through toxicological profiles and community accessible translation of these profiles. He thinks they can do better. Linda Birnbaum mentioned that NIEHS has been funded specifically to deal with Superfund issues, and they partner with EPA and ATSDR to address issues of concern, many of which involve children cohorts and community outreach. Tenya Steele, Center for Environmental Health, referred to Tom Burke's presentation where he discussed the difficulty of using new science to update risk assessments. She asked if processes are in place to push through those difficulties and if there are any concrete plans to update those risk assessments. Tom Burke answered yes, saying risk assessment has been an important decision-making tool, but it is often focused on one exposure medium or one type of individual, and that we have evolved to understand the contributions to risk beyond those factors. Cumulative risk is really challenging; when thinking in the context of a Superfund site, there are many factors that affect risk. They are pushing forward with risk assessment and problem formulation to ensure the right questions are being asked upfront. Dr. Burke said they are also complimenting risk assessment with other approaches like HIAs and baseline assessments of community health, and trying to improve exposure assessment. He said he wished funding 15 ------- included exposure/dose characterization from a biomonitoring perspective. While they are pushing forward in a number of ways, it is hard to move to policy without the help of researchers. Patrick Breysse stressed the importance of working together closely. Risk assessments are often limited in what they can say, in part because data that inform them are limited. They are thinking more about what types of data to collect, the characterization process, and how to use risk assessment to inform communities about broader health impacts. They are working to identify critical areas of data collection that the EPA can help early on so that the process will work better. He said they are working more closely with EPA to bridge those gaps. Session 2 - Keynote America Healing: A 21st Century Imperative Gail Christopher, D.N. | Vice President of Policy and Senior Advisor, W.K. Kellogg Foundation Moderated by Kari Nadeau, M.D., Ph.D. | Stanford University Dr. Gail Christopher began with a reminder that modern society has multiple sectors, each privileged and constrained by various factors. The philanthropic sector has historically tried to catalyze fund innovation and creativity, and to help frame the discussion to move agendas forward. The founder of the W.K. Kellogg Foundation said, "Do what you will with the money so long as it helps children." His primary concern was the well-being of "vulnerable children." Over 80 years ago, he recognized that children of color, and particularly children with disabilities, faced barriers to their success. More than 70 years later, the W.K. Kellogg Foundation revisited its mission. Taking an innovative approach to addressing these barriers accelerated the founder's mission, because most children born in the United States today are children of color, and most are from low-income families in impoverished communities. The Foundation believes it is in the best interest of the country to increase their investments and ensure all children face fewer barriers to success. This led them to the bold decision to become "the most effective anti-racist organization they can be," with an explicit and direct focus on issues of racism. After a decade of having this explicit focus, Dr. Christopher shared that the Foundation has learned greater resilience and interventions supported by research that can make a critical difference in children's lives. She believes it complements some of the work conducted at Children's Centers and other child-focused research and initiatives. As several movements in the public health field converge, Dr. Christopher said it is uncommon to be in a public health meeting that does not reference social determinants of health (SDoH). The World Health Organization (WHO) defines SDoH as the circumstances in which people are born, grow up, live, work, and age, and the systems put in place to deal with illness. SDoH include factors such as access to affordable healthy food, clean water, green space, safe housing, clean air, and supportive social networks. These circumstances are shaped by the distribution of money, power, and resources and are impacted by biological, chemical, and social factors resulting in inequities in disease burdens, health, and quality of life. Children have unique vulnerabilities to all forms of adversity within their environments. Non-chemical SDoH can exacerbate or mitigate related risks and exposures. Public health conversations now include the 16 ------- life-course perspective and exciting discoveries from the field of epigenetics. Consensus is emerging around adverse experiences in childhood, and how they predispose children to greater risk for chronic disease and substance abuse later in life. Dr. Christopher remarked that the environment, in both a macro and micro sense, is perhaps the most determining factor in terms of the opportunity to be healthy and to thrive. Dr. Christopher described how the Foundation has integrated the SDoH framework into their funding effort, focusing on food health and well-being, education and learning, and family economic security. The Foundation has been involved in the health care reform space for about ten years, and many of their investments contributed to bringing about the Affordable Care Act. Around 2007, the Foundation was interested in applying the SDoH framework to support communities in their efforts to mitigate excessive exposures to negative social determinants. They focused on young children to close gaps in infant mortality and other disparities, and concentrated resources in specific geographic areas around the country. Funded interventions in Michigan resulted in no infant mortality and no low birth weight within a high-risk group of teenage mothers over a four-year period, validating these social interventions. Another example is the "centering pregnancy" model, in which the mother gets support throughout the pregnancy in small groups. They found that companion care, companionship, and social networking with human interaction reduces stress levels and improves birth outcomes. The Foundation has also put resources into optimizing breast feeding rates, and increasing baby-friendly hospitals, which previously did not exist in low-income, high-risk communities. They have invested $15 million to help accelerate the movement of medical facilities within communities that adhere to guidelines to optimize breast feeding rates and have observed dramatic increases in initiating as well as sustaining breast feeding over time. All of these interventions were based on the science and done in partnership with the public sector and academia. It has been difficult getting other foundations on board. Even though the breast feeding optimization movement is a relatively low-cost intervention that can change the outcomes of at-risk populations, it continues to face pushback and resistance. Dr. Christopher shared examples of these specific interventions, which do not directly confront the issues of America's embedded belief in racial hierarchy or racism, because the Foundation's approach includes both. Although they need to work on changing hearts and minds and uprooting the 18th century belief in a hierarchy of human value, it is also necessary to put in place tools communities can use to help mitigate the unnecessary exposures they face on a daily basis. The Foundation is also working to optimize access to quality food in communities by funding the food systems change movement, among other initiatives. The Foundation has partnered with the White House Partnership for a Healthier America, Trust for America's Health, the school food movement, and other food groups. The paradigm starts with first food and breastfeeding, then moves to early food, and later to school food, which has the greatest traction. One example is the Farm to School movement, which gives schools access to fresh vegetables. Research demonstrates that when the diet is predominantly fresh vegetables, many inflammatory markers, along with the subsequent risk for chronic disease, are greatly reduced. Emerging science validates the importance of the holistic approach, yet communities that need it the most have the least access. Dr. Christopher said at least 50 foundations are actively engaged in food 17 ------- systems work to change this, but they need the help of the children's health research community to document the relationship between healthy diets and mitigating the effects of overexposure to environmental toxins. The Foundation also is working to bring the conversation about lead back into the mainstream public and environmental health conversation. In partnership with EPA, the Foundation recently funded the publication of a guide for communities to help school systems test lead levels in drinking water, as many still have these antiquated systems that provide unnecessary lead exposure. Dr. Christopher then discussed what she referred to as "the bravest thing our Foundation has done," which is to say all of the things discussed, including disparities in income and exposure, are in fact a symptom of a much deeper societal challenge we all face. The Foundation calls it a 21st century imperative; the challenge to move beyond denial of the fact that this country was not conceived in liberty, but in the false ideology of a hierarchy of human value. This concept was created in the 1700s, about the time the printing press proliferated, and found its way into the literature, the canon, and the consciousness of a nation becoming. Dr. Christopher described a belief that some people are more deserving that others based on their physical characteristics as part of the DNA of the United States. This mindset dominated the nation's consciousness for more than two and a half centuries and was embedded in the U.S. Constitution and throughout the country, not just in the South. The country had a Civil War and Reconstruction, and 50 years later had a civil rights movement, and subsequent to that movement, has experienced continuous backlash to turn that back. Both efforts were designed to address the consequences of this belief, but the belief itself has never been addressed in a straightforward way, nor has a campaign and a decision been made to uproot that belief. She asked the audience to imagine a country not characterized by residential segregation comparable to South Africa at the heart of apartheid and one in which school systems are equally funded, access to quality health care is not based on zip code, and zip code is not more important than genetic code. Dr. Christopher said she is proud to be part of a foundation that has invested more than $200 million in helping communities over the last decade, in an inclusive and straightforward way, challenging racial hierarchy. The Foundation has funded research in the area of bias and unconscious bias to allow professions and disciplines to offer training to help individuals, such as law enforcement officers, confront their biases and see how those biases shape their behaviors. The idea that humans are unconsciously programmed to adhere to the false concept of a hierarchy of value is a very viable idea that individuals can embrace without triggering shame, guilt, anger, and other emotions that prevent them from confronting the concept. The unconscious bias work needs to be implemented in every institution to avoid serious implications down the road. Just as the concept of a racial hierarchy proliferated during the first information revolution, these algorithms will perpetuate the same divisions if people do not intervene now. The manifestations of this belief system can be observed in the criminal justice system, as a consequence of that information revolution (e.g., cell phone cameras). Dr. Christopher then asked: How can people harness that opportunity and really make a difference in humans' capacity to relate to and appreciate one other as equals? Turning to a discussion of equality versus equity, Dr. Christopher explained that racial equity refers to principles of fairness and justice. Racial equity work describes actions designed to address historic burdens and remove present day barriers to equal opportunities. Identifying and eliminating systemic discriminatory policies and practices with specific remediating strategies accomplishes this. These actions address the effects of historic injustice and prevent present and future inequities. In terms of equality, 18 ------- philosophically, the Foundation is addressing the embedded false notion that there is a gradation of lesser value based on physical characteristics. The human genome makes it very clear that humans are 99.9 percent the same. Although some might use it as a basis for perpetuating the belief in racial hierarchy, the evidence is clear that there are more differences within the socially constructed races than between them. These adaptions and physical characteristics are consequences of how our ancestors evolved to adapt to their environments. Dr. Christopher then discussed the environmental justice movement and applauded efforts to increasingly incorporate it into EPA's work. Environmental justice is responsive to Executive Order 12898 to address inequities in the distribution of environmental hazards rather than addressing the broader context and root causes of such inequities. She argued the necessity of connecting the environmental justice paradigm and SDoH framework to consider resilience. Environmental exposure to toxic chemicals is one of many SDoH. The impact of such exposures can be influenced by non-chemical stressors and exposures or reduced access to needed resources, such as quality health care. Housing segregation, poverty, and civic engagement can shape the levels of risk and protections available to families within their communities. Cumulative exposure fits with the emerging paradigm around trauma and adversity. Looking at the body holistically, and seeing the pathways involved with inflammation and adaption, it is evident that they all fit together. Thus, it is important to educate and intervene to help people minimize the risks they are facing, both from a standpoint of chemical and environment risks in terms of trauma and adversity. The Foundation helped to fund a commission called the Courage to Love, which focused on the gap in terms of infant mortality and the degree of low birth weight outcomes experienced in communities where women faced disproportionate levels of discrimination. In terms of the excess exposures facing children of color, researchers have coined the term double jeopardy, which children experience when they live in both poor families and poor neighborhoods. Moving forward, Dr. Christopher emphasized the importance of incorporating the private sector into this discussion. The Foundation funded a study called the "Business Case for Racial Equity," as they argue there will not be significant changes in terms of SDoH until the private sector is involved. The inequities of today, left unchecked, will yield even more harm to our nation's children tomorrow, especially to minority children. A mother of color, no matter her education, faces a greater risk for low birth weight and higher infant mortality than a white mother that has not finished high school. Dr. Christopher concluded her talk with an invitation to join the effort. The Foundation believes the recent changes in public awareness of the need for the United States to address racism has led society to an unprecedented point in time. The Foundation will be accelerating its investmentto bring about an adaption of the internationally recognized approach to healing from a historic past: truth and reconciliation. They believe it is truth, racial healing, and transformation for this country that is part of bringing about environmental justice and equity. Session 2 Questions, Answers, and Comments Alan Woolfe, Boston's Children's Hospital/Harvard, applauded Dr. Christopher and the incredibly important work the Foundation is doing. He asked her to comment on the role of the Foundation and others in extending the work to students in schools of medicine and public health and teaching hospitals. 19 ------- Given the need to make racial and ethnic discrimination in healthcare an explicit curriculum to give students and trainees a safe environmentto approach a dialogue about increasing awareness of their own biases, he wondered how we can work together to eliminate disparities in healthcare. Dr. Christopher referred to her colleagues who have done brilliant work on documenting the racial disparities in terms of treatment options, not just access, which reflects unconscious bias. She felt that not enough was being done and hoped that the Foundation's new effort around truth and transformation will result in an examination of every major system in the country, inserting tools and resources for change. She reiterated that this is change at an individual level as well as an institutional level, so in addition to an explicit curriculum, she recommended a tool, the Intercultural Development Inventory, which allows individuals to assess where organizations and individuals are on a continuum. As none of us are without bias, Dr. Christopher emphasized the importance of tracking and identification and using resources and tools to overcome it, especially in systems where people are making life and death decisions. Dr. Christopher recommended the books Black Man in a White Coat and Sick from Freedom. Another audience member said U.S. EPA's ORD was looking to possibly support SDoH research, and asked Dr. Christopher how the picture would look if she was to focus on factors related to environmental components of SDoH. Dr. Christopher said the traditional models included healthy housing, proximity to toxins, and waste dumps. She believes more research is needed to document the biological and biochemical pathways that are engaged when we are exposed to discrimination. There is a study coming from Massachusetts where the researcher worked with second generation descendants of Holocaust survivors. She found differences in the stress responses of the grandchildren of survivors, in terms of a generational effect of exposure to trauma. Researchers have not even begun to ask the questions about all the communities that have had disproportionate exposure to continuous trauma based on environmental inequities. Dr. Christopher would ask that the investigation of the environment include interpersonal dynamics and exposure to individual and systemic racial discrimination. Session 3 Protecting Children's Health in the Future: Adapting to a Changing World Thomas Burke, Ph.D. | Science Advisor, U.S. EPA Dr. Thomas Burke began by saying how terrific it is to have this opportunity to reach across institutional barriers in the policy making process. He asked the audience, "What is the most important thing we can do together to protect and promote children's health from an environmental health perspective?" In his view, we need to improve the application and understanding of our science, improve the trust and credibility of our science, and make more effective changes to policies to protect public health, particularly for our children. Dr. Burke applauded U.S. EPA Administrator McCarthy as an advocate for children's health. The fundamental mission of the EPA is to protect the health of the public, and protecting children's health is 20 ------- a critical part of that mission. It is important to apply the science as best as possible and defend it against challenges. Dr. Burke described the timeline and progress of the EPA over the last few decades. Pre-1990, exposure was oversimplified: Everyone was a 70 kg man who drank two liters of water a day, never breast-fed, never ingested soil, and hung out on a porch for 30 years. In the early 1990s, changes were occurring to better characterize exposure. In 1993, the National Academy of Sciences published a groundbreaking report, Pesticides in the Diets of Infants of Children, which illustrated the importance of diet-related exposures. The Food Quality Protection Act of 1996 also addressed childhood exposures. Since President Clinton's Executive Order in 1997, children's health has moved to the forefront of exposure assessment. Today, research conducted at Children's Centers has provided federal, state, and local decision makers with vital information for making better-informed decisions that are more protective of children's health. Columbia Children's Center research informed a landmark environmental health law in New York City that required the use of integrated pest management (IPM) in public housing. A related law required that residents are notified 24-48 hours in advance of pesticide application in a neighboring property. The University of Washington Children's Center demonstrated that farmworkers were not the only receptors exposed to the pesticide azinphos-methyl in the fields. The workers were also bringing the contamination home where it built up in house dust; correlations were found between pesticide levels in house dust and child resident pesticide levels. This evidence was cited in EPA's decision to ban that pesticide by 2011. It is important that we continue to increase our understanding of childhood pathways to exposure in order to develop a broader approach to protecting children. Dr. Burke discussed the biggest problems ahead given environmental challenges and evolving science. Old-school environmental science was fragmented and compartmentalized; regulations focused on one thing at a time, and often scientists were trained in a single discipline. Today, scientists face difficult challenges (e.g., drought and climate change) that cut across multiple disciplines. Understanding within and across compartments is essential and consideration of emerging technologies, new understandings of the science, energy aspects, and community design factors is needed. Dr. Burke discussed his role in a National Academy of Sciences panel, Science for Environmental Protection: The Road Ahead, which looked at the evolution of environmental health science challenges. The challenges associated with environmental protection today are complex, often affected by many interacting factors. There are various spatial and temporal scales to consider; many environmental health issues have global implications. Some of these environmental challenges are difficult to define and are variable and socially complex with no clear solution or end point, and many extend beyond the understanding of one discipline. Dr. Burke believes that it is important to train people to deal with these complex issues and to work together to address them. At EPA, the sources-to-effects continuum (i.e., understanding the environmental concentration, exposure of a population, and health outcome) has been a basis of their work and represents one of the biggest challenges in epidemiology and risk assessment. Environmental public health tracking is key to conducting HIAs. This tracking follows a linear toxicology/epidemiology model of hazard: understanding of presence in the environment, route of exposure, host exposure, target tissue, adverse effect, and outcome of interest. The epidemiology triad denotes that health status depends on host factors, agent characteristics, and environment; dose is not the only important factor. 21 ------- The challenge is to understand how these factors interact. Dr. Burke questions whether past approaches are sufficient to address today's "wicked problems." In order to solve today's "wicked problems," society needs to understand the context of the problem; dimensions of a problem; and connections between ecosystem factors and human health. Our economy and human health and well-being cannot function without a healthy ecosystem. Health is not just about health care. Moving forward, Dr. Burke believes the following data and tools are critical to informing exposure assessment: thorough up-front problem formulation and scoping; systems approaches and tools; techniques and tools to integrate different types of data from multiple disciplines (e.g., ecological risk, human health risk, social sciences); new technologies (e.g., high throughput chemical screening); novel techniques (e.g., citizen science, which provides new sources of information and insights into exposures); science translation to address challenges of using evolving science to update old standards. The public health problem-solving approach comes from an instrumental paper in children's health, written by Bernie Guyer discussing what public health is all about. The general approach outlined in this paper consists of defining the problem; measuring the magnitude of the problem (using surveillance, hazard identification); developing a framework for key determinants (e.g., biologic, epidemiologic, social, cultural, economic, political); using research translation to identify and develop intervention and prevention strategies; setting priorities and recommending policies; implementing programs; and evaluating health outcomes. Dr. Burke concluded by saying that the Children's Centers have provided some of the groundwork and research needed to move forward in implementing new approaches for solving tomorrow's challenges in children's health—for example, use of multidisciplinary approaches; consideration of nonchemical stressors and social factors; efforts in translation/outreach; and focus on intervention/prevention—and this work needs to continue. Session 4 - Social Determinants of Health Moderated by Andrew Geller, Ph.D., M.A. | Deputy National Program Director, Sustainable and Healthy Communities Research Program, U.S. EPA Dr. Andrew Geller thanked the previous session speakers for a great opening session and introduced the social determinants panelists: Dr. Rosalind Wright, from the Icahn School of Medicine at Mount Sinai who discussed psychosocial stress and perinatal programming of chronic disease; Dr. Greg Diette, from Johns Hopkins University, who discussed asthma disparities and the indoor environment; Dr. Leslie Rubin, from Morehouse School of Medicine, who discussed how students break the cycle of environmental health disparities; and Mr. Emanuel Alcala, from Central Valley Health Policy Institute, who discussed CalEnviroScreen and Potentially Preventable Childhood Morbidity in California's Central Valley. EPA is considering community stressors in discussions for incorporating chemical and nonchemical stressors in cumulative risk assessments, specifically how their interactions with biologic systems and environmental exposures result in adverse health effects and health disparities. EPA considers these factors important to consider in cumulative risk assessments and current knowledge about applications 22 ------- of community stressors points towards including social determinants as critical factors in assessments used to set regulatory limits. Many social determinants of health are potentially modifiable factors that may be affected by changes in individual behavior, policy, and community infrastructure. Dr. Gail Christopher did an excellent job introducing the social determinant factors that should be prioritized, and EPA's Children's Health Protection Advisory Committee (CHPAC) identified a number of candidate factors in their letter to EPA, including quality of education, access to healthy food, access to health providers, breastfeeding, transportation conditions, housing conditions, segregation, income, and civic engagements, among others. Another way to examine these factors is presented in EPA's Draft Environmental Justice Technical Guidance document. EPA is considering the possibility that these societal factors come from a false hierarchy of human values and that the social stratification themselves are a function of multiple societal and political factors that shape social determinants of health. Dr. Geller stated his own personal bias that he feels strongly that children's environmental health and environmental justice have deeply converging interests and noted his enthusiasm about the inclusion of social determinates of health in EPA's environmental justice roadmap. Dr. Geller challenged meeting participants to consider other actions that emerge from our knowledge of social determinants of health such as decision contexts or other areas to which social determinants of health information can be critically important. He asked participants to examine the social determinant factors being considered, being missed, should be prioritized, and what actions should be taken moving forward for understanding prioritization. Dr. Geller introduced the first panelist, Dr. Greg Diette, from Johns Hopkins University, who researches diet and home modification and health disparities in the home environment. Asthma Disparities and the Indoor Environment Greg Diette, M.D. || Johns Hopkins University Dr. Greg Diette explained that his presentation will focus on asthma disparities. Asthma is not distributed evenly in society and it is commonly believed that those with lower income are more likely to have asthma. Dr. Diette presented a graph showing asthma prevalence in children and adults below the poverty line is higher than those above the poverty line. Being poor is a fairly potent issue that affects number of cases and asthma severity, and the relationship is not incremental. The function of having money and lower prevalence of asthma is not a consistent function (i.e., having more money does not result in less risk of asthma), but rather poverty is the issue. We see asthma disparities among many groups (e.g., sex, age, gender, and geography), and there are many factors that can coalesce and be mapped. For asthma, factors such as occupation, indoor allergens, and indoor pollution contribute to asthma disparity. Environmental exposure can cause health disparities in many ways, including differential exposure, susceptibility, and coping strategies. Differential exposures begin outside but move indoors to affect people where they live, study, and work. Two environmental factors that have the greatest influence on asthma are inhalant allergens and irritants. Dr. Diette presented an NIH-sponsored figure that illustrated different routes of pollution and irritants in rural and urban environments. For example, indoor cooking 23 ------- fires presented sources of asthma inducing pollutants in rural communities, and smoking affected asthma in urban areas. Health disparities from exposures occur because where people live is not a random phenomenon. Minorities are more likely to live in an area that fails the EPA standard. A Woodruff et al. study examined where pregnant women live to find the relationship between race and ethnicity and location and found that minority, pregnant women were exposed to the worst air. Studies also found that often indoor air quality, including allergens and air pollution, can be worse that outside. One study on the distribution of indoor particulate matter (PM) in children's bedrooms found that indoor fine particles failed an average of 70 percent of outside standards. Additional studies found that African Americans have the highest levels of exposure to second-hand smoke and suffer the highest codeine levels after PM exposure. Differences in how people cook is another factor in health disparities. Exposure from biomass burning cooking methods are linked to adverse health outcomes as is nitrogen dioxide (N02) exposure from cooking on an unventilated gas stovetop. Three billion people use biomass burning for cooking, which contributes to asthma. The odds ratio (OR) of cooking with solid fuel and asthma is 1.8, which is similar to the OR for tobacco and asthma. Allergens also play a role in health disparities. For example, African-American and Mexican-American children are at a higher risk of sensitivity to cockroaches and dust. Residential location also plays a large role in differences in allergen burden. For example, dust mites are a major allergen in New Orleans and Seattle, cockroaches are a major allergen in Chicago and New York, and mice are a major allergen in Baltimore. One editorial by D.R. Ownby compared children's sensitivity to mice and cockroaches to an allergen and found that mice had the largest spread of reaction and therefore were predicted to have the highest probability of resulting in an acute allergic reaction that requires a hospital visit. A study by Bell et al. examined the effects of having central air conditioning on exposure to PM and found a 39 percent reduction in respiratory hospital admission among the 20 percent of people with central air conditioning. This finding was consistent with less outdoor penetration of PM indoors. School location also plays a large role in asthma dipartites in children. The air quality surrounding the school will impact the children, given the amount of time they spend at school. One study in southern California examined ambient PM pollution and asthma in children and found a correlation between the risk of asthma and air quality in school. Another study in southern California examined traffic density near schools and found that locations where African-American and Hispanic children go to school experience higher traffic density, further supporting disparities of health. Another study by Sheehan et al. examined dust allergens in urban schools and homes and found that urban schools have higher pollution. Occupation is another contributor to health disparities. For example, bakers have high rates of asthma and respiratory conditions due to their professions. Approximately 15 percent of asthma cases are due to occupation, and occupational lung disease is the number one contributor to work-related illness in the United States. Different occupations pose different risk and different ethnicities have different sensitivities. For example, Asian-Americans have the lowest percent risk of lung disease in high risk occupations and Hispanics are most likely to have high-risk occupations such as painting, carpentry, working with textiles, or baking. Where people live, learn, and work affects their risk of asthma, and asthma disparities can be linked to indoor environment differences. Age, sex and gender, race and ethnicity, and geography groups are 24 ------- exposed to different mixtures, resulting in different adverse health outcomes and different disparities in health. Dr. Geller thanked Dr. Diette for his presentation and asked the audience to think about how to set standards to prevent asthma. He then introduced the next speaker, Dr. Rosalind Wright, to present on the window of opportunity for health improvements during pregnancy due to parents' heavy investment in life changes. Psychological Stress & Perinatal Programming of Chronic Disease Rosalind Wright, M.D., M.P.H. | Icahn School of Medicine at Mount Sinai Dr. Rosalind Wright explained that she would present on environmental risk and psychological stress, which is an area that is expanding and is important to the asthma picture as well as health more broadly. The first principle is that early-life experiences can influence later-life health and disease. In other words, the stages of life are a continuum, and life experiences and exposures have impacts over time. To understand disease, such as pulmonary disease, one must take a life-course perspective and see pregnancy and early childhood as the biggest levers for disease prevention, which is why Dr. Wright is an adult trained Pulmonary and Critical Care Medicine physician who now sits in a pediatrics department. Numerous studies have evidenced maternal exposure to air pollution, including particulates, carbon monoxide, sulfur and nitrogen oxides, ozone, and tobacco smoke, as associated with low birth weight, congenital defects, fetal and neonatal deaths, decreased lung growth, increased rates of respiratory tract infections, asthma, behavioral problems, and neurocognitive impairments. These outcomes can also have further health effects. For example, low birth weight is linked to obesity in teen years and adulthood and is a risk factor for adult cardiovascular disease, hypertension, and type 2 diabetes. As noted previously, these diseases in midlife (especially diabetes) are associated with increased risk for the development of Alzheimer's disease and dementia in later life. Dr. Wright leads a transdisciplinary team of scientists at Mount Sinai which is conducting a prospective birth cohort study to measure the components that contribute to asthma risk and other developmental disorders, such as psychological stress, diet, air pollution, home allergens, and tobacco exposure, in low-income populations to determine the large drivers and identify areas of intervention. Stress was identified as one of the top contributors and the study then looked at how it gets into the body to impact health. The physiological imbedding of stress is similar to inhalation exposure, as physiological disruption can result from the emotional-cognitive processing and response to an external stressor. Stress activates the central and peripheral components of the stress system, or the hypothalamic-pituitary-adrenal (HPA) axis and the arousal/sympathetic system, resulting in changes in levels of stress system principal effectors, including corticotropin-releasing hormone (CRH), arginine vasopressin, proopiomelanocortin-derived peptides alpha-melanocyte-stimulating hormone and beta-endorphin, glucocorticoids, and catecholamines such as norepinephrine and epinephrine. Stress response is normative and part of well- being, and people need stress to respond to daily challenges. There is an optimal level of stress, however, that we would like to operate under, and overwhelmed stress and coping mechanisms disrupt key stress 25 ------- regulators and can result in impaired growth and development and a number of endocrine, metabolic, autoimmune and psychiatric disorders. Asthma is a disorder of immune disruption, so it is reasonable to think that asthma risk is affected by disruptions in the stress system. There are critical windows during pregnancy and during the first two years of life when the respiratory system is rapidly developing, and thus these are critical windows where toxins like stress can alter lung development and structure and result in disorders such as asthma. This is not dissimilar to the story with tobacco exposure which is another known main driver of asthma risk in early life. Evidence suggests maternal stress during pregnancy alters the child's developing immune response. The Asthma Coalition for Community, Environment, and Social Stress (ACCESS) study used a prospective pregnancy cohort to quantify exposure to stress during pregnancy and early life to see health effects later in life and the dose effect of chronicity and severity of experienced stress. The cohort consisted of 955 pregnant women recruited from community health centers in Boston, Massachusetts from 2002 to 2009. These women had low socioeconomic standings (SES), 65 percent of whom had less than a high school education. The study used life event measures covering many life domains, including financial strain, relationship problems, racism discrimination, community violence, domestic violence, and maternal experiences prior to pregnancy, to quantify maternal cumulative stress. The study found that stress coping methods were overwhelmed when the mother experienced adverse events across multiple domains and adverse health outcomes occurred in a dose-response manner (i.e., the higher the stress, the greater effect on asthma risk in the child). When examining the relationship for prenatal and postnatal maternal stress and child repeated wheeze by age two to three years, both prenatal and postnatal wheeze showed a strong linear dose-response relationship to in-utero exposure to maternal stress. When adjusted for other exposures such as ambient air, tobacco, and diet, there was still a strong independent effect of stressors on child wheezing. The same study also looked at the relationship of exposure to maternal stress during pregnancy and up to two years to asthma in children followed up to seven years of age. The study found that postnatal stress impacted asthma rates in both boys and girls and found a positive increasing trend for in-utero exposure to maternal stress and asthma particularly in boys. This sex difference in response alludes to vulnerability of boys and some protection of girls from in-utero exposure to stress. The study then examined if the level of stress or if a particular period of exposure was driving asthma and found that chronicity of stress also matters and early life toxic stress that was high in both the prenatal and postnatal periods was associated with lower levels of lung function by age seven years. This is concerning as those with reduced lung function by age six to seven years have been found to be at greater risk for chronic obstructive lung disease and cardiovascular disease in adulthood as well at early mortality. In other studies done by Wright's group, cumulative prenatal stress in women has also been associated in a dose-response manner with altered immune function in infants at birth. Children with mothers who have higher day-to-day Cortisol levels, a biomarker indicative of higher stress, have also been found to be at higher risk of early respiratory problems. In other work by Wright's group, stress is identified as a key factor contributing to health disparities. Studies have shown that African-American women have the highest exposure to traumatic and non- traumatic stressors over their lifetime and more often suffer from post-traumatic stress disorder (PTSD) 26 ------- than women of other ethnicities. African-American women are more likely to report a history of childhood abuse and have higher levels of hair Cortisol across all three trimesters of pregnancy when compared to White women. Hispanic women also had significantly higher hair Cortisol levels than White women during pregnancy but lower levels than African-American women. These differences in in-utero exposures by ethnicity may result in health disparities in children as well as adults. Providing a better quality of life with fewer stressors from the beginning of life may have long range benefits throughout the life course. This is why the prenatal and early childhood periods are potentially the most effective lever for reducing chronic disease risk. Students Break the Cycle of Environmental Health Disparities Leslie Rubin, M.D. | Southeast PEHSIJ at Emory University and Morehouse School of Medicine Dr. Leslie Rubin remarked that previous presentations have done a great job explaining and providing evidence to what the health disparities are, and his presentation will focus on strategies to reduce these disparities and promote health equality, particularly in the Southeast. The Southeast was an area greatly affected by slavery and the civil war, and therefore it is no accident that it is the region with the greatest degree of health disparities. Poverty is a powerful force in health disparity issues, but also includes ethnicity, racial discrimination, drug and alcohol abuse, access to good health care, exposure to violence, and home insecurity, and children are the most at risk for these health disparities. The built environment is one factor that is greatly affected by income and plays a large role in health disparities. Poor communities are often unsafe due to traffic crime, trash, lack of access to grocery stores, and have limited green space, resulting in increased obesity among people in these communities, which in turn contributes to an increase in associated diseases such as diabetes and hypertension that reduce life expectancy and quality of life. Poor communities are also more likely to be exposed to contaminants such as lead from older homes and schools in poor condition. People in poor communities are exposed to more indoor and outdoor pollutants and children in those communities are three times more likely to suffer from and die from asthma. In addition, poor communities also have less access to education resources making students less likely to graduate and more likely to be unemployed and go to jail, which is extremely costly. Lower education levels are also associated with smoking. These cumulative and chronic health disparities are part of a self-perpetuating cycle involving social and economic, residential, environmental, health, and compounding factors. These cumulative factors and their consequences contribute to an intergenerational cycle which he termed the Cycle of Environmental Health Disparities. A collaborative effort between the Southeast PEHSU and Innovative Solutions for Disadvantage and Disability (ISDD) a private not-for-profit community organization created a program called Break the Cycle of Environmental Health Disparities to address these persistent health disparity issues that so dr. The program invites university students from all disciplines to develop projects that will break the cycle of environmental health disparities in children at any point. The students are required to have university faculty mentors and are guided in their projects by the Break the Cycle faculty and in the process are educated on environmental health and health disparities. At the completion of their projects, the students 27 ------- are required to present their project at a national meeting and to write up their project for publication. Examples of projects from the past Break the Cycle program were: Endocrine Effects and Metal Exposure in Children of Agricultural Working Mothers in Thailand, Racial and Socioeconomic Status (SES) Profiles in People Living Near Power Plants, Impact of Housing on Body Size and Pubertal Timing, Environment, Malnutrition and Teenage Mothers in Lusaka, Zambia, Community Supports Lessen Health Disparities for Premature Infants, and Home Environment, and Low Income and the Primary Care Medical Home. The goals of the program are to raise awareness of children's environmental health and environmental health disparities and to cultivate future leaders to continue to address these disparities far into the future. To date, Break the Cycle has had ten annual programs; has supported 93 students in 27 university departments; from nine U.S. states, Latin America, Europe and Africa; and has resulted in eight international journal supplements and six books. A program survey showed that the program is effective at increasing knowledge in children's environmental health and disparities and influencing participant's future career choices. This simple program with simple funding can make a big difference in future health disparities. The program supports the Southeast PEHSU's goal continue to address health disparities now and well into the future to reduce environmental health disparities as much as possible. CalEnviroScreen and Potentially Preventable Childhood Morbidity in California's Central Valley Emanuel Alcala, M.A. | Central Valley Health Policy Institute Mr. Emanuel Alcala thanked the meeting organizers for the opportunity to participate in the meeting and explained that his presentation will be focused on CalEnviroScreen and Potentially Preventable Childhood Morbidity in Central California. Central California, particularly the San Joaquin Valley, is more rural than southern California and CalEnviroScreen was California EPA's tool to measure cumulative impacts and population characteristics of communities identified by the tool as disproportionally burdened by pollution and exposure. The tool combines a population characteristics score and a pollution burden score to calculate the screening tool indicator to identify high risk and heavily burdened communities. The population characteristics score includes age, education, linguistic isolation, poverty, race/ethnicity, asthma, and low birth weight. The pollution burden score consists of ozone, PM, diesel PM, pesticides, toxic release inventory, traffic, cleanup sites, groundwater threats, hazardous wastes, impaired water bodies, and solid waste. The tool's objectives are to identify poor health outcomes in children and the tool components that are associated with childhood morbidity. The variables considered included children under 15 years old who resided in San Joaquin Valley from 2007 to 2012. Independent variables included age, gender, race/ethnicity, and zip code. The analysis used multilevel modelling that allowed data measurement at the individual- and zip code-level. The model first identified the variance in Hospitalization for ambulatory care-sensitive conditions (ACSC) including asthma, respiratory infection, and pneumonia. Then the model entered the CalEnviroScreen Score and separately entered the pollution burden score and population characteristics score to find the association between screening score components and ACSC. Mr. Alcala presented a table describing the hospitalization rates, or cases, by patient demographics in the San Joaquin Valley. Children from zero to four have the highest hospitalization rate by a 3-fold. African 28 ------- Americans have the highest rate of hospitalization from any racial/ethnic group, but due to the small percentage of the population and clustering effects in zip codes, these associations were not strong. The San Joaquin Valley population is mainly Mexican-Americans who exhibited a protective factor when compared to Whites. The tool model building strategy found that events vary by 23 percent between zip codes and the CalEnviroScreen Score accounted for 23 percent of that variance. There was also a positive association between the tool score and ACSC with a higher score associated with higher rates of hospitalization. The next step was to enter the pollution burden score and analysis found that the score only accounted for one percent of ACSC. However, the poverty rate accounted for 31 percent of ACSC. When the population characteristic scores were broken out into individual components, four indicators were highly correlated to ACSC in San Joaquin Valley: poverty, race/ethnicity, linguistic isolation, and education. Diesel particulate matter (DPM) was the only pollution burden characteristic that was significantly associated with ACSC. It accounted for a small but consistent and independent effect on hospitalization rates. Linguistic isolation, race/ethnicity, and education contributions to ACSC can be explained by poverty. From these results, one can see that the CalEnviroScreen can identify communities with poor health outcomes in children, specifically communities with the largest burden for hospitalization. The components of the CalEnviroScreen tool associated with childhood morbidity are poverty, race/ethnicity, linguistic isolation, education, and DPM. In addition, including neighborhood poverty eliminates the impact of individual race/ethnicity on health disparities. Session 4 Questions, Answers, and Comments Dr. Geller thanked the speakers for their presentations and invited them up to the podium for a panel discussion. He mentioned that EPA released the EJScreen tool, which pulls together social and environmental factors and provides an index that targets high risk communities, similar to the CalEnviroScreen tool that tells users locations where deeper examination should occur. Irva Hertz-Picciotto, UC Davis, cautioned against using the term "protective" when discussing results of health disparities analysis, because one of the factors that could be affecting lower hospitalization in a particular health disparity group could be that one group is not seeking medical care. This is seen in families with undocumented members in particular. Mr. Alcala responded that a large population in the San Joaquin Valley is undocumented and the reason the CalEnviroScreen analysis did not further investigate this was because they wanted to make a stronger point toward their indices. Kathleen Alexander, Virginia Polytechnic Institute and State University, asked what the vision is for seeking behavioral impacts on health and how vulnerability should be examined in that context. Mr. Alcala responded that ultimately the field needs better measures. He explained that other studies have examined the Hispanic paradox, or the finding that Hispanics tend to have lower mortality rates in poorer communities. When these studies adjust for age at death, African Americans are dying prematurely, so different measures need to be developed to identify the causes of premature death within that group. Dr. Wright added that population groups can be further broken down to give a more accurate examination of health disparities. For example, prevalence of morbidity from asthma is lower in Mexican Americas 29 ------- than Latinos, but that cannot be observed when Latinos are all grouped together. Dr. Rubin built off the issue of generalization and noted a publication on the heat crisis in Chicago in the mid-1990s. There was a higher number of deaths in Cook County than surrounding counties and when that number was further broken down, there was a higher proportion of average number of deaths in from African Americans than in Hispanic populations. The higher proportion of deaths could be attributed to African Americans who were old and lived alone in abandoned neighborhoods. Latinos typically have a rich sense of community. This attests to the value of social capitol in terms of individual and communal resiliency. Liam O'Fallon, NIEHS, asked what the public health message to pregnant women is from this discussion. In particular, knowing the health effects of in-utero exposure to stress, how this research would be translated in messages for pregnant women without stressing them out. Dr. Wright stated that this information needs to be delivered by clinicians. Physicians can validate that pregnant women need to reduce stress, discuss what those stressors are, and make a plan to eliminate those stressors. Additional approaches to translating this research include pregnancy centers that provide the opportunity for pregnant women to come together to discuss and share ways to reduce stress and by fixing poverty so poor women have less stress during pregnancy. Talking to people about the importance of stress and stress management is the most effective way to address this problem. Dr. Wright added that she has sent a lot of people to therapy and has seen a great reduction in their medical symptoms as a result. She has seen patients come off of steroids and other medications and asked meeting participants to think about different interventions that might work in different communities. She added that she hopes resources that allow medical practices to be reimbursed for mental health services are provided on a large scale in the near future. Kimberley Gray, NIEHS, noted that the earlier session speakers gave great recommendations on where the scientific community should head. Given all of the scientific evidence about the harmful effects of stress, diet, DPM, etc., she asked who the target audience for translating this information to is. She asked if it should be at the maternal or household level and if NIEHS is missing a specific population that this information can be disseminated to so as to avoid burdening mothers with additional messaging. Dr. Wright stated that it is easier to create a strong child than it is to repair broken adults. She recommended that NIEHS focus their efforts in the critical windows of early child development, specifically during pregnancy and early childhood. Obstetricians need to be educated on prenatal and early childhood environmental exposures, such as chemical and stress exposures, to address the issue that pregnant mothers are not thinking about how their exposures affect their child later in life. Dr. Diette explained the success of the Clean Air Act and noted that it is one of the most important public health regulations in the United States. The recent reduction in the permitted level of ozone is great, but it is not enough. He suggested that scientific research align with regulation review requirements so they can be used as evidence to support regulatory standards. Harmonization is key and Dr. Diette asked meeting participants to think about how their research could respond to regulator needs and be translated into policy when conducting future studies. Dr. Rubin agreed and noted that collaboration between agencies should take place to break the cycle of health disparities, address issues of poverty and race discrimination, and invest in education of young people. Addressing these issues will also benefit society as a whole and result in a positive feedback loop. Dr. Wright noted the indirect chemical environment and nutrition program that has shown the success of educating patients on how stress and diet can offset the toxicity chemical and 30 ------- ATnonchemical stressors that can be impacting their health. Similar programs can be done and have positive health impacts now. Dr. Geller noted that policy decisions are any opportunity for improving health outside of the clinic. HIAs include all of the factors that have been discussed and are essential to policy assessments. NIEHS and EPA should work together to ensure a comprehensive review of all the factors that play a role in a specific health outcome so that the appropriate considerations are included in the policy decision making process. Sally Darney, NIEHS, noted the issue of teenage pregnancy prevention and how this issue touches on interrelationship between poverty and culture. Poor communities are often more accepting of early pregnancies and large families. Family planning should be accessible and free in these locations and there is currently a lot of policy discussion surrounding this issue. David Evans, Columbia University, noted that the scientific community needs to think about developing a set of guidelines for straightforward and simple messages that can be easily disseminated by physicians. For example, successful asthma guidelines were developed for messaging to reduce risk of asthma. Physician practices and outside interest groups can use these guidelines as a standard to apply to their own materials when looking to advise parents on things to check for in the home and environment. Jennifer Lowry, Children's Mercy Hospital, noted that effective messaging is what PEHSU is tasked with doing. PEHSU is focused on creating guidelines for effective messaging and there are a lot of factsheets on www.pehsu.net that address the messaging issue. Linda Birnbaum, NIEHS, noted that the opportunity with PEHSUs is larger than was originally realized. She added that putting things on a website is not adequate communication