oEPA
United States
tnviror menial Protection
Agency
2017 Annual Meeting Proceedings
NIEHS/EPA Children's
Environmental Health and Disease
Prevention Research Centers:
Protecting Children's Health for a Lifetime
U.S. Environmental Protection Agency | National Institute of Environmental Health Sciences
San Francisco, CA | October 24-25, 2017
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National Institute of Environmental Health Sciences
Your Environment. Your Health.
PEHSU
Pediatric Environmental
Health Specialty Units-
Disclaimer
This document has been reviewed in accordance with U.S. Environmental Protection Agency (EPA) policy
and approved for publication. The National Center for Environmental Research, Office of Research and
Development was responsible for the preparation of this meeting report. The document provides the
abstracts, posters, and presentation slides from the 2017 Annual Meeting of the Children's Environmental
Health and Disease Prevention Research Centers (Children's Centers). This program is jointly funded by
the EPA under the Science to Achieve Results (STAR) grants program and the National Institute of
Environmental Health Sciences. This report is not a complete record of all details discussed. Statements
represent the individual views of meeting 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 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.
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Contents
Day 1 - Tuesday, October 24, 2017 1
Conference Overview and Welcoming Remarks 1
Quick Connections 1
Progress Review 2
Progress Review Part I 2
Progress Review Part II 5
Progress Review Part III 9
Day 2 - Wednesday, October 25, 2017 14
Lightning Talks 14
Tools Targeted to Pregnant Women and Parents 14
Tools Targeted to Children and Adolescents 16
Tools Targeted to Professionals 17
Science Sessions 19
Obesity 19
Cumulative Exposures and Stress 20
Immune Function and the Microbiome 21
Keynote 23
Appendices 25
Appendix A - List of Children's Centers A-l
Appendix B - Meeting Agenda B-l
Appendix C - List of Steering Committee Members C-l
Appendix D - List of Participants D-l
Appendix E - Progress Update Poster Presentations E-l
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Proceedings from the 2017 Annual Meeting of the
NIEHS/EPA Children's Environmental Health and
Disease Prevention Centers Annual Meeting
Day 1 - Tuesday, October 24,2017
^umererice Overview and Welcoming Remarks
- Nica Louie, M.S. | Project Officer, Office of Research and Development (ORD), U.S. Environmental
Protection Agency (EPA)
- Kimberly Gray, Ph.D. | Health Science Administrator, National Institutes for Environmental Health
Sciences (NIEHS)
- Alexis Strauss, M.A. | Acting Regional Administrator, EPA Region 9
- Claudia Thompson, Ph.D. | Branch Chief, NIEHS
- Elaine Cohen Hubal, Ph.D., M.S. | ORD, EPA
The 2017 Annual Meeting of the NIEHS/EPA Children's Environmental Health and Disease Prevention
Research Centers was hosted by EPA in collaboration with NIEHS and the Pediatric Environmental Health
Specialty Units (PEHSUs). Ms. Nica Louie (EPA) welcomed participants to the meeting held at the EPA
Region 9 offices in San Francisco. She thanked EPA Region 9 for accommodating the meeting and Ms.
Jacquelyn Menghrajani (EPA Region 9) for her tremendous help during the planning process. Ms. Louie
expressed appreciation to the conference steering committee for their efforts in preparing an inclusive
and collaborative conference agenda to foster partnership.
Ms. Alexis Strauss, Acting Regional Administrator of EPA Region 9, welcomed the participants to the EPA
Region 9 facilities and stated how excited she is that the Children's Centers have convened on the West
Coast which has been home to several Children's Centers. Following Ms. Strauss were Dr. Claudia
Thompson (NIEHS) and Dr. Elaine Cohen Hubal (EPA), representing leadership from NIEHS and EPA, who
discussed how the Children's Centers support the missions of both agencies and the importance of
protecting the health of the next generation. Dr. Kimberly Gray (NIEHS) then addressed the participants,
setting the stage and expectations for the two-day meeting. Please see Appendix A for a list of the
Children's Centers, Appendix B for the meeting agenda, Appendix C for a list of steering committee
members, and Appendix D for a list of meeting participants.
Quick Connections
The Quick Connections session provided meeting participants with an opportunity to meet and identify
new potential collaborators. Through a series of short conversations, participants were able to share their
work and what makes them passionate about children's environmental health. An open networking
session replaced the afternoon Quick Connections session to facilitate longer, more in-depth
conversations about collaboration.
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Progress Review
The meeting then transitioned to the Progress Review sessions, where the centers and PEHSUs were
prompted to present posters with the most compelling research finding they have made in the past two
years. The progress review poster session was broken into three parts, with five to seven posters being
presented simultaneously throughout the conference space during each part. Meeting participants
rotated between posters in groups of approximately 15 to 20, listening to short presentations and
engaging in small group discussions. Copies of the posters have been provided in Appendix E. Due to
concerns about unpublished data, presentations marked with an asterisk have not been included in the
appendix.
Progress Review Part I
The first Progress Review session included five poster presentations. Abstracts submitted by the centers
for these posters have been provided below. These abstracts and posters reflect the individual views of
meeting participants and centers, none of the statements represent analyses by or positions of EPA.
(1) Columbia University | Longitudinal Effects of Prenatal Exposure to Polycyclic Aromatic
Hydrocarbons on Mental, Behavioral, and Emotional Disorders as well as Obesity in Adolescence
| Frederica Perera, Ph.D., Dr. P.H., Virginia Rauh, Sc.D.
(2) Dartmouth College | Should Rice Cereal be an Infant's First Food? | Carolyn Murray, M.D., M.P.H.
(3) Duke University | Exposure to Tobacco Smoke During Pregnancy - and Even During
Preconception - Can Alter Baby's Brain Function | Susan Murphy, Ph.D.
(4) Emory University | African American Women in Metro Atlanta Have Higher Levels of Endocrine
Disrupting Plasticizers in Their Bodies Than Other African American Women | P. Barry Ryan, Ph.D., M.S.
(5) Johns Hopkins University | Obesity and Diet as Susceptibility Factors to Air Pollution Exposure |
Nadia Hansel, M.D.
TITLE: Longitudinal Effects of Prenatal Exposure to Polycyclic Aromatic Hydrocarbons on Mental,
Behavioral, and Emotional Disorders as well as Obesity in Adolescence
BACKGROUND: The Columbia University Children's Center is testing the hypothesis that prenatal and early
childhood exposures to polycyclic aromatic hydrocarbons (PAHs) disrupt development and maturation of
neural systems that support self-regulatory systems in the brain; and these disturbances create
vulnerabilities that lead to mental, behavioral, emotional disorders as well as obesity in adolescence.
SPECIFIC AIMS: Specific aims are to test whether: (1) Elevated prenatal PAH exposure is associated with
adverse effects on self-regulatory processes, clinical symptoms, and distinctive adverse developmental
trajectories from early childhood through ages 15 to 17 years; (2) Maternal exposure to higher
concentrations of airborne PAH during pregnancy is associated with distinct growth trajectories of body
mass index growth and fat mass index and greater adiposity, higher hedonic eating behavior, sedentary
pursuits, and poorer neuropsychological function at ages 15 to 17 years; and (3) Early PAH exposure
adversely affects the structure, function, and metabolism of neural systems known to support the capacity
for self-regulation at ages 9 to 12 years, and subsequently, these PAH-related disturbances mediate the
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emergence of conduct disturbance, substance use, depression, symptoms of attention deficit hyperactivity
disorder (ADHD), and adiposity measures through adolescence at ages 15 to 17 years.
KEY RESEARCH FINDINGS: We detected a significant interaction (p = 0.05) between PAH-DNA adducts in
maternal blood collected at delivery with time, in which the developmental trajectory of self-regulatory
capacity was delayed in the exposed children. Multiple linear regression revealed a positive association
between the presence of PAH-DNA adducts and problems with social competence (p < 0.04), level of
dysregulation and problems with social competence (p < 0.0001), and evidence that self-regulation
mediates the association of prenatal exposure to PAH with social competence (p < 0.0007).