and asked meeting participants to think about what is needed by women and children health care providers and the need to think more broadly than pediatrics. Session 5 - Lifestage Approach to Prematurity Moderated by Michael Hatcher, Ph.D. | Chief, Environmental Health Branch, ATSDR, CDC Dr. Michael Hatcher of the CDC explained that the goal of the Health Resources and Services Administration (HRSA) is to integrate environmental risk and exposure and to protect the 40 million people the program serves. He has found that working with the next speaker, Dr. Michael Lu, has been a great opportunity. The Life Course Perspective and Children's Environmental Health Michael Lu, M.D., M.S., M.P.H. | Heath Resources and Services Administration Dr. Michael Lu explained that his presentation will describe the life course perspective and the implications for children's environmental health. HRSA's Maternal and Child Health Bureau (MCHB) envisions an America where all children are healthy and have a fair shot to reach their fullest potential. Dr. Lu has a staff of 180 and an annual budget of $1.3 billion, about half of which goes to support the Title 31 ------- V Maternal and Child Health Services Block Grant which funds the public health system for maternal and child populations in 59 states and jurisdictions. The Block Grant also supports special projects of regional and national significance, including the MotherToBaby network through the Organization of Teratogen Information Specialists; a third of this support goes to the Maternal, Infant, and Early Childhood Home Visiting Programs and the rest goes to support a myriad of MCHB programs. MCHB categorical programs include topics such as autism and other developmental disabilities, traumatic brain injury, sickle cell service demonstration, universal newborn hearing screening, heritable disorders, emergency medical services for children, Family-to-Family information centers, and Healthy Start. MCHB runs approximately 100 different programs that touch the lives of more than 42 million women, children, and families, including half of all pregnant women and one- third of all infants and children in our nation each year. The MCHB can be thought of as a platform and partner for improving children's environmental health. Simply stated, the life course perspective is a way of looking at life not as disconnected stages, but as an integrated continuum. It is a conceptual framework—or paradigm shift—which recognizes that each stage of life is influenced by all the stages that precede it, and it in turn influences all the life stages that follow it. The life course perspective consists of two components: an early programming component and a cumulative pathways component. The early programming model posits that experiences and exposures early in life (i.e., in utero) can influence a child's health and function for life. This is the basis for the Barker Hypothesis, which is a series of studies that discovered a relationship between low birth weight and increased risk for coronary heart disease, hypertension, and diabetes later in life. Low birth weight adds to the risk factors that are typically associated with heart disease, such as smoking, high blood pressure, high cholesterol, and obesity. Barker and his colleagues hypothesized that there are critical periods in development during which the functions of an organ or system are being programmed, and if something goes wrong during fetal programming, then that organ or system may not function optimally over the entire life course. For example, if malnutrition were to occur for the fetus in the second trimester when the pancreas and kidney are rapidly developing, the pancreas could be smaller with fewer beta cells and/or the kidneys could be smaller with fewer nephrons, which would increase the child's susceptibility for diabetes and/or kidney diseases later on in life. Over the past two decades, there has been much scientific evidence to support the concept of fetal programming. Dr. Lu described his research at the University of California, Los Angeles (UCLA) that examined the effects of maternal stress on the fetus during pregnancy. Maternal brain and body stress hormones can cross the placenta in various ways: through incomplete inactivation of maternal Cortisol by 11B hydroxysteroid dehydrogenase (HSD), which can be exacerbated by stress or inflammation, or through activation of placental corticotropin-releasing hormone (CRH), which in turn activates the fetal HPA axis. In a sense, the baby bathes in these stress hormones, priming the fetal brain for stress and resulting in prenatal stress. The hippocampus and amygdala are two areas in the fetal brain that are particularly vulnerable to the neurotoxic effects of glucocorticoids. Maternal stress results in fetal exposure to high levels of glucocorticoids (Cortisol in humans and corticosterone in animals) which can downregulate or decrease 32 ------- the number of glucocorticoid receptors in the hippocampus and upregulate or increase the number of glucocorticoid receptors in the amygdala. The hippocampus is responsible for learning and memory formation. In animal studies, rats exposed to a great deal of prenatal stress have difficulty forming memories and learning new tasks. The amygdala mediates anxiety and fear, and rats exposed to a great deal of prenatal stress show increased anxiety and fear in aversive situations. The hippocampus and the amygdala regulate your hypothalamic-pituitary-adrenal axis, which mediates your fight or flight response. The hippocampus can bethought of as a brake pedal that halts action of the HPA axis, and the amygdala can be thought of as an accelerator pedal that stimulates the actions of the HPA axis. Downregulation of the number of glucocorticoid receptors in the hippocampus reduces the sensitivity of the brake pedal and upregulation in the amygdala results in an increase in accelerator sensitivity. This results in a hyper-reactive HPA axis (facilitating the fight or flight response) and is the mother's way of preparing the fetus for the outside world. In the short run, this hyper-reaction could have survival advantages, but in the long run it could have some serious health and developmental consequences. There are 13 studies that link maternal anxiety and stress during pregnancy to increased risk for attention-deficit/hyperactivity disorder (ADHD), suggesting that stress hormones influence the hardwiring of the fetal brain with long-term health and developmental consequences. Epigenetic regulation, or the ability to control gene volume, plays an important role. Gene expression can be modified by a methyl group (i.e., one carbon and three hydrogen atoms) at the front of a gene. Generally speaking, methylation turns off gene expression, whereas demethylation turns gene expression on or up. It is thought that exposure to prenatal stress may control the expression of fetal brain glucocorticoid receptors by simply methylating or demethylating the DNA. Two genetically identical individuals may have different levels of stress reactivity based on whether genes are methylated or demethylated. This attests to the importance of maternal stress in a child's health and development over a lifetime. The epigenetics phenomenon has been demonstrated in mice where different phenotypes and eating behaviors were exhibited by genetically identical mice. Differences in the expression of the agouti gene can change the animal's fur to blond or cause them to overeat, resulting in a higher risk for obesity, diabetes, and cancer later in life. The difference in agouti gene expression was the result of different maternal ingestion levels of folic acid during pregnancy. Folic acid is rich in methyl groups and can methylate or silence the obesity gene during pregnancy. Epigenetics provides great opportunity for intervention by controlling gene expression to prevent disease even before a child is born. This may not be a possibility in the near future, but this study shows how early nutrition can influence DNA methylation resulting in lifelong, and perhaps intergenerational, impacts on health and function. The second component of the life course perspective is cumulative pathways, which posits that chronic biological and psychological stress can cause wear and tear on the body's adaptive system, leading to a decline in health and function over time. Allostasis, or the body's self-regulating process to maintain stability, works well for fight or flight stress, but the body can lose its ability to self-regulate in the face of repeated or chronic stress. The elevated levels of Cortisol during chronic stress start to downregulate the glucocorticoid receptors in the brain, increasing the circulating levels of stress hormones, and causing individuals to produce more stress hormones than normal in response to stressful events. These events 33 ------- activate a sympathetic response that can lead to increased, chronic, and uncontrolled cardiac output which, over time, can lead to hypertension and cardiovascular diseases. Stress activates the body's HPA axis to produce the glucocorticoid (i.e., Cortisol), which mainly functions by converting stored energy into usable energy (i.e., glucose) through partially impeding insulin action. The HPA axis cannot be shut off when chronically stressed and excess glucocorticoid over time can lead to glucose intolerance and insulin resistance. This stressed out state can cause damage to the body as opposed to protecting it. Chronic stress also reduces the ability of the HPA axis to downregulate the immune system, wearing it out, depressing the immune function, and increasing the risk of infections and inflammation. Uncontrolled inflammation results in an increased likelihood of chronic diseases such as hypertension, diabetes, heart disease, Alzheimer's disease, lupus, nephritis, and all autoimmune diseases. Pregnant women can be more susceptible to infections like bacterial vaginosis, which can increase their risk for preterm birth. Lastly, acute stress can increase the growth of neurons inside the hippocampus and prefrontal cortex, the learning centers of the brain that allows us to learn from mistakes. Under chronic stress, however, neuron atrophy and death occur in these learning centers causing forgetfulness and memory loss. A 2007 report from the Institute of Medicine Committee discussed the need to rethink the causes of and preventative measures to address preterm birth. The cause of preterm birth was previously thought to originate during pregnancy or at the time of labor but is now thought to be due to maternal exposure, stress, and infection over her lifetime. This would support the need for more preconception care for women to stabilize stress. To improve children's health, further research and investment is needed to understand the types of exposures that matter the most. The most important influences on children's health (e.g., nutrition, toxic stress, and environmental exposures) are the things that are least examined in clinical practice. Ob-gyns and pediatricians must be adequately trained and equipped to deal with these issues. The American Academy of Pediatrics has been discussing the use of a team-based approach that includes health educators, social workers, and dieticians to address these issues. Reducing maternal exposures—not only during pregnancy but throughout her life course—is urgent and critical for ensuring healthy children. A target for this action should be communities with limited access to this type of information to help ensure that all children are healthy and have a fair shot in life. Session 5 Questions, Answers, and Comments Susan Buchanan, University of Illinois at Chicago, said she was thrilled to see Dr. Lu reaching out to meeting participants to foster future collaborative efforts. She took the opportunity to advise attendees that every other month the PEHSUs meet with the MCHB to discuss areas for collaboration. PEHSU is working with the MCHB as it already recognizes that environmental exposures are critical during preconception, in-utero, and adolescent stages, and PEHSU consists of the nurses and public health specialists who work with mothers to educate them on the risks described at this meeting. Susan asked for concrete actions that the MCHB is going to take to incorporate children's environmental health into their work and proceeded to answer her question with a recommendation that MCHB fund PEHSUs either through the Children's Centers or through a program that would train the next generation of public health 34 ------- professionals. Dr. Lu responded that the children's health scientific community first needs to determine what the goals for the state of the science by 2020 so that a national strategy can be developed that ensures the work is completed and the information reaches everyone who could benefit. He explained that this should be a collaborative effort between EPA OCHP, CDC, and other stakeholders. He suggested they come together on a regular basis to form a common vision and strategic plan for reaching 2020 goals. Edward Levin, Duke University, noted that he would like to avoid environmental contamination that harms children's health but asked the attendees to not abandon those children already harmed. This effort needs to include adequate treatment for children that are victims of past exposure. Dr. Lu explained that it is important to look at this issue from a life course perspective so as to avoid looking at prevention in buckets or silos but rather as a comprehensive strategy. Looking at exposure as a continuum across all life stages is what is needed to prevent and treat exposures. Paul Wax, American College of Medical Toxicology, explained that the American College of Medical Toxicology has a national program dedicated to health care professionals who work on these issues, but they can only do so part time due to lack of resources. He noted the opportunity to build upon what has already been created over the past ten years to help underserved populations gain access to this health care information. Session 6 - Neurodevelopmental Disorders Moderated by Susan Schantz, Ph.D. | University of Illinois at Urbana-Champaign Lessons Learned From the New Bedford Cohort Study Susan Korrick, M.D. | Harvard University Dr. Susan Korrick discussed the results and implications of research in the New Bedford Cohort Study, with a specific focus on prenatal polychlorinated biphenyl (PCB) exposure and subsequent neurodevelopment in children. She began her presentation by giving a brief background on PCBs, a family of structurally related compounds used in a wide range of industries for several decades before being banned in the United States in the late 1970s. Due to their chemical properties, PCBs accumulate in the environment and in the human body. Populations continue to be exposed, though at relatively lower levels than in the past. Also PCB production as an inadvertent by-product of pigment manufacturing, and unrelated to past legacy industrial use, has been described in recent years. In particular, green, blue, and yellow pigments can contain non-trivial PCB concentrations and are found in household paints, cosmetics, plastics, newsprint, magazines and other products. She explained this new source of PCB exposure has a unique congener profile compared to legacy PCBs and the potential health effects are not yet understood. Dr. Korrick then gave an overview of the current evidence of the association between PCBs and adverse childhood neurodevelopment. Prenatal PCB exposure appears to have the most deleterious effects and is related to memory function in a variety of contexts, including novelty preference, short- and long-term memory, and working memory. Fetal exposure to PCBs is also associated with negative impacts on impulsivity and attention, which are deficiencies characteristic of ADHD. 35 ------- Next, Dr. Korrick discussed the New Bedford Cohort (NBC) Study, which is comprised of 788 children born between 1993 and 1998 to mothers living in one of four communities near the New Bedford Harbor, a PCB-contaminated Superfund site. The aim of the study is to assess the impact of early-life exposures to a host of suspected neurotoxicants (e.g., metals, organochlorine pesticides, and PCBs) on child neurodevelopment and growth. Dr. Korrick noted that the mothers in the cohort are majority white with a large proportion low-income, unmarried, and with low educational achievement (high-school education or less), which generally reflects the population of New Bedford at the time of study recruitment. In comparison to nine other child development cohorts considering PCB exposure, the NBC study population had the lowest cord serum PCB concentrations. Many of these other cohorts had two-to four- fold higher concentrations than the NBC. Infants enrolled in the NBC study were assessed using the Neonatal Behavioral Assessment Scale (NBAS), which tests neonatal reflexes in addition to a battery of behavioral and supplementary items. The NBAS has been shown to be sensitive to a number of risk factors, including prenatal drug exposures, prematurity, and PCB exposure. To capture an attention measure in neonates, Dr. Korrick and her research team identified three NBAS measures of interest: alertness, quality of alertness, and cost of attention (i.e., how hard the baby has to work to participate in the exam). Across increasing quartiles of cord serum PCB levels, these babies scored more poorly on these attention measures even as neonates. At six months of age, infants were administered the Fagan Test of Infant Intelligence to assess visual memory and information processing efficiency. The Fagan Test is based on the principle that an infant should prefer to look at novel stimuli, which presumes the baby remembers something they have already seen is old. The test has two components. The first is the familiarization trials, where the baby is shown faces that it must learn. The second component is the novelty trials, where the baby is shown a learned face and a novel face and the proportion of time the baby spends looking at the novel face is a reflection of the baby's memory. The Fagan Test has been shown to be predictive of subsequent cognitive function. Dr. Korrick reported that when overall novelty preference was assessed, they observed no association with cord serum PCB levels. When the investigators considered only trial one novelty, which is a part of the Fagan Test and is a classic visual-memory paradigm without bias in the choice of faces or the order of the trials, they observed substantial decrements in novelty preference associated with increasing cord serum PCB levels. PCB-associated decrements in frequency of fixation were also observed. Dr. Korrick underscored the importance of carefully considering outcome measurements in analyses; for example, a priori identification of specific aspects of the outcome that are most relevant may achieve greater granularity than is possible with a more standard analytic approach. Dr. Korrick then explained the behavioral assessments conducted on the children at eight years of age. The Conners' Rating Scale was given to the child's teacher, who answered the 59 item questionnaire that rates problem behaviors in children. The four Conners' subscales analyzed were all related to behaviors characteristic of ADHD. These were the overall Conners' ADHD Index, in addition to three subscales that are based on clinical diagnostic criteria defined in the Fourth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV): DSM-IV inattention, DSM-IV impulsivity-hyperactivity, and the DSM-IV combined subscale. Dr. Korrick and her research team dichotomized the continuous outcome scores and considered the PCB-associated risk of having mild to moderately atypical ADHD-related 36 ------- behavior according to the Conners' Rating Scale. Across the different Conners' measures related to ADHD, there was a substantially increased risk of mild to moderate atypical behavior with increasing cord serum PCB levels. She noted that the association was stronger for the inattention subscales compared to the hyperactivity subscales, and that much of the increased risk was observed in the highest quartile of cord serum PCB concentrations. Dr. Korrick indicated that this suggests a potential for a threshold dose response relationship in the NBC. To complement the understanding of attention skills, the Neurobehavioral Evaluation System 2 (NES2) Continuous Performance Test (CPT), was used at age eight years. A CPT is a computer-based test that measures inattention and impulsivity. For the NES2 CPT, children were shown images of animals at random intervals and were instructed to press the key only when the image of a cat appeared. The CPT assesses the child's response time as a measure of attention, the number of errors of omission (e.g., when the child failed to click when a cat appeared) and the number of errors of commission (e.g., when the child clicked when an animal other than a cat appeared). The strongest finding of the CPT analysis was an association of higher cord serum PCBs with greater errors of omission, which is reflective of inattention. This association was sexually dimorphic; it was observed in boys but not in girls. Finally, Dr. Korrick discussed the results of the Wechsler Intelligence Scale for Children, Third Edition (WISC-III), which is an IQtest that the researchers conducted on their participants at age eight. There are two components of the WISC-III on which children with clinical ADHD often do poorly: processing speed and freedom from distractibility. Analyses of these two components of the WISC-III also suggested sexual dimorphism, with PCB-associated decrements in processing speed in boys but not in girls. Dr. Korrick discussed an analysis that considered whether there were potentially spatially variable risk factors associated with ADHD in the New Bedford Cohort. She showed a map of predicted Conners' Rating Scale ADHD scores based on residential address at time of birth. The image indicated hot spots with high ADHD scores west of the PCB contaminated New Bedford Harbor and cold spots with low ADHD scores in other areas. When the results were adjusted for socioeconomic indicators, the geographic variability in Conners' Rating Scale scores disappeared. Dr. Korrick explained that this reinforces the importance of considering all of the important risk factors, including sociodemographic risk factors, for behavioral outcomes in additional to chemical risk factors in analyses. Dr. Korrick reiterated that with systematic consideration of outcome measures, she and her colleagues were able to see decrements in basic skills that underpin intelligence associated with low-level cord serum PCB levels in children, including memory, attention, and information processing skills. She also noted that, when considering attention, these PCB-associated differences could be ascertained as early as infancy. This is critical in building a cohesive understanding of the impact of prenatal PCB exposures on attention- related skills in school-aged children as well as understanding the influence of PCBs and other contaminants as risk factors for clinical ADHD. The Long-Term, Brain-Based Effects of Prenatal Exposure to Two Environmental Neurotoxicants Bradley S. Peterson, M.D. | Children's Hospital Los Angeles 37 ------- Dr. Bradley Peterson presented on the effects of prenatal exposure to pesticides and air pollution on the developing brain. Dr. Peterson discussed the critical importance of neurodevelopmental events that occur during gestation. In the first half of gestation, neurons multiply rapidly. By mid-gestation, the full complement of what will become adult nerve cells has been established. These newly formed neurons must then migrate and form dendrites and axons to connect to other neurons to form synapses. Some of these processes, such as synapse formation, extend into early postnatal life. Most of these developmental processes are complete by the age of five. Other processes that refine the neurological "hardware" established in early life can continue into adulthood. For example, myelination begins around the time of birth and extends well into adulthood. Neuronal apoptosis also occurs during mid-gestation through the first few months of life, as early prenatal proliferation achieves nearly 150 percent of the neurons necessary for typical neurological functioning. He explained that each of these maturational events is uniquely vulnerable to the timing and type of environmental neurotoxicant to which a developing fetus might be exposed. Dr. Peterson discussed the impacts of chlorpyrifos, a pesticide used widely during the 1960s for residential pest control and agricultural purposes. In the early 2000s, EPA banned the indoor residential use of chlorpyrifos. However, it continues to be popular choice in the agriculture industry worldwide and remains in the food supply. Animal models have shown that prenatal chlorpyrifos exposure is directly toxic to the developing brain and nervous system. He showed images of normal rat neuroepithelium and a similar tissue sample taken from a rat prenatally exposed to chlorpyrifos. Compared to the control sample, the chlorpyrifos-exposed sample appears disorganized, with cell boundaries effaced and dark, abnormal nuclei. Despite the animal evidence, Dr. Peterson explained there was a lack of direct evidence of chlorpyrifos toxicity in the developing human brain. The Columbia University Children's Center sought to understand this relationship by recruiting 720 women 18-35 years of age from minority communities in northern Manhattan. Chlorpyrifos exposure was ubiquitous in this sample, and was detected in 99 percent of residential air samples as well as 70 percent of maternal and umbilical cord blood samples. Prenatal exposure to chlorpyrifos was associated with lower birth weight, poorer mental and motor development at age three, more ADHD symptoms at age three, and lower IQ scores at age seven. Dr. Peterson endeavored to understand the biological basis for these neurodevelopmental impacts by conducting an MRI study of chlorpyrifos-exposed children. Forty children of the original 720 mothers recruited by the Columbia University Children's Center were enrolled in the MRI study. Children 6-10 years of age were divided into high- and low-exposure groups, represented by the highest tertile of exposure or the middle and lower tertiles, respectively. Dr. Peterson compared the brain structure (i.e., the volume of brain tissue at each point across the surface of the brain) across the two exposure groups. Dr. Peterson showed a video that represented the samples that he identified in the preliminary sample of 40 children. At each point on the surface of the brain, millimeter by millimeter, the relative volume of tissue was represented by different colors, with turquoise indicating the two exposure groups did not have significantly different tissue volumes at that point. Purple indicated a significantly lower volume of tissue in the high-exposure group compared to the low-exposure group, while yellow and red shading signified a significantly larger tissue volume in the high-exposure group compared to the low-exposure 38 ------- group. The frontal lobe was enlarged on both sides, both on the lateral and medial surfaces of the brain. When prenatal chlorpyrifos exposures were plotted against brain tissue volume, a linear relationship was observed in the high-exposure group, which indicates the presence of a dose-response relationship. Regional enlargements in the parietal and temporal lobes have a linear dose-response relationship with full scale IQ in the low-exposure group; however, the relationship is eliminated in the high-exposure group. Dr. Peterson explained that a more formal statistical analysis suggested that the enlargement in the brain accounted for the observed discrepancies in IQ at 7-9 years of age. Dr. Peterson stated that the cellular basis for the observed neurodevelopmental impacts are unknown, but based on animal models, chlorpyrifos is known to be toxic to neurons in the developing brain. Scar tissue develops around the damaged neurons in response to cell injuries and it is speculated that the enlargements in human brains likely represent scarring from prenatal exposure. Next Dr. Peterson discussed the effects on the human brain that are associated with prenatal exposure to air pollutants, focusing specifically on polycyclic aromatic hydrocarbons (PAHs). PAHs are ubiquitous and toxic environmental contaminants generated by the incomplete combustion of organic materials. Significant contributors to PAH concentrations include diesel- and gasoline-powered vehicles, waste incinerators, and oil- and coal-based heat and electricity generation. PAHs have the ability to cross the placenta and, based on animal models, are known neurotoxicants to the developing fetal brain. Dr. Peterson explained that a second MRI study, considering third trimester PAH concentration as the exposure of interest, was conducted on a different sample of 40 children 7-9 years of age from the Columbia University Children's Center. Dr. Peterson displayed an image of an MRI scan, where purple indicated an inverse correlation between PAH concentration and brain tissue volume, red or yellow signified a positive correlation between PAH concentration and brain tissue volume, and green represented no significant correlation. He explained that a high number of inverse correlations were observed in the left hemisphere of the brain, but a similar effect was not observed on the right hemisphere. When associations with the underlying white matter were assessed, the magnitude and spatial extension of the effect were much larger on the left side of the brain. Dr. Peterson suggested this shows the abnormality in the surface of the brain is not coming from the grey matter, which is where the synapses are located, but from the underlying white matter. White matter contains the axons that connect one region of the brain to another, and it is this wiring of the brain that appears to be most disturbed. Importantly, in the same regions in the left hemisphere, a reduction in tissue volume is significantly associated with ADHD, aggression, and rule-breaking symptoms. Furthermore, in the right hemisphere, an increase in tissue volume is associated with slowing of cognitive processing speeds. Dr. Peterson noted that similar associations were observed with postnatal PAH exposures through the age of five, even after adjustment for prenatal exposures. These ADHD-related findings at the surface of the brain associated with reduced white matter are very different than wild-type ADHD findings. His research team's initial paper reported bilaterally symmetric volume reductions in brain matter, not white matter, in the frontal and temporal lobes associated with wild-type ADHD. PAH exposure seems to produce a specific morphological subtype of ADHD. Why would PAH affect the brain in such an asymmetric way? We know enough about the molecular processes that control asymmetry in neurological development, with the left and right sides of the brain different in 39 ------- structure and function. It has been suggested that PAHs cause effects through these complicated molecular pathways that control prenatal development. Dr. Peterson noted that prenatal and early postnatal life is a time when all the major architecture of the brain is established and the brain is, therefore, particularly sensitive and vulnerable to the effects of environmental insults. He reiterated that in the Columbia University Children's Center subsample, prenatal chlorpyrifos exposure produced bilaterally symmetric increases in tissue volume at the brain's surface, which is likely a consequence of tissue scarring. The increase in tissue abnormality accounted for the intellectual deficits associated with exposure. Finally, prenatal PAH exposure disrupted proper growth of white matter in the left hemisphere of the brain, which is associated with symptoms of ADHD, aggression, rule-breaking behavior, and cognitive slowing. It's about 4 Million Brains a Year - Toxic Chemicals and the In Utero Environment Tracey Woodruff, Ph.D., M.P.H. | University of California, San Francisco Dr. Tracey Woodruff presented on the effect of in utero exposures to toxic chemicals on neurodevelopment. She opened by stating that about every one in six American children has a neurodevelopmental condition and that neurotoxins, such as lead, mercury, PCBs, pesticides, flame retardants, air pollutants, and arsenic, are detected in more than 90 percent of American pregnant women. Dr. Woodruff pointed out that only a small fraction of the nearly 8,000 high-use chemicals have been subjected to thorough toxicity testing and there are potentially other neurotoxic chemicals that have not been identified. Dr. Woodruff noted that scientists are currently challenged with working through the existing evidence to determine potential health effects. She explained a method that she and her colleagues used to advance the current understanding of the scientific evidence surrounding the effects of polybrominated diphenyl ethers (PBDEs). The project applies an evidence-based systematic review approach to evaluating scientific evidence in a way that reduces the amount of bias and produces a clear summary of the state of the science. She did not go into detail on the specific steps of the approach, but underscored that the method is guided by an a priori protocol and the steps are systematic, transparent, and thorough. In terms of the assessment of PBDEs and IQ, she and her colleagues used this approach to identify 12 studies. Specifically, they considered fetal exposure to BDE 47, a marker for PDBE exposure, and full scale IQ among children between 5-7 years of age. Each of the individual studies indicated that an increase in PDBE exposure during pregnancy was associated with lower IQ in children, but the confidence intervals all crossed the null. Alternatively, the results of the meta-analysis, which increases the power of the analysis, indicated a statistically significant adverse effect on childhood IQ. These investigators also assessed the relationship between childhood exposures to PBDEs and childhood IQ and identified essentially the same findings. As part of the systematic review process, Dr. Woodruff and her colleagues also evaluated the quality of the evidence. The risk of bias of the internal and external validity were evaluated based on criteria used in clinical medicine and originally derived from the Bradford-Hill criteria. Based on these elements, the team found the overall evidence quality for the relationship between PDBE exposure and IQ to be moderate. 40 ------- Dr. Woodruff also discussed the team's counterfactual approach to evaluating strength of the relationship between PDBEs and IQ. The counterfactual approach explores the magnitude of an effect estimate that it would it take to drive the meta-analysis result to a null association. They determined that to nullify the results of the existing studies, a study would need to find that PDBEs improve IQ by a factor of eight. She noted the size and direction of the counterfactual assessment gave indicates that there is sufficient evidence of the toxicity of developmental exposures to PBDEs on IQ. To summarize, Dr. Woodruff presented the results of a completed assessment considering narrative reviews of perfluorooctanoic acid (PFOA) and birth weight conducted using the Navigation Guide. The Navigation Guide determines whether the individual reviews conducted high-quality analyses of the scientific evidence by evaluating the following eight elements: 1. Is there a clear study question? 2. Are the inclusion/exclusion criteria indicated? 3. Is the literature search reproducible? 4. Was the quality of included studies evaluated? 5. Did authors analyze data? 6. Is there a summary findings table? 7. Was the quality of evidence assessed? 8. Were the evidence streams integrated? A high-quality review incorporates all of the elements above. Dr. Woodruff noted that most of the narrative reviews of the association between PFOA and birthweight indicated the study question, but almost never gave any of the other information required to have confidence in the evaluation of the association. Dr. Woodruff pointed out that PBDEs resemble thyroid hormone structurally. She wondered whether scientist might have been able to predict the association to avoid fetal and childhood exposures, adverse neurodevelopmental outcomes, and studies required to assess the relationship. She explained that her goal is to move the decision-making process upstream by using early evidence. Dr. Woodruff reminded attendees that they have the ability to influence science policy. She discussed the Healthy Babies, Bright Futures alliance, which aims to reduce toxic exposures during the first 1,000 days of development. The three elements of Healthy Babies, Bright Futures are translating science into action, a focus on cities, and integrated campaigns. As an example of a successful integrated campaign, Dr. Woodruff noted the group's work to get the furniture industry to remove toxic flame retardants from their products. The goal of the alliance is to ensure that children have the developmental and intellectual capabilities to prosper and participate in their communities. Dr. Woodruff closed by admitting that the road to fully avoiding adverse impacts of industrial chemicals in children is a long one, but new approaches to evaluating the scientific literature and increased activism from the scientific community are critical. 41 ------- From Science to Policy: Targeting Environment and Neuro-Developmental Risks (Project TENDR) llirva Hertz-Picciotto, Ph.D., M.A., M.P.H. | University of California, Davis Dr. Irva Hertz-Picciotto presented on her work in the science-to-policy arena and the Targeting Environmental and Neurodevelopmental Risks (TENDR) project. A sizable and growing scientific literature links a host of environmental chemicals to learning, developmental, and behavioral problems and disabilities. In fact, autism, attention deficits, and hyperactivity disorders rates of diagnoses have been rising steadily for the past 25 years. She noted that only a fraction of the increase in autism can be explained by changes in criteria or diagnostic practice, although the data are still unclear in the case of ADHD. Given the rising rates and the wide array of chemical connections described in the peer-reviewed literature, it is time to consider taking action to reduce these chemical exposures. The mission of Project TENDR is to reduce the exposure levels of environmental chemicals or pollutants that contribute to risks for neurodevelopmental disorders as a means to lowering incidence of these conditions. Dr. Hertz-Picciotto explained that children are born with approximately 100 billion neurons and the proliferation of neurons and synapses occurs rapidly. The prenatal period is therefore a critical window in terms of neurodevelopment. Project TENDR explores the following neurodevelopmental disorders: Autism Spectrum Disorder (ASD), intellectual disability, attention deficits, hyperactivity and other deviant behaviors, learning disabilities, and other neuro-developmental conditions. Project TENDR brings together environmental health researchers, particularly those investigating children's environmental health, representatives from a number of societies of clinical health professionals, environmental health policy makers, and leaders of environmental and child health advocacy organizations. Initially, TENDR set several objectives: 1) to develop a consensus statement that would reflect the need to link scientific evidence to actions to reduce exposures; 2) to identify a specific group of chemicals for which there is a substantial body of evidence of environmental harm, highly prevalent exposures, and feasibility to intervene to reduce exposures; 3) to create specific recommendations to reduce exposure to those particular chemicals and prepare a dissemination and implementation plan. Dr. Hertz-Picciotto and her Project TENDR co-chair, Maureen Swanson, created an Organizing Committee that met for the first time in October 2014. The Organizing Committee developed a list of candidate chemical groups based on the scientific literature. The original list contained over a dozen classes of chemicals, but faced with limited resources, the group needed to reduce the number of chemical classes to set feasible goals for moving the science to action. To hone in on a smaller set of chemical/pollutant classes, the science team prepared summaries of the epidemiologic evidence and provided links to toxicological data. The considerations for selecting the environmental factors included the strength of the scientific evidence, prevalence of exposure in women and young children, and feasibility of intervention. To further narrow the focus, TENDR undertook an expert elicitation process, which is a formal, structured approach in which experts are systematically consulted on specific issues where decisions are needed despite incomplete data, uncertainty in the available information, stakeholders with differing values, and potential choices with various trade-offs. 42 ------- The expert opinions were then discussed at a workshop that brought together scientists, policy makers, and advocacy organizations from numerous entities, including NIEHS, EPA, the National Institute of Neurologic Disease and Stroke (NINDS), California EPA, American Academy of Pediatrics, Physicians for Social Responsibility, American College of Obstetricians and Gynecologists, National Medical Association, National Council of Asian-Pacific Islander Physicians, Alliance of Nurses for Healthy Environments, Alaska Community Action on Toxics, Autism Science Foundation (ASF), Collaborative on Health and the Environment (CHE), Children's Environmental Health Network (CEHN), Environmental Defense Fund (EDF), Learning Disabilities Association (LDA), Natural Resources Defense Council (NRDC), Pesticide Action Network of North America (PANNA), and The Endocrine Disruptors Exchange (TEDex). The workshop participants achieved a consensus on "examples of public health failures," or the set of chemicals on which TENDR will focus its recommendations for exposure reduction, which are: • air pollutants (fine and coarse particles, other criteria pollutants, and toxic air contaminants); • organophosphate pesticides; • PBDEs; • lead (due to continuing disparities); and • phthalates (considered to have less compelling evidence for neurodevelopmental disorders in humans, but which represents an example of the hundreds or more chemicals for which human evidence has yet to accrue, or studies have yet to be conducted. The workshop participants also formed working groups for each of the chemical/pollutant exposures selected; these working groups were tasked with drafting the recommendations for exposure reduction. Working groups were also formed for finalizing the consensus statement, outreach to scientific and health professional associations for endorsements, public messaging and social media, and scientific publications. Dr. Hertz-Picciotto commented that a second workshop will take place in 2016, when the group will refine the chemical-specific recommendations. The workshop participants will also consider overarching recommendations, such as the systematic monitoring of a wide range of environmental chemicals with a specific focus on women and children as well as the establishment of an authoritative body to perform regular, systematic review of chemicals with potential neurodevelopmental toxicity. Other goals of the 2016 workshop include evaluating the outreach to professional organizations, developing dissemination plans, considering implementation options, and other aspects of strategic planning. Session 6 Questions, Answers, and Comments A participant asked Dr. Woodruff whether the Navigation Guide considers animal evidence or only epidemiologic evidence. Dr. Woodruff answered that the Navigation Guide is built for both animal and epidemiologic evidence and noted that for the PFOA assessment, the investigators chose to focus on the human data. Darryl Hood, Ohio State University, commented that the group he is affiliated with described the same brain tissue volume decreases that Dr. Petersen described in a cohort of children from a specific zip code. He said he is pleased to see that Dr. Petersen is working to uncover associations with environmental 43 ------- pollutants such as PAHs. He noted, however, that the asymmetry observed in Dr. Petersen's cohort is not apparent in the animal models, and thatthis is somethingthat should be investigated further. Dr. Petersen clarified that no animal studies have considered the axons and white matter, specifically, and have only looked at grey matter. He added that normally animal models guide the direction of human studies. In this instance, however, the human investigations must guide the animal models to uncover the specific cellular elements that are damaged and to identify the molecular mediators of the damage. Susan Schantz, University of Illinois at Urbana-Champaign, asked Dr. Petersen to comment on the potential molecular mechanisms of the left-hemisphere effects. Dr. Petersen replied by saying that it might be attributable to a threshold effect and that perhaps there are sub-threshold effects occurring in the right hemisphere, but the left-hemisphere effects are more significant. In terms of the molecular mechanism, he said that there are very specific pathways that control left-right symmetry and he thinks that these pathways are involved. He explained another possibility is the asymmetric expression of other molecular drivers and growth factors, specifically neurotransmitters such as serotonin, which are critical in fetal brain development. Third, there are important genetic controllers of development that are also asymmetric. He added that it could also be due to a direct effect on myelin. A participant commented that breastmilk contains many toxic chemicals and asked whether the influence of exposures in breastmilk are also being studied to ensure the recommendation to breastfeed is a healthy one. Dr. Hertz-Picciotto replied by noting that in terms of PCBs specifically, postnatal exposure via breastmilk is, in fact, an order or magnitude higher than the dose delivered prenatally. However, the association with neurotoxic effects is extremely weak and potentially non-existent. She also reminded the attendees that breastmilk has undeniable health benefits, such as providing immune factors that aid in the detoxification of chemical exposures, and at this point there is no evidence indicating breastfeeding should not be recommended. Dr. Birnbaum added that is important to not stigmatize any young mothers who may not be able to breastfeed due to in utero chemical exposures that have impacted mammary development. Dr. Birnbaum mentioned a study out of the Netherlands that explored neurodevelopment in children of mothers who had elevated levels of PCBs and dioxins. Compared to the children who were not breastfed, the children who were breastfed had better neurodevelopmental outcomes. Despite both in utero and early life exposures to PCBs and dioxins, breastfeeding still had benefits. Kimberly Gray, NIEHS, asked the whole panel if there are new tools to early-life health implications. Dr. Peterson commented that the next generation of his investigation includes rapid imaging of newborns' brains to determine whether it can predict their future neurodevelopmental outcomes. Dr. Korrick added that developing new early-indicator measures and determining how to use existing tests at earlier ages is important. Dr. Gray followed by commenting that the new National Institutes of Health (NIH) Environmental Influences on Child Health Outcomes (ECHO) study will include 30,00 kids and aims to image 10,000 children at nine years of age for addictive behaviors. She asked if there is something to give the researchers, who will be looking at environmental exposures very broadly, some specific tools to analyze the data that will be collected to target the environmental toxicant influence on neurodevelopmental and behavioral health. Dr. Woodruff noted that tools to detect early influences are important, but they are also controversial in that there is not always consensus around which tool is best 44 ------- or whether they are better than tools used a bit later in life. Dr. Hertz-Picciotto advocated for the use of blood biomarkers. A participant reiterated the importance of integrating the human and animal evidence. In addition to mechanistic work, animal studies provide the opportunity to study potential lifespan impacts over the course of a few years and allow researchers to look ahead. Session 7a - Obesity Moderated by Dana Dolinoy, Ph.D. | University of Michigan i _ _ tribution of Efiwiioiiiiiciiicii t*|jo»uica 10 i-iiiujiioou wocaiif Rob McConnell, IVi.D. | University of Southern California Dr. Rob McConnell presented results from the Southern California Children's Health Study. He also discussed other influential epidemiological studies and the biological plausibility of the relationship between air pollution and obesity. There is very robust evidence that in utero exposure to maternal smoking is a cause of subsequent childhood obesity, and animal studies investigating the influence of nicotine demonstrate the mechanisms. Dr. McConnell suggested some alternative causes for the effects of in utero and secondhand smoking. Multiple cohorts were selected to represent the different mixtures and extremes of air pollutants in Southern California, part of a 23-year investigation. He showed images of two examples of mixtures in which they are interested. The first is the regional pollutant mixture that blankets an entire community and includes federally regulated pollutants (ozone, nitrogen oxides (NOx), etc.). The second is the much less studied mixture of pollutants that is emitted from the tailpipe of a car that exposes communities near traffic corridors [known as near-roadway air pollution (NRAP)]. A number of different outcomes have been looked at in the Children's Health study. Dr. McConnell focused on obesity and Body Mass Index (BMI) trajectory in cohorts that range from age five to high school age, although they are also extending exposure back to birth as part of the Southern California Children's Environmental Health Center. They have modeled NRAP exposure in many ways, based on traffic proximity and density, and estimates from land-use regression and dispersion models of N02 and NOx. Dr. McConnell said there are a number of cross-sectional studies that have examined the association between NRAP and obesity or increased BMI trajectory. Rather remarkably for a new area of study, there are three high-quality prospective cohort studies. In 2010, his team published a paper investigating the association between BMI and traffic density as a built environment variable. Their hypothesis was that children in a high-density traffic area would not be sent outside to play as much, and therefore would get less exercise and weigh more. Traffic density within 150 meters accounted for a 0.2-0.3 BMI unit difference and was relatively specific to a narrow buffer around the home. When physical activity was included in the model as a mediator, the effect of traffic on BMI did not go away as expected. It occurred to the team that an alternative explanation for this could be the effect of air pollution. In 2012, a second paper from the Columbia Children's Center came out investigating the association between BMI and prenatal polyaromatic hydrocarbon (PAH) exposure. Personal measurements of maternal PAH exposure 45 ------- were made. At ages five and seven, there was a significant dose-response relationship for BMI z-score across tertiles of PAH exposure. A third prospective study, published in 2014, followed a cohort from ages 5-6 to 10-11 years. Dr. McConnell shared a plot of predicted BMI comparing children in different percentiles of NOx distribution showing residential exposure accounted for approximately a BMI unit in difference. McConnell et al. revisited the first 2010 cohort and focused on the relationship between BMI and air pollution, not just traffic density. Using dispersion model estimates, they found an interesting and statistically strong interaction with NRAP and secondhand smoke exposure. For individuals only exposed to secondhand smoke, or only exposed to NRAP, there was an increase in one BMI unit by age 18. For individuals exposed to both secondhand smoke and a high NRAP there was a combined effect of three BMI units; this accounts for about ten percent of the body weight of a large man. If these effects are causal, there are potentially large public health implications. One interesting point is that in this interaction between secondhand smoke and NRAP, there is no nicotine in NRAP. This indicates that perhaps there are some complementary or overlapping pathways that account for the secondhand smoke exposure effects, and that other things in cigarettes could be accounting for these epidemiological observations. The cause of these effects is still very much an open question, as NRAP composition is a complex mixture of fresh particle and gaseous combustion products, debris from tires and brake wear, and metals from engine wear, all of which have inflammatory and oxidant properties. Dr. McConnell mentioned a few toxicological studies that have been done, including three papers conducted by a group at Duke that used diesel exhaust particulate as a model NRAP in mice studies. They dosed mice during gestation and found that prenatal diesel exhaust exposure resulted in increased weight in males in early life and primed female adults for weight gain on a high-fat diet. The team was interested in the effects on the central nervous system, and speculated that the mechanism might be through the damage diesel exhaust did to either feeding centers in the hypothalamus or to anxiety-associated eating. After reviewing the literature, McConnell et al. compiled a number of other potential mechanisms related to changes in basal metabolism, such as inhibition of catecholamine-induced lipolysis by PAHs, mitochondrial damage from early life urban particle exposure, reduced methylation and increased expression of PPARy induced by early life particle exposure, estrogenic effects of urban particles, and increased visceral adipose tissue and adipose tissue inflammation resulting from in utero PM exposure. Dr. McConnell finished his talk by discussing potential practices for clinicians and public health officials to use to reduce harm from air pollution. There is no substitute for good public policy to reduce ambient levels of air pollution, unlike other outcomes where behavioral factors have a bigger role. For example, annual average PM2.5 levels declined from 54 to 13 percent after regulation. Avoiding air pollution when engaging in outdoor activity is a good recommendation for patients; however, it is important to be cautious in crafting this public health message to avoid giving people the excuse they are looking for not to exercise and creating unintended negative consequences. Other options include chemoprevention and modulation through antioxidants and initiatives to put filters in schools next to major roadways. Initial data shows these filters can reduce exposure, but additional research is needed. 