PRELIMINARY FINDINGS TO BE EXPANDED: Co-exposure to socioeconomic disadvantage (lack of adequate
food, housing, utilities, and clothing) and prenatal PAH significantly increases the risk of ADHD behavior
problems, particularly high PAH and persistent hardship. Previously we have reported associations
between prenatal exposure to PAH and anatomical changes in children's brains when imaged by magnetic
resonance imaging (MRI) at ages 7 to 9 years. Follow-up MRI data at ages 9 to 12 years are currently
being analyzed.
CHALLENGES: Initially, researchers experienced delays in participant recruitment and the rate of
assessment due to the need to refine the MRI protocol for imaging the brain and abdomen in the same
MRI visit, but by scheduling more visits during the summer months and weekends, they are on target to
achieve their goals.
TITLE: Should Rice Cereal be an Infant's First Food?
SPECIFIC AIMS: The primary aims of the Dartmouth College Children's Center are to identify
environmental exposures to common contaminants such as arsenic during fetal development and
childhood; and the impact these exposures have on childhood immunity, growth, and neurological
development.
KEY RESEARCH FINDINGS: Maternal dietary exposure through rice consumption results in fetal exposure
and may impact risk of later disease risk, in particular, growth, immune-related, gene expression and
epigenetic outcomes. In addition to detecting arsenic in rice products, including those targeted to
infants, we reported that infants commonly consume these products in the first year of life.
PRELIMINARY FINDINGS TO BE EXPANDED: New results from work of our center's Community Outreach
and Translation Core (COTC) indicate that women who receive results of elevated well water arsenic
levels report less use of their tap water for drinking, cooking, and for mixing infant formula than women
who received reports of low or no arsenic.
CHALLENGES: Effectively communicating our findings about arsenic in food and water to relevant
stakeholders presented challenges, particularly as we sought to avoid unintended consequences, such as
inappropriate dietary changes. To address this challenge, we held focus groups with study participants,
produced web-tools, met with federal agencies and congressional offices, organized an interdisciplinary
collaborative, and published scientific reports to reach both the scientific and medical community to
inform ways to reduce children's exposure.
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TITLE: Exposure to Tobacco During Pregnancy-and Even Preconception-Can Alter Offspring's Brain Function
KEY RESEARCH FINDINGS: Exposures to toxic chemicals like those contained in tobacco smoke during early
life can lead to permanent changes in the programming of gene activity. The specific window(s) of
development during which such programming in the brain is most vulnerable to exposure has not been
clearly defined. Female rats were surgically fitted with osmotic mini pumps designed to deliver a defined
low-level dose of vehicle-only or tobacco smoke extract during three time intervals before and during
gestation, encompassing pre-mating (with termination of exposure prior to mating), early or late
gestation. Results showed that the most pronounced reprogramming of neuronal functions was from
exposure that occurred during late gestation. Remarkably however, pre-mating exposure also had
pronounced effects on neuronal functions. These results show that there is no time interval before or
during pregnancy during which tobacco smoke exposure is safe, and that cessation of exposure once
pregnancy is established may be too late to prevent detrimental effects. These findings may additionally
have substantial implications for the offspring born to women of childbearing age who are exposed to
tobacco smoke even prior to conception.
TITLE: American Women in Metro Atlanta Have Higher Levels of Endocrine Disrupting Plasticizers in Their
Bodies Than Other African American Women
SPECIFIC AIMS: The Emory University Children's Center is a multi-component investigation designed to
evaluate environmental exposures influencing the infant microbiome and leading to neurodevelopmental
sequelae in a population of African-American mothers in metropolitan Atlanta.