46 ------- Early Toxicant Exposures and Development of Child Obesity: Evidence and Gaps from Recent Research Karen Peterson, Sc.D. | University of Michigan Recent data in children demonstrate that overall rates of obesity differ by gender and region worldwide. This trend could reflect behavioral, genetic, cultural, or economic differences and is generally referred to as worldwide nutrition transition. Very broadly, it has been attributed to changes in health behaviors and environments, such as low levels of physical activity, increased screen time, and high intake of added fats and refined carbohydrates. These factors lead to obesity and noncommunicable chronic diseases. The risk factors for obesity are more prevalent in low SES households, especially in urban areas, and include low physical activity, poor dietary quality, educational attainment, and environmental toxicant exposures. In 2002, a published paper suggested a relationship between toxic exposures and obesity. Although based primarily on ecological evidence, it also pointed to nonmonotonic low levels where increases in childhood obesity could be observed. Dr. Karen Peterson explained that "obesogens" describe a class of chemicals that are considered endocrine disruptors, to which exposure during development can disrupt metabolic programming, leading to later obesity. They can disrupt metabolic programming both directly (e.g., increasing number of adipocytes and stored triglycerides) and indirectly (e.g., basal metabolic rate, shift energy balance to favor energy storage, alter appetite and satiety). She showed a figure highlighting sensitive developmental periods when both nutritional and toxicological exposures have a more prominent effect due to epigenetic plasticity (Figure 1). Generally, in utero and the prenatal period are considered to be the most important, but many researchers are starting to also look at adolescence and the pubertal transition. These sensitive periods also correspond with critical periods for obesity development. A growth chart depicted age and a classic BMI curve, with high levels in infancy and then lower levels between ages four to six years. If children enter this age period early in life, they tend to have higher rates of obesity later in life. The other critical obesity period is the peripubertal. There have been a few high profile papers relating some endocrine disrupting chemicals (EDCs) cross-sectionally to a higher prevalence of obesity in adolescence, but there might be more to the story. Studies using animal models, such as the twin agouti mouse sisters, can show life course impacts that differ by toxicant, offspring sex, and period of development. In contrast to the cross-sectional studies relating bisphenol A (BPA) to obesity in adolescence, the agouti mouse model shows that BPA exposure in the perinatal period is associated with a lean, hyperactive phenotype, and lower body weight and body fat in females, with no effect in males. Faulk et al. showed that lead, usually associated with growth deficits later in life, is related to higher weights across the entire lifespan of the male agouti mouse model. A recent review conducted at the University of Michigan took a life-course perspective, and included studies that were prospective, longitudinal, birth cohorts, primarily containing information on in utero and early infancy exposures to certain classes of chemicals. A total of 35 post-2011 studies were assessed in detail for how certain toxicants (22 studies regarding PCBs, DDE/T, PFCs, PDBE, BPA, and phthalates, and 13 regarding heavy metals) might be related to childhood obesity outcomes (e.g., weight gain, BMI, percent body fat). First Dr. Peterson talked about the results related to persistent organic pollutants (POPs), which despite being banned still tend to bioaccumulate, especially in tissues of special importance 47 ------- (e.g., breast milk, cord blood, placenta). For prenatal exposure to PCBs, five out of nine studies found no association with weight gain or BMI in infants or school aged children, but three out of nine showed increased waist and BMI only in girls at ages five to seven years. For postnatal PCB exposure, decreased weight from birth to 24 months was found in seven pooled European cohorts. The most clear evidence overall is for DDT and DDE. Previous reviews highlighted the association between early exposure and the development of childhood obesity; eight out of 12 studies confirmed this association, across life stages. DDE has been associated with rapid growth from birth to six months, as well as overweight infants at 14 months, and BMI change to overweight in girls ages five to seven years. Second trimester serum concentrations of DDT was found to be related to increased waist in nine-year-old boys. Turning to short-lived but ubiquitous pollutants, the six to eight studies that have been published since 2011 produced mixed, imperfect, and inconsistent evidence regarding the effects of BPA and phthalates. A Spanish cohort study showed a weak association between BPA and waist circumference at four years of age. The CHAMACOS study found an inverse relationship between BMI, percent body fat, and obesity of girls at nine years of age. Finally, increases in leptin in boys and adiponectin in girls at nine years of age were also found, which contributes to the need for more studies looking at adiposity. For phthalates, there are surprisingly few studies, but this is the first class of pollutants where the primary effects appear to be seen in boys. Cord blood MEOHP was related to lower BMI in infant boys. High molecular weight phthalates were associated with decreased weight gain in infants and lower BMI in boys agesfourto seven years. An inverse association between BMI, percent body fat, and waist was found in New York City boys ages five to seven years. A paper by Afeiche et al. found no effect of lead in males, and an effect on weight of females from birth to five years of age. Other papers found this effect persisted and was associated with a decrease in BMI as the girls went through puberty. Other papers related prenatal, but not postnatal, lead exposures to decreases in weight in infancy or lower BMI in school age girls. Cadmium, arsenic, and mercury were all found to be negatively associated with weight gains. In summary, for longitudinal prospective studies, there is the clearest evidence for DDE, primarily in girls. For BPA and phthalates, it is a mixed picture, with variations by age and gender, and for heavy metals it is decreased weight. Limitations include modest sample sizes, indirect measures of adiposity or fat distribution, few follow-ups into puberty or adulthood, and lack of repeat measures of maturational tempo to disentangle effects in boys and girls during the pubertal transition. Effect modifiers such as child sex; birth weight; maternal weight status; and maternal dietary intake of fat, vitamins, and minerals also should be considered moving forward. 48 ------- Figure 1 Sensitive developmental periods and environmental exposures (Barouki R et al, Env Health 2012) Genetics Epigenetic modifiers Epigenetic modifiers at early development during postnatal life In utero Chikjhood 4 Adolescence } Adulthood/Senescence Neonatal Puberty Figure 1 Periods of vulnerability to environmental influences. The most critical period is the perinatal period, during which epigenetic plasticity is high and can be influenced by a variety of environmental cues, including chemicals, nutrition, infection, ere). Later in life, growth and the hormonally active puberty period is also a vulnerability period. In adults it is believed that elder persons are more vulnerable to a variety of insults. Environmental Health and Childhood Obesity: From Research to Action Maida Galvez, M.D., M.P.H. | Mount Sinai Hospital Dr. Maida Galvez began by highlighting how the work of the Children's Centers has deepened the understanding of what is seen in a clinical setting. She showed an infographic from the American Public Health Association (APHA) entitled "Public health takes on obesity: A route to better health" that describes the growing problem of obesity in America. Obesity has nearly tripled among children and teens over the past 30 years. One in three U.S. children ages two to 19 years is overweight or obese, and the current obesity rate of 35 percent is more than double the rate in 1980. There are 112,000 obesity-related deaths each year, and obese children are more than twice as likely to die before age 55 as children with a health weight. This might be the first generation to have a lower life span than the preceding generation. The direct cost of obesity from medical care expenses is $152 billion per year. The indirect cost, from lost productivity, insurance premium compensation, and absence from work, is estimated at $73 billion per year. The emerging research in children's environmental health has pushed beyond individual risk factors to consider the broader context of the child. The ecological systems theory, specific to childhood obesity, examines the child's setting with regard to parenting styles, family characteristics, and the broader community, demographic, and societal characteristics. School lunch programs, work hours, and access to health-promoting resources are examples that can have an effect. One of the top drivers of the obesity epidemic is child poverty which magnifies risk of exposure to environmental hazards. Dr. Galvez showed an infographic from the American Academy of Pediatrics demonstrating poverty rates by state, including 20 percent in New York, 37 percent in Washington D.C., 56 percent in Puerto Rico, and 42 percent in East Harlem. Another major driver of obesity is educational attainment. Approximately 143,000 students in 49 ------- New York City are in failing schools, and concerns exist about neighborhood safety and crime. The leading cause of death due to injury in New York City youth ages five to 14 years is motor vehicle crashes, and for youth ages 15 to 19 years it is firearm injury. Risk factors for firearm injury include being from the Bronx, African American, and from a high-poverty neighborhood, which also keep children indoors and limit their physical activity. Dr. Galvez then discussed how New York City's Environment and Health Data Portal is a superb, user- friendly tool for exploring New York City environmental and health data. She provided the example of traffic density in East Harlem compared to Manhattan and New York City. For all vehicle types, East Harlem had more than double the amount of estimated millions of annual vehicle miles traveled, which is an indicator of emissions from automobile exhaust, brake wear, and tire wear. As the relationship between air pollution and childhood obesity is explored in more depth, this has important health implications. Besides staying indoors and limiting their physical activity, poor children are also living in substandard housing. In New York City, nearly a third of public housing tenants reported water leaks. East Harlem has the highest density of public housing in New York City and is ranked number one in average number of housing concerns for Manhattan. African Americans are the most likely to live in poorly maintained housing. Approximately 34 percent of black households reported three or more serious maintenance deficiencies in rent-regulated apartments, compared to 16 percent of white households. Teitelbaum et al. 2012 found an association between phthalate concentration and body size measures in overweight Hispanic and black children ages six to eight years, specifically in overweight girls. Dr. Galvez then discussed her research regarding the built environment in East Harlem, which examines whether there are physical features unique to an inner-city, minority community that impact dietary quality, physical activity and risk for childhood obesity. Childhood obesity is an epidemic in East Harlem with 40 percent of girls and 53 percent of boys were at risk or obese. There were striking disparities in access to healthy foods. In 2004 there were no grocery stores in predominantly African American blocks, compared to racially mixed or predominantly Latino blocks. Children living on a block with one or more convenience stores were more likely to have a BMI percentile in the top tertile. When researchers asked where children in New York City were making their food purchases, the top three answers were convenience stores, food stands, and fast food restaurants. One study showed that in the toxic food environment, the dose makes the poison. The more food stores a child passes on their way from school, the more likely they are to stop and purchase something. This has an associated impact on dietary quality of increased calories, servings of sugar-sweetened beverages, and servings of snacks and sweets. The children in Dr. Galvez's cohort also had low physical activity, averaging approximately two hours outdoors per week with zero hours of structured physical activity. The researchers then looked at the availability of physical activity resources and found that the more resources children had available (e.g., afterschool programs and playgrounds), the greater their level of unscheduled physical activity. Families with income less than $25,000 and with lower caregiver education, however, were more likely to have no resources on their block. Despite these figures, Dr. Galvez discussed how there is hope in this issue. Obesity rates have declined for the first time in recent years, but not in all racial and ethnic groups. Public health improves food choices and creates opportunities for physical activity, helping to curb obesity. Great efforts have been made to 50 ------- bring together diverse stakeholders to think about health policy frameworks, and how we can all work together to design health communities. One of Dr. Galvez's colleagues is being awarded this week by the APHA for her work with affordable low-income housing with active living design principles. She followed a cohort and demonstrated an improved BMI one year later. Many groups are programming existing resources and ensuring that children are actually using the green spaces and trails. The University of Southern California has done work regarding the benefits of urban parks on children's health. In terms of diet, processed foods are major sources of environmental chemical exposures, thus efforts have been made to encourage children to eat fresh fruits and vegetables. The New York City Commissioner of Health recently applauded the efforts of the Vision Zero campaign to reduce motor vehicle injuries related to shorter crossing distances, pedestrian islands and plazas, bike lanes, and other design changes. Other efforts include an "Obesity and the Environment" fact sheet from the University of Michigan, Columbia and WEACT materials promoting "Eat Fresh," a BPA wallet card from the Mount Sinai Children's Environmental Health Center (CEHC) along with NEEF prescriptions for nature. Dr. Galvez concluded her talk by emphasizing the important role research plays in providing evidence to enact policies, and that everyone plays a role in shaping health communities and promoting children's health. Session 7a Questions, Answers, and Comments Susan Korrick, Brigham and Women's Hospital, commented that she and her team were doing green space mapping in their New Bedford cohort to see how distance to parks and playgrounds affects various health outcome measures. When they did not see what they expected, they looked closer and found that the quality of the urban parks and playgrounds was horrible. She asked if they had recommendations for determining park and playground quality. Dr. Galvez responded that her team had partnered with New Yorkers for Parks, a group that systematically evaluates the quality of parks, and did end up seeing positive associations. Their reports are available online for neighborhoods they have completed. Dr. Peterson mentioned there was a group in Boston that catalogued parks. Dr. McConnell commented that it would be a good community outreach project to recruit a group of students or interested people to do some fast grading of city parks to try to streamline for research and policy purposes. Another audience member felt this initiative would tie into the current push at the federal level for citizen science efforts. The next audience member asked Dr. McConnell if he was aware of anyone looking into the impact of air pollution regulation in concert with anti-smoking regulation. The questioner wondered if anyone had looked at data from areas where legislation has made smoking less frequent, from an ecological method, and in relation to obesity rates. Dr. McConnell responded that studies have looked at what happens when smoking is banned with regard to other health outcomes. His team recently published a paper looking at lung function growth in three large cohorts, ages ten to 15 years, and how it changed in relation to pollutant exposure over different key periods. He said the same thing could be done with BMI, but it has not been done yet. It could not be done with secondhand smoke (SHS) in his cohort because CA has been quite successful at reducing SHS and in utero smoke exposure, so the sample sizes would not be large enough. 51 ------- Leyla McCurdy, Health and Environment Consulting, contributed to the previous park discussion, saying there is an excellent model in Washington D.C. where park quality information has been integrated into medical records. The lead pediatrician for the effort is at the Unity Community Health Center. Volunteers helped graded all the parks in Washington D.C., including many George Washington School of Public Health students. Session 7b - Exposome Moderated by Claudia Thompson, Ph.D. National Institute of Environmental Health Sciences Using a Risk Assessment Framework to Integrate Epigenetic Outcomes with Exposome Assessment for Neurodevelopment Elaine M. Faustman, Ph. _ versity of Washington Dr. Elaine Faustman's presentation focused on lessons learned in developing an exposome for children's health center cohort studies. Cumulative exposure studies require data at the individual, household, and community scale and across life stages but depend on a variety of sources for information, including biological and environmental measurements and survey data. The life-stage construct is at the center and is therefore critical to consider when studying children's health, along with social determinants of health, location, chemical exposures, physical and social environment, biology, and behavior. Dr. Faustman's study was inspired by Chris Wild's explanation of exposome and system biology, which suggests that external, internal, and specific external component data can be layered to provide information for individuals in a population. This systems-based approach for evaluating pesticide exposures was applied in the children's cohort study. The study acquired farmworker and non-farmworker couple and children information at the individual level for 15 years, household location at the community level, levels of 40 organophosphates pesticides (OPs) applied within the community at the exposure level, acetylcholinesterase levels at the early biologic response, and the genomic profile. The study used the environmental public health continuum to compile the pesticide exposure pathways and community-based participatory research to determine the genetic susceptibility and molecular mechanisms, particularly to determine the early biologic effect of pesticide exposure across communities. The goals of the study were to determine the factors that affect pesticide exposure and response, establish if the genotype or phenotype can identify key genes that metabolize OPs that can improve prediction of exposure, create pesticide assessment tools that incorporate genomics multiplied by exposure multiplied by time, and determine if an exposome-based approach could provide actionable data to improve and implement effective exposure preventions. The exposome-based method was applied to a study examining the impacts of OP and carbamate use on apples and potatoes in eastern Washington State on children's health. The longitudinal study assessed pesticide exposure to farmworker and non-farmworker children across seasons (spray versus non-spray seasons). Samples were taken every two days over multiple years. OPs are episodic (i.e., short half-lives), which allowed easier definition of 52 ------- exposome behaviors. The focus was on take-home pathways of exposure in the home or the individual contamination level. The study measured multiple biomarkers of exposure, the parent compounds chlorpyrifos (CP) and azinphos methyl (AZM), nonspecific diakyl phosphate (DAP) metabolites, and specific CP and chlorpyrifos-methyl metabolites. Dr. Faustman presented the metabolic scheme for CP and noted that a fair amount is known about CP, such as CP involvement in generating the reactive toxin and its ability to react with PON-1, which causes genetic variation, to produce the nontoxic chemical tricresyl phosphate (TCP). Less is known about azinphos methyl, but it is a prime compound that was found and used in many of the children's cohort studies. The study found that concentrations of pesticides, such as dimethylthiophosphate (DMTP), was higher in farmworkers than non-farmworkers, and this pattern was also reflected in the children of farmworkers. The study data were plotted against NHANES data, showing that the local population had DMTP levels at concentrations 10-fold higher than national levels. This pattern was seen in farmworker children at approximately a 5-fold higher concentration compared to national levels. The key to determining exposure is to measure body concentrations at peak exposure and link peak exposure to the time of agricultural use or pesticide application. The farmworker concentrations of DMTP reflect the spray season versus non-spray season pattern across OPs, which demonstrates the spatial and temporal robustness of this data and the importance of including season in the exposure model. The study also used heat maps to display multiple exposures, such as pesticides, metals, and phthalates, from multiple sources and metabolite concentrations in people over time to show exposure patterns. The map showed that most children in the area were exposed and experienced multiple exposures, linking exposure to occupation. House dust was not linked to metabolite levels, emphasizing the need to build a database that supports this research. Another unexpected finding of the study was that farmers who did not apply the pesticides had the highest concentration of pesticides, indicating that they are not wearing the appropriate protective wear in the field. The study used a multivariate correlational model to lay these exposures together, including data on exposure levels in adults and children, car dust, and home dust. Correlations between these exposures and metabolite concentrations in the blood and urine were made and then related acetylcholinesterase (AChE) inhibition attached to the compound in urine and blood. In other words, all of the biospecimens were linked to build the correlational model. The study then examined the possible role that genetics play and found that, for the first time in a human study, Atrazine (AZ-)AChE inhibition was not correlated with PON-1. Thus, the metabolism differences between compounds need to be determined to interpret the results. DMET chip, which looks at 200 genes that are associated with about 2,000 pathways in metabolism, was used for genomics and showed polymorphisms of genetic variations at CYP3A5 with significantly different slopes as a function of OP dose, which directly relates to AChE. The study also examined social determinants of health, publishing evidence of a biomarker specific to ethnicity and income. From this information, the study used a series of six different models to begin to combine the seasonal differences, blood and urine measurements, and polymorphism information to determine if knowing the exposome information and take-home pathway matter and if intervention is effective. An intervention period took place between years one and four and found an 8-fold higher level of pesticide concentrations 53 ------- in people after the intervention. This was attributed to seasonality differences and, once corrected for usage and land use differences, there was a 40-percent reduction in urine metabolites in children observed after the intervention. This finding illustrates the need for genomics, metabolites, seasonal, agricultural, and place-based information to use exposome information. High-Resolution Metabolomics for Sequencing the Exposome Dean IP .Jones, Ph.D. I Emory University For several years, Dr. Dean Jones' Clinical Biomarkers Laboratory at Emory University has been working to develop an affordable way to determine a broad coverage of exposure. The largest challenge to this effort is the cost limitation of analysis, which helps explain why there are so little data available on the 50,000 chemicals or more to which Americans are regularly exposed. Dr. Jones explained that his presentation, The Lightening Rod for Exposome Research, will highlight five key requirements for sequencing the human exposome, including establishing a standard operating procedure (SOP), sensitivity, quantifiability, affordability, and a central reference platform. There is a need to establish an SOP that covers a broad range of exposures. Dr. Jones' lab is among a small number of labs across the country with an SOP, but this is something that all labs should have moving forward. Dr. Jones' lab well-established protocols from analyzing about 20,000 human samples. His lab found ultra-high resolution mass spectrometry allows the rapid measure of a large number of chemicals, and that it is important to use dedicated facilities when measuring human samples to avoid contamination from experimental studies and maintain and improve equipment sensitivity. High abundance metabolite samples can be run one at a time, but for most samples, including low abundance metabolite or chemical samples, analysis should occur under rigorously defined, routine conditions with internal standards. Calibrated pooled reference samples also should be used to ensure measurement confidence. Detection is a challenge associated with the study of environmental chemicals, because most environmental chemicals are present at orders of magnitude lower abundance. This requires sensitivity of assays when measuring metabolomics. The high sensitivity of instruments understands the dynamic range of detection and expands the limit to allow for measure of low abundance metabolites and environmental chemicals. For example, Dr. Jones referred to a graph showing 4-chlorophenylacetic acid abundance ten orders of magnitude smaller than the graph scale of 10"5, highlighting the level of HRM instrument sensitivity and how critical sensitivity is for detecting environmental chemicals. Quantifiability is critically important for regulators when addressing issues; however, U.S. regulators have good information on less than 1,000 chemicals of the 50,000 to which the human population is exposed. Due to such little information available, he argued one option is to relax absolute quantification requirements to allow measurements within one order of magnitude of an unknown chemical to be used to estimate environmental chemical levels. Dr. Jones showed a graph exhibiting all of the measurements that can be taken with a single analysis: concentrations of glucose (mM), bilirubin (uM), cotinine (nM range in non-smokers), and pirimicarb (subnanomolar range). This shows the range, sensitivity and ability to quantify environmental chemicals and metabolites in low and varying abundance in the same analysis. 54 ------- Affordability is the driving force behind the development of routine HRM analysis methods. Dr. Jones explained his objective to provide affordable ways to capture information on environmental chemicals. It costs about $1 million annually to maintain one instrument with the current protocols. With Dr. Jones' protocol, his lab is ableto measure 5,000 samples a year, costing $200 per sample, but his lab has validated that the number of samples could be doubled to 10,000 samples annually, which would place operating costs around $98 per sample. This number could also be increased to 20,000 samples annually, which would cost about $50 per sample, depending on the analysis and how the system could be optimized. A lower cost would allow access to a large amount of information with affordable means compared to other analytical procedures. This could generate a large database to serve as a central reference platform. As an example, Dr. Jones used a manuscript submitted by Doug Walker from NCI as an example looking at a population of workers in China with high occupational exposure to trichloroethylene (TCE) that is measured both in their blood and externally. If the TCE metabolites found in the blood are proportional to the external measurements of TCE exposure, then these data can be used as a metabolomic platform. This information can be used to validate the first part of the exposure paradigm and, at the same time, provides information on the relationship of TCE exposure and biologic effect. A central reference platform could work for a number of exposures, internal burdens, and biologic responses such as using uric acid to measure renal function and measuring tryptophan to determine patterns in immune function. Current methodologies and technologies are available and affordable to sequence the human exposome. Using a uniform platform would allow the information to be anchored to one entity to ensure accuracy and efficiency as work to sequence the exposome progresses. Environmental Exposures in Early Life Influence Childhood Leukemia Stephen M. Rappaport, Ph.D. | University of California, Berkeley Dr. Stephen Rappaport's presentation focused on the use of dry blood spots to understand prenatal exposures, particularly the involvement of prenatal exposure in childhood leukemia. Fetal exposure during early development is critical to health and disease later in life, but fetal exposure is a challenging topic to study. In childhood leukemia, genomic studies show that genetic factors play a role in prognosis but account for less than ten percent of cases, which indicates that exposures are important. Exposure research, such as radiation, paternal smoking, and environmental chemicals, however, has not shown any relationship to childhood leukemia. This, coupled with the average age of diagnosis in California of 4.6 years old, lead Dr. Rappaport to investigate early-life and prenatal exposures. California hospitals save white blood spots taken at birth for research, which Dr. Rappaport used a reference to the prenatal blood exposome. The circulatory system integrates the entire human body, so the blood exposome is used to determine exposure from a variety of factors from different sources. The blood exposome can be used to determine exposures from outside the body (e.g., radiation and stress) and inside the body (e.g., lipid peroxidation, gut flora, and diseases) throughout the individual's lifecycle. Because all exposures are inherently chemical (either mediated or intrinsically chemical), the blood exposome incorporates all exposures and can be used to compile multiple exposures into one analysis. 55 ------- Dr. Rappaport complied all data from studies that measured chemical concentrations in the normal human population and plotted the 50 chemicals into a chemical space, organized by chemical structure and prevalence (i.e., chemicals with similar structures were close together and chemicals with higher blood concentrations was represented by a larger dot). About 100 different chemical classes were represented with diverse origins (i.e., endogenous, food, drug, or pollutant), demonstrating the diverse and complex exposures that are captured in a blood exposome. The focus of Dr. Rappaport's study was to discover the non-genetic or exposure causes of childhood leukemia by applying exposome-wide association studies (EWAS). EWAS matches biospecimens from healthy and diseased subjects to compare the exposomes to identify the associations with a diseased status and biomarkers of exposure. Once the associations are found, these areas in the exposome can be targeted as biomarkers of exposures in a larger population to find causal exposures with fewer measurements required. In California, there are approximately 1,000 cases of childhood leukemia and 2,000 controls matched at birth. Blood spots of these children are collected at birth and, in this study, are used to find the differences in exposures. Having access to one-tenth of one blood spot on which to conduct the exposome analysis, Dr. Rappaport developed an assay to measure small molecules and albumin adducts as measures of exposure to get all of the necessary information from the small blood spot sample. The assay uses solvent extraction that digests the protein and high spectrometry to determine untargeted metabolomics or metabolomic adducts and altered proteins or protein adducts that are indicative of highly reactive chemicals. Dr. Rappaport noted that it is essential to have dedicated equipment to take measurements when you have small sample sizes. The first experiment measured small molecules in 100 childhood leukemia and 110 controls, matched by gender and ethnicity. The analysis measured 15,000 features, which measured greater than twice the background, in 20 minutes. The study found that 2,420 features in childhood leukemia cases positively matched the controls and 2,660 features in childhood leukemia cases negatively matched the controls. Many of these matched features were derived from the same molecules, allowing simple modification to reduce the features to digestible clusters. This left 5,000 features to compare between leukemia and control patients. The test of association with the cases of childhood leukemia and the positive and negative matches to the controls created a Manhattan plot. Some of the associations were significant before being adjusted or taking into account the error rate, so covariates that significantly impacted the results can already be identified. This indicates the possibility of identifying a factor associated with childhood leukemia. The molecules were used to detect chemicals from a variety of sources including microbial metabolites, fatty acids, and lipids. The protein adducts were used for information on reactive species and to characterize exposures to reactive electrophiles, due to their inherent carcinogenicity. Human serum albumin (HAS) was used, which is the most abundant protein in serum and has a residence time in humans of 28 days allowing one to determine one month of exposure history. This adduct also has a nucleophilic hotspot Cys34 that accounts for 80 percent of the antioxidant capacity of serum. Dr. Rappaport developed an assay that digests the albumin, which results in peptides. If the peptide that contains the Cys34 reside is detected, the peptide is studied using high-resolution mass spectrometry to obtain the peptide profile and identify the area of modification. Once that area is identified, a method developed for this study 56 ------- acquires the peptide's signature ions to provide information on the presence and mass of the peptide with Cys34. The control blood samples were used to determine the prominent adducts. The study found a host of different modifications collected from adults, children, and in-utero samples. This information is being used to build the blood exposome for different life stages that might help illuminate the association between what and when exposures occur and childhood leukemia, among other diseases. Session 7b Questions, Answers, and Comments Cindy Folkers, Citizens Beyond Nuclear, commended Dr. Rappaport on his research and noted some scientists' reluctance to try new forms of radiation damage assessment and asked if he had examined blood spots for center chromosome malformations. Dr. Rappaport responded that he was not sure about chromosomal damage specifically, but one of his collaborators has been doing blood spot genomic analysis to obtain DNA methylation for epigenetic information. Dr. Rappaport guessed that information could be obtained from blood spot samples. Gary Ginsberg, Connecticut Department of Public Health, stated it would make sense that signals for leukemia in blood spot samples would be clearer than samples taken later in life and asked if the study looked at the correlation between when leukemia occurs and changes in fetal blood spot signals, specifically fetal binding adducts. Dr. Rappaport explained that he tried to identify adducts for use as biomarkers. This correlation would likely not be found in this study as there is not additional information other than what can be obtained from the blood spots themselves. Once a child is diagnosed with leukemia, a lot of exposome changes occur, so analysis after diagnosis would not be particularly useful. One meeting participant noted that all of the speakers' projects were very valuable. Referring to populations in vulnerable communities when exposure is not extremely high, he asked about the use of nonparametric measurements to analyze that problem and asked for the speakers' thoughts on the available frameworks that could address health disparities in smaller concentrations. Dr. Faustman explained that the cohort in her study was not large, with only 100 farmworkers and 100 non- farmworkers. The samples were frequent and longitudinal and accounted for sampling variability, allowing people to be used as their own controls for parametric and nonparametric data and making these techniques relevant. Her study discussed some epigenetic markers but those measurements are small and usually only measured once, making it difficult to control for genetic changes to account for small changes in epigenetics. Dr. Jones added that the field of epigenetics is moving toward taking epigenetic measurements during regular physical examinations to build a repository of samples for everyone that could be studied every year. This would also address the issue of large sampling sizes, close to 20,000 or 30,000 people, needed to detect epigenetic changes or environmental exposures. Dr. Faustman explained that, typically, one sample is run multiple times to account for variability. Dr. Rappaport added that the number of samples that need to be run depends on the effect being measured. If the effect is large, then a small sample size will suffice. Most gonadal white adipose tissues (GWATs) need large sample sizes to account for the small effect. 57 ------- Jose Cordero, University of Georgia, asked Dr. Rappaport if he was examining populations with Down syndrome that have high risk of leukemia based on genomics and exposomics. He asked what the interactions are between Down syndrome and the exposome and if those interactions appear to be more myositic or leukocytic. Dr. Rappaport explained that the research he discussed was the first step in a longer process to address Dr. Cordero's question, but he did find some preliminary data that looked promising. Dr. Faustman added that Dr. Cordero has a paper that is expected to be published soon examining the correlation between cancer and birth defect. Session 7c - Reproductive Health Moderated by Tracey Woodruff, Ph.D., M.P.H. | University of California, San Francisco Updates on Environmental Effects on Reproductive Health Marya Zlatnik, IVLO. | University of California, San Francisco Representing the clinician's perspective on the panel, Dr. Marya Zlatnik presented on recent updates regarding environmental effects on reproductive health. Pregnant women worry and inquire about many exposures during prenatal care visits. Due to time limitations, she chose to focus on hydrofracking, a topic that is receiving increased attention. Dr. Zlatnik reiterated that this is a new topic and that the scientific knowledge base of the association between unconventional natural gas extraction and pregnancy outcomes is extremely limited. She noted PubMed contains only four related citations. In the absence of peer-reviewed literature, the media has raised concern about possible health impacts due to the fact that chemicals used in the fracking fluid can include known and/or suspected carcinogens, developmental neurotoxins, and volatile organic compounds (VOCs). Dr. Zlatnik discussed potential health impacts that have been identified using in vitro cell and animal models. In one study, 39 well water samples were assayed in human cell lines for androgen and estrogen activities. Of the 39 samples, 89 percent had estrogenic activity, 41 percent had anti-estrogenic activity, 12 percent had androgenic activity, and 46 percent had anti-androgenic activity (Kassotis et al. 2014). In an in vitro assessment of 23 commonly-used fracking chemicals, estrogen, androgen, glucocorticoid, anti- estrogen, anti-androgen, and anti-glucocorticoid effects were reported (Kassotis et al. 2015). Furthermore, in laboratory mice exposed to a mixture of these 23 chemicals prenatally, male offspring had decreased sperm counts, despite increased testes weight and increased serum testosterone levels (Kassotis et al. 2015). Dr. Zlatnik also described the human health effects reported in the four peer-reviewed studies available in PubMed. The first study conducted in southwest Pennsylvania considered a woman's residential proximity to fracking wells and evaluated its relationship with women delivering small-for-gestational-age (SGA) infants. The exposure metric used was inverse distance weighted well count, which considered 58 ------- proximity and the number of fracking wells. In adjusted and unadjusted analyses, the authors reported a positive association between proximity to wells and the risk of delivering an SGA baby (Stacy 2015). A second study also used proximity to wells to estimate exposure, but examined the association between exposure and preterm birth. The authors identified an increased risk of preterm birth among babies born to mothers in the highest quartile of exposure (Casey 2015). Athird study used the number of wells within ten miles of the infants' birthplace as a proxy measure of exposure to explore its potential relationship with birth defects. The authors observed an increased risk of congenital heart defects and neural tube defects and a slight decrease in preterm birth and low birth weight among infants in the highest tertile of exposure (McKenzie 2014). The final study is an unpublished economics dissertation that considered proximity to fracking wells and a number of health outcomes, including birth weight and Apgar scores. Dr. Zlatnik stated that although the dissertation found a significant decrease in Apgar scores associated with proximity to wells, she does not see the association as biologically plausible from a clinical standpoint. She conceded, however, that the small number of inconclusive results warrant further study. Dr. Zlatnik framed exposure to fracking as an environmental justice issue, noting that it is not easy to evade and that often the effects are felt by those who are already disadvantaged. She discussed the discrepancy between the geographic locations of the fracking wells in comparison to the residences of the well owners in Texas. She added that the affected communities in Denton, Texas endeavored to have the wells closed due to suspected health effects, but the moratorium they sought was overturned by the state. Dr. Zlatnik emphasized this is not only a rural issue, pointing to an example of a fracking well in South Los Angeles that sits near a university, low income housing, and a school for disabled adults. Dr. Zlatnik closed by calling for more research to understand the potential health effects of hydrofracking and urged clinicians to get involved to bring a clinical voice to policy making. She referred to the moratorium on fracking in the state of New York as a prime example of health professionals coalescing to urge a precautionary policy approach. Impacts of Early-life Exposure to Endocrine Disrupting Chemicals on Puberty John Meeker, Sc.D., C.I.H. | University of Michigan Dr. John Meeker discussed his project at the University of Michigan CEHC that focuses on puberty. His team also investigates the influence of EDCs on fertility and early childhood development. Dr. Meeker began his discussion by explaining that the age at puberty onset has been declining. The specific age may differ across countries, but the declining trend is consistent, especially among girls. He used a graph indicating the timing of pubertal growth spurts and peak height velocity, two indicators of puberty onset, among boys and girls between 1930 and 1970 to demonstrate the trend of declining age at puberty. He displayed a second set of graphs showing onset of breast development and onset of menarche among European girls between 1991-1993 and 2006-2008, which also indicated a trend of decreasing puberty onset. Dr. Meeker discussed the health impacts of early pubertal timing that have been documented in the peer- reviewed literature. Health effects include increased risk of substance abuse and risky behaviors, depression and other mental health disorders, and long-term health impacts such as cardiovascular 59 ------- disease, diabetes, and cancer. Dr. Meeker also noted that delayed pubertal onset has been associated with increased risk of depression, substance abuse, and disruptive behavior among boys. Dr. Meeker proposed that the decreasing trend in pubertal timing is a result of increasing exposure to EDCs due to an exponential increase in chemical production in the post-World War Two era. He noted the extremely high number of chemicals registered for commerce in the United States, of which few have been thoroughly screened for toxicity. Although environmental health has traditionally been concerned with increased exposures at the workplace or at toxic waste sites, repeated low-dose exposures are becoming a focus within the field. The list of potential EDCs is growing, but currently, the main substances of concern are phthalates, phenols, parabens, pesticides, flame retardants, and metals. Dr. Meeker discussed the existing literature on EDC exposure and puberty, which is relatively small and comprises studies that consider different exposures and use varying study designs. He noted the limitations of using a cross-sectional study, which can obscure the direction of causality. For example, if a cross-sectional study identifies an association between phthalate exposure and early onset of puberty, that association may not be due to the exposure causing the outcome. Early puberty could have resulted from individuals using more phthalate-containing personal care products than their normally-developing peers. Dr. Meeker focused on BPA and phthalates for his presentation. Phthalates are found in PVC plastics, personal care products, and pharmaceuticals, while BPA is found in polycarbonate plastics, epoxy resins, and thermal paper. Both classes of chemicals have been associated with adverse pregnancy outcomes, fertility impacts, and childhood developmental effects, but their potential impacts on puberty are not well studied. Dr. Meeker gave an overview of his study at the University of Michigan called Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT), which is a longitudinal cohort study of pregnant women and their offspring in Mexico City. Nine phthalate metabolites and BPA were measured during each trimester of pregnancy to estimate in utero exposure. Children were also followed until age 8-14 years at which time phthalate BPA measures were collected. The health outcomes of interest included Tanner stages for genitalia size, breast size, pubic hair development, and testicular volume; age at menarche; and serum reproductive hormone levels. Dr. Meeker explained that phthalates and BPA were measured in nearly all study participants, but the intra-individual variability in metabolite measurements was high, which underscores the need for measuring exposure at multiple time points. Results indicated reduced odds of genitalia development (Tanner Stage >1) and pubic hair development at the time of the study visit associated with some specific phthalate metabolites in boys. In girls, the research team observed increased odds of menarche at the time of study visit, but reduced odds of breast development. He concluded his presentation by noting that the research team is continuing to examine exposure during in utero development and is currently in the process of increasing the study's sample size. The Pros and Cons of Testing Patients for Toxin Exposures Susan Buchanan, M.D., M.P.H. | University of Illinois at Chicago 60 ------- Dr. Susan Buchanan posed the question of whether clinicians should screen pregnant women for exposure to toxic exposures. She admitted that this is a controversial question, to which she does not have the answer, but her hope was to start a meaningful dialogue around the topic. She introduced the U.S. Preventative Services Task Force (USPSTF), which is an entity that makes evidence-based recommendations about clinical preventative services such as screenings, counseling services, and preventive medications. USPSTF assigns each of its recommendations a letter grade based on the strength of evidence and the balance of benefits and harms of a preventive service. To receive a high-level-of- certainty score, the available evidence must be based on studies that assess the effects of the preventive service on health outcomes. She underscored the importance of focusing on potential utility to improve health outcomes when considering new screening recommendations, such as screens for environmental contaminants among pregnant women. Dr. Buchanan used exposure to methylmercury in fish as her case example. Clinicians encourage pregnant women to consume fish because it is a source of high-quality, low-fat protein and is high in polyunsaturated fatty acids, especially the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosapentaenoic acid (DHA). Fish is recommended for its advantageous impacts on duration of gestation, birth weight, and infant visual acuity, but particularly because of its association with improved child neurodevelopment scores. However, fish is also contaminated with methylmercury, and there is a well-established dose-response relationship between maternal methylmercury concentrations and adverse effects on childhood neurodevelopment. Dr. Buchanan noted that in order to screen a population for those at risk of adverse health outcomes, a "safe" concentration cutoff must be established. She pointed out that the literature indicates incredible variation in both the range of observed maternal methylmercury levels and the levels at which adverse effects have been detected, which makes screening difficult. Adding to the complexity is the fact that many observed associations occurred below EPA's current reference dose (RfD). Dr. Buchanan stated that there are currently no guidelines for screening for methyl mercury in pregnancy. The Alaska Department of Health universally screens women of childbearing age for methylmercury exposure and follows up with women who have methylmercury concentrations in hair at or above five parts per million (ppm). Around 10 percent of the Alaskan population had hair samples with concentrations greater than one ppm, which is the current EPA RfD. The literature otherwise does not contain examples of screening pregnant women for methylmercury exposure although a few studies have suggested that such screening is needed. Dr. Buchanan discussed what a screening for methylmercury exposure might involve. She described an analysis she conducted to determine the potential results of screening of women of childbearing age using the EPA RfD as the level of concern and NHANES methylmercury concentrations in blood. The results indicated that using a simple universal blood draw approach yields fairly high sensitivity (96 percent) and specificity (99.4 percent). However, asking women about their frequency offish consumption first, and then, depending on the answer, pairing it with a blood sample increases the specificity to between 99.7 and 99.9 percent. Introducing the frequency of fish consumption question avoided 50-91 percent of the blood tests that would have been administered under the universal screening approach. 61 ------- Dr. Buchanan also discussed whether screening should be based on ethnicity. She noted that NHANES data indicate that Asians have a higher population prevalence of elevated methyl mercury levels. Universal screening among this population yields relatively high positive and negative predictive values. However, among other ethnicities that do not consume as much fish, these values are significantly lower, illustrating that universal screening would not be an efficient approach within these subpopulations. Dr. Buchanan noted two ongoing projects that are currently exploring different screening questions for methyl mercury among pregnant women in tribal clinics in Minnesota as well as in prenatal care clinics in the Great Lakes states more broadly. Dr. Buchanan also noted that two published studies reporting on the success of methyl mercury exposure screening programs have also been effective in reducing exposure. In the first study, recreational anglers with elevated levels of methyl mercury in hair, who were informed of their exposure and advised to decrease their consumption, had reduced hair concentrations by 30 percent after receiving this advice. Furthermore, in a study that informed high-end fish consumers of their methyl mercury levels and advised consumption of low-mercury fish, nearly all high-end participants (65 out of 67) reduced their blood levels below five ng/L after receiving this advice. Session 7c Questions, Answers, and Comments Dr. Shaina Stacy, Brown University School of Public Health, pointed out that she is the author of the first paper that Dr. Zlatnik discussed that evaluated the association between proximity to fracking wells and risk of having a SGA baby. She said her research team also found a lower risk for low birth weight, when considered as a dichotomous outcome, forthe mothers in the highest exposure quartile. Dr. Brown agreed with Dr. Zlatnik that the inconsistency highlights the need for more research. A participant commented on the issue of clinical provider compliance with screening guidelines. On the west coast, where lead concentrations are relatively low, risk-based screening of children is also low. Dr. Buchanan replied that there is a disconnect between CDC guidelines and actual clinical medical practices. Dr. Zlatnik said that one of the reasons that physicians may not follow the guidelines is a legitimate belief that they should not conduct the screening. A participant asked Dr. Meeker about his pubertal timing results, specifically about his hypothesis regarding the inconsistency in the directions of odds ratios both across and between genders. Dr. Meeker responded that one reason is that the results were based on varying phthalate metabolites that act on different hormonal axes. He conceded that he presented brand new data that are still in the process of being analyzed and interpreted. Paul Wax, American College of Medical Toxicology, said that it is becoming more common for patients to request a test to determine their exposure to environmental chemicals. He stated that the data on lead and mercury are relatively abundant compared with data for other chemicals and urged caution when discussing such tests with patients as it is not clear what a given concentration means. He also commented on the variation among laboratories in terms of quality of methods and accuracy of test results. He agreed that more research is necessary in the area of environmental exposures and screening of both children 62 ------- and pregnant women, but acknowledged that researchers and clinicians should move forward consciously and cautiously. Another participant agreed, stating that these test results are often returned as the individual's percentile within the population's overall exposure with no explanation of what the toxic level is or is thought to be. Wayne Garfinkel, U.S. EPA Region 4, recalled a meeting several years prior in which concerns were raised over the appropriateness of using hair as a screening tool to assess pregnant women's methylmercury exposure; he also mentioned there were also concerns related to laboratory procedures for analyzing the samples. He said it seemed as though Dr. Buchanan was validating that specific screening method and asked whether these concerns have been addressed. Dr. Buchanan stated that hair is considered a legitimate measure of exposure, but noted that samples need to be sent to legitimate laboratories that report results in absolute concentrations, not relative percentiles, and treat the sample before analysis as samples can be contaminated by hair dyes or cigarette smoke. Dr. Buchanan reiterated that she does not have an answer to the question of whether or not pregnant women should be screened and added that all of the issues raised are legitimate concerns. One participant noted that increased blood lead levels are associated with delayed puberty and asked Dr. Meeker whether decreasing lead levels at the population level could be responsible, at least in part, for the observed shift in pubertal timing. Dr. Meeker commented that it is an interesting hypothesis. Mark Miller, Western States PEHSU, commented that, for him, the bottom line question related to screening pregnant women for toxic environmental exposures is: Will it result in clinicians giving different recommendations than the common-sense fish consumption recommendations they would otherwise be giving pregnant women? He wondered if there was truly an added value. Dr. Buchanan replied that his concern is valid and the potential unintended consequence would be scaring women away from consuming fish at all. Dr. Woodruff suggested giving women recommendations on the specific fish that they might consume. Laura Geer, SUNY Downstate, commented that some of the identified risk factors for blood lead screening in pregnant women overlap with those that might be risk factors for mercury screening in the same population. She explained that the population that she studies in Brooklyn, New York, is predominantly Caribbean immigrants who are also heavy fish consumers. She added that there could be combined risk screening for certain chemicals in specific populations that are at higher risk of exposure. Session 8 - Keynote Moderated by Margaret Karagas, Ph.D. | Dartmouth College Little Things Matter: The Impact of Toxins on Children's Health Bruce Lanphear, M.D., M.P.H. | Simon Fraser University Dr. Bruce Lanphear gave a keynote address on the impact of toxins on children's health. He began by explaining that conducting high-quality science and identifying important risk factors does not always 63 ------- translate into policy action, noting that it is crucial to understand why science isn't translated to regulations or policy. Dr. Lanphear used the impact of toxins on the developing brain as a case study of the difficulty of translating science to health protective action. Brain-based disorders affect an estimated one in six to one in five children, but national surveillance systems are lacking. These disorders are associated with a variety of genetic and environmental factors including gender, nutrition, preterm birth, social stressors, the built environment, maternal depression and genetic susceptibility. Dr. Lanphear noted that society is fixated on curing chronic diseases, but pointed out that beyond vaccines and antibiotics, there are few "cures". As a society, he said, we fail to acknowledge that the epidemic of death and disability due to chronic disease is largely a result of the innovative technologies of the past: automobiles, tobacco, processed foods, and environmental toxins. As an example, he stated that over one billion dollars spent on understanding the etiology of autism between the years 2000-2010 was spent on genetic research; only 40 million (four percent) was spent on environmental health research. Dr. Lanphear suggested that most of the cognitive or brain-based disorders result from complex interactions of genes and the environment, underscoring the irrelevance of genetic susceptibility if risk factors are identified and can be removed. Prevention is particularly important in the context of children's environmental health, because the developing fetus is uniquely vulnerable to environmental insults and the regulatory system used to identify toxins is insufficient. The majority of established environmental toxins were only identified after major environmental disasters. Dr. Lanphear pointed out that environmental toxins are insidious and the disasters only represent just the tip of the iceberg. The population is exposed daily to air pollutants, cigarette smoke, pesticides and other insidious toxins. He reiterated the importance of translating the science into action. Dr. Lanphear then showed a video he produced titled "Little Things Matter: The Impact of Toxins on Children's Health," which illustrated the effect of low-dose exposure to several environmental contaminants on neurodevelopment, specifically IQ, at the population level. The video may be viewed at the following link: https://www.youtube.com/watch?v=E6KoMAbzlBw. Dr. Lanphear noted that the studies discussed in the video suggest that there is no acceptable level for some of the most well- established neurotoxins, which is troubling because our regulatory system assumes there is an acceptable level. On the other hand, he said this can also be viewed as a hopeful message, because it implies there is enough evidence to act in a manner that would prevent disease and disability. Dr. Lanphear explained the concept of a supralinear dose-response relationship, which means there are proportionately larger health impacts at the lowest levels of exposure. He pointed out that reducing these low exposures would have the largest impact. He noted that about ten studies have observed supralinear effects on IQ scores or academic abilities among children in association with lead exposures below five micrograms per deciliter of blood. He noted, however, that this relationship is not just observed with lead. Four studies indicate a similar phenomenon for PM2.5 and premature death from heart disease. A meta- analysis of benzene exposure and leukemia shows a proportionately steeper increase in risk at the lowest levels of exposure. This pattern has also been observed in studies of tobacco smoke and birth weight, where the largest drop-offs in birth weight are seen at the lowest exposures. Dr. Lanphear described a Scottish study that identified a 15 percent decrease in preterm deliveries and a 25 percent decrease in 64 ------- very preterm deliveries among non-smoking women after the establishment of a public smoking ban. Furthermore, he cited a study in which a five microgram per deciliter increase in blood lead levels among British pregnant women was associated with a two-fold increase in preterm delivery. Dr. Lanphear discussed his own work, which found that a 10-fold increase in organophosphate pesticide exposure was associated with a 150 gram reduction in birth weight and a half-week reduction in the duration of gestation; the results were deemed as "clinically irrelevant/' by a commentator. Dr. Lanphear agreed that it might be relevant if babies were exposed to only a single risk factor, but he underscored that this is not the case; birth weight and pregnancy duration are impacted by the cumulative effects of a variety of moderate, subtle risk factors, each of which result in small impacts on birth weight or gestational age. Dr. Lanphear discussed the Prevention Paradox, which states that the majority of disease and disability occurs in those who are at low to moderate risk. He used this idea to focus resources on children in the top 2.5 percent of lead exposure as an example, acknowledging that it is efficient to address those at highest risk. He explained that focusing resources on the 0.5 million children with exposures that exceed the current reference value of five micrograms per deciliter of blood, which is associated with an average loss of 6.1 IQ points, an estimated 3.1 million lost IQ points might be prevented. However, by only focusing on those children, we fail to address the majority of the nearly 24 million lost IQ points that occur at exposures below five micrograms per deciliter. He clarified that he is not suggesting that abandon those who are at high risk, but that we need to strengthen a population or universal approach. Dr. Lanphear commented that a population approach necessitates an emphasis on prevention, but the focus, in terms of lead poisoning, has been on screening. He underscored the key to preventing lead poisoning is remediating homes and removing the exposures before the child is born or before the mother becomes pregnant, but this is not the primary practice. For every dollar spent to protect children against lead hazards in housing, it is estimated that society benefits by anywhere between 17 to 220 dollars. To put these numbers in context, vaccines, which have been touted as the single most cost-effective medical or public health intervention in developed countries, have a cost-benefit ratio of 1:16.5. Although lead is at least as cost-effective, the resources to prevent exposure are lacking. Dr. Lanphear urged attendees that now is the time to give prevention a chance. He said that the scientific evidence indicates adverse health outcomes are associated with environmental toxins, some of which we know how to avoid. He noted that a starting place for individuals includes eating unprocessed foods, minimizing the use of pesticides near the home, reducing the use of cosmetics and personal care products, and supporting bans on smoking and cosmetic pesticides in addition to movements to update chemical risk assessment policies and reduce the use of industrial pollutants. Dr. Lanphear concluded by underscoring that society cannot continue to rely on cures. It has worked well with infectious disease, but it has not worked as well for chronic disease. Session 8 Questions, Answers, and Comments A participant noted that Dr. Lanphear might also emphasize the environmental justice implications of environmental chemical exposures, wherein the cost is borne by the majority of the population, while the financial benefits accrue to a small percentage. 65 ------- A second participant commented that parents and the public health community struggle against consumerism and peer pressure to combat the idea that adolescents need cosmetics or other products that increase their environmental exposures. She noted that the exact behaviors the public health community attempts to counteract are those they are socialized to carry into adulthood. A third participant commented on food additives, pointing out that this is an important aspect of exposure, because the population eats a diet increasingly consisting of processed foods. A fourth participant noted that part of the struggle to act preventatively is that it requires upfront investments. She proposed the idea of selling public health bonds that would be backed through reductions in health care costs. A fifth participant complimented Dr. Lanphear on his message of the impact of many small things and the effectiveness of his graphics but urged him to capture cascading effects and the notion that these relationships are much more complex. Dr. Lanphear agreed that it is an important message and informed attendees that he is currently searching for a dataset that would allow him and his team to present on synergistic effects. Mark Miller, UCSF, commented that there are many deaths, diseases, and disabilities that can be prevented, and that scientists must also play an advocacy role. He praised his colleagues at the meeting who have passionately stepped into this role. Frederica Perrera, Columbia University, commented that early-life exposures have ramifications throughout the life course. As an example, she said even modest decreases in IQ may result in a less productive life in terms of social contributions and earnings. She suggested it might be interesting to attempt to monetize these impacts and emphasize the costliness of these seemingly small impacts. She agreed with Dr. Miller that scientists must do their part to relay the importance of these small changes and advocate for action. Another participant noted changes to the health care system that have been brought through the Affordable Care Act force providers to move away from a fee-for-service model toward primary prevention. She stated that having a value-based dialogue might be very effective and that public health and clinical data systems ought to converge. Dr. Lanphear agreed, saying that well-resourced, high- performing health care systems do not necessarily translate into healthy children, particularly in the United States. He noted that the major player is the environment in which they live. Sally Darney, NIEHS, added to Dr. Lanphear's discussion of fresh and healthy foods by noting that the marketing of foods derived from genetically modified organisms (GMOs) as safe does not consider pesticide use. Claire Barnett, Healthy Schools Network, reiterated a story of a California special education teacher who returned to a refurbished classroom after spring break and, as a result, experienced severe asthma attacks and had to be transferred to a different location. She asked whether there is any tracking of children who experience exposures in what is otherwise considered an adult workplace (i.e., schools). Dr. Lanphear agreed that it is important to consider health when building and renovating buildings and noted that the green building movement is gaining traction. 66 ------- A final participant commented that perhaps existing disparities in health and access to health care are the primary driver of the discrepancy between health care expenditures and health outcomes observed in the United States. He urged focusing on underserved populations. Session 9 - Community Outreach and Research Translation Moderated by Catherine Karr, Ph.D., M.D., M.S. | University of Washington Environmental Health Perspectives (EHP): Your Partner in Research Translation Sally Darney, Ph.D. | Editor-in-Chief, Environmental Health Perspectives Dr. Sally Darney came to Environmental Health Perspectives (EHP) with 31 years of research experience at the U.S. EPA. At EPA and previously as an educator at a junior college, she learned that perceptions of health and biology differ widely across audiences, especially regarding reproductive health. Her commitment to research and teaching health and well-being to a variety of audiences drew her to EHP, where she continues to learn about the breadth of the environmental health field and the importance of science communication The title of her talk references an inherent partnership between EHP and the research community wherein EHP disseminates meaningful and relevant environmental health research and knowledge to different audiences. Dr. Darney explained the vision of EHP, which is "to publish credible, useful and impactful environmental health research and information in ways that are relevant to and understandable by diverse groups," including the scientific community, regulators and risk assessors, health care providers, community advocates, local governments, parents, educators, and the general public. She discussed the variety of article types published by EHP which are intended to provide content that is "fit-for-purpose" to a variety of audiences. Most EHP articles are peer-reviewed original research journal articles. Reviews are also important as syntheses of information for readers who are not able to read the literature on a day-to-day basis, but still want to know what has been learned in the past ten years, what it means, and how it can be used (e.g., Uses of NHANES Biomarker Data for Chemical Risk Assessment: Trends, Challenges, and Opportunities by Sobus et al., 2015). Commentaries are intended to be thought-provoking, and to encourage debates and opinions on emerging issues about which there may be uncertainty and political and economic implications (e.g., The NIEHS Super fund Research Program: 25 Years of Translational Research for Public Health by Landrigan et al., 2015). The News section consists of articles contributed by a variety of scientific writers, includes the most important topics that resonate with the broadest audience, and are often translated into other languages made available through partnerships with international organizations and journals. Letters and editorials are another type of article that disseminates information. Dr. Darney also discussed the new category of Brief Communications, which are more informational and intended to spread information on new resources, documents, websites, etc. 67 ------- The October 2015 issue of EHP included a focus on the influence of the environment on children's health and development. Relevant News articles included, "Environmental Influences on Child Health Outcomes" and "Just What the Doctor Ordered: Using Parks to Improve Children's Health." EHP also publishes special collections including abstracts from the International Society of Environmental Epidemiology, and the annual Children's Health Collection which draws from all types of EHP articles on the topic. . Another EHP strategy is to pick a research article and write a corresponding news article to make available both the technical documentation and data and a reader-friendly article for a broader audience. For example, a 2014 study by J.R. Shelton et al. entitled "Neurodevelopmental Disorders and Prenatal Residential Proximity to Agricultural Pesticides: The CHARGE Study" was published along with a feature article by David C. Holzman entitled "Pesticides and Autism Spectrum Disorder. New Findings from the CHARGE Study." Dr. Darney reminded the audience that EHP is an open access and accessible without cost via the internet (www.ehponline.org), and acknowledged NIEHSfor supporting the journals part of its mission of research and translation across fields related to environmental health. She ended by inviting the audience to provide suggestions for enhancing the relevance, accessibility, and usefulness of EHP moving forward. Why Are Doctors Talking Toxics? Patrice Sutton, MJP.II _ versity of California, San Francisco Ms. Patrice Sutton explained that the science translated at her UCSF Children's Center revolves around two facts: in utero exposure to toxic chemicals can harm not only children's health but also future generations and pregnant women around the world have toxic chemicals in their bodies. She gave a brief and incomplete history of why doctors talk about toxic chemicals, beginning with pediatricians' concern about atmospheric testing of nuclear weapons raining down radioactive isotopes on children. This led to the formation of a Committee on Radiation Hazards and Epidemiology of Malformations by the American Academy of Pediatrics (AAP) in 1957, which served as the predecessor to the current Council on Environmental Health. Arguments about funding between Congress and U.S. EPA coincided with AAP's interest in moving beyond radioactive isotopes to toxic chemicals. This ultimately led to production of the "Green Book," which is the "Bible" for pediatricians regarding toxic chemical exposure. In the 1990s, Ted Schettler, Gina Solomon, Maria Valenti, and Annette Huddle, from Greater Boston Physicians for Social Responsibility, published, "Generations at Risk: Reproductive Health and the Environment." This pointed to reproductive health as the issue and highlighted the important role of reproductive health professionals in prevention of adverse health outcomes in children. Under the leadership of Alison Carlson, Linda Giudice, and Tracey Woodruff, UCSF held a summit on reproductive health and the environment in 2007, bringing together 400 leaders of reproductive health professionals, pediatricians, and government agencies. The UCSF Program on Reproductive Health and the Environment was founded shortly thereafter. In 2012, U.S. EPA Administrator Lisa Jackson recognized then American College of Obstetricians and Gynecologists (ACOG) President Jeanne Conry as an environmental health champion, emphasizing the important relationship between reproductive health professionals and government agencies involved with toxic chemicals. That same year, PEHSUs and the 68 ------- UCSF Pregnancy Exposure to Environmental Chemicals Children's Center helped organize a strategic meeting in Chicago, made possible by support and funding from EPA and ATSDR. The meeting brought together NIEHS, AAP, ACOG, the American Society for Reproductive Medicine (ASRM), and other health professional societies and environmental agencies to endorse a common agenda about prevention. In 2013, ACOG and ASRM issued a joint statement stating reproductive health professionals should pay attention to toxic chemicals and take action in the policy arena. As leading women's health professional societies in America, this represented the coupling of science and leadership in this area and set the stage for global action. The International Federation of Gynecology and Obstetrics (FIGO), comprised of 125 countries and territories, held a World Congress in October 2015 in Vancouver for "Advancing Reproductive Environmental Health for All." The organizing committee, consisting of WHO, UCSF Program on Reproductive Health and the Environment, ASRM, ACOG, Society of Obstetricians and Gynecologists of Canada, and the Royal College of Obstetricians and Gynecologists, met for over a year to produce an opinion on reproductive health impacts of exposure to toxic environmental chemicals. Published October 1, 2015, they determined that it is very bad to expose pregnant women to toxic chemicals and made four recommendations: 1) Advocate for policies to prevent exposure to toxic environmental chemicals, 2) Work to ensure a healthy food system for all, 3) Make environmental health part of health care and its delivery systems, and 4) Champion environmental justice. Twelve other health professional organizations around the world endorsed this opinion, which cited 11 Children's Centers studies as a reflection of all the science funded by NIEHS and EPA. A Summit on Shaping Our Planetary Legacy was held on October 4, 2015, to develop an action plan. The FIGO opinion was disseminated globally in multiple languages, which received a lot of press coverage in the United States and Europe and included a large social media campaign with infographics and a video that went viral. Ms. Sutton emphasized that money from NIEHS and EPA helped the Children's Center leverage the foundation money, giving them the legitimacy they needed to seek other funding for science that matters. Reproductive health professionals around the world own, embrace , and want to act on the science and FIGO has a Reproductive Developmental Environmental Health (RDEH) Work Group ready to bring the recommendations discussed in the opinion to fruition. Do No Environmental Health Harm - An Updated Oath Jennifer Lowry, M.D. || Children's Mercy Hospital Dr. Jennifer Lowry discussed translating science to health care professionals who tend to patients. Wikipedia defines knowledge translation as the "umbrella term for all of the activities involved in moving research from the laboratory, the research journal, and the academic conference into the hands of people and organizations who can put it to practical use." Dr. Lowry explained that she sees patients at both an environmental health clinic and one looking at children with adverse drug reactions, many of whom have autism or ADHD. She discussed the medications being taken by children that come to see her; for example, Matthew was on "serotonin support" and "methylation support." She suggested some practitioners prescribe "methylation support" to change a person's epigenomes to "fix" ADHD or autism, but argued it is impossible to "methylate everything." She consulted a website that had a list of clinics and academic 69 ------- medical centers that are associated with the Walsh Research Institute and discovered a list of biochemical features of autism, including "undermethylation," and a list of popular biochemical therapies for autism, which included "Methyl-B12 and other methylation therapies." This is only one example of misuse of this data as other practitioners are recommending similar "treatments" Dr. Lowry argued that the published science has been misinterpreted this way and emphasized the need to do better translation of this science to avoid these misinterpretations. Dr. Lowry explained the hierarchy of evidence to move through ideas, case series, cross-sectional studies, case-control studies, cohort studies, randomized controlled trials, metanalyses, and systematic reviews. Clinical trials are important, but not specific enough for application to the individual patient, and population-level epidemiologic association studies also are not useful for the individual patient. NIEHS and EPA Children's Centers engage in community-based, participatory research, and PEHSUs engage in clinical consultation, education, and referrals. Both are community partners that work to achieve translation, as well as training the "next generation." The PEHSU website also has fact sheets, FAQs, and other resources, and support for general public education and community and legislative advocacy. PEHSUs want to work with researchers and professionals and the Children's Centers to do a better job of informing the public with regard to science. AAP's Council on Environmental Health has developed policies based on published science, although it acknowledges the difficulty of basing policy on population association studies. Healthychildren.org is another resource; AAP also provided a list of terms searched for on the site, which included water quality and lice rather than lead and epigenetics, which demonstrates how the public's view of what is needed differs from that of researchers. Dr. Lowry finished her talk by providing an example of what can be done to improve research translation. In the October 2015 issue of EHP, an article was published along with a "comment" in response. If Children's Centers partner with a PEHSU, a similar approach can be used to point out important publications and discuss how the results can be used and interpreted. She concluded with the story of canaries and coal mines, explaining how canaries were used to test the air quality of coal mines to ensure it was safe for workers to go down. Unfortunately, children are currently serving as our canaries in the coal mine. Simplifying the Complicated: Leveraging Digital Media for More Effective Community Engagement and Research Translation Carolyn Murray, M.D., M.P.I _ tmouth College The Children's Environmental Health and Disease Prevention Research Center at Dartmouth is focused on understanding the health effects of in utero and early life exposure to arsenic. Arsenic exposure is difficult to communicate effectively to parents and the public. People associate arsenic with poison and cancer and also link it to apple juice, which is a beverage consumed primarily by children despite pediatrician recommendations to the contrary. The Food and Drug Administration (FDA) assessed arsenic concentrations in commercial apple juice and reported that children's exposure was not significant, yet Dr. Oz, a trusted health source for a large segment of the population, raised issues with the FDA's assessment and stated that apple juice could pose a health risk to children. This demonstrated the 70 ------- hallmarks of challenging risk communication. Risk perception is increased when exposures cannot be seen, tasted, or smelled; if the exposures disproportionately affect children; are involuntary; and have health effects about which experts disagree. Adding to this perfect storm of risk perception elevation, the media covered the issue, and researchers published new information on the presence of arsenic in chicken feed and rice. Under the leadership of Dr. Margaret Karagas, the Dartmouth Children's Center has been systematically identifying the sources of arsenic in the food supply, beginning with in utero and maternal exposure through well water and in food, focusing on rice products and continuing on through infancy and into childhood. The amount of arsenic these women and children consume is expressed in their urine and in other biomarkers, raising the challenge of how to best communicate this in a responsible way. Dr. Karagas presented findings to the Food Advisory Committee at the FDA last year, which is looking at vulnerable populations in their own regulatory policy. The FDA is being asked to set regulatory limits for arsenic in rice and rice products, but they are in the midst of their risk assessment, and no decision has been made. In the absence of a regulatory limit, we must determine what to tell pediatric health care providers and parents about arsenic in their food in the interim. Dr. Carolyn Murray explained that the message is confusing and conflicting. For example, "organic" brown rice syrup can have toxic levels of arsenic, and "healthy" snacks are often sweetened with it. There is also the conundrum of brown rice versus white rice; brown rice is considered healthier from a glycemic index and nutritional standpoint but can have higher arsenic concentrations. The Children's Center sought a way to get this message across to consumers to empower them without frightening them. To tackle this issue, the Dartmouth Children's Center partnered with the Digital Arts Leadership and Innovation (DALI Lab) in the Department of Computer Science at Dartmouth College. The DALI Lab's first idea was to develop an app, where you could scan the barcode of a food to find out how much arsenic it contained. This idea did not make it off the group, but as the students of the DALI Lab grappled with other ideas, they learned the science. This iterative process helped clarify messaging, and got both students and the Children's Center researchers excited about using digital media to present an environmental health message. Dr. Murray found it inspiring that, in terms of thinking about environmental health, the current generation gets it, wants to own it, and has the ability to display the concepts in creative ways. Ultimately, they told the science-based story of how arsenic gets in food visually using an interactive tool. The undergraduate students developed logos and other ways to make these complex concepts more simple- a very difficult task. The tool describes what arsenic is, and the ecosystem effects causing it to be persistent in the environment, emphasizing the interplay with the food system. The tool follows the life cycle of arsenic, moving through bedrock wells, soils contaminated by pesticides from use decades ago, arsenical antibiotics in chickens and manure, apples, rice, and farmland. In all of these stages, the viewer can see how arsenic migrates through the system by water. The tool emphasizes rice products as the most common source of dietary exposure. The bottom of the interactive tool focuses on the idea of empowerment and education, including tips on how to minimize arsenic exposure with links to more detailed information on the science and ways for parents to protect their kids given the lack of current regulation. 71 ------- When it was launched, a write-up appeared in the Partnerships for Environmental Public Health (PEPH) Newsletter, which led to an increase number of hits on the Children's Center's Facebook page and website. It has only been out a few months, but they are able to track website traffic and Facebook responses related to the DALI Tool. Dr. Murray said they were looking for further leveraging opportunities, perhaps in EHP, to encourage the use and dissemination of science-based digital tools funded by EPA and NIEHS. Dr. Murray is eager to hear other ideas about how to leverage this further, and encouraged the audience to consider digital tools moving forward. The non-science community is harnessing this, and Dr. Murray stressed the need for the science-based advocacy side to do the same. Build It and Will They Come? Lessons Learned from A Story of Health e-Book Mark Miller, M.D., M.P.H. | University of California, San Francisco Dr. Mark Miller opened his presentation on outreach to healthcare providers by discussing a survey of pediatric oncology providers regarding their environmental health training experience. Six percent of survey respondents indicated they received the basic training, in taking an environmental history. Fifty percent responded that they were uncomfortable speaking with patients and their families about environmental exposures. Ninety-two percent of respondents indicated they would value more information and education related to environmental health. In order to fill the knowledge gap amongst practitioners, the Western States PEHSU collaborated with the Boston and San Francisco Physicians for Social Responsibility and a team of pediatricians to develop the Pediatric Environmental Health Toolkit (PEHT). The Toolkit includes information about key environmental exposures to children and their health effects of concern and how parents might reduce their child's individual exposures. The Toolkit is now available as an online continuing education course. Dr. Miller acknowledged that the PEHT developed as a single exposure-single outcome paradigm. Given the complexity of environmental health impacts, however, the Western States PEHSU developed a new CE program, the Story of Health with partners including PSR, ATSDR, California EPA, the Collaborative on Health and the Environment, and Science and Environmental Health Network. A Story of Health centers on an event—a family reunion—and illustrates complex environmental health issues based on stories told by several reunion attendees (http://coeh.berkeley.edu/ucpehsu/soh.html). In one story, 3-year-old Stephen was occasionally exposed to pesticides at a garden center owned by his parents. His mother who noticed his lack of energy and fever took him to the doctor who ran blood tests and diagnosed him with childhood leukemia. The story addressed other potential risk factors. Another story addressed the impacts of family and community stressors on the exacerbation of childhood asthma. The stories included short embedded videos with clips of experts discussing the topic in further detail. Dr. Miller underscored that one of the lessons learned was that people prefer approachable, visually- pleasing, real-life scenarios as a tool for learning as opposed to reading a textbook. Dr. Miller noted that a second lesson learned was that simply making a good product available online does not ensure its proper use; repeated outreach is necessary. He explained that the funding partners were able to leverage their listservs, webpages, blogs, and social media sites to increase the use of A Story of Health as tracked by the views of the embedded videos. 72 ------- Dr. Miller noted that the continuing education course has been downloaded 2,500 times, and 1,500 individuals have registered with the CDC to receive the continuing education credit. Approximately 3,000 hours of continuing education credit had already been given. Those who completed the course were given the opportunity to comment on its format, and A Story of Health received much positive feedback. Ninety- seven percent of those responding indicated that "the content and learning materials addressed a need or gap in my knowledge or skills." Ninety-six percent agreed that "the instructional strategies (lecture, case scenarios, figures, tables, media, etc.) helped me learn the content." Furthermore, 94 percent said they "will be able to apply the knowledge gained from this activity to increase or maintain (their) competence." #duetoepigenetics #whatdoesthatmean ffmustbewoodooscience Susan Murphy, Ph.D. || Duke University Dr. Susan Murphy presented on what can be done when a scientific message is misconstrued. She conveyed personal examples of research findings being mistranslated by the media and what can be done when that occurs. Example one: After Dr. Murphy received funding for a study to assess whether the increased risk of ADHD associated with tobacco smoke exposure in utero is mediated by epigenetics she was contacted by a reporter who then came to her office to discuss her research findings. During that discussion, Dr. Murphy included details of her own family. She shared that her mother had smoked while pregnant. She also shared that her oldest son was born prematurely and died of hepatoblastoma at three years old. She revealed that her youngest son was diagnosed with autism and her daughter has ADHD. When the story was published, it was entitled "From Great Grandma to You." She underscored the importance of only discussing topics you are comfortable with seeing in print. Example two: Dr. Murphy's postdoctoral research included work on gene imprinting in sheep, during which she and her coauthors identified the mutation that gives rise to the 'callipyge' phenotype, which causes fast-twitch muscle hypertrophy and reduced adipogenesis. The sheep with this phenotype have larger buttocks than their wildtype counterparts. Nature wrote an accurate representation of the study, but the media ran stories titled "Why Your Bum Looks Big in This" and stated that the experts found that if "you are endowed with larger size buttocks than the average person... it's in your genes." Dr. Murphy assured participants that she and her coauthors never made such comments. Example three: The issue of public perception on the topic of epigenetics. She described what she found after a quick Google search of "epigenetics." One of the search results was for the Epigenetics Healing Center, which did not discuss epigenetics on its website in any form. Another result was for Dr. Soram's Enlightened Medicine website, which described epigenetics as "the future of medicine." Dr. Soram was quoted as saying that he had studied epigenetics for many years and "one of Mother Nature's strongest epigenetic molecules is vitamin D." Dr. Murphy said that fact was simply false and Dr. Soram could not be found in PubMed. Dr. Murphy admitted that epigenetics is an extremely complex topic that is difficult to communicate. She explained that communication is easier among scientists in the same laboratory or same field who share 73 ------- a high level of understanding. Communication becomes increasingly difficult among audiences with lower levels of understanding, such as scientists in other fields, general undergraduate students, your family physician, or the press. Analogies are a common tool used to communicate ideas that are new or difficult to grasp, and analogies can be used to elucidate epigenetics. One example analogy described the genome as the hardware of a computer and the epigenome as the software of the computer, both of which are required for the machine to function. Dr. Murphy used another analogy that described the genome as a road (without lines, signs, or traffic signals) and the epigenome as the lines, signs, and signals that control traffic. She added that the methyl groups that attach to DNA at certain positions are, in effect, the molecular stop signs that tell the cellular machinery to skip that region of the DNA. Dr. Murphy noted that while analogies are sometimes helpful in explaining a complicated subject, they lack any real resemblance to what actually occurs and can be easily misconstrued. Dr. Murphy concluded by noting the importance of high-quality scientific communication. Scientific curiosity is growing, and public awareness combined with citizen science means there is more urgency to translate research findings. Fragmented and misleading information at the infancy of understanding has the potential for harm. She underscored that the taxpaying public who funds much of the scientific research deserves careful and meaningful explanations of epigenetics, so that they appreciate it as an important research area that deserves funding. Session 9 Questions, Answers, and Comments Darryl Hood, Ohio State University, commented on the focus on prenatal exposure and the maternal-fetal unit, saying that preconception exposures are also important. He stated that the American College of Obstetricians and Gynecologists (ACOG) are developing preconception and maternal guidelines. He asked whether the panelists and their organizations interface with ACOG on these matters. Dr. Miller responded that the PEHSUs are collaborating with ACOG on research efforts, and that these research efforts center around preconception and maternal environmental health. Dr. Lowry replied that she is unsure about whether or not a maternal or child guideline for exposure will be written. She said the key to treatment is preventing the exposures in the first place. Becky Ofrane, U.S. EPA Region 2, stated that the Dartmouth parallax came across her Facebook newsfeed during the summer and she then shared it on her own page, saying it was a fun way for both children and adults to learn about the health effects associated with arsenic exposure. Her most cynical friend commented that nothing says fun to kids like arsenic! She noted that, despite the critics, it is important to continue to share information in any way possible. Ms. Ofrane also pointed out that each regional EPA office has a children's health coordinator that works closely with their community. She encouraged attendees to contact their regional children's health coordinator when they need assistance with community outreach. Elaine Cohen-Hubal, U.S. EPA, commented that the priority within EPA's Office of Research and Development (ORD) is actionable science. She noted that the CEHCs are producing fundamental science that identifies important signs, and she wondered what additional science is needed to move the research toward policy translation so the Agency can act. She noted that different aspects of children's 74 ------- environmental health science are at different levels of maturity, so the focus will be on specific decision- making contexts and case examples that can highlight the tools that academic and government researchers have been developing and refining. Finally, she encouraged the scientists and science communicators to think critically about their scientific message, especially about what may or may not be actionable. Dr. Murray replied that scientists have a responsibility to anticipate the unintended consequences of their science and scientific messages. Dr. Catherine Karr (University of Washington) pointed out that, traditionally, communication is something tacked on at the very end of a research project; however, scientists must consider effective communication in the design phase of a study to ensure the results will be actionable and translatable. Dr. Patrice Sutton (UCSF) responded to Dr. Cohen- Hubal's inquiry about what additional science is needed to move toward policy action. She noted that the UCSF Navigation Tool and similar tools developed by the National Toxicology Program are designed to synthesize the current scientific evidence for decision-making. She stated that there is an abundance of published environmental health science information; the next step is not to produce more science, but to gather the evidence in a rigorous way and deliver it to the decision-makers. Dr. Lowry replied that the scientific messages do not only reach decision-makers; they also travel through the internet. Healthcare providers and patients may interpret aspects of the science as "fixable" without understanding the nuances of the findings. She underscored the importance of reaching out to the unintended audiences. Wayne Garfinkel, U.S. EPA Region 4, noted that most of the work conducted by the regional Children's Environmental Health Coordinators and their teams is community-based work within vulnerable populations, which is similar to the work done by the PEHSUs and the CEHCs. He asked how the Children's Environmental Health Coordinators might better learn from the work of PEHSUs and CEHCs in order to make a bigger difference within vulnerable communities. Dr. Sally Darney said that Dr. Garfinkel is getting at how success in one community might provide a useful lesson for other communities. She suggested reinstating printing case studies in Environmental Health Perspectives as a way to share success stories more broadly. Dr. Lowry commented that it will also be critical to reach out to populations and organizations that are further outside the box, but are still somewhat interested. Dr. Miller responded with two points. In response to Dr. Cohen-Hubal's comments, he said that decision-makers can still act on science even if the evidence base is not fully developed. He added that studies are more valuable, in terms of what actions should be taken, when they reflect real-life scenarios. Dr. Miller provided a few examples of how to reduce exposure among vulnerable populations, including reducing traffic-related air pollution and eliminating mold within schools. Dr. Murray responded that she has used environmental health tools to bring stakeholders together in her own work. She partnered with community-based pediatric and family medicine clinics and used a GIS mapping tool to indicate the geographic probability of increased water contaminants within the state of New Hampshire and overlaid this with locations of the clinics to raise awareness of clinicians about environmental exposures they may want to discuss with their patients. Dr. Murray stated that these types of tools will play a critical role in converging the healthcare and public health communities although specific collaborations will vary geographically. Dr. Garfinkel agreed that different communities will have different needs. He added that he considers PEHSUs as one of the major tools in improving children's environmental health. Dr. Murphy underscored the importance of prevention with a focus on pre-pregnancy populations. As an example based on her own work on epigenetic changes associated with prenatal tobacco smoke exposure, she said that PEHSUs might help 75 ------- facilitate the message of potential harm to high school students as a means of prevention within the pre- pregnancy population. Ed Levin, Duke University, agreed that prevention is key, but urged the panelists to not forget the individuals who have already been adversely impacted. He stated that those affected are typically the most motivated to encourage action, and are likely more interested in studies considering therapeutic treatments and treatment effects. Dr. Lowry replied that it is our job to consider treatment as well as prevention of ongoing exposure. She reminded the group that they must be careful when discussing treatments because the message may be misinterpreted as illustrated by several of the panelists' earlier presentations. Dr. Miller added that there are no intervention studies in the literature base to draw upon. He used lead as an example, pointing out that there are plenty of data on its effects and data indicating that treatment is ineffective. He also noted that the animal literature shows an enriched environment may be beneficial and noted that more data of this type in human populations will be critical. Dr. Levin agreed that there is no magic bullet solution, but wondered whether the evidence that an enriched environment can attenuate the effects of lead exposure warrants interventions. Dr. Miller replied that it is always good practice to reinforce the importance of beneficial exposures among parents who may be worried about exposures over which they have little control, such as eating a healthy diet and reading to their children. Dr. Lowry urged caution when applying results of a population study to a single individual, noting that relying on scientific data that is not ready to support an intervention may actually cause serious unintended harm, as she has seen in her own practice. Dr. Sutton commented that people who are directly impacted (either exposed or already experiencing health impacts) intervene by changing their environment. Dr. Murphy agreed that it is important to make sure affected individuals do not feel abandoned. She highlighted the importance of frequent communication and outreach, even on projects that have not yet produced concrete steps forward, to reassure the communities that researchers are working hard to make progress. MaryGant, NIEHS, retired, commented that education and communication programs need to help young people understand the science so that they can make better, more informed value judgements. She gave the example of individuals undervaluing the science of vaccinations and the recent increase in specific, vaccine-preventable diseases. She said the goal should be improving the analytical capabilities of the public to empower good decision-making around health care. 76 ------- Session 10 - The Pediatric Environmental Health Specialty Units Present: Emerging Topics in Children's Health Moderated by Carl Baum, M.D., M.Sc. | Yale University A Blueprint for Protecting Children's Environmental Health: An Urgent Call to Action Nsedu Witherspoon, M.P.H. | Children's Environmental Health Network Ms. Nsedu Witherspoon began by explaining that the Children's Environmental Health Network (CEHN) is a national nonprofit organization that has been working 23 years on the same core issue: making sure that children grow up in safe, healthy environments and live to their full potential. To achieve this mission, CEHN has several goals: to stimulate and support prevention-oriented research; to elevate public awareness of environmental hazards to children; to educate community members, health professionals, policy makers, and key public health leaders in developing strategies to prevent exposures to these hazards; and to promote the development of sound public health and child-focused national policy. CEHN has worked to support peer-reviewed science, to translate that science effectively in a variety of ways for multiple stakeholders, and to develop child protective policies based on the vulnerabilities of children. CEHN acknowledged that over the past 20 years, there has been much advancement in children's health; however, they are discouraged that, despite these efforts, trends for some health outcomes are still moving in the wrong direction. In response, CEHN has recommitted itself to reversing those negative trends. For the past three years, CEHN has been building momentum in constructing a new blueprint for protecting children's health, organizing a number of meetings to bring together a variety of experts with a range of perspectives—including communication experts, legal experts, business leaders, community leaders, policy and science experts, and health economists. CEHN was lead author of a background paper that described U.S. advances in children's health and gaps and opportunities moving forward. Last October, CEHN was invited to a Wingspread summit in Racine, Wisconsin coordinated by the Johnson Family Foundation; Ms. Witherspoon explained that this was a big deal because the Foundation recognized a groundswell of interest in children's health and they wanted to be a part of it. All of this has led to what CEHN calls "A Blueprint for Protecting Children's Environmental Health: An Urgent Call to Action". Ms. Witherspoon reviewed five themes of the Blueprint and their respective call to actions. The first theme was to mobilize society to take action. Science has demonstrated irreversible and severe risks to children's health and urgent action is needed. A comprehensive strategy to communicate environmental health issues facing children is essential. The second theme was to marshal the engine of the economy to manufacture and utilize safer products. We must encourage the production and purchasing of safer products by creating a market demand. The third recommendation was to build the political will in institutions of government; this will has waned over the years and is necessary for transformative change to occur. Society also should better recognize elected leaders who are champions of children's environmental health, take charge in developing talking points and briefs on key children's environmental 77 ------- health issues for elected officials, advocate for a Children's Bill of Rights, and promote children's health in all policies. The fourth recommendation was to establish a vibrant children's health environmental community in order to strengthen and align efforts. Bridging collaboration among health care professionals, urban planners, the environmental justice movement, and the public (including marginalized communities) is critical. Ms. Witherspoon referenced the social determinants of health discussed by Dr. Gail Christopher in her talk the previous day as being central to this theme. For the fifth and final theme, Ms. Witherspoon described the importance of strengthening our understanding of environmental impacts on children's health; this is essential for effective action. This can be accomplished by developing a research agenda to address knowledge gaps; crafting ways to overcome funding obstacles for research in the area of pediatrics and prevention; developing comprehensive mass media materials as part of the communications strategy; disseminating information to engage members of the public; and creating curricula for elementary and high schools on children's environmental health issues to ensure the next generation is well equipped to handle these issues. This Blueprint is a high-level framework and resource; CEHN is very proud of its leadership and ability to bring others onboard. Ms. Witherspoon concluded by saying that this work is also part of the 21st century imperative discussed by Dr. Christopher the previous day, which should be critical to all the work being done. Potential Health Hazards of Increasing Cell Phone Use Laura Anderko, PhD., M.S., R.N. | Georgetown University It is well known that technology is evolving and becoming more widespread. Cell phone usage has become part of the fabric of society and is integral to the lifestyle of many people. There are an estimated 6.9 billion cell phone subscriptions globally. More frequent and longer calls mean that global society is spending more time on the phone; that creates some potential hazards. Dr. Laura Anderko displayed a graph showing how cell phone ownership in the United States has gone from 65 percent in 2004 to 91 percent in 2013. Cell phone usage by children has increased greatly; three out of four 12-year-old children own a phone, and 53 percent of children own a phone by age six. There has been increased marketing to get kids to start using cell phones earlier and earlier. These trends bring about concerns of emerging health risks, both thermal and nonthermal. Like a microwave, a cell phone is a nonionizing radiation device; our exposure to radiation increases as it gets closer to our body. Dr. Anderko showed a graphic illustrating the differences between the penetration of radiation in the brains of five- and ten-year-old children versus an adult. Children have thinner skulls and more water in their brain, thus they are much more likely to absorb radiation. In 2011, the International Agency Research on Cancer (IARC) classified cell phones and other wireless devices as possibly carcinogenic to humans due to radiation emissions. Cell phone health advisories are cropping up worldwide, including in Belgium, Australia, France, Turkey, and Italy. Another issue of concern related to cell phone usage is the status of regulatory standards; 19 years ago the FCC created standards for cell phones that have remained unchanged despite dramatic increases in average cell phone use. 78 ------- The risks associated with cell phones include putting it close to the head, putting it in the pocket, using it during pregnancy (exposing the fetus), using it excessively, and operating with low bandwidth. There are serious concerns for kids who are exposed to cell phones for long periods of time. Dr. Christopher Wild, Director of IARC, said in 2011 that "it is important to take pragmatic measures to reduce exposure such as hands-free devices or texting" particularly for children. Looking forward, there have been many studies but currently nothing is conclusive or causal; additional studies will be coming out in the near future. Dr. Anderko mentioned that for some studies, significant differences in results are seen depending on whether the telecommunications industry funded the study. Mobi-Kids is an international, multicenter study that examined the risk of brain cancer from exposure to radiofrequency fields in childhood and adolescence. The National Toxicology Program is finishing up its third phase of study on rats and mice exposed to cell phones for nine hours/day in utero and through adulthood. Dr. Anderko concluded her talk by saying that we should rethink marketing phones to children and reconsider what we as clinicians are telling people regarding the pros and the cons of cell phone usage; the data are still emerging, but there are legitimate concerns out there. Studies of Children's Exposure to Chemicals on Artificial Turf Fields Gary Ginsberg, Ph.D. || Connecticut Department of Public Health Dr. Gary Ginsberg described a risk assessment conducted by the Connecticut Department of Public Health (CTDPH) that evaluated exposures to chemicals in ground-up recycled tires used in artificial turf fields. This risk assessment was performed in response to community concern over the potential health impacts to children exposed to the chemicals in the turf. Dr. Ginsberg noted that community concern associated with this potential exposure stemmed from the perception that tires contain toxic elements. He clarified that tires are in fact treated differently from everyday household trash accepted into community landfills. This special treatment for tires, however, is less about toxicity and more about preventing fires that can occur when tires are exposed to high temperatures, which release naphthalene, other PAHs, BHA, phenols, benzothiazole, and other hazardous chemicals. In conducting the risk assessment, CTDPH sought to provide scientific data to address public concern over this issue. Dr. Ginsberg described a headspace analysis conducted for crumb rubber—the material used in the artificial turf tested by the CTDPH. In a headspace analysis, material is heated to cause the off-gassing of chemicals, which are captured and analyzed using gas chromatography mass-spectrometry (GS-MS). Results of headspace analysis help to identify the chemicals that might be explored in subsequent field analyses. Dr. Ginsberg noted that during these lab analyses, crumb rubber released toxic chemicals, including naphthalene and other PAHs, phenols, and benzothiazole. In order to fully understand the potential risk to children's health associated with these chemicals, CTDPH conducted a risk assessment using real-life exposure levels and evaluated the risks in the context of other environmental exposures. Unlike previous assessments, the CTDPH study conducted personal monitoring, evaluated both outdoor and indoor fields, considered acute risks, and focused the risk assessment on exposures to benzothiazole, a chemical released specifically by tires. CTDPH field sampling included personal monitoring for particulates and gases at hip height and stationary monitoring at locations up- and down-wind of the field 79 ------- at hip height and ground level. Stationary monitors were used to evaluate inhalation risks posed by VOCs, SVOCs, particulates, lead, and zinc during active play in mid-summer. The results of the exposure analysis identified relatively faint signals from PAHs (0.01-0.1 ng/m3), mostly naphthalene, at four outdoor fields. A stronger signal of PAHs (around 100 ng/m3) was observed at the single indoor field. Benzothiazole registered relatively faint signals at the four outdoor fields, while a markedly increased signal was observed at the indoor field. Increased particulate concentrations were not observed at outdoor or indoor fields, and no increase in lead was observed at outdoor fields. Dr. Ginsberg added that new crumb rubber rapidly "weathers" (within 10 to 30 days) with chemicals off-gassing at a high rate, after which much lower exposures would be expected. For the risk assessment, CTDPH evaluated a scenario that assumed three hours of play on the field per day over a total of 138 days during the year at a moderate level of exertion. The risk assessment did not identify a significant increase in noncancer or cancer risks associated with acute exposures at outdoor fields. Marginal cancer and noncancer risks associated with acute exposures were observed at indoor fields. Dr. Ginsberg noted that the results of the CTDPH study are consistent with findings from a 2006 Norway study that identified elevated VOCs on indoor fields, but minimal increases in risk levels. He also mentioned a 2008 analysis out of New York City that found no significant increase in VOCs or particulate exposures in outdoor fields and a 2009 EPA analysis of outdoor fields that also observed no significant increase in VOCs. Despite consistent findings that indicate low risks associated with crumb rubber in artificial turf, Dr. Ginsberg explained that the public remains concerned for several reasons. A recent study from Yale University reported results of a crumb rubber chemical analysis, without a field study, that identified carcinogens and irritants. He noted that media reports on the anecdotal collection of cancer cases being tracked by the women's soccer coach at the University of Washington have also contributed to public concern. Dr. Ginsberg mentioned the importance of using solid epidemiologic studies, which not only enumerate cases but also identify the size of the source population (e.g., the risk denominator) when assessing risk. He also underscored the influence of self-reporting and the absence of personal exposure histories, especially given potential pesticide exposures on natural grass fields. To conclude, Dr. Ginsberg emphasized the importance of advanced safety testing for children's products and conducting exposure assessments under an actual use scenario. He reiterated that the CTDPH did not identify elevated risk levels associated with exposure at four outdoor fields although slightly higher risks were found at indoor fields. He also noted the uncertainty surrounding new, "unweathered" fields, and the possibility that higher exposures could occur on warmer days than those evaluated by the CTDPH. He closed his presentation by repeating that the CTDPH is not endorsing the use of crumb rubber and reminded the audience that concerned communities have several alternative options in terms of materials for artificial turf fields. 80 ------- Not So Pretty - Endocrine Disrupting Chemicals in Cosmetics and Perfumes Katie Huffling, R.N., M.S., C.N.M. | Alliance of Nurses for Healthy Environments Ms. Katie Huffling presented on EDCs in cosmetics and perfumes. She began her presentation by asking the audience members to consider the number of personal care products they used that morning while getting ready. She reported that the average American adult uses nine products daily, which translates to over 125 individual ingredients each day. Further, over a quarter of American women and one in 100 men use at least 15 products per day. Notably, the average teenage girl uses over 17 products daily. The extent to which consumers use these personal care products is also relevant. Users are exposed to personal care products daily via dermal absorption, inhalation, and ingestion, but the FDA has a weak regulatory authority in the context of personal care products. The Federal Food, Drug, and Cosmetics Act (FFDCA) was enacted over 75 years ago and does not give FDA the power to require premarket testing, premarket approval, product recalls, or data reporting. Ms. Huffling gave an overview of EDCs and how they act within the body. She explained that EDCs are chemicals that interfere with the body's natural chemical messengers. They act either by blocking or mimicking the actions of natural hormones. The growing fetus is extremely sensitive to EDCs. She noted a wide variety of examples, but focused on a few chemicals in particular: parabens, phthalates, and triphenyl phosphate. Parabens provide antimicrobial properties in products such as deodorant, antiperspirant, shampoo, conditioner, and lotion. These chemicals are so common that the average person is exposed to multiple parabens from several sources each day. Parabens are estrogen mimickers and have been found in breast tumor biopsies. Ms. Huffling cautioned that although this does not indicate causation, it has raised interest in the ways the estrogenic properties of parabens may influence breast carcinogenesis. She noted a recent study that showed the estrogenic effects of parabens was significantly amplified when combined with a specific protein associated with breast cancer tumors. Parabens have also been observed to reduce sperm production and testosterone levels in males. Finally, to highlight the importance of everyday exposures to parabens, Ms. Huffling pointed to a cohort study of pregnant women and their newborns conducted in Brooklyn, New York. Women in this cohort had the highest levels of methyl- and propyl-paraben among pregnant women ever measured, and 95 percent of the cord blood samples contained at least one paraben. To avoid parabens in personal care products, consumers should lookforthe "paraben-free" label or check the ingredient lists for chemicals ending in "-paraben." Phthalates are used in a wide variety of products, but are typically listed on ingredient labels simply as "fragrance." Dibutyl phthalate (DBP) has typically been used in nail polish to increase the flexibility and durability of the product. In recent years, manufacturers have phased out the use of DBP due to consumer concern over potential health impacts. Phthalates are a component of everyday exposures, and these EDCs are inhaled or readily absorbed through the skin. Phthalates are found in the majority of the American population and impact a number of biological pathways. Some phthalates act as a weak estrogen and act in combination with estradiol. Phthalates also interfere with androgen receptors. In animal models, in utero exposures to phthalates have been shown to disrupt the development and 81 ------- function of both male and female reproductive systems by interfering with the production of testosterone and estradiol, respectively. In humans, phthalates have been associated with decreases in anogenital distance in male infants, which is an indicator of feminization of external genitalia. In a study of breast development among young girls, participants with premature breast development had significantly higher levels of phthalates than participants with normal breast development. To avoid phthalates, consumers should look for phthalate, DEP, DBP, DEHP, and fragrance/parfum on product labels. Ms. Huffling also mentioned triphenyl phosphate, which manufacturers are using to replace DBP in nail polish. Triphenyl phosphate is a suspected EDC and has been shown to absorb quickly through the skin after nail polish application. The possible health consequences are not currently known, but potentially regrettable substitutions will continue to occur until the regulatory system is updated. Maternal Exposure to High Levels of Electromagnetic Fields During Pregnancy and the Long- Term Health Impact on Their Offspring Pe-iwii Li, M.D., Ph.D., M.P.H. | Kaiser Permanente Division of Research Dr. De-Kun Li presented on the adverse health effects of electromagnetic fields (EMFs) on fetal development and children's health. He began by underscoring the importance of accurately measuring EMFs when considering the exposure-health effect relationship. He explained that there is a misconception that EMFs are not associated with adverse health effects, but this misconception is due primarily to inadequate exposure measurements conducted in the majority of studies exploring this association. Another factor contributing to this misconception is that most studies of EMFs and health outcomes investigate cancer. Cancer is an insensitive health outcome to study due to its long latency period and rare incidence and requires reliance on retrospective exposure assessments. He summarized that inaccurate exposure measurements and insensitive health outcomes will, by definition, yield results that indicate no association. Dr. Li provided a historical overview of the concern over EMF exposure. Concern over EMF exposure from power lines—which give off low-frequency EMFs—began 20 to 30 years ago. He pointed to the initial EMF study by Wertheimer and Leeper (1979), which found an association. Dr. Li thinks that although the study was based on crude exposure measurements and an insensitive health outcome (childhood leukemia), Wertheimer and Leeper were incredibly lucky to find the association. But luck, by definition, cannot be easily replicated, said Dr. Li. Subsequent studies followed the template of Wertheimer and Leeper and resulted in many of them reporting null findings, contributing to the misconception that there are no EMF- associated health risks. Recently, there has been a revival in concern over EMF exposure as cell phone usage becomes increasingly common and evidence of adverse health effects associated with magnetic field exposure emerges. He noted that determining the true association between high-frequency cell phone EMF and various health outcomes may require conducting prospective studies which can take time to complete. But we have to start collecting data now. At the same time, we can borrow from findings based on studying low-frequency exposures which may be directly applicable to high-frequency EMF exposure such as cell phone and other wireless devices. He likened the finding of high- and low-frequency EMF exposure to the findings of health effects from alcohol consumption—for example, alcohol could 82 ------- come from wine, beer, hard liquor. However, they all contain alcohol. It is hard to argue that the finding of alcohol's effects from studying beer does not apply to alcohol from hard liquor or wine. However, ironically, some are arguing that the health effect observed by studying low-frequency EMF, which is more advanced than high-frequency EMF research, does not apply to high-frequency EMF health effects, wiping out significant amount of existing scientific evidence of adverse EMF health effect. Dr. Li provided a high-level overview of the prospective cohort studies he conducted to explore the association between low-frequency EMF exposure during pregnancy and the occurrence of miscarriage as well as childhood asthma and obesity. Pregnant women wore personal meters to monitor their EMF exposure for 24 hours during the first or second trimester. Subjects kept a log of their daily activities and indicated whether the activities were representative of a typical day during pregnancy. Results of the study indicated that high-level of EMF exposure during pregnancy is associated with high risks of miscarriage, childhood asthma, and childhood obesity. Due to insufficient time, Dr. Li encouraged conference attendees to read his peer-reviewed publications on this cohort for more details on study methodologies and findings. Trends in Consumption of Artificial Sweeteners and their Metabolic Effects Allison Sylvetsky, Ph.D. | George Washington University Dr. Allison Sylvetsky began by providing examples of artificial sweeteners as well as their common brand names—e.g., sucralose (Splenda), saccharin (Sweet 'N Low), and aspartame (Equal). She also provided examples of noncaloric, plant-based natural sweeteners such as rebaudioside A, commonly known as Stevia. All of these products are low calorie and are potent in terms of their sweetness, but they differ greatly in their physical and chemical structures. Because they are low in calories, artificial sweeteners are used as a substitute for high caloric sugars in sweetened beverages. There is a public health emphasis to reduce the consumption of these sugar-sweetened beverages and switch to low calorie alternatives. Artificial sweeteners are not just in soft drinks labeled as diet or light. They also exist in packet form and are used in some highly consumed foods that are eaten by children. Their use is more obvious in products that say "diet" or "light," but sometimes there are hidden artificial sweeteners in the food supply. For example, they may be found in high fiber sweet cereals, lower carb ice creams, and high fiber oatmeal. Other non-diet applications of artificial sweeteners include toothpaste, mouthwash, and children's medications to increase palatability and compliance. Using NHANES data, Sylvetsky et al. published consumption data in 2012 showing a clear overall increase in consumption of artificial sweeteners in children, a trend driven by the increase in artificially sweetened beverage consumption. The trend for diet sodas has stayed consistent, while consumption of light and diet fruit juice and diet lemonade has increased dramatically. One concern is there are inconsistent recommendations regarding artificial sweetener consumption in kids. In 2010, the AAP reported that artificial sweeteners are "inadequately studied for use among children," but, in 2009, the ADA stated that "children can safely use artificial sweeteners." Much of this inconsistency is due the discrepancy among studies. Epidemiological studies have shown a positive association between artificial sweeteners and body weight and adverse metabolic outcomes; in contrast, randomized trials have shown marginal weight loss 83 ------- and modest benefits associated with artificial sweetener consumption. An epidemiological prospective cohort study in San Antonio showed that as consumption of diet soda increased in adults, so did BMI. Two randomized control trials recently published in the New England Journal of Medicine showed that when kids replace sugar beverages with artificially sweetened beverages, there are modest benefits on weight. Dr. Sylvetsky mentioned that this discrepancy could be due to reverse causality in that artificial sweeteners may not be causing weight gain, but rather that individuals who are already overweight are choosing to consume diet soda as a weight management tool. Mechanisms have been proposed and supported in animal models that have provided a connection between artificial sweeteners and adverse outcomes. These mechanisms include altered taste perception (higher preferences for sweetness), altered nutrient absorption, changes in gut hormones, caloric compensation, and changes in dietary patterns. Sylvetsky et al. recently published a study showing there are artificial sweeteners present in human breast milk, even in mothers who did not report consuming artificial sweeteners. Their data showed that saccharin, sucralose, and acesulfame-potassium are all present in human breastmilk; however, the implications in terms of taste preferences in infants are not yet known. Data from rodent studies have shown that when rodents are exposed in utero to artificial sweeteners, they have higher preferences for sweetness in adulthood. Another emerging area of study examines the influence of artificial sweeteners on the gut microbiome; some recent studies have shown that artificial sweeteners change the gut microbiome with regard to glucose intolerance and increased host energy harvest. Whether this is true in humans is currently unknown. Dr. Sylvetsky acknowledged that researchers in this field have their work cut out for them. Children's Health Impacts of Climate Change Perry Sheffield, M.D. || Mount Sinai Hospital Dr. Perry Sheffield presented on the impacts of climate change on children's health. She began her presentation by noting that an average global temperature increase of less than one degree Celsius may not seem like a major problem, but it is enough to drive changing rainfall patterns, expand oceans, and melt major ice shelves. Even in low-emission scenarios, models indicate that ten million Americans are currently living in areas that will be submerged at high tide in year 2100. At the current emission rate, this number increases to over 26 million Americans. Dr. Sheffield stated that increases in atmospheric carbon levels impact plant life. Carbon-rich environments enable plants such as poison ivy and ragweed to grow bigger and release more pollen. Furthermore, research on agricultural crop growth shows that high levels of carbon result in lower protein and micronutrient content across common whole-food crops (wheat, rice, soybeans, maize, sorghum, and field peas); this is notable given that approximately three billion people worldwide depend on these crops as their primary source of micronutrients. Dr. Sheffield pointed out that actions to reduce emissions can also have health benefits. One way to reduce personal emissions is to consume less meat, which might also have positive impacts on saturated fat levels in our bodies and incidence of heart disease. Furthermore, green school buildings, with high- 84 ------- performance lighting, improved ventilation, and temperature controls, have shown decreased energy and water usage in addition to reductions in absenteeism and asthma. In addition, changing transportation patterns—such switching from a car to a bicycle for one's daily commute—has been shown to decrease the risks of certain cancers and heart disease. Dr. Sheffield pointed to the growing number of post-secondary academic training programs and professional job postings related to climate change and human health. She reiterated the importance of understanding the health implications of climate change and underscored the value in framing mitigation and adaptation approaches around their associated public health co-benefits. Global Children's Environmental Health Kathleen Alexander, Ph.D., D.V.M. | Virginia Tech Globally, infectious disease is one of the most important causes of mortality and morbidity in children. Dr. Kathleen Alexander explained how the environment plays an important role in increasing childhood exposures to pathogens; not only in terms of the incidence, but also in the manner in which pathogens move across the landscape. This is particularly true for children who are minorities and/or living in poverty. Landscapes are changing; there is more overlap between humans and animals, and we cannot always predict the consequences of these changes. In low resource environments, such as Botswana, where Dr. Alexander has conducted extensive research, there are additional challenges; if there is a disease outbreak, we do not always know what caused it. Most research has used case data that are influenced by health-seeking behaviors and driven by culture that changes according to geographic scale (regional to national to community to household). In an effort to improve children's health in these low resource areas, we must try to integrate behavior and culture, including for example, consideration of health behaviors that may be used by a family may engage in to mitigate some of these impacts can have unintended health consequences. Dr. Alexander explained how diarrheal disease provides a unique opportunity for asking important questions about how host attributes interact with the environment to create multi-causal infectious disease dynamics. Water is the dominant source that brings people together with animals across diverse landscapes. Annual bimodal diarrheal disease outbreaks in children under five years of age are observed and significantly correlated with declines in water quality, meteorological and hydrological dynamics, and land use impacts from both animals and humans. For example, in Botswana, huge populations of elephants are constrained in their water access because of competition with human development in dry regions which can impact water quality in a spatially associated manner. Diarrheal disease dynamics in Botswana at the national level also correlated with meteorological variables, identifying increased vulnerability to the impacts of forecasted climate change for the region. These observations and trends make it apparent that environmental drivers may be critical in understanding infectious disease dynamics in these systems and need to be considered by researchers. Dr. Alexander next described how multidrug antibiotic resistance in animals, both domestic and wild, is common in her study site in Africa where drugs and antibiotics are freely used and available for human use. Level of multidrug resistance may be influenced by life history attributes of the animal (i.e., where 85 ------- and how they live). For example, there were higher levels of multidrug resistance in animals that live in the water (versus just drinking it), animals that live with humans, and animals that were at the top of the food chain. This information provides mechanistic insight into this global health threat and can be used to pinpoint pathways of antibiotic resistance exposure and transmission. Dr. Alexander concluded by reiterating that environmental factors are important in driving infectious disease incidence and researchers need to consider these factors in their studies. In addition, what we learn at the global level is important for children's health internationally and here in the United States given our increasingly diverse population and the importance of health disparities that occur both internationally and domestically and have important influence on the impact of infectious disease in general. Session 10 Questions, Answers, and Comments Diana Conway', Independent attendee, expressed concern about the elevated risk of adverse health effects from exposure to artificial turf given the uncertainty surrounding unstudied chemical combinations. Dr. Ginsberg clarified that he only studied five fields, and they are not sure if their sample is representative. He reiterated that the study did not find much PM exposure outdoors and that crumb rubber off-gasses quickly outside, although this is not necessarily the case indoors. He stated that together with the rest of the published data, it does not appear that a large cohort study of crumb rubber is warranted. Dr. Susan Buchannan, University of Illinois at Chicago, commented that she has received many phone calls from concerned parents regarding these exposures. The participant asked Dr. Ginsberg to clarify the potential risks of off-gassing and his confidence in the findings. Dr. Ginsberg stated that his study did not identify an issue, and his task was to provide information to cities in his jurisdiction that would help them decide whether they might use crumb rubber as a field material. He underscored that communities have alternatives available. Tracy Stewart, Independent Attendee, commented on the documentation provided by companies that produce crumb rubber. She noted that the Material Safety Data Sheets suggest the use of personal protective equipment when handling the chemicals involved in its production and wondered how it can be safe for children to play on such a surface. Dr. Ginsberg replied that he studied exposures that occur during the intended use of the product, not necessarily direct handling of the materials. He again reiterated that communities have a number of choices in terms of field materials. Devra Davis, Environmental Health Trust, commented on the growing evidence of male-mediated teratogenesis and asked Dr. Li whether he has any data on the fathers and how he might set up a study if he were designing one today. Dr. Li responded that he conducted a study of the effects of electromagnetic fields (EMF) on sperm quality, which found that high-frequency EMF exposure is associated with increased risks of poor sperm quality. A participant asked Dr. Li what high-level EMF exposure equates to quantitatively. Dr. Li replied that the actual numbers are less important than the relative exposures, though the average high-frequency exposure measures around 2.5 millihertz and the 75th percentile is typically near five millihertz. 86 ------- Becky Ofrane, U.S. EPA Region 2, asked whether there is research being conducted that explores the replacement chemicals for endocrine disrupting compounds. Ms. Huffling answered that phthalates are being replaced with regrettable substitutes, as the current regulatory system does not require pre-market testing. She added that even if industry identifies an adverse health effect, they are not required to notify the Food and Drug Agency. Dr. Linda Birnbaum (NIEHS) added that regrettable substitutions occur because it is easy to change one atom in a compound without changing the industrial process necessary to manufacture it. She pointed out that this also likely does not alter the biological response. A participant stated that cell phone technology has changed over time and asked whether the different technologies have different risks. Dr. Anderko responded that the recent National Toxicology Program study used the wavelengths currently emitted by cellphones. She pointed out that our cellphone use habits and patterns have also changed. Dr. Li added that generally EMF associated with digital technologies are lower, although the problem lies in the uncertainty of whether the effect is associated with energy levels of the house. He noted that cell-to-cell communication uses weak EMF signals and outside influences can affect cell division processes that have implications on fetal development and oncogenesis. Session 11 - Next Steps for Collaboration between the Children's Environmental Health Centers and the Pediatric Environmental Health Specialty Units Moderated by Kimberly Gray, Ph.D. | National Institute of Environmental Health Sciences Overview of Pediatric Environmental Health Specialty Units Ruth Etzel, M.D., Ph.D. | Director, Office of Children's Health Protection, U.S. EPA Dr. Ruth Etzel shared a story about one of the early experiences in her career that solidified her interest in children's environmental health. She told about a previously healthy, happy, and energetic four-year- old boy whose parents reported that he would not get out of bed, and was burying his head in his pillow as if he were sensitive to light. When he visited the clinic, he was squinting due to photophobia and had a rash, low-grade fever, leg cramps, and swelling, redness and peeling of his hands, feet, and nose. These signs and symptoms were similar to those seen in childhood illnesses, including infectious diseases such as measles and Rocky Mountain Spotted Fever. Environmental exposure to mercury can also cause these signs and symptoms. Mercury poisoning is now rare because mercury has been eliminated from many products. The four-year-old boy was diagnosed with mercury poisoning, or acrodynia, also known as "pink disease," which is characterized by pain in the extremities, pink discoloration with desquamation of the skin, hypertension, sweating, insomnia, irritability, and apathy. Pediatricians of the 1950s used to diagnose acrodynia more frequently than today's pediatricians because mercury was contained in some teething powders and other products. It was unclear how this healthy child had been exposed to mercury. It turned out that the boy's family had had a fire in their home that completely burned the inside, and the 87 ------- family decided to repaint the interior walls. The child's father purchased 17 gallons of paint for this project. The four year old boy was home during the time the painting occurred. Mercury had been used as a paint preservative and mercury off gassed from the freshly-painted walls into the air. Because mercury is heavier than air, its highest concentrations were near the floor. Thus, the four-year old child, who played on the floor, had higher exposure to mercury than older children or adults in the family. Additionally, this particular batch of paint had much more mercury added to it than was permitted. This history and subsequent testing of the hone's indoor air by the Department of Health allowed doctors to identify the actual cause of the child's acrodynia. The child's parents decided they did not want this to happen to other children, so they shared their story. At the time, it was not required that mercury be listed on the paint label. The family shared a video of the boy trying to get out of bed, and stumbling and falling because his limbs were so painful. . The father brought the video to regulators at the U.S. EPA. EPA quickly reached a voluntary agreement with paint manufacturers to stop adding mercury to interior latex paints. Dr. Etzel told this story, because it demonstrated the need for parents and physicians and health departments and environmental regulators and industry to work together to prevent environmental health problems for children. The clinicians and scientists working in the PEHSUs and CEHCs play an influential role in bringing issues that arise in communities to the attention of researchers and regulators working in federal agencies. How Pediatric Environmental Health Specialty Units and Children's Environmental Health Centers Can Inform Children's Environmental Health Policy Sheela Sathyanarayana, M.D., M.P.I _ versity of Washington Dr. Sheela Sathyanarayana shared her experiences working in multiple arenas and explained how these arenas can work together to advance children's environmental health. She began with a tweet from President Obama: "Every child should have the chance to fulfill their potential. #OpportunityForAII." Dr. Sathyanarayana argued the goal that every child should have this chance despite their race, gender, zip code, etc., is one where focus is needed as it has not traditionally been addressed in children's environmental health. She showed a Venn diagram of the policy, research, and clinical areas and identified the point in the middle where all three overlap as most desirable. Although most people feel comfortable in their niche spots, she emphasized that they can contribute to the overall progress of children's environmental health no matter where they fall on the diagram. AAP, EPA, and state and federal government regulators read the research of the Children's Centers and observe the clinical trends and translation efforts of the PEHSUs to inform the development of children's environmental policy. For Dr. Sathyanarayana, EPA's CHPAC, of which she has been a member for six years and the chair for four years, demonstrates this. Experts from state government, public sector, private sector, and academia advise EPA on children's health issues in environmental policy. The work products are letters to the Administrator that often outline gaps in literature or places where further research is needed. Dr. Sathyanarayana went on to highlight some of these work products, and explain how they relate to the work done by Children's Centers and PEHSUs. 88 ------- In 2013, CHPAC assembled a prenatal letter: "As requested, CHPAC provides EPA with recommendations on research priorities to be included in the EPA ORD's children's health research roadmap that will increase understanding of the scope of preconception and prenatal environmental exposures that can be harmful, the communities most at risk, and effective exposure prevention strategies." This letter highlights how EPA relies on CHPAC for high level questions. This letter was focused toward U.S. EPA ORD, but the information can be extrapolated to the entire Agency. CHPAC also designated a list of priorities in the 2013 letter: "Research on the health effects of prenatal and preconception exposures; research on the interactions of environmental exposures, socioeconomic factors, and characteristics of sensitive populations with poor birth outcomes, and incorporation of these types of data into mapping tools such as EJView; research the effectiveness of commonly recommended exposure reduction measures; and research on translation of scientific findings into actionable information for policy efforts as well as individual prevention and reduction of exposures to harmful environmental chemicals." In 2014, CHPAC produced a social determinants of health letter stating that "CHPAC sees a need for continued research in the combined effect of stresses related to children's physical/social conditions and chemical/immunological/pathogenic environmental hazards. CHPAC considers that the most practical steps forward may include identifying a few, broad categories of stress, both social and environmental, developing testable hypotheses for demonstrating the plausible synergistic effect of combined stresses." Dr. Sathyanarayana emphasized the need to put physical and social conditions on the same level as chemical and environmental hazards going forward. Although risk assessors want to use human data, Dr. Sathyanarayana said it is not always presented in a usable way and risk assessors frequently use animal data instead. Ways to make human epidemiologic research more useful to policy makers include modeling exposure using continuous variables, showing actual exposure concentrations and ranges (i.e., not just geometric means), and considering using the same endpoints as those in animal studies. Many ongoing efforts have impressed Dr. Sathyanarayana. The Endocrine Society, comprise of clinicians and research scientists, recently released a "Scientific Statement on Endocrine-disrupting chemicals (EDCs)," proposing evidence-based guidelines on EDCs. Tracey Woodruff worked on the "Clinical Practice & Policy: Navigation Guide," detailing one of the first systematic approaches to evaluating evidence without bias and has been validated multiple times. Leo Trasande estimated burden and disease costs of EDCs and other exposures. These are three different ways where policy and research and clinical work has come together to move forward the agenda for children's environmental health. Irva Hertz-Picciotto's project, "Targeting Environment and Neurodevelopmental Risks (TENDR)," brings together senior experts and policymakers to put forth a grading mechanism and guidelines on how to consider environmental exposures and neurodevelopmental outcomes. Dr. Sathyanarayana shared needs she sees moving forward: a national surveillance network to document disease and exposure-outcome relationships, better communication and harmonization across multiple efforts, incorporation of environmental health into health care delivery, improved understanding of how policy is made, and better translation to the public. Dr. Sathyanarayana concluded with some discussion points: 1) How can we begin to look at specific non-traditional stressors such as non-chemical or hazards outside the home in a more focused manner? 2) How can clinicians and researchers inform one another in their combined goals? 3) How can all of us be more involved in translation of results and communication 89 ------- to the appropriate bodies: patients, public, government, and policymakers? She believes we are at the tipping point of the intersection of policy, research, and clinical work, and there are many people working in the policy arena that are ready to move forward in a profound way. Preventing Childhood Leukemia: A Fruitful Partnership for Action Catherine Metayer, M.D., Ph.D. | University of California, Berkeley The UC Berkeley Center for Integrative Research on Childhood Leukemia and the Environment (CIRCLE) started five years ago. The goal of their research is to understand why children develop leukemia and how it can be prevented. The steps toward the answers include identifying chemicals and other risk factors, identifying critical windows of exposures, measuring risk in vulnerable populations, describing underlying mechanisms, assessing the influence of genetic make-up, and disseminating and translating their findings into preventative measures to limit exposure. The Western States PEHSU representatives are true coinvestigators with the Children's Center. Not only they are actively involved in translating research and coordinating outreach, but they are fully engaged in the research activities from the study onset and every subsequent stage. Dr. Catherine Metayer meets with her PEHSU colleague, Mark Miller, on a monthly basis to discuss progress made and opportunities for collaboration. Below are few examples. Working with the PEHSUs brought an outside perspective to the current trend and disparity in childhood leukemia incidence, which helped Dr. Metayer and her Children's Center strengthen their mission to bridge research to prevention. Indeed, over the past 30 years, there have been increasing incidence rates of childhood leukemia, especially in Hispanic children. African American children have the lowest risk in the early years, but the trend rises over time. Such increase is likely due to change in exposures, either alone and or in combination with genetic susceptibility. The Children's Centers and PEHSUs have partnered with the California Cancer Registry to conduct a detailed descriptive analysis on childhood leukemia trend in California, which exemplifies real collaboration. Dr. Metayer then discussed the risk factors for leukemia in which they are interested such as smoking, paints, solvents, and pesticides. Most of them are known carcinogens in adults, and CIRCLE has focused on assessing their impact on children. The PEHSUs provided insight into some other factors not looked at before, including social stressors, prompting the Children's Center to edit their data collection questionnaire to include indicators of stress. Dr. Metayer emphasized that translation and dissemination of their findings was a large component of their work. Mark Miller from the PEHSUs developed the "Story of Health" e-book, which prompted the Children's Center to think about where they are and what they want the key message of their research to be. This process was fully integrated in ongoing discussion for what they want to do next. They expanded access to and contact with hospitals to present their work to physicians, and also conducted a survey for health care providers to understand their knowledge, and learn what health professional think are the causes of leukemia. The results were published in the Journal of Pediatric Hematology/Oncology. Physicians for Social Responsibility invited them to write a short piece on the causes of leukemia, which was a short introduction to their research that has since evolved. Indeed, Dr. Metayer was invited to be part of a CDC workshop to understand early exposure and development of cancer later in life, which was an opportunity to work with Dr. Miller to write a paper on preventable factors for childhood leukemia. 90 ------- The PEHSUs helped enlarge the vision of the Children's Center by sponsoring activities around climate change, which does not impact current research but helps them become part of the larger effort to improve children's environmental health. Dr. Metayer concluded that the relationship between PEHSUs and Children's Centers is reciprocal, sharing expertise for both research and translation activities. Many chemicals found to increase the risk of childhood leukemia are also known to increase the risk of other diseases in children. The PEHSUs are part of a larger network and broad vision to address cumulative impact of these exposures, which is why it is important to continue working together on these challenges. Session 11 Questions, Answers, and Comments The Q&A session began with a question from the moderator, Kim Gray, of NIEHS. She discussed how the relationships between Children's Centers and PEHSUs are organic. There is no requirement making them work together, but they find themselves working together quite frequently. As there is currently no official process, she asked the PEHSU representatives in the room if they had any ideas on some collaborative efforts they should focus on together. Bruce Lanphear of Simon Fraser University responded that when he worked in Cincinnati, they were adopted by the Chicago PEHSU. They started reporting biomarkers back to families, a lot of which was done without funding as it was the right thing to do. They sent out letters, hosted a hotline, and the PEHSU representative served as a point person to answer questions about exposure levels. This collaboration worked out very well. Dr. Sathyanarayana said that one thing she sees is that the Children's Centers do a lot of research, and sometimes have an adverse health outcome in their cohort they did not expect to see (i.e., it is a statistical outlier, but means a lot clinically). One example in Bruce Lanphear's cohort was a significant abnormal neonatal neurobehavioral exam, which turned in to a published case study about BPA exposure. The Children's Centers can keep data that the PEHSU clinicians know what to do with, ensuring that the information gets translated and not buried in the research world. An affiliate of the Children's Center at the University of Illinois at Urbana-Champaign said it was helpful for PEHSU members to be on advisory boards of Children's Centers to assist with crafting messaging. Frontline health care providers are not in marketing, but they do communicate one-on-one with patients. It is helpful to interact with Children's Centers about their messaging for the findings. She wondered if the Children's Centers should require a PEHSU member, and was informed they were required to have a pediatric specialist of their choosing. Although it is recommended they partner with a PEHSU, it is not a formal requirement. Dr. Sathyanarayana felt that communication is the first step to building relationships between PEHSUs and Children's Centers. A good example is when the arsenic findings on apple juice and rice came out in the media. If there was a PEHSU member on the advisory board, they could have been preemptive against concerned calls from parents or put out a one-page clinical handout for clinicians and providers. Regarding the arsenic issue, Dr. Jennifer Lowry, with the Region 7 PEHSU and the Chair of the Council for Environmental Health for AAP, added that when the information went out, there was mass coverage and response in the media. PEHSUs are very good at responding quickly, and if there had been some warning from the Children's Centers, they could have preempted some of the panic and confusion 91 ------- that occurred. Much of the Children's Centers' research is published in journals not necessarily read by OBGYNs, pediatricians, or family practice clinicians. If someone is concerned about an illness or exposure, they will go to Google, not PubMed. She feels there needs to be a dialogue on how we can accurately get Children's Centers' research from the scientific journals in which it is published to the people that actually need it. Dr. Metayer thought that was a good point. Recently, she has been involved in showing research at society meetings, which has been underutilized up to now. She thinks there is a need to speak to a broader audience of health providers. Research could be published in journals aimed at the target audience, but Dr. Lowry warned that the target audience will not necessarily understand how to translate the research to their practice, which could lead to misunderstandings and miscommunication. A commentary or other co-effort to send them digestible and practical information would be helpful. An affiliate of the Region 1 PEHSU said the formal collaboration between PEHSUs and CEHCs is especially important when data are about to go out and context needs to be given to providers; however, funding for PEHSUs is often limited. Dr. Metayer agreed that the resources for PEHSUs are give-and-take, and they need resources to collaborate with the Children's Centers. The next questioner said that the discussion has been focused on individual partnerships between one PEHSU and one Children's Center. He wondered how they can maximize the information exchange in the wider network. Dr. Kim Gray said there is a Children's Centers meeting every month if there is something to discuss. Dr. Sathyanarayana said that something that cannot be ignored is that some of this is a higher-level funding discussion, asking whether we want the two to combine and work together in a mandated way. Dr. Gray explained that the Children's Centers have been built since 1998 and have a very strong infrastructure. They need to work within the built structure and current RFA and embrace the collaboration. Dr. Lowry pointed out that the Children's Centers get a lot more money. Dr. Gray responded that the mission of NIH is biomedical research. Children's Centers have three research projects and are running very thin, similar to the PEHSUs, so they need to work together. Dr. Metayer said something they have been discussing in their group is looking for additional side funding for outreach and translation, because it is a great platform for targeted projects. Dr. Gray agreed, saying leveraging the two programs together is a potential new idea to think about for a program. The final question came from an affiliate of the Southeast PEHSU and Break the Cycle program, who said that a listing of subject matter experts that PEHSUs and Children's Centers could use as resources to answer questions would be helpful. Dr. Gray said NIEHS funds over $115 million in children's environmental health, so they have subject matter expertise outside the Children's Centers available on the NIEHS website. She agreed that would be a very good tool to potentially add to the Children's Centers' websites. Session 12 - Keynote Moderated by Frederica Perera, Ph.D., M.P.H. | Columbia University Adam Smith and the Business Case for Children's Environmental Health Leonardo Trasande, IVi.D. | New York University 92 ------- Dr. Leonardo Trasande began his presentation by referencing Adam Smith, a Scottish philosopher, best known for conducting the first modern work in economics, outlining the conditions for a properly functioning market economy. Dr. Trasande argued that Adam Smith would be passionate about children's environmental health, because environmental hazards produce market failures that are costly to society. The two sets of market inefficiencies introduced by environmental hazards are externalities and information asymmetry in economic and business transactions. In a typical business transaction, there is an expectation that goods and money will be exchanged without external effects on those not involved in the transaction. An externality is a "spill-over" effect, with one person's activity influencing the utility of others outside of that activity. Point-source air pollution is a good example. Electricity producers emit PM and other respiratory irritants into the air, which results in children developing respiratory illnesses. Children are not participating in the economic transaction but are experiencing adverse health effects as a result. Ultimately society pays for this in the form of additional health care costs (hospitalization, emergency room, prescription drugs) and other downstream costs from loss of work, school, and productivity. This results in an over-production of electricity that is not accounted for in the transaction. The cost is not appropriately perceived by the producer, and therefore, electricity is produced above the societally optimal amount at a cost below the societally optimal amount. This is referred to as deadweight loss; a cost to society we all bear as a result of an activity that should not occur. The second problem of information asymmetry relates to food contamination. The label tells you the nutritional value when you buy a product, but it does not include the finer details of the product. When you want to compare two different products, you might not have all the information necessary to make the optimal selection. Ideally, you know everything that you are getting insofar as it impacts your well- being, which, in theory, drives your decision-making in pricing things differentially. At a theoretical level, you attach an implicit value that might be greater or less than the product's true value, depending on your current state of health. "Lemons competition" refers to a situation in which one side of the transaction has more information than the other. The purchaser then has an uncertainty that results in erring on the side of caution, which brings down the value of certain goods out of fear of contamination and drives other goods out of the market. Two sets of problems exist: the producer has more information than the consumer, and the risk uncertainty incurred as a result leads to mispricing of products compared to the societally optimal amount. In the context of food contamination, organic labeling is a partial solution as it levels the playing field and pricing mechanisms. Complications remain, however, regarding the complexity of that communication. There can still be incomplete information about what is in organic food, and there are controversies over what can be included in organic food. As long as there is still an unwillingness to disclose ingredients in a food item, a partial amount of that problem will still cause market dysfunction. Dr. Trasande discussed the estimated costs to society of these market inefficiencies, which are largely unknown. This is partly due to the current regulatory framework set up by the Toxic Substances Control Act of 1976, which employs an "innocent until proverbially guilty" mindset to chemicals, in that premarket testing of chemicals is not required. Epidemiological and toxicological studies investigate exposure and response relationships. Latencies to disease, many potential confounders to outcomes, issues with reproducibility of studies and consistency of data, and uncertainty about dose-response relationships and thresholds lead to policy debates about what the effects are, and what to do about them at a societal 93 ------- level. In the context of uncertainty, subclinical effects that might exist from multiple factors that cause chronic disease delay acting on information, which has a cost. The amount of this cost remains equally uncertain, because epidemiologic and toxicological research is needed to quantify the relationship between exposure and response. The best and most recent estimates are that the costs of environmental hazards to children are quite substantial. In 2011, Trasande and Liu looked at conditions for which evidence was greatest for environmental causation, including lead poisoning, intellectual disability, and ADHD. Their best estimate of aggregate costs of environmentally mediated diseases in U.S. children in 2008 was $76.6 billion, roughly three percent of U.S. health care costs. Bartlett and Trasande did a follow- up analysis in 2014 looking at environmentally attributable costs of lead exposure, methylmercury exposure, developmental disabilities, asthma, and cancer in the European Union (EU), and found it to be $70.9 billion in 2008, roughly 0.48 percent of the EU's gross domestic product (GDP). In 2013, Attina and Trasande looked at the costs of lead exposure in low- and middle-income countries and found there was a $992 billion annual cost from lost productivity resulting from IQ losses. The costs in developing countries are even greater than in the United States and Europe, perhaps speaking to the need to allocate resources for prevention differentially. The other problem is the economic impact of environmental injustice. People who bear the brunt of exposure often have the lowest income, thus environmental hazards magnify social inequality. Faced with these market failures from environmental hazards, Dr. Trasande asked what would Adam Smith do? In theory, Adam Smith would potentially sign off on government intervention. Although the government might improve the situation by correcting the mechanism, it can also worsen the situation. When government intervention is presented as a solution, there is resistance in part due to potential market inefficiencies. This argument was made during the Affordable Healthcare Act debate. There are three examples of government intervention as an economic solution in environmental health. The first example is phasing out lead in gasoline, which is the landmark example of the economic benefits that can result from corrective government action and environmental prevention. The phasing out of lead in gas was a benefit for children and for facilitating the ongoing use of catalytic converters in cars. It was due to National Health and Nutrition Examination Survey (NHANES) data on lock-step decreases in children's blood levels that stopped the reinstitution of lead in gas. This was a wise health and economic decision. Grosse et al. did a series of analyses in 2002 showing that the 15 microgram/deciliter drop off in blood lead led to a four to seven point increase in IQ. Across society that magnifies into billions of dollars, with every IQ point resulting in a roughly two percent increase in a child's lifetime economic productivity. Across the population, on average one IQ point is worth $20,000, so multiplying that by four IQ points by roughly four million births per year leads to a very large number; approximately $219 billion of economic stimulus simply by phasing out lead in gasoline. The global benefits are even larger. The best estimate is approximately $2.45 trillion per year, or four percent of global GDP. This serves as a great example of how inefficiencies can be reversed and yield huge economic benefits. Another option Adam Smith might suggest is a Pigovian tax, which is a tax on producers equal to the amount of the economic damage suffered by those who experience the externalities of the activity. Ideally, this would ensure producers perceive the economic inefficiency their actions create, and change their behavior. Hypothetically speaking, there are two issues with this strategy. One is that the children who have suffered the externality would need to receive the payout from the tax, but taxes go to a general 94 ------- revenue. The other issue is accurately quantifying the exact amount of damage at the individual level and aggregating to the population level to place the right amount of economic cost on the producers. On a theoretical level, this is hard to do. The third government intervention is the "polluter pays provision/' which is a penalty on a polluter equivalent to the economic harm suffered. In some ways this is the prime premise of the Superfund program. It is difficult to actualize in part due to a long latency in identifying a problem, and the potential lawsuits brought by EPA against companies that are now defunct. It is not possible to ensure the financial transaction to compensate for damages inflicted on society by toxic environmental exposure occurs. In general, regulation is the most straightforward way to correct market inefficiencies. Dr. Trasande then explored a case study involving EDCs, which are a broad category of widely used chemicals with limited epidemiological evidence linking them to health conditions. Prevention of EDC- mediated disease will occur by phasing out their use, but there is a trade-off between the cost of safer alternatives and the economic benefits of prevention. In Europe, in 2009 and 2011, in the aftermath of Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) legislation, there was an effort to identify principles for regulating pesticides and biocides with endocrine disrupting properties that might have harmful health and environmental effects. This process has been long and arduous. A risk assessment is being pursued to identify the proper criteria for identifying and then eliminating EDCs. At the time, there were no data quantifying the economic benefits of regulating EDCs insofar as they improve health. Trasande et al. pursued a series of analyses to quantify a range of health and economic costs that can be reasonably attributed to EDC exposures in the European Union. Before explaining the analysis, Dr. Trasande provided some background information on the principles one should use in identifying causation, set forth by Sir Austin Bradford Hill. The only principle required for causality is the temporal relationship, that is, exposure must happen before the effect. There are a series of other optional, but still important, criteria to determine whether an exposure-outcome relationship is causal: consistency, substantial effect size, dose-response relationship, biological plausibility, effect specificity, coherence with existing knowledge, experimental evidence, and consideration of alternate explanations. When you look at the literature to see how principles have been applied, causation is usually binary (i.e., yes or no). Current practice, however does not follow what Sir Austin Bradford Hill proposed: "I do not believe...that we can usefully lay down some hard-and-fast rules of evidence that must be obeyed before we accept cause and effect." More recently, the Intergovernmental Panel on Climate Change (IPCC) embraced the probability of causation, and developed a series of criteria for grading probability of causation. Trasande et al. were able to leverage this framework for thinking about the probability of causation in the context of the European Union EDC project. They also took advantage of the GRADE (Grading of Recommendations Assessment, Development and Evaluation) scheme, WHO's framework for evaluating and ranking evidence by quality. In addition to study design (cohort, cross-sectional, randomized controlled trial, etc.), there are other items that can affect rank, such as study limitations, uncertainty, and bias. They also adapted the Danish Environmental Protection Agency criteria for toxicological evidence. By adapting the IPCC criteria to integrate the toxicological and epidemiological evidence, they were able to create working groups to evaluate the types of evidence available and derive a probability of causation. 95 ------- During a two-day workshop in Spring 2014, five expert panels identified conditions in which the evidence was strongest for causation and developed ranges for fractions of disease burden that could be attributed to EDCs. To quantify attribution, they prioritized dose-response relationships from the epidemiologic literature and used peer-reviewed cost-of-illness data whenever possible. Much of the evidence for developmental neurotoxicity, organophosphates, and brominated flame retardants is rated highly due to strong toxicological evidence of thyroid effects and consistent dose-response relationships in longitudinal birth cohorts. This led to high probability of causation for those relationships. The evidence for the obesogenicity of phthalates was rated as more moderate. In addition, multiple male reproductive effects were identified with moderate probability of causation, and neurobehavioral outcomes such as autism and ADHD had low or moderate probabilities. Trasande et al. 2015 identified substantial costs due to decreased economic productivity from lost IQ points from exposure to pesticides: €124 billion lost earning potential and an additional €21.4 billion lost from increased incidences of intellectual disability. There was also modest attribution with persistent pesticides totaling approximately €850 million. For phthalates, they found substantial costs due to early mortality from cardiovascular health outcomes, primarily in adult males: 24,800 additional deaths among 55-64 year old men, totaling €7.96 billion in lost economic productivity. They also identified a cost of €4.71 billion from 618,000 additional assisted reproductive technology procedures in men, and substantial attributions to obesity and obesity-related diseases (e.g., diabetes). Flame retardants had moderate disease burdens in the form of lost IQ points, totaling €6.4 billion in lost earning potential, and they were also associated with new cases of testicular cancer and undescended testis. Additional cases of autism, ADHD, and childhood obesity had moderate associations. Dr. Trasande explained how all of the burden of disease cost numbers assume certainty; at this point probability of causation is introduced. The team conducted Monte Carlo analyses to model potential costs and the cumulative probability. On average, they calculated an estimated €157 billion, with the possibility that the cost could be as high as €270 billion. They broke down the €157 billion estimate and found that pesticides were the most costly chemical type (accounting for €120 billion of the total cost) and neurological impacts were the most costly health effect (accounting for €132 billion of the total cost). Dr. Trasande explained that the €157 billion is likely a substantial underestimate of the true cost of EDC exposure. They only considered less than five percent of EDCs, many health conditions were not examined, and the numbers did not consider all of the costs associated with these chronic conditions. Given that a similarly large burden of disease may be attributable to EDCs in the United States, costs are likely to be the same, if not higher. For example, costs of flame retardant use may be higher in the United States, as use is more stringently limited in Europe. Levels of phthalates (DEHP), however, have decreased in the past decade and thus might have lower costs of attributable disease. In general, these findings support the need for an international strategic approach to chemicals management. Dr. Trasande closed with an example in the United States. They conducted an analysis of the health costs that can be attributed to BPA, recognizing uncertainty and all the exposure-outcome responses to date, due to U.S. FDA's decision to not phase out BPA in aluminum cans. The cost of oleoresin, a BPA alternative (leaving aside the actual safety of oleoresin), is $0,022 per can, or about $2.2 billion annually. Trasande et al. did a series of cost-of-illness methods for childhood obesity and adult coronary heart diseases, using 96 ------- exposure data from NHANES. They also modeled a counterfactual scenario using intervention studies that quantified decrements in BPA associated with the removal of BPA in food sources. The best-case scenario costs of BPA-associated childhood obesity was $748 million, and $987 million for adult coronary heart disease. The counterfactual model documented a benefit on the order of $1.9 billion annually. Compared to the $2.2 billion it would cost to replace BPA in aluminum cans, it is a close call, and potentially indicates there could still be more costs than benefits associated with replacing BPA. A sensitivity analysis of the benefits, however, suggests they could actually be 6-fold higher ($13.8 billion annually) than the associated costs. Dr. Trasande summarized the key points: environmentally mediated diseases are costly, create market inefficiencies, and prevention methods can result in large economic benefits. Ultimately there is a strong business case for proactively intervening. He also emphasized that it is time for the field to accept uncertainty in exposure-outcome relationships to be able to inform policymakers. If the data are not at the table, recognizing the caveats raised about the probability of causation, there will never be an educated decision by policymakers on whether or not to intervene in chemical regulation. Session 12 Questions, Answers, and Comments The moderator, Dr. Frederica Perera, asked if Dr. Trasande had considered life-course benefits. He responded that all the analyses he described did consider life-course benefits wherever possible. In fact, the research on the benefits of childhood obesity prevention included discounting for longer-term benefits that aggregate over time, for example, adjusted expected life years. The next questioner said she appreciated how difficult this research is, and why for the business case, it makes sense to focus on potential losses as a result of IQ points. She pointed out that there are also real losses associated with neurodevelopmental disabilities that do not necessarily manifest in IQ decrements (e.g., cost to medical care providers, lost parent time at work, pharmaceuticals not covered by insurance), and asked to what extent they could account for them. Dr. Trasande agreed and said the reality is that they do their best to document what they cannot quantify. As long as they underestimate and the costs are large, that provides the fuel for the fire in decision-making in health and environmental policy. If these analyses are not grounded in the most rigorous economic, environmental, biomarker, and epidemiological data, the economic estimates will be dead on arrival from a policymaking perspective. Bruce Lanphear, Simon Fraser University, said he saw online that if you take into account all the externalities, relatively few of the Fortune 500 companies would be profitable. He asked if this was true. Dr. Trasande said it was not correct, because when those externalities are corrected, there are ultimately some other entities that produce more appropriately and experience gains. There are internally winners and losers. In the current scenario the winners are winning at the cost of others, whereas winners in the scenario of corrective prevention are the companies that are proactively identifying safer alternatives, intervening, and recouping those economic benefits. 97 ------- Conclusions Nica Louie congratulated the participants of the 2015 NIEHS/EPA Children's Centers Meeting. She thanked and honored everyone who worked to put the meeting together, including the planning Committee, speakers, and ICF team. She said she hoped they had met the expectations of everyone who participated. She remarked there was enough information presented in a variety of ways that can be helpful to all as they work toward helping and protecting children, which is why they do what they do. Ms. Louie said she was grateful and thankful for Children's Health month and all the events that occurred. 98 ------- Appendix A - Agenda 2015 NIEHS/EPA Children's Centers Annual Meeting October 29-30, 2015 Day 1: Thursday, October 29, 201 7:30-8:30 a.m. 8:30-9:30 a.m. 9:30-10:15 a.m. 10:15-10:30 a.nr 10:30-11:00 a.rr 11:00-12:30 p.m EGISTRATION Session 1 - Welcome and Introduction Moderated by James H.Johnson, Ph.D., M.S. | Director, National Center for Environmental Research, U.S. EPA The Role of NIEHS in Supporting Children's Environmental Health Linda Birnbaum, Ph.D. | Director, National Institutes for Environmental Health Sciences CDC/ATSDR's Role in Children's Environmental Health Patrick Breysse, Ph.D. | Director, National Center for Environmental Health/Agency for Toxic Substances and Disease Registry, Centers for Disease Control Children's Environmental Health: From Knowledge to Action Ruth Etzel, M.D., Ph.D. | Director, Office of Children's Health Protection, U.S. EPA Session 2 - Keynote Moderated by Kari Nadeau, M.D., Ph.D. | Stanford University This session will provide a holistic, conceptual framework and describe programmatic interventions designed to help minimize toxic exposures and mitigate related risks throughout early stages of life. America Healing: A 21st Century Imperative Gail Christopher, D.N. | Vice President of Policy and Senior Advisor, W.K. Kellogg Foundation Session 3 The future of children's environmental health is a public health issue. Healthy children lead to healthy adults, and healthy adults lead to a prosperous, healthy society. This session will highlight successes of the Children's Environmental Health and Disease Prevention Research Centers, and of the collaborative efforts between EPA and NIEHS. Protecting Children's Health in the Future: Adapting to a Changing World Thomas Burke, Ph.D. | Science Advisor, U.S. EPA BREAK Session 4 - Social Determinants of Health Moderated by Andrew Geller, Ph.D., M.A. | Deputy National Program Director, Sustainable and Healthy Communities Research Program, U.S. EPA Children who grow up in circumstances of social and economic disadvantage are at greater risk for exposure to adverse environmental factors and are more likely to suffer consequent adverse health and developmental outcomes. This session will address the 99 ------- role of the environment in health disparities, focusing on where we live, learn and work and the contribution of pollutants and allergens. Asthma Disparities and the Indoor Environment Greg Diette, M.D. | Johns Hopkins University Psychological Stress & Perinatal Programming of Chronic Disease Rosalind Wright, M.D., M.P.H. | Mount Sinai Hospital Students Break the Cycle of Environmental Health Disparities Leslie Rubin, M.D. | Emory University CalEnviroScreen and Potentially Preventable Childhood Morbidity in California's Central Valley Emanuel Alcala, M.A. | Central Valley Health Policy Institute 12:30-2:00 p.m. LUNCH 1:00-1:50 p.m. Brownbag Lunch Session - Community Outreach and Translation Core Wilson/Roosevelt Room Kelly Widener | Communications Director, National Center for Environmental Research, U.S. EPA Virginia Guidry, Ph.D. | Office of Communications and Public Liaison, National Institute of Environmental Health Sciences 2:00-2:30 p.m. Session 5 - Keynote Moderated by Michael Hatcher, Ph.D. | Chief Environmental Health Branch, Agency for Toxic Substances and Disease Registry, CDC This session will provide examples of two component models of the life course perspective - Early Programming and Cumulative Pathways - and discuss implications for children's environmental health. The Life Course Perspective and Children's Environmental Health Michael Lu, M.D., M.S., M.P.H. | Heath Resources and Services Administration 2:30-4:00 p.m. Session 6 - Neurodevelopmental Disorders Moderated by Susan Schantz, Ph.D. | University of Illinois at Urbana-Champaign There has been a tremendous increase in understanding of early brain development and how this can be impacted by environmental influences. Evidence of developmental neurotoxicants will be presented, using case examples. This session ends with a panel discussion that identifies new opportunities for application as well as discussion on how these novel methods will impact clinical practice. Lessons Learned From the New Bedford Cohort Study Susan Korrick, M.D. | Harvard University The Long-Term, Brain-Based Effects of Prenatal Exposure to Two Environmental Neurotoxicants Bradley S. Peterson, M.D. | Children's Hospital Los Angeles It's about 4 Million Brains a Year - Toxic Chemicals and the In Utero Environment Tracey Woodruff, Ph.D., M.P.H. | University of California, San Francisco From Science to Policy: Targeting Environment and Neuro-Developmental Risks (Project TENDR) 100 ------- Irva Hertz-Picciotto, Ph.D., M.A., M.P.H. | University of California, Davis 4:00-4:30 p.m. BREAK 4:30-5:30 p.m. Session 7 - Concurrent Sessions • Session 7a - Obesity (Constitution C) • Session 7b - Exposome (Constitution D) • Session 7c - Reproductive Health (Constitution E) Session 7a - Obesity (Constitution C) Moderated by Dana Dolinoy, Ph.D. | University of Michigan Emerging evidence indicates that environmental exposures may contribute to the development of obesity. This session aims to provide an overview of environmental factors that may contribute to childhood obesity, as well as examples of innovative collaborations working towards addressing the role of the environment in childhood obesity. As the evidence grows so too has the outreach and education tools for use with diverse audiences including the general public, community based organizations, health care professionals, public health officials, policy makers and others. This session will also provide examples of publicly available educational outreach tools. The Contribution of Environmental Exposures to Childhood Obesity Rob McConnell, M.D. | University of Southern California Early Toxicant Exposures and Development of Child Obesity: Evidence and Gaps from Recent Research Karen Peterson, Sc. D. | University of Michigan Environmental Health and Childhood Obesity: From Research to Action Maida Galvez, M.D., M.P.H. | Mount Sinai Hospital Session 7b - Exposome (Constitution D) Moderated by Claudia Thompson, Ph.D. | National Institute of Environmental Health Sciences The exposome encompasses the totality of human environmental exposures, and complements the genome. Although at this stage it may not be possible to measure or model the full exposome, some recent projects have made first attempts. This session will provide examples of how the exposome may affect causal pathways in childhood disease, and present potential platforms to initiate sequencing of the human exposome. Using a Risk Assessment Framework to Integrate Epigenetic Outcomes with Exposome Assessment for Neurodevelopment Elaine M. Faustman, Ph.D. | University of Washington High-Resolution Metabolomics for Sequencing the Exposome Dean P. Jones, Ph.D. | Emory University Environmental Exposures in Early Life Influence Childhood Leukemia Stephen M. Rappaport, Ph.D. | University of California, Berkeley 101 ------- Session 7c- Reproductive Health (Constitution E) Moderated by Tracey Woodruff, Ph.D., M.P.H. | University of California, San Francisco New issues in reproductive health with reference to environmental exposures will be discussed. Evidence from recent research will be presented to suggest potential relationships between early-life exposures to endocrine disrupting chemicals and adverse reproductive health outcomes. Updates on Environmental Effects on Reproductive Health Marya Zlatnik, M.D. | University of California, San Francisco Impacts of Early-life Exposure to Endocrine Disrupting Chemicals on Puberty John Meeker, Sc.D., C.I.H. | University of Michigan The Pros and Cons of Testing Patients for Toxin Exposures Susan Buchanan, M.D., M.P.H. | University of Illinois at Chicago 5:30-7:00 p.m. Poster Session Wilson/Roosevelt/Cabin John/Arlington Rooms Day 2: Friday, October 30, 2015 7:30-8:30 a.m. REGISTRATION 7:30-8:30 a.m. Coffee* with Dr. Sally Darney, Editor-in-Chief, Environmental Health Perspectives Wilson/Roosevelt Room *Please come with your morning beverage 8:30-9:30 a.m. Session 8 - Keynote Moderated by Margaret Karagas, Ph.D. | Dartmouth College The impact of toxins are usually subtle for an individual child, but they can be substantial at the population level. This session will provide an overview of the population impact of toxins on children's health to set the stage for dialogue about ways to articulate the impact and importance of toxins on child health. Little Things Matter: The Impact of Toxins on Children's Health Bruce Lanphear, M.D., M.P.H. | Simon Fraser University 9:30-10:20 a.m. Session 9a - Community Outreach and Research Translation, Part I Moderated by Catherine Karr, Ph.D., M.D., M.S. | University of Washington A long-term goal of the Children's Environmental Health Centers is promoting translation of basic research findings into intervention and prevention methods to prevent adverse health outcomes. The Children's Centers provide credible and high impact environmental health research results in ways that are relevant and understandable to the general public. Examples from Children's Centers researchers and the National Pediatric Environmental Health Specialty Unit Program will demonstrate opportunities to ensure children's environmental health is efficiently, effectively, and meaningfully transmitted to clinical and public health practitioners. Environmental Health Perspectives (EHP): Your Partner in Research Translation Sally Darney, Ph.D. | Editor-in-Chief Environmental Health Perspectives 102 ------- Why Are Doctors Talking Toxics? Patrice Sutton, M.P. H. | University of California, San Francisco Do No Environmental Health Harm - An Updated Oath Jennifer Lowry, M.D. | Children's Mercy Hospital Simplifying the Complicated: Leveraging Digital Media for More Effective Community Engagement and Research Translation Carolyn Murray, M.D., M.P.H. | Dartmouth College 10:20-10:50 a.m. BREAK 10:50-11:50 a.m. Session 9b - Community Outreach and Research Translation, Part II Moderated by Catherine Karr, Ph.D., M.D., M.S. | University of Washington Build It and Will They Come? Lessons Learned from A Story of Health e-Book Mark Miller, M.D., M.P.H. | University of California, San Francisco #duetoepigenetics #whatdoesthatmean #mustbevoodooscience Susan Murphy, Ph.D. | Duke University 11:50-1:15 p.m. LUNCH 12:20-1:00 p.m. Brownbag Lunch Session with Linda Birnbaum and Ruth Etzel Wilson/Roosevelt Room 1:15-2:45 p.m. Session 10 - The Pediatric Environmental Health Specialty Units Present: Emerging Topics in Children's Health Moderated by Carl Baum, M.D., M.Sc. | Yale University Children are exposed to environmental factors that may affect their health and development. This session allows the PEHSUs to present on lesser known and emerging environmental issues. The goal is to present the state of the science on questions raised by parents and other caregivers and stimulate discussion about the science and practical applications of the research with the presenters in a concluding panel. The session is organized into five-minute presentations on each topic. A Blueprint for Protecting Children's Environmental Health: An Urgent Call to Action Nsedu Witherspoon, M.P.H. | Children's Environmental Health Network Potential Health Hazards of Increasing Cell Phone Use Laura Anderko, PhD., M.S., R.N. | Georgetown University Studies of Children's Exposure to Chemicals on Artificial Turf Fields Gary Ginsberg, Ph.D. | Connecticut Department of Public Health Not So Pretty - Endocrine Disrupting Chemicals in Cosmetics and Perfumes Katie Huffling, R.N., M.S., C.N.M. | Alliance of Nurses for Healthy Environments Maternal Exposure to High Levels of Electromagnetic Fields (EMFs) During Pregnancy and the Long-Term Health Impact on Their Offspring De-Kun Li, M.D., Ph.D., M.P.H. | Kaiser Permanente Division of Research Trends in Consumption of Artificial Sweeteners and the Metabolic Effects Allison Sylvetsky, Ph.D. | George Washington University Children's Health Impacts of Climate Change Perry Sheffield, M.D. | Mount Sinai Hospital 103 ------- Environmental Drivers of Diarrheal Disease among Children in Botswana Kathleen Alexander, Ph.D., D.V.M. | Virginia Polytechnic Institute and State University 2:45-3:45 p.m. Session 11 - Next Steps for Collaboration between the Children's Environmental Health Centers (CEHCs) and the Pediatric Environmental Health Specialty Units (PEHSUs) Moderated by Kimberly Gray, Ph.D. | National Institute of Environmental Health Sciences This session will highlight how effective collaborations that capitalize on research and clinical expertise can lead to important gains for the CEHCs, PEHSUs, and the environmental health field. The presentation will give some concrete examples of current successful partnerships and ideas for future partnerships. We will then open the session to audience questions and a panel discussion. Overview of Pediatric Environmental Health Specialty Units (PEHSUs) Ruth Etzel, M.D., Ph.D. | Director, Office of Children's Health Protection, U.S. EPA How PEHSUs and CEHCs Can Inform Children's Environmental Health Policy Sheela Sathyanarayana, M.D., M.P.H. | University of Washington Preventing Childhood Leukemia: A Fruitful Partnership for Action Catherine Metayer, M.D., Ph.D. | University of California, Berkeley 3:45-4:30 p.m. Session 12 - Keynote Moderated by Frederica Perera, Ph.D., M.P.H. | Columbia University While much attention is given to conducting studies of early life environmental exposures in the laboratory and humans, less focus is placed on the costs of failing to protect children. This session will present the economic benefits for proactive regulations that protect children, and the business case for children's environmental health. Adam Smith and the Business Case for Children's Environmental Health Leonardo Trasande, M.D. | New York University 4:30 p.m. Closing Remarks and Adjourn 104 ------- Appendix B - Speaker Biographies 2015 NIEHS/EPA Children's Centers Annual Meeting Thomas Burke | U.S. EPA Session 3 Dr. Thomas Burke is the Deputy Assistant Administrator of EPA's ORD as well as EPA's Science Advisor. Before coming to EPA, Dr. Burke served as the Jacob I. and Irene B. Fabrikant Professor and Chair in Health, Risk and Society and the Associate Dean for Public Health Practice and Training at the Johns Hopkins Bloomberg School of Public Health. He was also a Professor in the Department of Health Policy and Management, with joint appointments in the Department of Environmental Health Sciences and the School of Medicine Department of Oncology. Additionally, he was the founder of and served as the Director of the Johns Hopkins Risk Sciences and Public Policy Institute. His research includes the development of new approaches to environmental health risk assessment and environmental health surveillance, and their applications to environmental health policy. Before his time at Johns Hopkins, Dr. Burke was Deputy Commissioner of Health for the State of New Jersey and Director of the Office of Science and Research in the New Jersey Department of Environmental Protection. In New Jersey, he directed initiatives that influenced the development of national programs, such as Superfund, the Safe Drinking Water Act, and the Toxics Release Inventory. Dr. Burke also served on EPA's Science Advisory Board, as well as advisory boards for the Centers for Disease Control and Prevention, and on various committees for the National Academy of Sciences (NAS). Dr. Burke chaired the NAS committee that wrote the "Science and Decisions: Advancing Risk Assessment" report. The report, commonly known as the Silver Book, examines some of the greatest challenges to the country's assessment, management and communication of environmental risks. Dr. Burke received his Ph.D. in epidemiology from the University of Pennsylvania, his M.P.H. from the University of Texas, and his B.S. from Saint Peter's College. Linda Birnbaum | National Institute of Environmental Health Sciences Session 1 - Welcome and Introduction Dr. Linda Birnbaum became the Director of NIEHS and of the National Toxicology Program (NTP) in January 2009. In these roles, she oversees federal funding for biomedical research to discover how the environment influences human health and disease. Several advisory boards and councils provide Dr. Birnbaum and NIEHS/ NTP staff with input to accomplish this large task. She is the first toxicologist and the first woman to lead the NIEHS/NTP. She has spent most of her career as a federal scientist. Dr. Birnbaum also serves as an Adjunct Professor in the Gillings School of Global Public Health, in the Department of Environmental Sciences and Engineering at the University of North Carolina at Chapel Hill, and in the Integrated Toxicology Program at Duke University. Dr. Birnbaum's research and many of her publications focus on the pharmacokinetic behavior of environmental chemicals; mechanisms of actions of toxicants, including endocrine disruption; and linking of real-world exposures to health effects. Dr. Birnbaum has received numerous awards and recognitions, including election to the Institute of Medicine of the National Academies in October 2010, one of the highest honors in the fields of medicine and health. A native of New Jersey, Dr. Birnbaum received her M.S. and Ph.D. in Microbiology from the University of Illinois at Urbana-Champaign. 105 ------- James H. Johnson, Jr. | U.S. EPA Session 1 - Welcome and Introduction (moderator) Dr. James H. Johnson, Jr., is the Director of the National Center for Environmental Research in EPA's ORD. In this role, Dr. Johnson continues a life-long career dedicated to sustaining and advancing scientific research and education initiatives supporting environmental protection, q u a I ity-of-l if e programs, and environmental workforce development. Dr. Johnson has served on numerous committees and boards for the National Academies, EPA, and academic institutions. He is a member of the Anne Arundel Community College (Maryland) Board of Trustees, and is Professor Emeritus of Civil Engineering and Dean Emeritus of the College of Engineering, Architecture, and Computer Sciences at Howard University. Dr. Johnson is a member of the American Water Works Association and the Association of Environmental Engineering and Science Professors. He is also a fellow of the American Society of Civil Engineers and Board Certified Environmental Engineer of the American Academy of Environmental Engineers and Scientists. Dr. Johnson earned his Ph.D. in Applied Sciences from the University of Delaware and received a M.S. from the University of Illinois and a B.S. in Civil Engineering from Howard University. Ruth Etzel | U.S. EPA Session 1 - Welcome and Introduction Session 11 - Next Steps for Collaboration Between the Children's Environmental Health Centers and the Pediatric Environmental Health Specialty Units Dr. Ruth Etzel is the Director of EPA's Office of Children's Health Protection. During 20 years as a Commissioned Officer in the U.S. Public Health Service, she served in a variety of public-sector leadership positions including: U.S. Centers for Disease Control and Prevention (Founding Chief of the Air Pollution and Respiratory Health Branch), U.S. Department of Agriculture (Director of the Division of Epidemiology and Risk Assessment), and U.S. Indian Health Service (Research Director at the Alaska Native Medical Center). Dr. Etzel is the founding editor of Pediatric Environmental Health (a 3rd edition was published by the American Academy of Pediatrics in 2012). This influential book has helped train thousands of doctors who care for children about how to recognize, diagnose, treat, and prevent illness in children from hazards in the environment. She has worked extensively with international organizations to educate health professionals about environmental health and to build their capacity to conduct environmental investigations. From 2009 to 2012, Dr. Etzel served as the Senior Officer for Environmental Health Research in the Department of Public Health and Environment at the World Health Organization in Geneva, Switzerland. Dr. Etzel has a broad background in public health, with specific training and expertise in pediatrics, preventive medicine, and children's environmental health. After completing a residency in pediatrics, she became a Robert Wood Johnson Clinical Scholar at the University of North Carolina at Chapel Hill. Patrick Breysse | ATSDR, CDC Session 1 - Welcome and Introduction Dr. Pat Breysse joined CDC in December 2014 as the Director of the National Center for Environmental Health and ATSDR. In this role, Dr. Breysse leads CDC's efforts to investigate the relationship between 106 ------- environmental factors and health. He is also a board certified Industrial Hygienist and an editorial review board member for the Journal of Exposure Science and Environmental Epidemiology. Dr. Breysse came to CDC from The Johns Hopkins University where he served as Associate Chair for Educational Programs within the Department of Environmental Health Sciences, Program Director for the Industrial Hygiene Training Program, and Co-Director of the Johns Hopkins Center for Childhood Asthma in the Urban Environment. During his 30 years at Johns Hopkins, Dr. Breysse established a long-standing expertise in environmental health and a strong record as a leader in the field. He has published over 200 peer-reviewed journal articles and has presented at more than 25 scientific meetings in just the past 5 years. Dr. Breysse's research has focused on the evaluation and control of chemical, biological, and physical factors that can affect health, with a particular concentration on risk and exposure assessment. Dr. Breysse received his Ph.D. in Environmental Health Engineering from The Johns Hopkins University in 1985 and completed postdoctoral training at the British Institute for Occupational Medicine in Edinburgh, Scotland. Gail Christopher | W.K. Kellogg Foundation Session 2 - Keynote Speaker Dr. Gail Christopher is Vice President for Policy and Senior Advisor at the W.K. Kellogg Foundation. In this role, she serves on the President's cabinet that provides overall direction and leadership for the foundation. Since joining the foundation in 2007, she has served as Vice President for Program Strategy with responsibility for multiple areas of programming, including Racial Equity; Food, Health & Weil-Being; Community Engagement and Leadership. She is also responsible for place-based programming in New Orleans and New Mexico. Bruce Lanphear | Simon Fraser University Session 8 - Keynote Speaker Dr. Bruce Lanphear is a Clinician Scientist at the Child & Family Research Institute at the British Columbia Children's Hospital and a Professor in the Faculty of Health Sciences at Simon Fraser University in Vancouver, British Columbia. His primary goal is to help quantify and ultimately prevent disease and disability (asthma, learning problems and ADHD) due to exposures to environmental contaminants and pollutants. Over the past decade, Dr. Lanphear has become increasingly displeased by our inability to control the "pandemic of consumption"—the highly preventable, worldwide epidemic of chronic disease and disability due to industrial pollutants, environmental contaminants, and excess consumption. He is leading an effort to build the online Atlas of Environmental Health to enhance public understanding of how environmental factors influence human health. Michael Lu | Health Resources and Services Administration Session 5 - Lifestage Approach to Prematurity Dr. Michael Lu was named associate administrator of maternal and child health of the Health Resources and Services Administration (HRSA) in 2011. HRSA is an agency of the U.S. Department of Health and Human Services. He is also Director of the Maternal and Child Health Bureau (MCHB), which aims to provide leadership, in partnership with key stakeholders, to improve the physical and mental health, safety and well-being of the maternal and child health population. Through its Title V program, MCHB 107 ------- serves 40 million women, infants, children, adolescents, and their families each year, including fathers and children with special health care needs. Dr. Lu joined HRSAfrom the University of California, Los Angeles Schools of Medicine and Public Health, where he was associate professor of obstetrics, gynecology and public health. Dr. Lu brings years of experience in MCH research, practice, and policy to his post at HRSA. Prior to his appointment to head up MCHB, Dr. Lu chaired the Secretary's Advisory Committee on Infant Mortality. He has served on two Institute of Medicine (IOM) Committees (Committee on Understanding Premature Birth and Assuring Healthy Outcomes, and Committee to Reexamine IOM Pregnancy Weight Guidelines), and the Centers for Disease Control and Prevention Select Panel on Preconception Care. While at UCLA, Dr. Lu was a lead investigator for the National Children's Study. He also led a project to monitor and improve the quality and safety of maternity care in California. He was best known for his research on racial-ethnic disparities in birth outcomes, and his visionary leadership on life course. Dr. Lu taught obstetrics and gynecology at the David Geffen School of Medicine at UCLA, and maternal and child health at UCLA School of Public Health. He has received numerous awards for his teaching, including Excellence in Teaching Awards from the Association of Professors of Gynecology and Obstetrics. As an obstetrician, Dr. Lu has attended over a thousand births, and has been voted one of the Best Doctors in America since 2005. Dr. Lu received his B.S. in political science and human biology from Stanford University, his M.S. and M.P.H. from UC Berkeley, M.D. from UC San Francisco, and residency training in obstetrics & gynecology from UC Irvine. Leonardo Trasande | New York University Session 12 - Keynote Speaker Dr. Leonardo Trasande is an Associate Professor of Pediatrics and Environmental Medicine at the NYU School of Medicine, of Health Policy at the NYU Wagner School of Public Service, and in Public Health at the NYU Steinhardt School of Culture, Education and Human Development. His research focuses on identifying the role of environmental exposures in childhood obesity and cardiovascular risks, and documenting the economic costs for policy makers of failing to prevent diseases of environmental origin in children proactively. Dr. Trasande is perhaps best known for a 2012 Journal of the American Medical Association study associating BPA exposure in children and adolescents with obesity, and a 2011 study in Health Affairs which found that children's exposures to chemicals in the environment cost $76.6 billion in 2008. His analysis of the economic costs of mercury pollution played a critical role in preventing the Clear Skies Act (which would have relaxed regulations on emissions from coal-fired power plants) from becoming law. Dr. Trasande has also published a series of studies documenting increases in hospitalizations associated with childhood obesity and increases in medical expenditures associated with being obese or overweight in childhood, studies that have been cited in the Presidential Task Force Report in Childhood Obesity. He also published another landmark study identifying that a $2-billion annual investment in prevention would be cost-effective even if it produced small reductions in the number of children who were obese and overweight. Dr. Trasande has testified before the Senate's Environment and Public Works Committee and Democratic Policy Committee. His work has been featured on the CNN documentary Planet in Peril and in National Geographic, and frequently appears on national media, including NBC's Today Show, ABC's Evening News, and National Public Radio. 108 ------- Dr. Trasande received his M.D. from Harvard Medical School, and his M.P.P. from Harvard School of Public Policy. He completed a residency in pediatrics at Boston Children's Hospital, a Dyson Foundation Legislative Fellowship in the office of Senator Hillary Rodham Clinton, and a fellowship in Environmental Pediatrics at the Mount Sinai School of Medicine. Emanuel Alcala | California State University, Fresno, Central Valley Health Policy Institute Session 4 - Social Determinants of Health Emanuel Alcala joined the Central Valley Health Policy Institute team in May of 2013. As a statistician he explores data from the Central Valley in an effort to uncover health outcomes. Management of these data produce reports, graphs, and maps that strive to achieve CVHPI's mission. After graduating with a B.A. in Psychology at California State University, Fresno, Emanuel earned a M.A. in Psychology with an emphasis in General/Experimental Psychology. Emanuel has more than four years of experience in a research setting. His past work includes working with underprivileged children as a Family Specialist. Emanuel is delighted to contribute to the Valley that has nurtured his education and hopes to give back to the community. Kathleen Alexander | Virginia Polytechnic Institute and State University Session 10 - Emerging Topics in Children's Health Dr. Kathleen Alexander is Associate Professor in the Department of Fish and Wildlife Conservation at Virginia Tech. Her research program is directed at exploring and understanding the factors that influence the emergence and re-emergence of diseases at the human- wildlife-environmental interface. The program embraces a systems biology approach to ecosystem health integrated with public health, beginning within host - pathogen dynamics and extending to the livelihoods of communities living with wildlife, including the impact on ecosystem function and local communities themselves. Dr. Alexander is also the board president of the Center for African Resource: Animals, Communities, and Land Use (CARACAL). CARACAL is a not for profit agency dedicated to the conservation of natural resources and improved rural livelihoods for local communities in Chobe Botswana. Dr. Alexander received her Ph.D. and D.V.M from the University of California, Davis. Laura Anderko | Georgetown University Session 10 - Emerging Topics in Children's Health Dr. Laura Anderko holds the Robert and Kathleen Scanlon Endowed Chair in Values-Based Health Care at the Georgetown University School of Nursing & Health Studies and serves as Director of the Mid-Atlantic Center for Children's Health and the Environment (Region 3's Pediatric Environmental Health Specialty Unit, Centers for Disease Control and Prevention). She is a scholar and educator in the fields of epidemiology, public health, and environmental health. Dr. Anderko serves as Co-Chair of the National Environmental Health Partnership Council and is Vice President of the Healthy Schools Network, a member of the Regional 3 Health Equity Council (Office of Minority Health), Research Co-Chair for the Alliance of Nurses for a Healthy Environment, and Chair for the National Center for Children's Vision and Eye Health Advisory Board (Maternal Child Health Bureau, HRSA). She is a former member of EPA's federal advisory committees: Children's Health Protection Advisory Committee, National Drinking Water Advisory Committee, and National Environmental Justice Advisory Committee's Research Workgroup. In July 2013, Dr. Anderko was honored by the White House for her work in climate change and public health. 109 ------- Dr. Anderko earned her Ph.D. in Public Health and her B.S. in Nursing from the University of Illinois, and her M.S. in Community Health Nursing at Northern Illinois University. Carl Baum | Yale University Session 10 - Emerging Topics in Children's Health (moderator) Dr. Carl Baum is a Professor of Pediatrics at the Yale University School of Medicine, specializing in Pediatric Emergency Medicine and Medical Toxicology. Dr. Baum is also the Medical Director of the Pediatric Environmental Health Specialty Unit Program - Western Operations. He is Director of the Center for Children's Environmental Toxicology at Yale-New Haven Children's Hospital. In 2005, Dr. Baum received the Children's Environmental Health Recognition Award from the U.S. EPA Office of Children's Health Protection. He received his M.D. from the University of Pennsylvania, a M.Sc. in Geological Sciences from Brown University, and a B.A. in Earth Sciences from Dartmouth College. He completed his residency in pediatrics at Children's Hospital of Philadelphia and fellowships in Pediatric Emergency Medicine and Medical Toxicology at Boston Children's Hospital. Susan Buchanan | University of Illinois, Chicago Session 7c - Reproductive Health Dr. Susan Buchanan is a Clinical Associate Professor of Environmental and Occupational Health Sciences at the University of Illinois at Chicago School of Public Health. She is also the Associate Director of the Occupational Medical Residency Program at the University of Illinois Hospital. Dr. Buchanan is dual certified in Family Medicine and Preventive Medicine. She practiced primary care for more than a decade before joining the department, adding teaching and research to her active practice. Her practice involves the evaluation of pediatric and adult patients with health problems related to their environment in the workplace and community. Dr. Buchanan also directs the Great Lakes Center Pediatric Environmental Specialty Unit for Region 5. Her research interests include the health of children and minority, low-income, and immigrant workers and reproductive environmental health, areas in which she has published a series of peer-reviewed studies. Dr. Buchanan received her M.D. from Ohio State University and her M.P.H from the University of Illinois at Chicago. Sally Darney | National Institute of Environmental Health Sciences Session 9a - Community Outreach and Research Translation, Part I Dr. Sally Darney is Editor in Chief of the NIEHS Journal Environmental Health Perspectives (EHP). International in scope, EHP covers the wide spectrum of the environmental health sciences, with emphasis on innovative and interdisciplinary approaches. The journal strives to be a focal point for information dissemination about the latest research and news in environmental public health, and serves as a forum for diverse perspectives of science, government, industry, private, and public-interest groups on important and emerging issues of environmental health. Dr. Darney previously led an independent research program in reproductive toxicology and epidemiology in EPA's ORD, publishing over 100 research papers and review articles. In addition to conducting research, she served as the Director of the Reproductive Toxicology Division in the National Health and 110 ------- Environmental Effects Research Laboratory, contributed to EPA reproductive toxicology testing and risk assessment guidelines, and represented EPA on the Interagency Coordinating Committee for the National Children's Study and the Children's Health Federal Taskforce workgroup on Reducing Racial and Ethnic Asthma Disparities. Most recently, Dr. Darney helped develop the research frameworks and strategic directions for ORD's National Research Programs in Sustainable and Healthy Communities and Chemical Safety for Sustainability. In the broader scientific community, she is Past President of the Society for the Study of Reproduction and the American Society for Andrology, and has served as an Associate Editor for Biology of Reproduction, and the Journal of Toxicology and Environmental Health, and as Co-Editor-in- Chief of the Journal of Andrology. Dr. Darney received her Ph.D. in Anatomy and Reproductive Biology from the University of Hawaii and completed a postdoctoral fellowship at The Johns Hopkins University Bloomberg School of Public Health. Greg Diette | Johns Hopkins University Session 4 - Social Determinants of Health Dr. Gregory Diette is Professor of Medicine, Epidemiology and Environmental Health Sciences. He is a pulmonologist with a practice devoted to the care of patients with obstructive lung diseases, including asthma and chronic obstructive pulmonary disease (COPD). He has an extensive portfolio of patient-based research in asthma and COPD, supported by the National Institutes of Health and other sponsors. Dr. Diette's current research focuses on identifying factors that cause or provoke asthma with special interest in air pollutants (PM, N02, secondhand smoke) and allergens (including mouse) that are especially problematic in inner-city homes. His research includes the effects of these pollutants and allergens on inflammation and oxidative stress. More recently, his research has been examining how dietary patterns, especially a Western-style diet, may increase susceptibility to inhalable pollutants and allergens. Dana Dolinoy | University of Michigan .»ess i on a C3 si ^ in cyclic? a tC3^ Dr. Dana Dolinoy serves as Associate Professor in the Departments of Environmental Health Sciences and Nutritional Sciences at the University of Michigan School of Public Health and leads the Environmental Epigenetics and Nutrition Laboratory. This laboratory investigates how nutritional and environmental factors interact with epigenetic gene regulation to shape health and disease. She also contributes as an investigator in the NIEHS/EPA University of Michigan Children's Environmental Health and Disease Prevention Research Center, investigating early exposure to bisphenol A, lead and phthalates, epigenetics, and later-in-life body weight and hormone outcomes. Dr. Dolinoy also leads the Biological Response Indicators Resource of M-CHEAR, a laboratory hub within the NIEHS-funded Children's Health Exposure Analysis Resource network (Principal Investigator: John Meeker). In 2011, she received the Norman Kretchmer Memorial Award from the American Society for Nutrition and the Classic Paper of the Year Award from Environmental Health Perspectives. Dr. Dolinoy holds a Ph.D. in Genetics and Genomics and Integrated Toxicology from Duke University, an M.Sc. in Environmental Sciences and Engineering from the Harvard School of Public Health, and a B.A. in Environmental Sciences and Policy and Spanish from Duke University. Ill ------- Elaine Faustman | University of Washington Session 7b - Exposome Dr. Elaine Faustman is a Professor of Environmental and Occupational Health Sciences at the University of Washington School of Public Health. She is an elected fellow of the Society of Toxicology and the American Association for the Advancement of Science and has served on the National Toxicology Program Board of Scientific Counselors, the National Academy of Sciences Committee on Toxicology, and numerous editorial boards. She currently chairs the National Academy of Sciences Committee on Developmental Toxicology. Dr. Faustman is Director of the NIEHS/EPA Center for Child Environmental Health Risks Research, which aims to understand the biochemical, molecular, and exposure mechanisms that define children's susceptibility to pesticides. In addition, researchers are working to assess pesticide risks to normal development and learning. Her research interests include understanding mechanisms of developmental and reproductive toxicants, characterizing in vitro techniques for developmental toxicology assessment, development of biologically based dose-response models for noncancer risk assessment, and development of decision-analytic tools for incorporating new scientific findings into risk assessment and risk management decisions. Dr. Faustman received her Ph.D. in Toxicology from Michigan State University in 1980. Mai da Galvez | Icahn School of Medicine at Mount Sinai Session 7a - Obesity Dr. Maida Galvez is an Associate Professor in the Departments of Preventive Medicine and Pediatrics at the Mount Sinai Icahn School of Medicine. A board certified Pediatrician, she completed the Academic Pediatric Association-sponsored fellowship in Environmental Pediatrics at Mount Sinai in New York. She directs the Region 2 Pediatric Environmental Health Specialty Unit serving New Jersey, New York, Puerto Rico, and the U.S. Virgin Islands. She served as Co-Principal Investigator and as a New Investigator of the community-based participatory research project "Growing Up Healthy in East Harlem," examining the environmental determinants of childhood obesity. She is also Co-Investigator of an NIEHS/NCI-funded project assessing environmental determinants of puberty in girls, part of the multicenter Breast Cancer and the Environment Research Project. Her areas of interest include community-engaged research, urban built environment, endocrine disruptors, and childhood growth and development. Dr. Galvez currently serves on EPA's Scientific Advisory Board and CDC's National Environmental Health Partnership Council. She received her M.D. and M.P.H. from Mount Sinai School of Medicine, trained in the Social Pediatrics Residency Program at Children's Hospital at Montefiore, Albert Einstein College of Medicine, and completed her Pediatric Chief Residency at Jacobi Medical Center, Bronx, New York. Andrew Geller | U.S. EPA Session 4 - Social Determinants of Hea derator) Dr. Andrew Geller is the Deputy National Program Director for the Sustainable and Healthy Communities Research Program at EPA. Dr. Geller has worked with scientists across the Agency to develop EPA's research and public education initiative on Aging and Environmental Health. He became engaged with the Agency's Environmental Justice efforts as a result of involvement with U.S. EPA's Region 5 and as co-lead of the EPA's 2009 workshop on Advancing the Science and Practice of Cumulative Risk Assessment. 112 ------- Dr. Geller earned his M.S. and Ph.D. in Cognitive and Experimental Psychology at the University of Michigan and received his B.A. in Biological Basis of Behavior/Psychology from the University of Pennsylvania. Dr. Geller completed postdoctoral training in Neurotoxicology at the University of North Carolina at Chapel Hill's Center for Environmental Medicine and Lung Biology and with NHEERL through a National Research Service Award from NIEHS. Previously, Dr. Geller was Chief of the Exposure Modeling Research Branch. He also served as the Assistant Laboratory Director for the core research program in Human Health and Computational Toxicology at the EPA National Health and Environmental Effects Research Lab (NHEERL). Gary Ginsberg | Connecticut Department of Public Health Session 10 - Emerging Topics in Children's Health Dr. Gary Ginsberg is a toxicologist for the Connecticut Department of Public Health and a lecturer at the Yale School of Public Health. He serves on a number of national committees including EPA's Science Advisory Board, the National Academy of Sciences, and EPA's Children's Health Protection Advisory Committee. His research focuses on the unique susceptibilities of children to environmental toxicants. He evaluates risks and sets standards for contaminants in soil, drinking water, food, air and consumer products. Dr. Ginsberg has been called on by other federal agencies to provide reviews including OSHA (silica workplace standard), CPSC (cadmium in children's jewelry) and FDA (dental amalgam). His risk assessments on fish contaminants, syntheticturf fields, acrylamide, cadmium, and assessments pertaining to risks in children and those with genetic polymorphisms have been published in peer review journals. Dr. Ginsberg won the Society of Toxicology best risk assessment paper of the year award in 2009, and in 2006 he co-authored a book for the lay public called "What's Toxic What's Not". He received his doctorate degree from the University of Connecticut. Kimberly Gray | National Institute of Environmental Health Sciences Session 11 - Next Steps for Collaboration Between the Children's Environmental Health Centers and the Pediatric Environmental Health Specialty Units (moderator) Dr. Kim Gray is the Health Scientist Administrator for the Population Health Branch at NIEHS. She directs the Children's Environmental Health and Disease Prevention Research Centers Program for NIEHS. She is a member of the World Health Organization's Collaborating Centres Network for Children's Environmental Health at NIEHS. The Network supports translation of children's environmental health research findings into effective public health strategies to improve children's health around the world. She is the NIEHS Senior Advisor for Certificates of Confidentiality and a member of the NIEHS Protocol Advisory Board and the NIEHS Institutional Review Board. Dr. Gray returned to NIEHS in 2001 after completing a postdoctoral fellowship in the NIEHS Epidemiology Branch, for which she examined the long-term effects of polychlorinated biphenyl exposure during pregnancy and childhood development using specimens and data collected from the Collaborative Perinatal Project. Dr. Gray received her B.S. degree in Behavioral Neuroscience and her Ph.D. in Epidemiology from the University of Pittsburgh. During her graduate training, Dr. Gray gained experience as an interviewer and assessor while working on the Women's Health Initiative and Cardiovascular Health study. She received a National Research Service Award from the National Institute on Alcohol Abuse and Alcoholism for her work with Dr. Nancy Day examining the long-term effects of prenatal exposure to alcohol, marijuana, and 113 ------- tobacco and her work with childhood outcomes on the Maternal Health Practices and Child Development pregnancy cohort. Michael Hatcher | ATSDR, CDC Session 5 - Lifestage Approach to Prematurity (moderator) Dr. Hatcher is a public health professional with 38 years of health promotion and disease prevention experience at the local, state, and federal levels of public health. He has led health promotion and disease prevention planning, initiative development and implementation that resulted in measurable population- level health improvements. His experience includes health system operation and performance improvement as well as health services research at the interface of population health and personal health care. His career has offered him many opportunities to participate in and undertake leadership roles in new state and national public health initiatives, including: • Managing development and implementation of the 1990 Texas Health Promotion Disease Prevention Objectives, • Consulting with states establishing year 2000 Healthy People Objectives, • Responding to the public health capacity development needs identified in the 1988 Future of Public Health report published by the Institute of Medicine, • Developing training and other tool to introduce managed care to public health departments, • Developing and testing National Public Health Performance Standards, • Articulating principles of community engagement and leading writing of the 1997 edition of Principles of Community Engagement and guiding design and participating in writing the 2011 Principles of Community Engagement: Second Edition, and • In 2003 he took the lead on ATSDR's primary care provider and health systems engagement to improve environmental exposure recognition, exposure prevention, and treatment of illnesses resulting from exposures to hazardous substances in the environment. Dr. Hatcher is a native of Tennessee. He received his undergraduate public health degree and his Masters of Public Health from the University of Tennessee. His doctorate of public health was earned from the University of North Carolina at Chapel Hill, where he was a Fellow in the Leadership Doctorial Program within the Department of Health Policy and Administration. Irva Hertz-Picciotto | University of California, Davis Session 6 - Neurodevelopmental Disorders Dr. Irva Hertz-Picciotto, Professor at the University of California Davis MIND Institute and Director of the NIH-funded UC Davis Environmental Health Sciences Center, is an environmental epidemiologist with over 300 scientific publications addressing environmental exposures, including metals, pesticides, air contaminants and endocrine disrupting compounds; their interactions with nutrition, genes or social factors; and their effects on pregnancy, the newborn, and child development. She designed and directs CHARGE (Childhood Autism Riskfrom Genes and Environment), the first large, comprehensive population- based study of environmental factors in autism, and MARBLES (Markers of Autism Risk in Babies - Learning Early Signs) to search for early markers that will predict autism, starting in pregnancy. Hertz- Picciotto has also led several cohort studies of toxic chemicals and both pregnancy outcomes and early child development in Mexico, Chile, and Eastern Europe. 114 ------- She has served on scientific advisory panels for the U.S. Environmental Protection Agency, the NIH National Toxicology Program, and the California Governor's Proposition 65 committee. She was elected President of two major professional epidemiology societies, and chaired four National Academy of Sciences/Institute of Medicine Panels on: Agent Orange and Vietnam Veterans, and Breast Cancer and the Environment. Dr. Hertz-Picciotto has taught epidemiologic methods on four continents and mentored over 75 graduate students and postdoctoral scholars. In 2011, she received the Goldsmith Lifetime Achievement Award from the International Society for Environmental Epidemiology. Recently she co- founded (with the Learning Disabilities Association) Project TENDR (Targeting Environment and Neuro- Developmental Risks), a collaborative effort of scientists, clinicians, policy-makers and advocates that aims to decrease the incidence of neurodevelopmental disorders by reducing neurotoxicant exposures that contribute to them. Dr. Hertz-Picciotto received her B.A., M.P.H., M.A., and Ph.D. from the University of California, Berkeley. Katie Huffling | Alliances of Nurses for Healthy Environments Session 10 - Emerging Topics in Children's Health Katie Huffling is a Certified Nurse-Midwife and is the Director of Programs for the Alliance of Nurses for Healthy Environments where she directs projects related to environmental health nursing practice, research, education, and policy and advocacy. She is part of a national and international network of nurses that work to integrate environmental health into nursing education and provide guidance and resources to pregnant women, parents, and others about health risks to children and their families. Ms. Huffling has also written numerous peer-reviewed articles on environmental health problems and their relationship to pregnancy. In addition, she has developed an assessment tool for nurses and other clinicians to assess for environmental exposures of pregnant women. In 2011, she was a fellow for Reach the Decision Makers program at the University of California, San Francisco's Program on Reproductive Health and the Environment. Dean Jones | Emory University Session 7b - Exposome Dr. Dean Jones is a professor in the Department of Medicine (Pulmonary Division) with secondary appointments in Biochemistry and Pediatrics at Emory University, Atlanta, Georgia. He joined Emory University as an Assistant Professor of Biochemistry in 1979 and was subsequently promoted to Associate Professor in 1985 and to Professor of Biochemistry in 1990. He became Professor of Medicine and Director of the Clinical Biomarkers Laboratory in 2003. Dr. Jones also serves as the Integrated Health Sciences Facility Core Director of the NIEHS-supported HERCULES Exposome Research Center. Dr. Jones' research career has included studies of mitochondrial mechanisms of toxicity, redox systems biology, oxidative stress and antioxidant systems, compartmentation of metabolism, and high-resolution metabolomics. He currently is focused on applications of ultrahigh-resolution mass spectrometry for precision medicine, with a long-term goal to use this as a foundation to sequence the exposome. These methods enable measurement of thousands of low abundance metabolites, including those derived from innate metabolism, the environment, diet, drugs, and the microbiome. Dr. Jones has recently focused on low-level environmental exposures, such as dietary cadmium, which can influence onset and progression of chronic diseases, and has active NIH-supported research programs on the metabolomics of cardiovascular, lung, eye, neurodegenerative, and infectious diseases and aging. He collaborates extensively on studies of diverse populations and disease processes. 115 ------- Dr. Jones received his Ph.D. in Medical Biochemistry from Oregon Health Sciences University, Portland, in 1976. He studied Nutritional Biochemistry at Cornell University and MolecularToxicology atthe Karolinska Institute as a postdoctoral fellow. Margaret Karagas | Dartmouth College Session 8 - Keynote Speaker (moderator) Dr. Margaret Karagas is Professor and Department Chair of Epidemiology at the Dartmouth College Geisel School of Medicine and Director of the Dartmouth Children's Environmental Health and Disease Prevention Research Center. Dr. Karagas' research encompasses several epidemiological studies focusing on the etiology of human cancers and on adverse pregnancy and children's health outcomes. Her studies focus on identifying key factors—prevalent environmental exposures, host factors, and mechanisms—that affect health from infancy to adult life, and application of novel methods and technologies to understand disease pathogenesis. These include interdisciplinary studies of temporal changes in the incidence rates of keratinocyte cancers and emergent exposures, such as indoor tanning, and drinking water contaminants. Dr. Karagas has established a cohort of pregnant women and their offspring in New Hampshire to assess the sources and potential health impacts of arsenic and other exposures—on childhood infection, allergy/atopy, growth and neurodevelopment—through the Children's Center. Her work involves collaborative studies of exposure biomarkers, individual susceptibility, and biological response to environmental agents, including the developing microbiome and immune response. Dr. Karagas received her Ph.D. from the University of Washington. Catherine Karr | University of Washington Session 9 > immunity Outreach and Research Translation, Part I ant derator) Dr. Catherine Karr is a pediatric environmental medicine specialist and environmental epidemiologist. She has a primary appointment in the Department of Pediatrics, Joint in Environmental & Occupational Health Sciences, and Adjunct in Epidemiology. She is affiliated with the University of Washington Center for Children's Environmental Health Research and the Pacific Northwest Center for Agricultural Safety and Health. Dr. Karr has a general pediatric practice at the University of Washington Pediatric Clinic at Roosevelt and provides specialty pediatric environmental medicine consultation at this site and at the Harborview Medical Center. As Director of the Northwest Pediatric Environmental Health Specialty Unit, she sets the direction for outreach and education and for responding to queries from health care providers, government officials, and families regarding health risks associated with environmental exposures. She is involved in policy and education through the American Academy of Pediatrics National Council on Environmental Health. Her research areas include environmental contaminants and pediatric respiratory health, including asthma, health of farmworker children, and global children's environmental health. Dr. Karr received her Ph.D. in Epidemiology, M.D., and M.S. in Toxicology at the University of Washington, and her B.S. in Biology at the University of Michigan. 116 ------- Susan Korrick | Harvard University Session 6 - Neurodevelopmental Disorders Dr. Susan Korrick is an Assistant Professor of Medicine at Harvard Medical School and an Assistant Professor in Environmental Health at the Harvard T.H. Chan School of Public Health, with an appointment as an Associate Physician at Brigham and Women's Hospital. She is an Investigator with the EPA/NIEHS Children's Centers at Dartmouth College and the University of Illinois. Dr. Korrick's research focuses on the developmental and neurocognitive toxicities of environmental contaminants, including metals, organochlorine pesticides, and polychlorinated biphenyls, and short half- life compounds such phenols and phthalates. The core of her research is the development (as Principal Investigator) of the New Bedford Cohort, an ongoing birth cohort study, results of which have expanded understanding of the neurobehavioral impacts of a variety of early life metal (e.g., methylmercury) and organochlorine exposures. More recently, Dr. Korrick has extended her research to include collaborative studies of outcomes-based risk assessment and methods development for analyzing exposure mixtures in the New Bedford Cohort. She has segued her experience with birth cohort studies into close collaborative efforts with other longitudinal studies, most notably two pregnancy cohorts developed via NIEHS/EPA Children's Centers at the University of Illinois and Dartmouth Medical School. De-Kun Li | Kaiser Permanente Session 10 - Emerging Topics in Children's Health Dr. De-Kun Li is a Senior Research Scientist at the Division of Research, Kaiser Permanente Northern California. He is a reproductive and perinatal epidemiologist with extensive experience conducting epidemiologic studies examining in-utero exposures in relation to pregnancy outcomes and early childhood diseases, including childhood obesity and asthma, preterm delivery, low birthweight, birth defects, miscarriage and SIDS. He has more than 88 peer-reviewed publications, of which he first-authored 41 and was the senior author for another 18. He is an existing member of an advisory committee for the Dartmouth Children's Environmental Health and Disease Prevention Research Center, and currently serves as the Associate Editor of the American Journal of Epidemiology. Dr. Li's current research focuses on developmental origins of pregnancy outcomes and childhood diseases which include examination of (1) in-utero environmental exposures including endocrine disruptors (e.g., BPA) and electromagnetic fields (EMF), (2) safety and effectiveness of medication use during pregnancy, and (3) gene-environment interactions. Throughout his professional life, he has made important contributions to the understanding of (a) factors associated with reduction in SIDS risk, (b) health effects due to exposure to EMF, (c) adverse effects of in-utero exposure to caffeine, (d) impact of exposure to environmental endocrine disruptors, (e) risk and benefit of treating maternal depression during pregnancy, (f) parental genetic contribution to the risk of preterm delivery, and (g) benefits of treating herpes infection during pregnancy. Dr. Li completed his medical training and master's degree in Public Health at Shanghai Medical University, Shanghai, China. He then received his Ph.D. in epidemiology and post-doctoral degree in environmental and molecular epidemiology from the University of Washington, Seattle. Jennifer Lowry | Children's Mercy Hospital Session 9a - Community Outreach and Research Translation, Part I Dr. Jennifer Lowry is the Director for the Mid-America Pediatric Environmental Health Specialty Unit for EPA Region 7 and a Medical Toxicology liaison to the Region 7 ATSDR. She is the Chair of the American 117 ------- Academy of Pediatrics' Council on Environmental Health and a current member of the Children's Health Protection Advisory Committee for EPA. Dr. Lowry is board certified in Pediatrics and Medical Toxicology and spent 5 years as the Medical Director to the Kansas Poison Control Center. She is the Chief for the Section of Clinical Toxicology at Children's Mercy Hospital and Professor in Pediatrics at the University of Missouri. Dr. Lowry received her M.D. at the University of South Dakota School of Medicine. She completed a Pediatric Residency and Clinical Pharmacology/Medical Toxicology Fellowship at the Children's Mercy Hospital in Kansas City, Missouri. Rob S. McConnell | University of Southern California Session 7a - Obesity Dr. Rob McConnell is Professor of Preventive Medicine and Director of Southern California Children's Environmental Health Center at the University of Southern California, where he has studied the effects of air pollution on children's health. The role of air pollution in obesity and its metabolic consequences is a major current focus of interest and the theme of the Children's Center. He has examined associations of air pollution with asthma and lung function, autism, and early markers for cardiovascular disease. Other interests include developing methods for estimating the burden of disease associated with near-roadway air pollution and for assessing exposure in environmental epidemiology. He directs the Career Development Program of the NIEHS-supported Southern California Environmental Health Sciences Center and a fellow of the American Association for the Advancement of Science. John Meeker | University of Michigan Session 7c - Reproductive Health Dr. John Meeker is a Professor of Environmental Health Sciences and Associate Dean for Research at the University of Michigan School of Public Health. He is also a Certified Industrial Hygienist. Dr. Meeker is the Principal Investigator on numerous large-scale research studies, Associate Editor of Environmental Health Perspectives, and has served on various peer-review and advisory panels for EPA, NIH, and others in recent years. His work is wide-ranging and focuses on defining sources, magnitudes, and consequences of human exposure to environmental and occupational contaminants, and on identifying and evaluating strategies to control harmful exposures. Dr. Meeker's current research involves human exposure science and reproductive and developmental epidemiology studies of known or suspected endocrine-disrupting chemicals, such as phthalates, bisphenol A, pesticides, and flame retardants. Dr. Meeker holds an M.S. and a Sc.D in Environmental Science & Engineering and Exposure, Epidemiology & Risk, respectively, from Harvard University, where he also completed a postdoctoral fellowship in Environmental and Reproductive Epidemiology. He received a B.S. in Industrial Technology from Iowa State University. Catherine Metayer | University of California, Berkeley Session 11 - Next Steps for Collaboration Between the Children's Environmental Health Centers and the Pediatric Environmental Health Specialty Units Dr. Catherine Metayer is the Principal Investigator of the California Childhood Leukemia Study and Director of the Center for Integrative Research on Childhood Leukemia and the Environment, a federally 118 ------- funded Program Project for a Children's Environmental Health Center in the United States. She is also the Chair of the Childhood Leukemia International Consortium Studies. Dr. Metayer is an epidemiologist currently focusing on genetic and environmental risk factors of leukemia and other cancers in children, adolescents and young adults. Her research portfolio focuses on the associations between environmental exposures, birth characteristics, medical conditions, nutrition, and genetic factors and the risk childhood leukemia. She is now expanding her research to other early-onset solid cancers. Dr. Metayer received her Ph.D. in Epidemiology from Tulane University School of Public Health and her M.D. from the University of Bordeaux II in France. Prior to joining UC Berkeley, she was a Visiting Scientist at the U.S. National Cancer Institute investigating the risk of second primary cancers. Mark Miller | University of California, San Francisco Session 9b - Community Outreach and Research Translat t II Dr. Mark Miller is an Assistant Clinical Professor of Pediatrics and Internal Medicine in the Division of Occupational and Environmental Health at the University of California, San Francisco (UCSF). He is also the Co-Director of the Western States Pediatric Environmental Health Specialty Unit at UCSF and the Director of the Children's Environmental Health Program at the California Environmental Protection Agency. Dr. Miller leads the COTC Core at the University of California, Berkeley's Center for Integrative Research on Childhood Leukemia and the Environment, where a diverse team of scientists is investigating possible environmental causes of childhood leukemia. Dr. Miller has worked with Physicians for Social Responsibility to develop the Pediatric Environmental Health Toolkit, a resource to help clinicians incorporate preventive environmental health messages into routine pediatric care. He spent 13 years as a pediatrician in private practice in a small town in California. He is a co-author of A Story of Health, a multimedia e-book examining multiple environmental contributors to health and how they interact with genetics across the lifespan. Dr. Miller was greatly influenced as a college student when he had the opportunity to visit Minamata, Japan as a guest of the Minamata Disease Victim's group. Minamata was the site of one of the world's first mass industrial poisonings, a result of mercury released from a company making material for the plastics industry. In his own pediatric practice, he began to develop educational materials for patients and their families to alert them to how environmental exposures could be affecting their health. Dr. Miller received his M.D. and completed a pediatric residency at Michigan State University. He received his M.P.H. in Environmental Health Sciences from the University of California, Berkeley and completed a residency with the California Department of Health Services in Preventive Medicine. Susan Murphy | Duke University Session 9b - Community Outreach and Research Translation, Part II Dr. Susan Murphy is an Associate Professor in the Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, at Duke University Medical Center, where her laboratory is focused on the developmental origins of disease and on the epigenetics and novel therapeutic approaches in gynecologic malignancies. She leads the Duke Epigenetics Research Laboratory and is Director of the NICHES Children's Environmental Health and Disease Prevention Research Center and Co-Principal Investigator leading the molecular biology efforts of the Duke-based Newborn Epigenetics Study (NEST). NEST is a longitudinal 119 ------- birth cohort study providing new insights regarding the in utero environment's effects on the epigenetic regulatory regions of imprinted genes. Her long-term research goals are to identify and utilize epigenetic changes that occur due to early life exposures, to improve diagnostics, and to develop new intervention and prevention strategies based on these findings. Carolyn Murray | Dartmouth College Session 9a - Community Outreach and Research Translation, Part I Dr. Carolyn Murray is Director of the Community Outreach and Translation Core for the Dartmouth Children's Environmental Health and Disease Prevention Research Center. She is a clinician in the Section of Occupational and Environmental Medicine at Dartmouth-Hitchcock Medical Center and holds faculty appointments at the Dartmouth Institute for Health Policy and Clinical Practice where she teaches in the MPH program, and in the Departments of Medicine and Community and Family Medicine at the Geisel School of Medicine at Dartmouth where she teaches medical students and resident physicians. Dr. Murray received her M.D. from the University of Virginia, and her M.P.H. and B.S. from the University of California, Los Angeles. She completed residency training at the University of Colorado and is board certified in General Preventive Medicine/Public Health and Occupational Medicine. Kari Nadeau | Stanford University Session 2 - Keynote Speaker (moderator) Dr. Kari Nadeau is an Associate Professor of Pediatrics—Immunology and Allergy and Associate Professor of Otolaryngology at Stanford University School of Medicine. She is also the Director of Basic Science and Clinical Research at the Sean N. Parker Center for Allergy and Asthma Research at Stanford. Dr. Nadeau has a broad background in immunology, with specific training and expertise in key research areas on T cells. Dr. Nadeau's research focuses on the role of ambient air exposure on the developing immune system in children, with a focus on understanding the interaction between environment and the immune system by studying detailed mechanistic studies in T cells. She is working with Drs. Katharine Hammond and Ira Tager at the University of California, Berkeley, to link mechanistic immunology studies with epidemiological outcomes of ambient air pollution exposure. Dr. Nadeau has authored and co-authored more than 100 original papers, many of which focus on T cells and health outcomes. Dr. Nadeau received her Ph.D. in Biochemistry and Immunology from Harvard University, an M.D. degree from Harvard Medical School, and a B.S. degree from Haverford College. Frederica Perera | Columbia University Session 12 - Keynote Speaker (moderator) Dr. Frederica Perera is a Professor of Environmental Health Sciences. Since 1998, she has served as Director of the Columbia Center for Children's Environmental Health. Dr. Perera is internationally recognized for pioneering the field of molecular epidemiology, using biomarkers to understand links between environmental exposure and disease. Currently, she and her colleagues are applying advanced molecular and imaging techniques within longitudinal cohort studies of pregnant women and their children, with the goal of identifying preventable environmental risk factors 120 ------- for developmental disorders, asthma, obesity, and cancer in childhood. These include toxic chemicals, pesticides, and air pollution, with particular focus on adverse effects of prenatal and early childhood exposures. Dr. Perera's areas of specialization include prevention of environmentally related developmental disorders and disease in children, cancer prevention through the use of novel biomarkers, environment- susceptibility interactions, and risk assessment. Her recent research also addresses the multiple impacts on children's health and development of fossil fuel combustion—both from the toxic pollutants emitted and climate change related to C02 emissions. She has written more than 350 publications, including 300 peer-reviewed articles. Dr. Perera has received numerous honors, including, most recently, the Pearl Award and the Heinz Award for her lifetime achievement in research for the protection of children's health. Bradley Peterson | Children's Hospital Los Angeles Session 8 - Neurodevelopmental Disorders Dr. Brad Peterson is currently the inaugural director of the Institute for the Developing Mind at Children's Hospital of Los Angeles. Dr. Peterson also holds a secondary appointment in the Department of Psychiatry at the Keck School of Medicine of the University of Southern California, where he is director of the Division of Child and Adolescent Psychiatry. His research includes brain-imaging technologies to gain understanding of the origins of neurodevelopmental disorders and to map the complex pathways between the genetic and environmental influences that can trigger their onset or progression. Dr. Peterson earned his M.D. from the University of Wisconsin School of Medicine in 1987. He completed his residency in general psychiatry at Massachusetts General Hospital and his postdoctoral research fellowship at the Yale Child Study Center. Dr. Peterson also completed a clinical fellowship in child psychiatry at Yale. He has trained adult and child psychoanalysis at Yale and Columbia. Previously, Dr. Peterson served 13 years as the director of the Center for Developmental Neuropsychiatry at Columbia University. Before that, he spent 12 years at Yale University, where he served as Director of Neuroimaging at the Yale Child Study Center. He has published hundreds of papers and received numerous awards for his accomplishments in childhood neurodevelopmental disorders. Karen Peterson | University of Michigan Session 7a - Obesity Dr. Karen Peterson is a Professor and Chair of the Department of Nutritional Sciences at the School of Public Health, Research Professor for the Center for Human Growth and Development, and Director of the Momentum Center: Driving Discovery to End Child Obesity (www.momentumcenter.org), all at the University of Michigan. She is also an Adjunct Professor of Nutrition at the Harvard School of Public Health. Dr. Peterson is the Contract Project Investigator for the University of Michigan Children's Environmental Health and Disease Prevention Center, "Lifecourse Exposures & Diet: Epigenetics, Maturation & Metabolic Syndrome." Dr. Peterson's research focuses on understanding the influence of adverse exposures to metals and endocrine-disrupting chemicals on physical growth, maturation, and markers of metabolic homeostasis during sensitive developmental periods. She also studies the potential role that dietary quality and lifestyle behaviors might play in modifying the relationships between environmental exposures and child health and conducts substantial research on testing interventions to reduce child obesity. 121 ------- Stephen Rappaport | University of California, Berkeley Session 7b - Exposome Dr. Stephen Rappaport is a Professor of Environmental Health Sciences at the University of California, Berkeley's School of Public Health. He is a pioneer in the emerging field of Exposure Biology and a prominent advocate of the concept of the "Exposome" as a new paradigm for Environmental Health. To discover unknown causes of chronic diseases, Dr. Rappaport's laboratory is conducting exposome-wide association studies that use untargeted analysis of small molecules and protein adducts in archived blood samples from diseased and healthy people. He has used environmental measurements and biomarkers to elucidate the human metabolism of several toxic chemicals, notably benzene, and to quantify interindividual variability in biomarker levels due to genetic, environmental, and lifestyle factors. Dr. Rappaport has published extensively in areas related to the assessment of long-term chemical exposures for purposes of controlling hazards and investigating exposure-response relationships. He has written more than 230 peer-reviewed publications and has collaborated extensively with investigators throughout the world. Dr. Rappaport received his Ph.D and M.S.P.H in Environmental Science and Engineering from the University of North Carolina and his B.S. in Chemistry from the University of Illinois. Leslie Rubin | Emory University Session 4 - Social Determinants of Health Dr. Leslie Rubin is the President and Founder of Innovative Solutions for Disadvantage and Disability and a Research Associate Professor in the Department of Pediatrics at Morehouse School of Medicine in Atlanta, Georgia. He also serves as Co-director of the Southeast Pediatric Environmental Health Unit in the Department of Pediatrics at Emory University and Medical Director of Developmental Pediatric Specialists in Atlanta, Georgia. Dr. Rubin currently provides clinical services, teaches at Morehouse and Emory Schools of Medicine, and is on several local, regional, national, and international committees and projects that address the needs of children with developmental disabilities, especially those from low income, minority, and undeserved communities, with a focus on environmental health disparities. Dr. Rubin is originally from South Africa where he trained in Pediatrics and came to the United States in 1976. He was at the Hospitals of the Case Western Reserve University in Cleveland, Ohio until 1980 when he moved to The Children's Hospital in Boston and the Harvard Medical School where he spent 14 years. In 1994, Dr. Rubin relocated to Atlanta, Georgia to become Director of Developmental Pediatrics at Emory University. Since 1998, he has been involved with the Southeast Pediatric Environmental Health Specialty Unit at Emory. In 2004, he joined the faculty at Morehouse School of Medicine and started ISDD, a private, nonprofit organization, to address the challenges of environmental health disparities in children. Sheela Sathyanarayana | University of Washington, Seattle Children's Research Institute Session 11 - Next Steps for Collaboration Between the Children's Environmental Health Centers and the Pediatric Environmental Health Specialty Units Dr. Sheela Sathyanarayana is an Associate Professor of Pediatrics and Adjunct Associate Professor in the Department of Environmental and Occupational Health Sciences at the University of Washington. Dr. Sathyanarayana serves as the co-director of the Pediatric Environmental Health Specialty Unit in Region X. Her research interests focus on exposures to endocrine disrupting chemicals including phthalates and 122 ------- BPA and their impact on reproductive development. Dr. Sathyanarayana serves as the center director for The Infant Development and Environment Study, which is a multi-center cohort study of phthalate exposures in pregnancy and health outcomes in children. She was named Outstanding New Investigator within the University of Washington Center for Ecogenetics and Environmental Health. She currently serves as chair for the U.S. Environmental Protection Agency's Children's Health Protection Advisory Committee and serves on the National Academies of Sciences, National Research Council Committee on Endocrine-Related Low Dose Toxicity. Susan Schantz | University of Illinois Session 6 - Neurodevelopmental Disorders (moderator) Dr. Susan Schantz is a Professor of Comparative Biosciences at the University of Illinois Beckman Institute for Advanced Science and Technology. She is also Director of the University of Illinois Children's Environmental Health Research Center. Dr. Schantz's research focuses on exposures to endocrine-disrupting chemicals during the prenatal and adolescent periods, two stages when the nervous system is particularly vulnerable to toxic insult. Her approach includes laboratory-based animal studies and parallel epidemiological studies. An important goal of these studies is to determine whether a high fat diet or obesity modify the effects of endocrine- disrupting chemicals on nervous system development and function. Dr. Schantz received her Ph.D. from the University of Wisconsin, Madison. Perry Sheffield | Icahn School of Medicine at Mount Sinai Session 10 - Emerging Topics in Children's Health Dr. Perry Sheffield is Assistant Professor of Preventive Medicine and of Pediatrics at the Icahn School of Medicine at Mount Sinai. Her clinical focus is environmental pediatrics. Much of her research focuses on the health impacts of air pollution, temperature extremes, and climate change and potential adaptation strategies. Dr. Sheffield is Deputy Director of the EPA Region 2 Pediatric Environmental Health Specialty Unit. Dr. Sheffield received her M.D. from the Medical College of Georgia and completed her Pediatrics Residency at Johns Hopkins Hospital and a fellowship in Pediatric Environmental Health at Mount Sinai. Patrice Sutton | University of California, San Francisco Session 9a - Community Outreach and Research Translation, Part I Patrice Sutton is a Research Scientist spearheading the University of California, San Francisco's Program on Reproductive Health and the Environment's clinical outreach and translation efforts. She has over 27 years of experience in occupational and environmental health research, industrial hygiene, public health practice, policy development, and community-based advocacy. As a contractor to California's state health department from 1987 to 2006, Ms. Sutton was responsible for conducting all aspects of research investigations spanning a disparate range of issues, including lead poisoning, tuberculosis, asthma, and pesticide illness. She has extensive experience collaborating with directly impacted workplace and community-based populations, labor, and governmental and non-governmental organizations in the development of research strategies and policy recommendations. Ms. Sutton also has extensive experience as a volunteer in support of communities and workers impacted by the nuclear weapons production cycle and has published over 50 peer-reviewed scientific articles and government technical reports. 123 ------- Allison Sylvetsky [ George Washington University Session 10 - Emerging Topics in Children's Health Dr. Allison Sylvetsky is a Visiting Assistant Professor in the Department of Exercise Science at the George Washington University Milken Institute School of Public Health. Dr. Sylvetsky joined the Milken Institute School of Public Health in 2014 from the Intramural Program at the National Institutes of Health (NIH) where she was a post-doctoral fellow in the Diabetes, Endocrinology, and Obesity Branch of the National Institute for Diabetes, Digestive, and Kidney Diseases (NIDDK). Dr. Sylvetsky enjoys teaching and mentoring undergraduate students and is passionate about her primary research interest studying the metabolic and health effects of artificial sweeteners. Her research interests also include national trends in beverage consumption, prevention and treatment of childhood obesity, and psychosocial interventions for treating obesity-related conditions in children and adolescents. Additionally, Dr. Sylvetsky researches the development of taste preferences and how exposure to specific foods and beverage ingredients early in life may influence long-term dietary patterns as well as the development of the intestinal microbiome. In addition to her research and teaching, Dr. Sylvetsky looks for opportunities to translate nutrition science into clinical and public health practice. Claudia Thompson | National Institute of Environmental Health Sciences Session 7b - Exposome (moderator) Dr. Claudia Thompson is Chief of the Population Health Branch at the National Institute of Environmental Health Sciences. The Population Health Branch supports diverse programs in population-based, laboratory-based, and community-engaged research on environmental exposures and their effects on human health, with an emphasis on how timing of exposure affects health outcomes across the lifespan. Dr. Thompson has led NIEHS research efforts in response to national disasters, including the coordination of World Trade Center research and outreach activities; assisted in the NIEHS response to Hurricanes Katrina and Rita; and most recently, led a trans-NIH Deepwater Horizon Disaster Academic Community Research Consortium, which she developed to understand the potential health impacts of the Deepwater Horizon Disaster on community members residing in the Gulf States. Currently, Claudia is co-leading a trans-NIH working group on household air pollution and cook stoves and has a portfolio of grants related to cookstove research. She is Program Director for the Environmental Health Sciences Core Centers. Dr. Thompson received her B.S. in Biology from Bradley University in Peoria, Illinois, and her Ph.D. in Biochemistry and Nutrition from the University of North Carolina at Chapel Hill. Nse Witherspoon | Children's Environmental Health Network Session 10 - Emerging Topics in Children's Health Ms. Nsedu Witherspoon serves at the Executive Director for the Children's Environmental Health Network (CEHN), where her responsibilities include successfully organizing, leading, and managing policy, education/training, and science-related programs. She is a leader in the field of children's environmental health, and for the past 14 years has served as a key spokesperson for children's vulnerabilities and the need for their protection, conducting presentations and lectures across the country. Ms. Witherspoon has held past appointments on the Children's Health Protection Advisory Committee for the Environmental Protection Agency and the Board for the American Public Health Association. Ms. Witherspoon has a variety of publications and has the distinct honor of having one of CEHN's leadership awards, the Nsedu Obot Witherspoon (NOW) Youth Leadership Award, named in her honor. She is also the recent recipient 124 ------- of the William R. Reilly Award in Environmental Leadership, from the Center for Environmental Policy at American University. Ms. Witherspoon has a B.S. in Biology from Siena College and an M.P.H. in Maternal and Child Health from The George Washington University, School of Public Health and Health Services. A mother of three children, Ms. Witherspoon is a passionate advocate for all children today and tomorrow. Tracey Woodruff | University of California, San Francisco Session 6 - Neurodevelopmental Disorders Session 7c - Reproductive Health (moderator) Dr. Tracey Woodruff is a professor in Department of Obstetrics, Gynecology, and Reproductive Sciences and Philip R. Lee Institute for Health Policy Studies at the University of California, San Francisco and the Director of the Program on Reproductive Health and the Environment. She conducted extensive research and developed policy on environmental health issues, with a particular emphasis on early-life development. Her research includes evaluating prenatal exposures to environmental chemicals and related adverse pregnancy outcomes and characterizing developmental risks. She has authored numerous scientific publications and book chapters, and has been quoted widely in the press, including USAToday, the San Francisco Chronicle, and WebMD. Previously, Dr. Woodruff was a senior scientist and policy advisor in the Office of Policy at was previously at the U.S. EPA. She was appointed by the governor of California in 2012 to the Science Advisory Board of the Developmental and Reproductive Toxicant Identification Committee. Dr. Woodruff received her Ph.D. and M.P.H. in the environmental health sciences from the University of California, Berkeley. She completed a Pew Postdoctoral Fellowship at the University of California, San Francisco's, Institute for Health Policy Studies. Rosalind Wright | Mount Sinai Hospital Session 4 - Social Determinants of Health Dr. Rosalind Wright is Professor of Pediatrics, a pulmonary physician, and the Dean for Translational Biomedical Research at the Icahn School of Medicine at Mount Sinai in New York. She is a developmental epidemiologist with transdisciplinary training in medicine, environmental health, multi-level modeling and stress mechanisms. Dr. Wright has an overarching interest in explaining health disparities across the lifecourse, and her research has primarily focused on early life (prenatal and early childhood) predictors of developmental diseases including asthma, obesity, neurobehavioral development, and lung growth and development. A particular focus is on the implementation of studies considering the role of both social (e.g., individual- and community-level psychosocial stress and other socioeconomic risk factors) and physical (e.g., air pollution, chemicals, dietary factors, allergens) environmental factors in explaining health disparities among lower-SES urban populations. Dr. Wright is the PI and Director of the Asthma Coalition on Community, Environment, and Social Stress (ACCESS) project as well as the Programming of Intergenerational Stress Mechanisms (PRISM) study funded by the National Institutes of Health at Harvard Medical School and is a member of the adjunct faculty in the Department of Environmental Health at the Harvard School of Public Health. This research program explores underlying mechanisms by incorporating biomarkers of physiological pathways through which psychological stress as well as chemical stressors may influence health (e.g., altered hypothalamic-pituitary-adrenal axis functioning, altered maturation of the immune system, disruption of the autonomic nervous system, and epigenetics). 125 ------- Marya Zlatnik | University of California, San Francisco Session 7c - Reproductive Health Dr. Marya Zlatnik is a Professor of Obstetrics, Gynecology, and Reproductive Sciences at the University of California, San Francisco, and a Maternal Fetal Medicine specialist, with clinical expertise in the diagnosis of fetal anomalies. She has a long-standing interest in environmental toxins in pregnancy. Dr. Zlatnik is a member of UCSF's Program in Reproductive Health & the Environment, Associate Director of UCSF's fellowship in Maternal Fetal Medicine, and Associate Director for Maternal Fetal Health & the Environment Program of the UCSF Pediatric Environmental Health Specialty Unit. Dr. Zlatnik earned her M.D. at the University of Iowa and completed a residency in OB/GYN, a fellowship in Maternal-Fetal Medicine, and received her Masters of Medical Science at the University of Texas Medical Branch in Galveston. 126 ------- 2015 NIEHS/EPA Children's Centers Annual Meeting October 29-30, 2015 Appendix C - Poster Session Abstracts Poster ID Presenting Author and Affiliation Abstract Title k Number 1 Margaret Adgent National Institute of Environmental Health Sciences Measuring Estrogen Response in Postnatal Uterus and Breast Growth: A Study of Soy- Protein Based Infant Formula 129 2 Emanuel Alcala Central Valley Health Policy Institute Pollution and Preventable Child Illness in California's Central Valley 129 3 Allison Appleton University at Albany School of Public Health The Albany Infant and Mother Study: Prenatal Environmental Toxicant and Psychosocial Stress Exposures, Epigenetic Mechanisms, and the Gestational Origins of Health Disparities 130 4 John Capitman Central Valley Health Policy Institute/California State University, Fresno Children's Health and Air Pollution Study—San Joaquin Valley: Transit Exposures During Pregnancy 130 5 Gustavo Carlo University of Missouri Pilot Data on Air Quality and Exposure to Environmental Toxicants in Early Childhood Education Centers 131 6 Kathryn Cottingham Dartmouth College Associations of Early Life Water and Dietary Arsenic Exposure With Subsequent Growth and Neurodevelopment 131 7 Kathryn Cottingham Dartmouth College Elemental Signatures in Infant Urine Reflect Dietary Patterns 132 8 Brett Doherty University of North Carolina at Chapel Hill Prenatal Exposure to Phthalates and Performance on the Bayley Scales of Infant Development-ll in a Population of Young Urban Children 132 9 Elaine Faustman University of Washington Center for Child Environmental Health Risks Research: Epigenetics and Exposome Assessment for Neurodevelopment 133 10 Lisa Gilmore The Cadmus Group, Inc. Spreading the Word: Home Visits Reduce Indoor Triggers and Improve Asthma Control 133 11 S. Katharine Hammond University of California, Berkeley Children's Health and Air Pollution Study in the San Joaquin Valley—the UC Berkeley- Stanford CEHC 134 127 ------- E 12 13 14 15 16 17 18 19 20 21 S. Katharine Hammond University of California, Berkeley I Spatial and Temporal Trends in Traffic-Related Air Pollution From 1990 to 2015 in Fresno, California 134 Darryl Hood The Ohio State University Application of Citizen Science Risk- Communication Tools in a Vulnerable Urban Community 135 Darryl Hood The Ohio State University Exposure to Benzo(a)pyrene Confers Enhanced Susceptibility to Bacterial Infection: Validation of Research Trajectory One for the Public Health Exposome Framework 135 Margaret Karagas Dartmouth College The Children's Environmental Health and Disease Prevention Research Center 136 Catherine Karr University of Washington/Northwest PEHSU Residential Use of a Pyrethroid Pesticide and Facial Paresthesias in a Toddler 136 Rachel Locke Children's Environmental Health Network Cancer Free Economy Network 137 Sara Lundgren Dartmouth College The Effect of Maternal Prenatal Diet on the Six-Week Infant Stool Microbiome Depends on Delivery Mode 137 Meredith McCormack Johns Hopkins University Healthy Eating Better Breathing: A Dietary Intervention Study in Asthma 138 Shawn McElmurry Wayne State University Two Contemporary Sources of Child Lead Exposure: Resuspended Soil and Avgas 138 Catherine Metayer University of California, Berkeley Center for Integrative Research on Childhood Leukemia and the Environment (CIRCLE) 139 128 ------- E 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 Mark Miller Western States PEHSU (at UCSF), CIRCLE, Cal EPA I Increasing Environmental Health Literacy via A Story of Health Multimedia eBook and CE Course 139 Hua Fan-Minogue (and Kari Nadeau) Stanford University Mass Cytometry Identifies Unique Monocytes and T-cell Alterations After Pollution Exposure 140 Meghan Moynihan University of Michigan Predictors of Urinary Cadmium Among Mothers and Children in Mexico City 140 Susan Murphy Duke University Neurodevelopment and Improving Children's Health Following Environmental Tobacco Smoke Exposure (NiCHES) 141 Amy M. Padula Stanford University Traffic-Related Air Pollution, Neighborhood Socioeconomic Factors and Neural Tube Defects in the San Joaquin Valley of California 141 Thomas Palys Geisel School of Medicine at Dartmouth Biorepository at Dartmouth: A Resource for Children's Environmental Health and Disease Prevention 142 Tracy Punshon Dartmouth College Imaging the Placental Metallome in the New Hampshire Birth Cohort 142 Leslie Rubin Southeast PEHSU Break the Cycle of Environmental Health Disparities in Vulnerable Children 143 Susan Schantz University of Illinois New Findings from the Illinois Children's Center: Spotlight on BPA 143 Brianna Sleezer Children's Environmental Health Network A Blueprint for Protecting Children's Environmental Health: An Urgent Call to Action 144 Judy Van De Water University of California, Davis UC Davis Center for Children's Environmental Health and Disease Prevention (CCEH) 144 Marya Zlatnik University of California, San Francisco PEHSU, PEEC Story of Health Multi-Media eBook— Storytelling to Translate Science for Health Promotion and Disease Prevention. The Next Installment: Infertility 145 Zehang Chen University of Pennsylvania Low-Level of Environmental Lead Exposure and Children's Proactive Aggression 145 Jianghong Liu University of Pennsylvania Children's Dietary Pattern is Associated With Blood Lead Levels 146 Jianghong Liu University of Pennsylvania Low Blood Lead Concentration is Associated With Sleep Disturbance in Preadolescents 146 129 ------- 37 Jianghong Liu University of Pennsylvania Low-Level Lead Exposure is Associated with Delayed Brain Maturation 147 38 Bowen Yao University of Pennsylvania Low Level of Lead Exposure is Associated With Prolonged P300 Latency Among 12 Year Old Children 147 130 ------- 1 - Measuring Estrogen Response in Postnatal Uterus and Breast Growth: A Study of Soy- Protein Based Infant Formula Margaret Adgent'; David Umbach'; Babette Zemel2; Andrea Kelly2; Joan Schall2; Eileen Ford2; Kassa Darge2; Walter Rogan'; Virginia Stallings2 'National Institute of Environmental Health Sciences; 2ChiIdren's Hospital of Philadelphia (CHOP) Soy contains estrogenic isoflavones. Infants exclusively fed soy-protein based formula are exposed to high concentrations of these estrogenic compounds, but the physiologic response remains uncharacterized. We examined the postnatal growth of estrogen-responsive tissues in a study of soy- protein based infant formula. Methods: Our study included 283 infants, all fed either breast milk (BF) (n=70), cow milk formula (CMF) (n=lll), or soy formula (SF) (n=102) since birth. We estimated uterine volume (cm3) and breast bud diameter (cm) from repeated ultrasound measurements of the uterus and breast buds (male and female), obtained at birth and at 4 - 8 week intervals until 28 (boys) or 36 (girls) weeks. We used natural cubic splines to estimate postnatal organ growth trajectories by feeding group and tested whether trajectories differed after adjustment for organ size differences at birth (i.e., differences that preceded initiation of feeding). Results: Uterine volume decreased rapidly in the first several postnatal weeks. The rate of involution was significantly slower in SF girls, compared to CMF (p< 0.01) and BF girls (p = 0.01). SF girls' breast buds tended to be larger than those of CMF and BF girls but grew at a similar rate (p = 0.72 and 0.73, respectively). Boys' breast buds decreased in size with age, more rapidly among BF boys than among CMF (p=0 .05) or SF (p< 0.01) boys. These feeding-group differences in boys attenuated after body-weight adjustment. Conclusions: Soy formula feeding was associated with a slower rate of uterine involution, suggesting an estrogen response. 2 - Pollution and Preventable Child Illness in California's Central Valley Emanuel Alcala; Lauren Lessard; John A. Capitman Central Valley Health Policy Institute Health inequalities among children are prevalent in California's Central Valley and are linked to unique social and environmental factors that impact adult health and capacity. In this study, we measure ecological relationships between neighborhood pollution burden, poverty, race and pediatric preventable disease hospitalization rates. Methods: Preventable disease hospitalization rates were obtained from the 2012 California Office of Statewide Health Planning and Development database, for 8 Central Valley counties. The pollution burden score was calculated by the California Office of Environmental Health Hazard Assessment using 11 indicators. We examined the components of the pollution burden index for any association with potentially preventable respiratory hospitalizations. Poisson-based negative binomial regression was used for final analysis controlling for poverty, primary care-shortage areas, and racial/ethnic diversity at the zip code-level. Stratification of sample by race/ethnicity and age was also incorporated. Results: A 31% reduction in preventable disease hospitalizations for children under 15 living in low poverty compared to those living in high poverty was found. With every unit increase in pollution burden, hospitalizations rates increase by 25%, 20%, and 20% in age groups under 1, 1-4 and 5-14, respectively. In most sub-groups of age and race/ethnicity, hospitalizations increased as neighborhoods became more racially diverse. Conclusion: Understanding the geographic distribution of disease and impact of individual and community level factors is essential to expanding access to care and preventive resources to improve the health of children in California's most underserved population and region. 131 ------- 3 - The Albany Infant and Mother Study: Prenatal Environmental Toxicant and Psychosocial Stress Exposures, Epigenetic Mechanisms, and the Gestational Origins of Health Disparities Allison Appleton1; Kevin Kiley1; Alex Pieterse'; Carmen J. Marsit2; Lawrence Schell' 1 University at Albany; 2Dartmouth College Background: Adverse gestational exposures may shape offspring health for a lifetime, likely via epigenetic mechanisms. The Albany Infant and Mother Study (AIMS) was developed to identify the molecular mechanisms through which prenatal toxicant and non-chemical/psychosocial stressors influence child growth and neurodevelopment. AIMS examines these factors among a more disadvantaged population than has previously been considered. Here, we review AIMS methods and provide a first look at participant characteristics. Methods: Participants enroll mid-pregnancy at Albany Medical Center (target n=300). The prenatal assessment includes stress and indoor environment questionnaires, and biomarkers for trace metals. Outdoor air quality is assessed via geocoding and spatially resolved models. Epigenetic alterations to growth and neurodevelopment genes will be analyzed from cord blood. Clinical information and birth size characteristics are abstracted from medical records. Follow-up at 12 months will assess child neurobehavior and obesity risk. Results: To date, 85 women have enrolled. Participants are from disadvantaged backgrounds: 44% are black or Hispanic, 20% did not complete high school, and 60% are not married. High levels of prenatal environmental and psychosocial risks have been observed: 17% smoked during pregnancy, 48% experienced passive smoke exposure, 22% were depressed, and 52% had >3 major adverse events. Conclusions: AIMS participants experience a substantial burden of environmental and social risks, which may set infants on health risk trajectories for a lifetime. Our future work will examine the cumulative impact of these exposures for epigenetic modulation of child growth and neurodevelopment. Doing so may yield new insights and opportunities to ameliorate health disparities. 4 - Children's Health and Air Pollution Study—San Joaquin Valley: Transit Exposures During Pregnancy John Capitman1,2; Jaymin Kwon2; Kara Zografos2; Katherine Hammond3; Betsey Noth3; Emanuel Alcala1 1 Central Valley Health Policy Institute 2California State University, Fresno; 3UC Berkeley To understand the health effects of the polycyclic aromatic hydrocarbons (PAHs) on pregnant women and children, one component of the Children's Health and Air Pollution Study in the San Joaquin Valley (CHAPS-SJV), is continuously measuring the spatial and temporal environmental exposure concentrations to multiple air pollutants. Neighborhood exposure concentrations to multiple air pollutants are being characterized by real-time monitoring along with time-location data for proximity to traffic emission. Structured social observation of neighborhood conditions that promote or impede walking and/or public transportation are also being implemented. The real time concentration of PM2.5, ultrafine particle number concentrations, black carbon, particle-bound PAHs were continuously and simultaneously measured from January to February of 2015. Three zip codes in Fresno that also include EPA approved fixed air monitoring sites were selected. Walking routes (10 routes) were designed to reflect variability in neighborhood conditions within the three zip codes. The PM2.5, ultrafine particles, black carbon, and particle-bound PAHs concentrations are compared with stationary PAHs concentrations and other PM2.5 components as measured by fixed sites. The time-location data were mapped using GPS loggers. The sharp elevations of air pollutant concentrations were observed when the mobile air pollutant monitors were closer to roadways with high volume of vehicles. Neighborhood 132 ------- mobile air samples were influenced by roadway traffic conditions immediately, such as encountering with diesel trucks, approaching in close proximity to freeways and/or busy roadways, passing cigarette smokers, and gardening activity. Average route social disorder correlated with average route PM2.5. 5 - Pilot Data on Air Quality and Exposure to Environmental Toxicants in Early Childhood Education Centers Gustavo Carlo; Chung-Ho Lin; Danh Vu; Alexandra Davis; Phuc Vo; Thi Ho; Jane MeElroy; Francisco Palermo; Susan Nagel University of Missouri Background: Children spend as much as ten hours per day, five days per week, in preschool centers. Preschoolers can be at risk from toxicant exposure from various sources (e.g., cleaning and art supplies, toys). These compounds can have adverse health effects on the endocrine system. Chemical exposure has been linked to a number of disorders (e.g., reproductive disorders, autism, depression, diabetes, ADHD). Children are particularly susceptible to chemical exposures for several reasons: 1) children breathe more air, eat more food, and drink more water per unit of body weight compared to adults, 2) children have more direct contact with contaminated surfaces, and 3) children have developing brains, neuroendocrine and immune systems. Despite these risks, research that examines airborne chemicals in preschool centers is sparse. Aim: To assess airborne chemicals and toxins in preschool centers with low- income children. Methods: We selected four Head Start preschool centers with diverse physical characteristics from a large urban area. Indoor air samples were collected over six months. Outdoor and residential comparison samples were also collected. Volatile Organic Compounds (VOCs) were sampled by thermal desorption samplers and concentrations were determined by a thermal desorption gas chromatography-mass spectrometry (TD-GC-MS) methods. Results: A series of Bonferroni-adjusted t- tests showed significantly higher levels of several chemicals (e.g., benzenes, chlorinates, endocrine disruptors, organic solvents) inside classrooms at Head Start centers as compared to residences. Further analyses revealed significant differences across classroom types (e.g., ground floor, playroom, basement). Conclusions: We discuss the potential implications of exposure for children's learning and health. 6 - Associations of Early Life Water and Dietary Arsenic Exposure With Subsequent Growth and Neurodevelopment Kathryn Cottingham1; Diane Gilbert-Diamond1; Susan Korrick2; Margaret R. Karagas1 1Dartmouth College; 2T.H. Chan Harvard School of Public Health Background: Exposure to high doses of arsenic via contaminated drinking water adversely impacts child growth and neurobehavioral development. However, less is known about the effects of lower doses of arsenic exposure typical of U.S. populations, which occur primarily through food instead of drinking water. Aims: To assess (1) diet and water as sources of arsenic exposure in pregnant women and their children and (2) the relation of early life arsenic exposure with subsequent growth and neurodevelopment. Methods: The New Hampshire Birth Cohort (NHBC) study enrolls women during the 2nd trimester of pregnancy. We evaluate arsenic exposure in mothers and children via drinking water and diet using urinary and toenail arsenic biomarkers. We then evaluate how those biomarkers are related to the children's altered growth and adiposity (weight, height, body mass index, waist circumference, skinfold thicknesses) and neurodevelopment (behavior impairments, cognitive decrements, motor proficiency alterations and deficits related to autism spectrum disorders). Progress: 133 ------- Approximately 1500 pregnant women have enrolled in the NHBC to date and ~15% have private wells with arsenic concentrations above the current maximum contaminant level of 10 ng/L. Dietary analysis suggests that arsenic exposure via breastmilk and typical formula during the first year of life is low unless formula is mixed with arsenic-contaminated water, and that rice cereal at weaning is a significant exposure pathway. Maternal second trimester urinary arsenic is associated with altered birth outcomes. Analyses of the relation of arsenic exposure with postnatal growth and neurobehavioral development through age 5 years are underway. 7 - Elemental Signatures in Infant Urine Reflect Dietary Patterns Kathryn Cottingham; Kassaundra L. Amann; Tracy Punshon; Brian P. Jackson; Margaret R. Karagas Dartmouth College Background: Understanding low-level metal exposure during early infancy is important given the heightened vulnerability of neonates to environmental toxins. Although previous research has reported that powdered formulas have higher levels of both essential and toxic elements than breastmilk, to date no one has quantified whether levels for elements other than arsenic are related to increased exposure as measured by urinary biomarkers. We hypothesized that formula-fed infants would have higher levels of urinary arsenic for the essential and toxic elements found at higher levels in formula than breastmilk. Aim: To quantify differences in elemental signatures in the urine of breastfed versus formula-fed infants at 6 weeks of age Methods - We measured concentrations of essential and toxic elements in urine samples collected as part of the New Hampshire Birth Cohort Study and used general linear models to relate the observed concentrations to diet type (breastfed, formula-fed, or mixed-fed), taking into account urinary dilution (as specific gravity) and potential confounders such as age and sex. Progress: Analyses to date suggest a relationship between feeding mode and increased exposure to non-essential elements such as molybdenum, as well as the essential elements phosphorus, potassium, and selenium. Overexposure to some of these toxic and essential elements could impact both short and long-term infant health, and these effects will be explored in future work. 8 - Prenatal Exposure to Phthalates and Performance on the Bay ley Scales of Infant Development-ll in a Population of Young Urban Children Brett Doherty'; Stephanie M. Engel1; Mary S. Wolff2 1 University of North Carolina at Chapel Hill; 'Mount Sinai School of Medicine Background: Previous epidemiologic studies have reported inconsistent associations between prenatal exposure to phthalates and cognitive development in young children. Methods: We recruited 404 mother-child pairs from prenatal care facilities in New York City from 1998 to 2002. We measured concentrations of nine phthalate metabolites in maternal urine collected during the third trimester of pregnancy. We administered the Bayley Scales of Infant Development II (BSID-II) to children who returned for follow-up examinations at approximately 24 months. We used generalized linear models to estimate associations between concentrations of phthalate metabolites in maternal urine and BSID-II indices (Mental Development Index (MDI), Psychomotor Development Index (PDI)). Results: In multivariable adjusted models, we found no associations between maternal phthalate metabolite concentrations and the MDI or PDI overall. However, we found strong evidence of effect measure modification by child sex. The strongest associations were found for the metabolites mono-n-butyl phthalate, mono-isobutyl phthalate, mono-benzyl phthalate, and mono-(3-carboxylpropyl) phthalate. Among girls, associations were generally inverse for both MDI and PDI scores, indicating poorer 134 ------- performance across multiple metabolites, with estimates equal to a ~1.5 point decline per In-unit increase in exposure. Conversely, associations in boys for both MDI and PDI scores were generally positive, indicating improved performance of a slightly smaller magnitude (~1 point increase in score per In-unit increase in exposure). Conclusions: We found evidence of associations between prenatal phthalate exposures and child neurodevelopment in a cohort of young, urban children. Moreover, these associations differed meaningfully by sex: associations were mixed among boys and often negative among girls. 9 - Center for Child Environmental Health Risks Research: Epigenetics and Exposome Assessment for Neurodevelopment Elaine Faustman University of Washington The University of Washington's Center for Child Environmental Health Risks Research uses a risk assessment framework to integrate laboratory research with epidemiological data collection. Much of our laboratory research has focused on neurodevelopmental impacts of pesticide exposure. We recently characterized epigenetic outcomes following exposure to arsenic and chlorpyrifos in a human neuroprogenitor cell line during proliferation and differentiation. We found that proliferation and differentiation status influence histone modification and methylation patterns, suggesting important changes in susceptibility across the lifestage. In our field studies, we have assessed social determinants of health and multiple contaminant exposures, including 87 pesticides, 22 metals and 18 phthalates. We found that hair Cortisol concentrations varied by season and were negatively correlated with income. Pesticide exposure varied between seasons and years and was reflective of annual use statistics. Concentrations of pesticides measured in dust were significantly correlated to concentrations of metabolites in urine, however, this relationship was dependent on occupational status (farmworker or nonfarmworker) and lifestage (adult or child). Overall, this Center has leveraged laboratory analyses of epigenetic mechanisms to understand the implications of seasonal exposure to over 100 contaminants of interest to child health and wellbeing. 10 - Spreading the Word: Home Visits Reduce Indoor Triggers and Improve Asthma Control Lisa Gilmore; Allison Robinson The Cadmus Group, Inc. Home visits for asthma are an effective but underutilized intervention. Strong evidence shows that home visits for children and adolescents that address asthma triggers in the home, such as mold and dust, through environmental assessment, education, and remediation can significantly reduce asthma symptoms, missed school days, and costly hospitalizations and emergency department visits. Approximately seven million children in the United States have asthma, a common chronic childhood disorder and a leading cause of school absenteeism. The indoor environment, especially the home environment, is a key contributor to poor asthma control and disparities in asthma outcomes. The Cadmus Group has been promoting in-home interventions as a way to identify and then mitigate environmental asthma triggers for more than a decade. In 2006, Cadmus launched the Asthma Change Campaign for U.S. EPA to promote management of environmental asthma triggers as standard medical practice and to support the emergence of comprehensive community-based asthma care systems. Today, the campaign's AsthmaCommunityNetwork.org engages almost 3,500 members across more than a 1,000 programs to provide real-time access to cutting-edge tools to facilitate collaboration, 135 ------- problem solving, and learning among leaders of asthma programs; and the most current strategies for making your program a thriving and comprehensive asthma management resource. To date, AsthmaCommunityNetwork.org has hosted more than seven popular webinars on asthma home visits attracting an average 250 attendees each. With rapidly growing interest among asthma programs looking to secure sustainable financing for their home visit services, the site recently expanded to include tools and resources on funding opportunities. 11- Children's Health and Air Pollution Study in the San Joaquin Valley—the UC Berkeley- Stanford CEHC 5. Katharine Hammond; G Shaw; J Balmes; K Nadeau; E Eisen; J Mann; J Capitman; A Padula; K Zografos; J Kwon; Jenny Sakar; E Noth; F Lurmann University of California, Berkeley The UC Berkeley-Stanford Children's Environmental Health Center is studying the relationship between air pollution in the Californian San Joaquin Valley and children's health. The health effects upon which we are focused include 1) preterm birth and birth defects, 2) allergic diseases and immunologic impacts, and 3) obesity and glucose dysfunction. The poster will highlight projects 1 & 4 and the COTC. An analysis of the relationship between PAH during several periods during pregnancy with categories of gestational age at birth found associations between PAH during the last 6 weeks of pregnancy and birth at 20-27 weeks (OR=2.74; 95% CI: 2.24-3.34) comparing the highest quartile to the lower three quartiles. An analysis of Air Pollution, Neighborhood Socioeconomic Factors, and Neural Tube Defects is reported in an accompanying poster. The fourth project, with Fresno State, developed methods to compare structured social observation of indicators of order and disorder for walking and institutions and began walking surveys in 10 routes in 3 zip codes; preliminary data underscore variability among neighborhoods much greater than reported by CES Deprivation Score. The real time concentrations of PM2.5, ultrafine particle number, black carbon, particle-bound PAHs were measured on these same routes and compared with stationary monitors that measured continuously in Fresno Air Monitoring Sites. The COTC completed a field project where students from an environmental science program at a science & technology high school carried pollution monitors, GPS devices and activity monitors while in- transit. Students mapped concentrations to learn about spatial and temporal variations in transit-related exposures. 12 - Spatial and Temporal Trends in Traffic-Related Air Pollution from 1990 to 2015 in Fresno, California S. Katharine Hammond'; Elizabeth M. Noth1; Jay mi n Kwon2; Fred W. Lurmann3; Hilary A. Minor3; David Vaughn3; Charles Perrino1 1 University of California, Berkeley; California State Univeristy, Fresno; 'Sonoma Technology, Inc. Nitrogen dioxide (N02) and nitrogen oxides (NOx) are air pollutants that are associated with numerous adverse health effects. N02 and NOx are used as markers for combustion, especially traffic-related exposures. To evaluate the spatial and temporal changes in N02 and NOX, we examined data from spatial sampling in 2002-2003 and in 2014-2015, as well as continuous fixed site monitoring from 1990 to 2015 in Fresno. N02 was measured using a chemiluminescent monitor (CM) from 1990 to 2015 at a centrally located air monitoring station. In 2002-2003, we collected N02 and NOX by CM at 4 routine and 9 school sites. In 2014-2015, N02 and NOX were collected by CM at 4 locations and with passive Ogawa samplers at 50 locations for three 4-day periods. N02 collected at the central site exhibited a 136 ------- statistically significant trend in annual median concentration of -2.3% from 1990 to 2015. In 2002-2003 spatial sampling, we did not see a wide variation in N02 or NOX concentrations across Fresno. The mean 24-hr range for N02 during the cool season (October-March) was 15-26ppb, an approximate 2-fold spatial variation. In 2014-2015, we also observed a 2- to 3-fold range in the N02 in November 2014 and December 2014. We also compared the N02 model built from 2002-2003 data with the N02 concentrations observed in 2014-2015. In conclusion, while we observed decreasing annual trends in the N02 concentrations from 1990-2015, we saw slightly wider spatial variability in our 2014-2015 data. 13 - Application of Citizen Science Risk-Communication Tools in a Vulnerable Urban Community Darryl B. Hood'; Yuqin Jiao1; Julie K. Bower1; Wansoo lm3; Nicholas Basta1; John Obrycki1; Mohammad Z. Al-Hamdan4; Allison Wilder1; Claire Bollinger1; Tongwen Zhang1; Luddie Hatten Sr.2; Jerrie Hatten2 1The Ohio State University; 2Stambaugh-Elwood Citizens for the Environment; 3VERTICES; ^Universities Space Research Association at NASA Marshall Space Flight Center A citizen science-geographical information systems (SC-GIS) demographic, environmental, health status portal was developed for the Stambaugh-Elwood (SE) community in Columbus, OH. We hypothesized that soil at SE residences would have metal concentrations above natural background levels. Three aims were developed that allowed testing of this hypothesis. Aim 1 focused on establishing partnerships between academia, state agencies and communities to assist in the development of a community voice. Aim 2 was to design and conduct soil sampling for residents of the SE community. Aim 3 was to utilize our interactive-customized portal as a risk-communication tool by allowing residents to upload sampling results toward educating themselves as to the potential risks from industrial emissions in close proximity to their community. Multiple comparisons of means was used to determine differences in soil element concentration by sampling location at P<0.05. The results demonstrated that 8-metals (As, Cd, Cu, Pb, Mo, Se, Tl, Zn) occurred at statistically significant greater levels than natural background levels but most were below risk-based residential soil screening levels. Results were conveyed to residents via an educational, risk-communication informational card. SE residents also utilized the USEPA EJSCREEN tool. The SE EJ index for zip code 43207 was found to approach the US 80th percentile in five of seven categories signaling that the SE community is likely vulnerable to environmental impacts. This study demonstrates that community led coalitions in collaboration with academia and local state agencies can effectively address environmental concerns. 14 - Exposure to Benzo(a)pyrene Confers Enhanced Susceptibility to Bacterial Infection: Validation of Research Trajectory One for the Public Health Exposome Framework Darryl B. Hood1,3; Ryan S. Clark'; Samuel T. Pellom1,2; Burthia Booker1; Aramandla Ramesh1,2; Tongwen Zhang3; Anil Shanker1,2; Mark Maguire1; Paul D. Juarez1; Patricia Matthews-Juarez1; Michael A. Langston4; Maureen Y. Lichtveldg5 1Meharry Medical College; 2Vanderbilt University; 3The Ohio State University;4University of Tennessee; 5Tulane University The goal of this study was to validate the basic science research trajectory of our recently described Public Health Exposome framework. This was accomplished in 2 aims designed to examine the resulting effects of exposure on CD32-lipid raft interactions in the regulation of IgG binding to CD32. Aim 1 interrogated the effect of exposure on the fundamental requirement for activation of macrophage 137 ------- effector functions. FcyRlla (CD32a), has been reported to preferentially bind to IgG within lipid rafts. Aim 2 interrogated exposure-induced insult on CD32-lipid raft interactions in the regulation of IgG binding to CD32. The results describe a mechanism(s) for B(a)P-exposure induced suppression of macrophage function. We demonstrate that exposure of macrophages to B(a)P alters lipid raft integrity by decreasing membrane cholesterol by approximately 25% with a concomitant increase in CD32 into non-lipid raft fractions. This diminution in membrane cholesterol and 30% exclusion of CD32 from lipid rafts effectively causes a significant reduction in CD32-mediated IgG binding to ultimately suppress critical effector functions in the macrophage. These results offer a molecular level mechanism that is particularly relevant to critical windows of development in a number of organ systems (central nervous system, reproductive and particularly immune). Such exposures have the capacity to result in suppression of macrophage effector function by disrupting lipid raft integrity to result in reduced IgG- CD32a binding to possibly induce an immunosuppressive endo-phenotype likely leading to a subset of disparate health outcomes that are observed in vulnerable populations. 15 - The Children's Environmental Health and Disease Prevention Research Center Margaret Karagas Dartmouth College The Center's core purpose is to identify and address key emerging issues related to health impacts of early life environmental exposures on children. Our Center builds on a model of quantifying in utero, infant and childhood exposure to environmental contaminants, their mechanisms of action, and adverse health impacts in a US population. Our ultimate goal is to translate these findings into public health and clinical practice change, and policies to mitigate harmful exposures. Highlights of the year include findings elucidating the sources of arsenic exposure among infants; use of placental tissue as a biomarker of arsenic exposure and for assessing the impact of arsenic on mechanistic outcomes such as placental DNA methylation; interaction of methylmercury and arsenic on cord blood methylation; and fetal growth and developmental gene expression changes related to in utero arsenic exposure. New clinical outcome data on increased infant infections and respiratory symptoms associated with in utero arsenic exposure over the first year of life in a US population were published this past year that parallel more highly exposed populations from Bangladesh. We presented to the FDA Food Advisory Committee regarding susceptible populations and assisted in drafting legislation that would require the FDA to regulate arsenic in rice and rice products. We produced an interactive web tool on drinking water and dietary sources of arsenic exposure that communicated recommendations on reducing exposure and published these recommendations in the Journal of Pediatrics and other sources to reach pediatric health care providers as well as researchers. 16 - Residential Use of a Pyrethroid Pesticide and Facial Paresthesias in a Toddler Catherine Karr1; Alexandra Perkins'; Frederick Walters2; Jennifer Sievert3; Blaine Rhodes3; Barbara Morrissey3 ^University of of Washington/Northwest PEHSU; 2Bainbridge Pediatrics/Northwest PEHSU; 3Washington State Department of Health/Northwest PEHSU In this report, we document a 13-month-old healthy male who presented to his primary care pediatrician with symptoms of facial paresthesias after a period of exposure to a consumer home-use insecticide. History taking revealed that the interior of the house had been recently sprayed with a product containing a combination of pyrethroids. Consultation with the Northwest Pediatric Environmental Health Specialty Unit (PEHSU) raised suspicion that the symptoms reflected pesticide 138 ------- toxicity, given the evidence for related findings in occupational settings. Urinary metabolite testing confirmed elevated concentrations of pyrethroid metabolites during but not after the symptomatic period. Approximately two weeks after initial symptom onset, the home was cleaned to remove residues and symptoms resolved. This case underscores the importance of environmental history taking in the recognition and management of pediatric pesticide toxicity and the potential for pediatric pesticide related illness from the widely used pyrethroid class of insecticides. 17 - Cancer Free Economy Network Rachel Locke; Nsedu Obot Witherspoon; Polly Hoppin; Fred Brown Children's Environmental Health Network The Cancer Free Economy Network (CFEN) is a network of diverse organizations and funding partners working to achieve an ambitious overall goal: "Within a generation, we (CEFN) will lift the burden of cancers and other diseases by driving a dramatic and equitable transition from toxics to effective clean and safe alternatives." Founded in 2014, the CFEN is developing a strategic plan, using a systems map built by participants to describe the dynamics among institutions/sectors/organizations/interests that influence the existence and impacts of toxic chemicals in the economy, to achieve this goal. The CFEN includes working groups organized around certain areas of the systems map - called clusters, or areas of capacity, called hubs. These working groups strive to: promote prevention of cancer and other diseases caused by chemical exposures; shift the supply and demand chains to safer chemicals and safer jobs; create diverse, "non-traditional" partners, holding equity as a highest-order principle; and develop interconnected communications, popular education, organizing, policy and fundraising strategies. This poster will highlight a specific cluster and portion of the larger systems map - the health cluster. The goal of the health cluster, within the overall goal, is to: "Contribute to a national effort to eliminate exposure to toxics to prevent cancer and other chronic diseases and promote healthy and healing environments, particularly for overburdened and vulnerable populations (such as children), by expanding the focus of all health-related organizations to include an understanding of the role of chemicals in contributing to the disease process, and a commitment to promoting primary prevention." 18 - The Effect of Maternal Prenatal Diet on the Six-Week Infant Stool Microbiome Depends on Delivery Mode Sara Lundgren1; Juliette C. Madan1; Jennifer A. Emond1; Hilary G. Morrison2; Mitchell L. Sogin2; Brock C. Christensen1; Margaret R. Karagas1; Anne G. Hoen1 'Dartmouth College;2Josephine Bay Paul Center, Marine Biological Laboratory Background: Emerging evidence supports diet's strong influence on the human gut microbiome, and of the microbiome on health, notably immune-mediated conditions. Maternal diet during pregnancy and lactation has been associated with childhood allergy risk, but the contributing mechanisms remain incompletely characterized. One possible link between maternal diet and infant health is through delivery, where the infant acquires maternal gut microbes. We seek to examine the effect of maternal prenatal diet on the infant gut microbiome at 6 weeks of age. Methods and Results: We used 16S V4-V5 targeted sequencing to examine the microbial composition of 148 6-week-old infant stool samples from the New Hampshire Birth Cohort Study, and a food frequency questionnaire to assess maternal diet. Microbial community structure based on generalized UniFrac distances was related to maternal prenatal diet only in delivery mode-stratified analyses. We adjusted for delivery mode, feeding method, maternal BMI, parity, and batch. Maternal fruit consumption in the vaginal delivery group (p=.02), and dairy in the 139 ------- cesarean delivery group (p=.04), were associated with infant stool microbiome composition at 6 weeks. Analyses excluding antibiotic-exposed infants show the same trend, but the cesarean stratum-dairy association was no longer statistically significant after adjustment. Conclusions: Maternal diet during pregnancy is associated with the 6-week infant intestinal microbiome differentially by delivery mode; the observation of an effect in both delivery mode groups suggests multiple routes of influence for maternal diet on the infant gut microbiome. 19 - Healthy Eating Better Breathing: A Dietary Intervention Study in Asthma Meredith McCormack Johns Hopkins University Rationale: Observational evidence suggests a Mediterranean-like diet may improve asthma health. We conducted a randomized, crossover dietary intervention study to assess the impact of Mediterranean- like, healthy diet on asthma outcomes and to determine feasibility of a larger scale dietary trial in asthma. Methods: Participants with doctor-diagnosed asthma were randomized to initially receive a 4- week dietary intervention or to continue their usual diet. After a 4-week washout, participants received the alternate assignment. In the intervention arm, participants ate 3-5 meals per week on site at the Johns Hopkins ProHealth Research Center in Baltimore, MD. All remaining meals and snacks were provided by the study for participants to consume off-site. Asthma clinical outcomes and biomarkers relevant to asthma and dietary intake were assessed at 0, 2, and 4 weeks after starting each treatment. Results: Seven participants completed the study protocol. The average age was 42 years, six participants were female, and six were African American. Serum carotenoids (lutein, alpha carotene, retinyl palmitate), biomarkers assessing adherence to the intervention, increased in the intervention versus control (p<0.05) (Figure 1). Asthma Control Test Scores and lung function (FEV1/FVC) tended to improve with intervention versus control diet although results did not reach statistical significance. There was no difference in change in exhaled nitric oxide between intervention and control. Conclusions: The findings from this randomized, crossover study suggest that a dietary intervention trial in participants with asthma is highly feasible and findings support the need for a larger, future study to determine the effect of a healthy dietary intervention on asthma symptoms and lung function. 20 - Two Contemporary Sources of Child Lead Exposure: Resuspended Soil and Avgas Shawn McElmurry1; Sammy Zahran2; Terrence Iverson2; Stephan Weiler2 1 Wayne State University; 'Colorado State University Historical sources of Pb to the environment include leaded gasoline, paint and solder. The quantity of Pb entering the environment from these sources has greatly diminished; yet, legacy contamination in soils continues to be a source of exposure. Currently, in the United States, over half of the Pb discharged into the atmosphere is attributable to lead-formulated aviation gasoline (avgas). In this study we evaluate the impact of two of these contemporary sources of Pb exposure: resuspended soil and avgas. To evaluate exposure from resuspended soil and Pb aerosols, the blood lead levels (BLLs) of 367,839 children (ages 0-10) in Detroit, Michigan USA were analyzed from 2001 to 2009. A 1% increase in the amount of resuspended soil results in a 0.39% increase in the concentration of Pb in the atmosphere (95% CI, 0.28 to 0.50%). Resuspended soil was found to be a significant underlying source of atmospheric Pb and explain age-dependent variation in child BLLs. Next, the BLLs of 1,043,391 children living near 448 airports in Michigan were evaluated over time and compared to the volume of piston- engine aircraft traffic that utilize avgas. Based on our analysis, we find that child BLLs: 1) increase dose- 140 ------- responsively in proximity to airports, 2) decline measurably among children sampled in the months after 9-11, 3) increase dose-responsively in the flow of piston-engine aircraft traffic, and 4) increase in the percent of prevailing wind days drifting in the direction of a child's residential location. Overall, leaded avgas contributes significantly to child BLLs near airports. 21 - Center for Integrative Research on Childhood Leukemia and the Environment (CIRCLE) Catherine Metayer University of California, Berkeley Background: The etiology of childhood leukemia (CL) involves the interplay of environmental, genetic, and epigenetic factors. PROJECT 1 Aim: To assess the association between chemical exposures and CL subtypes. Methods: We combined data for ~9,000 acute lymphoblastic leukemia (ALL), 1,300 acute myeloid leukemia (AML), and 15,000 controls from the Childhood Leukemia International Consortium. Results: We strengthened evidence of modest and/or dose-dependent relationships between paternal smoking, and exposure to paints and pesticides. The magnitude of the associations varied by ALL, AML and the presence of chromosome abnormalities. A new finding suggested an association between maternal smoking during pregnancy and AML among Hispanics only. PROJECT 2 Aim: To compare fetal exposures between ALL cases and matched controls. Methods: We employed untargeted liquid chromatography-high resolution mass spectrometry of small molecules in neonatal blood spots from 100 ALL cases and 100 matched controls. Results: We detected small-molecule features that discriminate between ALL cases and matched controls. PROJECT 3 Aim: To determine the relationship of cigarette smoking to DNA methylation changes in CpG loci that contribute to leukemogenesis. Methods: We characterized DNA methylation patterns in neonatal blood spots from 397 CL cases and 439 controls by reported smoking status, accounting for DNA methylation in blood cell types. Results: Several of the CpG sites that we found previously to contribute to leukemogenesis were also sensitive to cigarette smoking. Conclusions: We will continue working to identify in utero chemical risk factors for CL, and to understand how these chemicals increase risk via immunological, genetic and epigenetic mechanisms. 22 - Increasing Environmental Health Literacy via A Story of Health Multimedia eBook and CE Course Mark Miller1,2,3; Maria Valenti4; Ted Schettler5; Vickie Leonard' 1 Western States PEHSU (at UCSF);2CIRCLE at UC Berkeley; 3Cal EPA; 4Collaborative on Health and the Environment; sScience and Environmental Health Network Background: In recent surveys pediatricians agree that children suffer preventable illnesses of environmental origin but feel ill-equipped to educate families about common exposures. Narrative approaches are emerging as powerful health promotion tools that can increase understanding of determinants of health and translate complex science. Objective: A Story of Health multimedia eBook and continuing education (CE) course were designed to harness the power of storytelling to improve environmental health literacy for health professionals and others. Methods: The peer-reviewed eBook uses fictional stories to convey how multiple environmental factors affect health across the lifespan, encourage inclusion of anticipatory guidance, and stimulate policy changes. Readers can explore risk factors for asthma, developmental disabilities and childhood leukemia. Each story features the latest research about disease origin and prevention and examines how our natural, built, chemical, food and socioeconomic environments interact with our genes to influence health. We have drawn content from 141 ------- the collective expertise of the PEHSU network and the NIEHS Children's Centers, among others. Each story is enriched with illustrations, videos, and links to hundreds of online resources and references. Free CE's are offered through the CDC. Results and conclusions: The eBook provides an alternative method of developing competency in environmental health, as it can be accessed online and reviewed at an individual's time and pace. Over 1000 health professionals have already registered for the course. In recent evaluations, 90% say they will be able to apply what they learned from the eBook to their practices and provide intervention strategies to patients. 23 - Mass Cytometry Identifies Unique Monocytes and T-cell Alterations After Pollution Exposure Hua Fan-Minoguel; Kan Nadeau Stanford University Short-term and long-term air pollutant exposures are linked with adverse health outcomes; however, how they affect immune responses and contribute to disease pathogenesis remains unclear. We tested whether air pollution modulates multiple immune cell subsets in subjects with and without underlying disease. Using a single-cell mass spectroscopy-based flow cytometry, we studied blood samples from four groups: healthy controls with low- vs. high-polluted environments (LPE vs. HPE) and asthmatic subjects with LPE vs. HPE. Seven ambient air pollutants (AAPs) were simultaneously measured at short- term (< 6 month) and long-term (> 6 month) exposure periods in HPE groups. In healthy subjects, we found that HPE is associated with significant increases of innate lymphoid type 2-like cells (ILC2-like) and decreases in CD8+ T-cells and tetanus vaccine responses. In asthmatic subjects, alterations in immune cells by HPE were dramatically affected by disease status with significant increases in "alternative"- monocytes and activated CD4+T-cells and decreases in "classical"-monocytes and B-cells. In summary, these findings indicate that, in healthy individuals, AAP could begin to skew the immune system towards atopy and diminished immunity. Additionally, having underlying asthma could significantly worsen AAP- associated innate and adaptive immune responses leading to further pathogenesis and exacerbation of disease. 24 - Predictors of Urinary Cadmium Among Mothers and Children in Mexico City Meghan Moynihan1; Karen E. Peterson1; Alejandra Cantoral2; Peter Song1; Nil Basil'; John Meeker1; Martha Maria Tellez-Rojo2 1 University of Michigan; 2Nationat Institute of Public Health Cadmium is a naturally-occurring heavy metal with anthropogenic activities contributing to the contamination of agricultural land. Most relevant non-occupational exposures include tobacco and diet. Exposures, both acute and chronic, have been associated with adverse health effects including renal and bone, cardio-metabolic, and cancer. Urinary cadmium (UCd) is measure of long-term exposure used to assess cadmium exposure in epidemiological studies. Estimated dietary cadmium (DCd) has similarly been used in studies, the validity of which is disputed. This study aimed to describe the distribution of UCd; quantify DCd estimated from food frequency questionnaires; and determine the relationship of DCd and UCd, among other predictors of UCd in mothers and their children in a well-characterized Mexico City birth cohort. 214 third trimester maternal urines and 250 child urines were analyzed for cadmium. The analytic sample was limited to 192 mothers and 223 children based on availability of DCd (primary exposure), UCd (outcome), maternal history of smoking, and significant covariates. UCd was specific-gravity corrected and log transformed; DCd was energy adjusted using the residual method. 142 ------- Linear regression models showed a positive association between DCd and UCd among mothers and children without a maternal history of smoking, adjusted models (3=49.76, p-value=0.03 and (3=26.12, p- value=0.03, respectively. Other significant covariates include age and BMI: age was positively associated in mothers with a smoking history ((3=0.031, p-value=0.03) and BMI was negatively associated in children without a maternal smoking history (|3=-0.098, p-value=0.049). Diet is an important source of cadmium exposure among nonsmoking mothers and their children in Mexico City. 25 - Neurodevelopment and Improving Children's Health Following Environmental Tobacco Smoke exposure (NiCHES) Susan Murphy; Scott Kollins; Bernard Fuemmeler; Cathrine Hoyo; Edward Levin; Theodore Slotkin; Fred Seidler; Lisa Satterwhite; Brandon Hall; Joseph Lucas; Michele Taylor; Rochelle Schwartz- Bloom; Kathryn Pollak; Paul Bloom Duke University NiCHES is determining how epigenetic mechanisms are altered by early life environmental exposures and how this affects later neurodevelopmental outcomes. Project 1: We conducted deep neurodevelopmental phenotyping on ~190 children-mother dyads. We implemented our new cohort management platform that sends automated text, interactive voice response and emails to enhance engagement, conduct ecological momentary assessments, and facilitate retention. Recruitment will continue through 2016 followed by a second assessment of participants. Project 2: Early exposure of rats to tobacco smoke extract (TSE) causes more pervasive neurobehavioral impairments than does nicotine. Behavioral effects include adolescent locomotor hyperactivity and impaired cognitive performance. Early life TSE exposure disrupts neural systems involved with cognition and locomotor activity; cholinergic and serotonergic systems were more disrupted in rats exposed to TSE than nicotine. Similar enhanced damage with TSE was seen in in vitro models. Project 3: gDNA and RNA from rat frontal cortex, hippocampus and blood are ready for generation of WGBS and transcriptome data to identify responsive loci showing correlations with expression and the same epigenetic changes in peripheral blood. COTC: We field tested an educational brochure and website on exposure of pregnant women to secondhand smoke and risk of ADHD in their children. A public Instagram contest was held to view the brochure and website and submit images depicting the message to help babies avoid smoke. We will conduct a public field-test to determine social media most likely to engage the public to learn more about the effects of secondhand smoke and risk of ADHD. 26 - Traffic-Related Air Pollution, Neighborhood Socioeconomic Factors and Neural Tube Defects in the San Joaquin Valley of California Amy M. Padula Stanford University Neural tube defects, including spina bifida and anencephaly, are one of the most common types of birth defects. Environmental pollutants and socioeconomic factors have been associated with neural tube defects. The potential impact of interaction between ambient air pollution and neighborhood socioeconomic factors on the risks of neural tube defects is not well understood. We investigated whether associations between traffic-related air pollutant exposure in early gestation and neural tube defects were modified by neighborhood socioeconomic factors in the San Joaquin Valley of California, 1997-2006. Five pollutant exposures, three outcomes and 9 neighborhood socioeconomic factors were included for a total of 135 investigated associations. Estimates were adjusted for maternal race- 143 ------- ethnicity, education, body mass index and multivitamin use. We present below odds ratios whose accompanying confidence intervals do not include 1 and a chi-square test of homogeneity p-value <0.05. We observed increased odds of spina bifida comparing the highest to lowest quartile of PM<10 micrometers (PM10) among those living in a neighborhood with: a) median household income of less than $30,000 per year (OR=3.9; 95% CI: 1.3, 12.1); and b) more than 30% with less than or equal to a high school education (OR 2.7; 95% CI:1.1, 6.2). Among women who lived in higher SES categories, there was no association between PM10 and neural tube defects. When analyzing both case types together, these odds were attenuated. Our results demonstrate effect modification by neighborhood socioeconomic factors in the association of fine PM and spina bifida in California. 27 - Biorepository at Dartmouth: A Resource for Children's Environmental Health and Disease Prevention Thomas Palys; Marsit, C.J.; Wells, W. A.; Karagas, M.R. Dartmouth College The Biorepository at Dartmouth involves a combination of manual and advanced robotic liquid handing processes, as well as traditional and state-of-the art automated archival storage strategies (e.g. ambient temperature, 4°C, -20°C, -80°C, and liquid nitrogen) to support the Children's Environmental Health and Disease Prevention Research Center at Dartmouth and other members of the Dartmouth research community. The Biorepository encompasses a broad range of subject ages and specimen types, i.e., blood and its components, urine, nails, meconium, stool, placenta, breastmilk, DNA and RNA, as well as various environmental samples. Services include blood fractionation, lymphocyte isolation, aliquoting of specimens into various storage formats, human and microbiome nucleic acid extraction, quantification and normalization, tissue separation and fixation, specimen retrieval, shipping and referral management services and individual consultation for study design and execution. Comprehensive specimen management is tracked using eVelos-eSample software, with capabilities of linkage to and querying of archival databases in i2B2. Since its inception in 2013, the Biorepository has processed over 14,000 adult and infant specimens and archived over 80,000 aliquots, many of which are being stored in robotic freezers. Additionally, the Biorepository manages the Dartmouth Biospecimen Storage Facility, a secure, off-site facility dedicated to long term storage of specimens, with real-time video surveillance, continuous and redundant monitoring of freezer temperatures and emergency response to users. The availability of environmental and biologic samples that can be efficiently processed and retrieve can dramatically advance the pace at which high dimensional and other analyses can be performed, and provide critical information on children's health. 28 - Imaging the Placental Metallome in the New Hampshire Birth Cohort Punshon, T.1; Jackson, B.P.1; Ornvold, K.2; Marsit, C.J.1; Karagas, M.K.1 1 Dartmouth College; 'Dartmouth Hitchcock Medical Center Background: Metal contaminants readily cross the placenta, potentially having tangible effects on growth, development and lifelong health. Toxicant metals are recognized as targets by transporters for biologically essential mineral nutrients. We use elemental imaging to characterize genes encoding membrane-bound metal transporters in biological tissue. In many cases, the spatial location of an element overlaps with expression of the gene encoding for the responsible membrane-bound transporter. We extended our approach to the human placenta, an organ where controlled, bidirectional membrane transport mediates all of the nutrient, waste and gaseous transport between 144 ------- mother and fetus. Aims: To understand maternal-fetal transfer of metal(loid)s and mineral nutrients across human placenta, particularly metal-nutrient interactions, relationships with other biomarkers of metal exposure. Methods: We collected multi-element profiles from >750 placental biopsies from women enrolled in the New Hampshire Birth Cohort Study, a study initiated to study the effects of drinking water arsenic on infant health. We compared this to maternal and infant toenail metal concentrations. We developed methods for elemental imaging of placenta via Synchrotron X-Ray Fluorescence, as well as multi-elemental approaches for both spatial analysis and speciation using laser ablation and liquid chromatography-ICP-MS. Results: Metal(loid) toxicants are readily transported across the human placenta. Arsenic levels in placenta correlate with levels of arsenic in maternal urine, maternal nails, infant nails and household drinking water. Conclusions: Evaluating the placental metallome as part of a large-scale epidemiologic study provides novel insights into early life environmental determinants of children's health, and the function of the human placenta. 29 - Break the Cycle of Environmental Health Disparities in Vulnerable Children I Leslie Rubin1,2,3,4; Robert J Geller2,5; Kurt Martinuzzi2,6; Maeve Howett2,6; Benjamin A Gitterman7; L Laura Wells1,2; Joav Merrick8,9,10,11,12 'Innovative Solutions for Disadvantage and Disability;2Southeast PEHSUf Emory University; 3Morehouse School of Medicine; 4Developmental Pediatric Specialists; sGeorgia Poison Center; 6Emory University; 7George Washington University; ^National Institute of Child Health and Human Development, Israel; 9Ministry of Social Affairs and Social Services, Israel; 10Hadassah Hebrew University Medical Center; "Kentucky Children's Hospital; 12Georgia State University Children who grow up in circumstances of social and economic disadvantage are at greater risk for exposure to adverse environmental factors and are more likely to suffer consequent adverse health and developmental outcomes. Break the Cycle supports a set of student driven research projects that creatively explore the environmental and social factors that adversely affect children's health and well- being and develop creative ways to Break the Cycle. Students work with their academic mentors and the Break the Cycle team to complete their projects for presentation at an annual conference with other students from around the country and internationally. They then write up their projects for publication in an international peer-reviewed journal. To date, Break the Cycle has partnered with over 30 different university departments in 9 States in the USA and internationally, worked with over 90 students and published 7 monographs and 6 themed books of the student projects. A survey of past students found that they rated their experience with Break the Cycle valuable in: conducting a research project, presenting at a conference and having a publication; many reported that they continued to pursue career interests related to their work on the Break the Cycle projects. We propose that the Break the Cycle Program is a cost effective way of raising awareness of environmental health disparities among university students in their early years, encouraging their involvement in the field of children's environmental health and environmental health disparities, and cultivating their potential for future leadership in the field. 30 - New Findings from the Illinois Children's Center: Spotlight on BP A Susan Schantz University of Illinois The Children's Environmental Health Research Center at Illinois studies the impact of endocrine disrupting chemicals on reproductive and neural development. The group is evaluating exposures during the prenatal and adolescent periods, and is conducting complementary studies in animal models and 145 ------- human infants and children. Recent animal studies have yielded important new findings regarding BPA. The Flaws' group investigated the transgenerational effect of prenatal BPA exposure on female fertility. Pregnant mice (FO generation) were exposed to low doses of BPA (0, 0.5, 20 or 50 ng/kg), and the fertility of female mice from the Fl, F2 and F3 generations was evaluated. BPA reduced fertility in all three generations of mice. Strikingly, the most dramatic reductions in fertility were seen at the lowest (0.5 ng/kg) BPA dose. The Juraska group evaluated the effect of BPA exposure during adolescence on neuron and glia numbers in the prefrontal cortex—a brain region important for cognitive functioning. Male and female rats were exposed to 0, 4, 40 or 400 ng/kg BPA on postnatal days 27-46. There was no effect on neuron number, but BPA increased microglia number—the immune cells of the brain—in females, and decreased microglia number in males. This year the Illinois COTC hosted a state-wide conference for childcare providers. The conference increased awareness and knowledge of environmental health issues among childcare providers, and lead to a call for the formation of a task force to investigate alignment of childcare practices and policies with current recommendations to protect children's health. 31 - A Blueprint for Protecting Children's Environmental Health: An Urgent Call to Action Brianna Sleezer; Tracy Kolian; Nse Witherspoon Children's Environmental Health Network A historic meeting was convened by the Children's Environmental Health Network at Wingspread, headquarters of the Johnson Foundation, in Racine, Wisconsin on October 21-23, 2014. Over 30 visionary leaders representing perspectives from academia, non-profit advocacy, environmental justice, child health, urban planning, public health, business, economics, public policy, law, and agriculture gathered in urgent recognition that children are increasingly suffering from an array of chronic diseases and developmental conditions linked to environmental exposures. This diverse group of leaders drafted a dynamic vision statement calling for transformative change through renewed and collective action to provide all children with the protections from harm that they deserve. In the weeks following the retreat, these leaders developed a Blueprint for Action to move the vision to reality. The recommendations and actions outlined in this Blueprint are the framework for moving forward. This is just the beginning. Bold and comprehensive action is necessary. 32 - UC Davis Center for Children's Environmental Health and Disease Prevention (CCEH) Judy Van De Water University of California, Davis The principal goals of the UC Davis Center for Children's Environmental Health and Disease Prevention (CCEH) are to identify and understand environmental, immunologic, and genetic risk factors contributing to the incidence and severity of childhood autism. Currently we are: (1) Leveraging our existing studies and biobanks for specimens to expand our research and capitalize upon the Center's research findings to date. Through Project 1, we are cultivating our numerous resources from the CHARGE study, as well as the epidemiological and clinical studies involving prospective parents, pregnant women and children from the ongoing MARBLES study — both of which grew out of previous years of CCEH funding; (2) Through Projects 2-4, we are building upon our earlier findings of calcium dysregulation in cultured neurons and immune cells in the context of understanding the epigenetic effects and ramifications of toxicant exposure on gene pathways and immune function. We have found that children with ASD have a differential response to total body burden of PBDEs compared to TD controls; (3) Working to develop 146 ------- and apply new biomarkers of autism risk, through analysis of gestational immune dysfunction (Project 3), genetic susceptibility (Projects 1-4), epigenetics (Project 2), and environmental exposures (Projects 1- 4, Core C), to best characterize the potential health effects at various life stages and predict longer-term clinical and behavioral consequences. We have defined genes associated with folate insufficiency during conception and early gestation and how folate supplementation remediates some toxicant risks associated with altered neurodevelopment; (5) Continue to expand the successful Community Outreach and Translation Core (Core B) to continue the active engagement of our ASD families, as well as the California Department of Health Services and the broader cross-cultural community in the research process, and the translation and application of our research findings. We have liaised with the CAL-EPA on assessment of global warming on children's health. 33 - Story of Health Multi-Media eBook—Storytelling to Translate Science for Health Promotion and Disease Prevention. The Next Installment: Infertility Mary a Zlatnik1; Mark Miller'; Ted Schettler2; Brian Tencza3; Maria Valenti4 'University of California, San Francisco PEHSU; 2Science and Environmental Health Network; iATSDR; 4Collaborative on Health and the Environment Narrative approaches and storytelling are powerful health promotion tools that can help increase understanding of determinants of health and translate complex science. The Story of Health multi-media eBook capitalized on this approach by using fictional stories to help convey how environmental factors affect health across the lifespan. The first installment, which included chapters on asthma, developmental disabilities, and childhood cancer, has been viewed many times (see abstract ##) by clinicians and others seeking to understand environmental determinants of these conditions. The stories are accessible to an educated lay audience, with more technical sections for scientists and medical professionals, who can access free continuing education credits through the eBook. A forthcoming installment is in development, which will expand the story-telling approach to the clinical areas of reproductive health and infertility. Reproductive health forms the substrate for later child and family health, however environmental influences on reproductive health have long been overlooked. This installment aims to ground the science of environmental health in stories of people struggling with infertility. Topics included in the eBook include endometriosis, thyroid function, endocrine disrupting chemicals, healthy eating, pesticides, and preconception health for men and women. The audience for the new installment would include primary care physicians, obstetrician/gynecologists, nurse midwives, other clinicians caring for patients struggling with infertility, as well as lay audiences. 34 - Low-Level of Environmental Lead Exposure and Children's Proactive Aggression Zehang Chen; Yuli Li; Jianghong Liu University of Pennsylvania Background: Lead exposure has been linked to externalizing behavior including aggression in children. However, the type of aggression was not previously reported. The aim of this study is to identify the proactive and reactive forms of aggression in relationship to lead exposure in community children. Methods: A population-based sample of 971 children who are part of NIEHS funded Jintan cohort study participated in this study. Children's blood lead level (BLL) data and self-reported Reactive-Proactive Questionnaire (RPQ) were collected at the same time with mean age 12 years old (SD=0.4). The RPQ contains 23 items and tested two forms of aggression: proactive aggression and reactive aggression. Generalized linear models (GLMs) with main effects and an interaction between children' sex and BLL 147 ------- were conducted to test the relationship between BLL and children's aggression, controlling for children's residence, siblings, and parental education level and occupation. Results: The mean (SD) blood lead concentration was 3.1 (1.2) ng/dL, with the median value being 2.9ng/dL. GLMs results showed that boys with increasing BLL have more aggression (Ps<0.05). Children with median higher BLL (BLL>2.9ng/dL) had more proactive aggression and total aggression (Ps<0.05). This effect is particularly stronger for boys than girls. BLL is not significantly related to reactive form of aggression. Conclusions: Low-level of lead exposure below 5 ng/dL with mean BLL of 3.1 ng/dL is associated with both total aggressions and proactive form of aggression in community children. Lead exposured boys are particular vulnerable. Further studies are needed to understand the underlines of this relationship. 35 - Children's Dietary Pattern is Associated With Blood Lead Levels Jianghong Liu1; Zumin Shi2 University of Pennsylvania1; University of Adelaide2 Background: The role of diet has been suggested to be linked with blood lead levels (BLL). However, few studies have assessed the type of dietary pattern. Methods: This cross sectional study is part of the China Jintan cohort study, children's BLL and self-reported food frequency data were collected at age 12 years old (SD=0.4). Factor analysis was used to derive dietary patterns. 896 children with dietary intake and BLL were included in the analysis. Results: In this sample, the mean BLL was 3.1(SD 1.2) ng/dL with 6.4% of children's BLL >5 ng/dL. Three dietary patterns were identified. The first pattern (snack and drink) was characterised by unhealthy with high intake of chips, sweets, beverages and soymilk. The second pattern had high loadings of meat and fish. The third pattern was classified as healthy with high intake of fruit, vegetable, milk, cereal, and water. After adjusting for gender, parental education, residence and schools, for every one standard deviation increase in the food pattern score, the regression coefficient for BLL was -0.12(95%CI -0.22 to -0.03) for healthy pattern, 0.18(0.09-0.27) for snack and drink pattern. The odds ratio for high BLL (>5 ng/dL) were 1, 3.26(95%CI 1.34-7.99), and 3.80(1.52-9.46) (p for trend <0.001) across tertiles of snack and drink pattern; 1, 0.43(0.19-0.95), and 0.63(0.28-1.40) (p for trend 0.405) for healthy pattern, respectively. No association between meat and fish pattern and BLL was found. Conclusion: Healthy dietary pattern is inversely but snack and drink pattern is positively associated with BLL among Chinese adolescents. 36 - Low Blood Lead Concentration is Associated With Sleep Disturbance in Preadolescents Jianghong Liu; Qi Xia; Xiaopeng Ji; Linda McCauley; Alexandra L Hanlon University of Pennsylvania Background: We previously reported that high blood level lead exposure (>10.0 ng/dL) is related to sleep disturbance in childhood. However, it is not known if the lead-sleep relationship is extended to low blood level lead exposure. Methods: As part of the China Jintan Cohort Study, 806 school children had BLL assessed at 12 years and sleep assessed around the same time using the parent-reported Child Sleep Health Questionnaire (CSHQ). Results: Mean age of the sample at BLL and sleep assessment was 12 years old (SD =0.88). Mean BLL was 3.03 ng/dL (SD = 1.19). There were significant positive correlations between BLL and 4 CSHQ subscales: sleep duration (r =0 012, P <0.05), bed resistance (r =0.018 , P < 0.10), sleep anxiety (r= 0.015 , P < 0.05) and parasomnia (r =0.019 , P <0.05 ). By dichotomizing BLL with value 5 ng/dL, mean (3.03 ng/dL) and median (2.8 ng/dL) respectively, all showed positive correlations between dichotomized BLL and total scores (r=2.218, P<0.10; r=1.331, P<0.05; r=1.163, P<0.10). The results are controlled for parental educations, parental occupations, gender, schools and grades. 148 ------- Conclusion: Our findings indicate that even BLL at mean 3.03 ng/dL in childhood are also associated with increased risk for sleep problems 37 - Low-Level Lead Exposure is Associated with Delayed Brain Maturation Jianghong Liu; Yuli Li; Naixue Cui; Anna 5. Rudo-Hutt; Adrian Raine University of Pennsylvania Background: The effect of lead (Pb) exposure on children's brain function as measured by electroencephalograph (EEG) is not well documented. We aim to test the hypothesis that environmental lead exposure will be associated with increased slow-brainwave EEG (delta and theta wave) in community children. Methods: As part of the China Jintan Cohort Study, 517 children aged 12 years (SD=0.4) were tested for blood lead level (BLL) and EEG. Resting-status EEG (alphal, delta, and theta wave) was recorded using an Electro-Cap with tin (Sn) electrodes. Generalized linear models (GLMs) and repeated ANOVA analyses were conducted to test the relationship between BLL and the global resting- status EEG power in each band, controlling for children's sex, grade, residence, siblings, and parental marital status. Results: The mean (SD) BLL was 3.1 (1.1) ng/dL, with the median value being 2.9ng/dL. GLMs results showed that increasing BLLs correlated with increasing global EEG Delta power (B=0.002, P=0.002) and decreasing global EEG alphal power (B= -0.001, P=0.010). The interactions between lobes and BLL indicated that increasing BLL were associated with increasing frontal (F4/F3) EEG theta power. Furthermore, the repeated ANOVA analyses showed that children with relatively higher BLLs (pb> 2.9 Hg/dL) had increased delta EEG power (F(l,396) =5.74, P=0.017) in each hemisphere. Conclusion: Slow- brainwave EEGs are usually reduced with increased age throughout childhood. Consequently, our finding that low-level lead exposure is associated with increasing theta and delta power suggests that even with a median BLL below 3pig/dL Pb can slow brain maturation and result in neurodevelopment delay. 38 - Low Level of Lead Rxposure is Associated With Prolonged P300 Latency Among 12 Year Old Children Bowen Yao; Naixue Cui; Jianghong Liu University of Pennsylvania Background and Objectives: Low-level lead exposure has been associated with decreased IQand neurocognitive deficits in childhood. However, the neurophysiological mechanism underpinning these relationships remains unknown. The present study aims to examine the association of low-level lead exposure with P300, a positive component recorded by event related potential (ERP) as an indicator of neurocognitive capacity in a community sample of Chinese children. Design/Methods: As a part of the China Jintan Child Cohort Study, 327 children with mean age 12 years (SD=0.64) participated in 2012- 2013 period of data collection. Their blood lead levels (BLLs) were measured. ERPs were recorded from Ag/AgCI electrodes using the ECI Electro-Cap System (Electro-Cap International) with International 10-20 placement sites using Biopac hardware and software in a NIEHS funded psychophysiology Lab in Jintan Hospital in China. A standard auditory oddball task (constituted by novel, target and non-target auditory stimuli) was used to generate P300 after stimulus presentation. The P300 amplitude and latency were recorded. Results: The mean BLL in this sample was 3.16ng/dl (SD=1.17). Compared to those with BLLs lower than the mean level, children with BLLs higher than the mean had prolonged P300 latency to novel stimuli (P = 44.45, robust s.e.=19.41, p=0.02) after adjusting children's sex and paternal education levels. Conclusion: In this population based community sample of Chinese children, BLL with mean level 149 ------- 3.16|J.g/dI is associated with impaired capacity during processing of novel stimuli indicating impaired cognitive function. The results provide important implications that early detection and intervention of lead exposure in childhood are warranted to prevent cognitive deficits. 150 ------- 2015 NIEHS/EPA Children's Centers Annual Meeting October 29-30, 2015 Appendix D - Participant List Margaret Adgent NIEHS Hayley Aja U.S. EPA/NCER Emanuel Alcala California State University, Fresno/Central Valley Health Policy Institute Cecilia Alcala U.S. EPA/NCEA Kathleen A. Alexander Virginia Polytechnic Institute and State University Laura Anderko Georgetown University Daniel Axelrad U.S. EPA/NCEE Claire Barnett Healthy Schools Network Carl Baum PEHSU West Britni Belcher University of Southern California Martha Berger U.S. EPA/OCHP Cassie Bernardi American Academy of Pediatrics Linda Birnbaum NIEHS Susan Blaine ICF International Maggie Brevile U.S. EPA/NCER Pat Breysse ATSDR/CDC Charlotte Brody BlueGreen Alliance Rebecca Bruhl Baylor College of Medicine Susan Buchanan University of Illinois at Chicago Michele Burgess U.S. EPA/OSWER/OSRTI Tom Burke U.S. EPA/ORD Trisha Calabrese American Academy of Pediatrics Rich Callan U.S. EPA/NCER Ryan Canavan Georgetown University John Capitman Central Valley Health Policy Institute/California State University, Fresno Gustavo Carlo University of Missouri Zehang Chen University of Pennsylvania Gail Christopher W.K. Kellogg Foundation Elaine Cohen Hubal U.S. EPA/CSS Diana Conway 151 ------- Jose Cordero University of Georgia Sadie Costello University of California, Berkeley Kathy Cottingham Dartmouth College Sally Darney NIEHS Diane DArrigo NIRS Matthew Davis U.S. EPA/OCHP Alexandra Davis University of Missouri Natasha DeJarnett American Public Health Association Carrie Dickenson American College of Medical Toxicology Greg Diette Johns Hopkins University Brett Doherty UNC Chapel Hill Dana Dolinoy University of Michigan Brenda Doroski U.S. EPA/ORD Christie Drew NIEHS/DERT Rebecca Dzubow U.S. EPA/OCHP Stephanie Engel UNC Chapel Hill Ruth Etzel U.S. EPA/OCHP Sandy Evalenko U.S. EPA David Evans Columbia University Elaine Faustman University of Washington Robert Felix MotherToBaby/Organization of Teratology Information Specialist Timothy Fennell RTI International Barbara Fiese University of Illinois at Urbana-Champaign Michael Firestone U.S. EPA/OCHP Cindy Folkers Beyond Nuclear Stella Fonkeng University of Maryland Brenda Foos U.S. EPA/OCHP Erica Forrest Children's Mercy Hospital Mai da Galvez Mount Sinai Hospital Mary Gant NIEHS Laura Geer SUNY Downstate Andrew Geller U.S. EPA/SHC Heidi Gerbracht Bright Cities Lisa Gilmore The Cadmus Group, Inc. Gary Ginsberg Connecticut Department of Public Health AM Goldstone ICF International 152 ------- Robert Gould University of California, San Francisco Natalie Grant HHS Kimberly Gray NIEHS Rachael Greenberg National Nursing Centers Consortium Peter Grevatt U.S. EPA/OGWDW Virginia Guidry NIEHS Office of Communications Intaek Hahn U.S. EPA Katharine Hammond University of California, Berkeley Michael Hatcher ATSDR/CDC Marissa Hauptman Region 1 New England PEHSU/Boston Children's Hospital Julie Herbstman Columbia University Irva Hertz-Picciotto University of California, Davis Jane Houlihan Healthy Babies Bright Futures Valerie Hu The George Washington University Katie Huff ling Alliance of Nurses for Healthy Environments Luz Huntington Moskos University of Louisville Anna Jeng Old Dominion University Jill Johnston University of Southern California Dean Jones Emory University Elizabeth Kamai UNC Chapel Hill Catherine Karr University of Washington Kevin Kennedy Children's Mercy Hospital Jina Kim ASPPH Fellow at U.S. EPA Sue Kirdly Cohen Children's Hospital Andrea Kirk U.S. EPA/OSWER Katherine Kirkland Association of Occupational and Environmental Clinics Kristen Kocher The George Washington University Brenda Koester University of Illinois at Urbana-Champaign Susan Korrick Brigham and Women's Hospital/Harvard Medical School Kim Lambert U.S. Fish and Wildlife Service Bruce Lanphear Simon Fraser University Patricia Las ley University of Illinois at Chicago Christopher Lau U.S. EPA/ORD/NHEERL/TAD Nancy LaVerda The George Washington University 153 ------- Cindy Lawler NIEHS Pamela Lein University of California, Davis Victoria Leonard University of California, San Francisco Edward Levin Duke University De-Kun Li Kaiser Permanente Sylvana Li U.S. EPA/NCER Yuli Li University of Pennsylvania Chung-Ho Lin University of Missouri Jianghong Liu University of Pennsylvania Rachel Locke Children's Environmental Health Network Nica Louie U.S. EPA/NCER Jennifer Lowry Children's Mercy Hospital Michael Lu HHS/HRSA Sara Lundgren Dartmouth College Michelle Mabson ORISE Fellow at U.S. EPA Jaime Madrigano RAND Corporation Chikezie Maduka University of Maryland Maureen Malloy ICF International Jennifer Mann Berkeley/Stanford CEHC Linda McCauley Emory University Rob McConnell University of Southern California Meredith McCormack Johns Hopkins University Amy McCune 4-H National Headquarters/USDA Leyla McCurdy Health and Environment Consulting Shawn McElmurry Wayne State University Cynthia Mcoliver U.S. EPA/NCER John Meeker University of Michigan Suril Mehta U.S. EPA/OCHP Jacquelyn Menghrajani U.S. EPA/OCHP Catherine Metayer University of California, Berkeley Gregory Miller U.S. EPA/OCHP Mark Miller Western States PEHSU (at UCSF)/CIRCLE/Cal EPA Lindsey Mitchell University of Michigan Stormy Monks Texas Tech University Health Science Center El Paso Meghan Moynihan University of Michigan 154 ------- Susan Murphy Duke University Carolyn Murray Dartmouth College Nathan Mutic Emory University Kari Nadeau Stanford University Olga Naidenko AAAS Science and Technology Policy Fellow Chris Nidel Nidel Law PLLC Bridget O'Brien U.S. EPA/OSWER Barbara O'Brien Westat Liam O'Fallon NIEHS Rebecca Ofrane U.S. EPA Region 2 Kim Osborn ICF International Thomas Palys Dartmouth College Mili Pate I HHS/ASPR Laura Paulin Johns Hopkins University Emma Pennea Mid-Atlantic Center for Children's Health 6t the Environment Frederica Perera Columbia University Bradley Peterson Children's Hospital Los Angeles/University of Southern California Karen Peterson University of Michigan Anna Pollack George Mason Unviersity Lesliam Quiros-Alcala University of Maryland, College Park Stephen Rappaport University of California, Berkeley Chris Rea ORISE Fellow at U.S. EPA Khesha Reed U.S. EPA/OCHP Linda Reese-Smith Rebecca Rehr Maryland Environmental Health Network Joshua Robinson University of California, San Francisco John Rogers U.S. EPA/ORD/NHEERL Melissa Rose University of California, Davis Angana Roy The Cadmus Group, Inc. Leslie Rubin Morehouse School of Medicine/Emory University Sheela Sathyanarayana University of Washington/Seattle Children's Research Institute Susan Schantz University of Illinois Racquel Segall BlueGreen Alliance Perry Sheffield Mount Sinai Hospital 155 ------- Chris Sibrizzi ICF International Brianna Sleezer Children's Environmental Health Network Meghan Smith Maryland Department of Health 6t Mental Hygiene Agnes Soares da Silva WHO/PAHO Shaina Stacy Brown University School of Public Health Tenya Steele Center for Environmental Health Tracy Stewart Rita Strakovsky University of Illinois William Suk NIEHS Patrice Sutton University of California, San Francisco Maureen Swanson Learning Disabilities Association of America Allison Sylvetsky George Washington University Siobhan Tarver U.S. EPA Laura Thomas ICF International Claudia Thompson NIEHS Caitlin Tompkins Georgetown University Kate Topalis Mid-Atlantic Center for Children's Health 6t the Environment Leonardo Trasande New York University Kristie Trousdale Children's Environmental Health Network Maria Valenti Collaborative on Health and Environment Judy Van de Water University of California, Davis Lisa Vasquez HHS/HRSA Prentiss Ward U.S. EPA Region 3 Deborah Watkins University of Michigan Paul Wax American College of Medical Toxicology Lois Wessel Georgetown University Todd Whitehead University of California, Berkeley Joseph Wiemels University of California, San Francisco Nsedu Witherspoon Children's Environmental Health Network Tracey Woodruff University of California, San Francisco Alan Woo If Boston Children's Hospital Katherine Worden ICF International Rosalind Wright Mount Sinai Hospital Bowen Yao University of Pennsylvania Mahsa Yazdy Harvard University 156 ------- Zhenzhen Zhang University of Michigan Marya Zlatnik University of California, San Francisco Ami Zota George Washington University David Zucker Healthy Babies Bright Futures 157 ------- |