METHODS: In the first phase, we have collected environmental and biological data on toxicant exposures
from samples collected at prenatal and home visits. C-CHEM2's first project, Characterizing Exposures in
an Urban Environment (CHERUB), is designed to validate protocols for office and field sampling and
determine the relationship between environmental media concentrations and biomarkers relevant to the
microbiome of infants. Environmental and biological samples are taken from mothers during pregnancy
and in-home environmental samples, prior to delivery. These samples will be analyzed for: bisphenol A
(BPA), phthalates, parabens, alkylphenols, organophosphate insecticides, pyrethroid insecticides, air
pollutants (PAHs), and brominated flame retardants or appropriate metabolites
KEY RESEARCH FINDINGS: Presently, researchers have collected 212 first hospital visit and 126 second
hospital visit urine samples from expectant mothers and followed that with home visits gathering 101
urine samples, 108 serum samples, 101 prenatal home dust samples, 55 postnatal home dust samples, 25
home air samples. In addition, researchers have collected 42 urine samples from babies 1 week old, 28
from babies 3 months old, 14 urine samples from babies 6 months old, and 1 sample from a baby 12
months old. Analysis has been completed for urinary BPA and phthalates, and this data is reported on
here. Further, recruitment continues with an ultimate target of 300 participating women and
approximately 100 individual homes each monitored several times. Currently researchers have completed
approximately one-third of the projected first home visits and started second home visits on early
recruits.
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CONCLUSIONS: Results for BPA and phthalate metabolites indicate that the study population shows
concentrations higher than the national average as measured in NHANES investigations and higher than
the African-American sub-population from the same investigations. Analysis continues correlating results
from other measures on environmental exposure and biomarkers of such exposure.
TITLE: Obesity and Diet as Susceptibility Factors to Air Pollution Exposure
SPECIFIC AIMS: The Johns Flopkins University Children's Center is currently investigating the role of
obesity as a determinant of susceptibly to air pollution among children with asthma. This is a key step in
achieving the Center's overall goal of developing strategies to reduce asthma morbidity by modifying
indoor allergen and pollutant exposures.
KEY RESEARCH FINDINGS: Recent findings that children who are overweight and obese have increased
asthma symptoms in response to secondhand smoke compared to normal weight children builds on the
evidence that has been reported by the Center investigators. Obesity is often linked to diet, comorbidities
and physical activity thus there are challenges to understanding the different pathways by which obesity
may lead to susceptibility. Recent findings of the Center also suggest fatty acid intake may modify
susceptibility to indoor air pollution. Furthermore, the high prevalence of obstructive sleep apnea among
our children suggests that sleep disordered breathing may be an important consideration as the Center
aims to better understand the complex interactions between obesity and pollution susceptibility. The
Center's work with low-income children with asthma in Baltimore City reveals the environmental
challenges faced by families in real-world settings that must be overcome to improve health disparities.
Progress Review Part II
The second Progress Review session included six poster presentations. Abstracts submitted by the
centers for these posters have been provided below. These abstracts and posters reflect the individual
views of meeting participants and centers, none of the statements represent analyses by or positions of
EPA.
(6) Northeastern University | Exposure to Triclosan in Pregnancy is Associated with Increased
Inflammation | Akram Alshawabkeh, Ph.D., John Meeker, Sc.D.
(7) University of California, Berkeley (CERCH) * | Mixtures of Pesticides Used near Homes During
Pregnancy Associated with Decreased 10 in Children | Kim Harley, Ph.D.
(8) University of California, Berkeley (CIRCLE) | Toxic PCBs Still Harming Children, Despite Long-Time
Ban | Todd Whitehead, Ph.D.
(9) University of California, Berkeley/Stanford University | Ambient Air Pollution Impairs Immune
Function, which Impacts Allergy and Asthma | S. Katharine Hammond, Ph.D.
(10) University of California, Davis | Neonatal Cytokine Profiles Associated with Autism Spectrum
Disorder] Judy Van de Water, Ph.D.
(11) PEHSU Region 2* | Effectively Integrate Environmental Health into Clinical Practice | Perry
Sheffield, M.D.
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TITLE: Exposure to Triclosan in Pregnancy is Associated with increased Inflammation
SPECIFIC AIMS: The Northeastern University Children's Center studies the impact of a mixture of
environmental exposures and modifying factors on fetal and early childhood health and development in
the children of the heavily-contaminated northern coast of Puerto Rico - an underserved, highly-exposed,
and low-income population with significant health disparities. CRECE has developed an innovative and
scientifically distinct program that leverages the ongoing cohort study of the PROTECT NIEHS Superfund
Research Center. CRECE is following-up 600 infants born to the PROTECT cohort, for whom a rich prenatal
dataset and biological samples already exist, following them from birth to age four. CRECE is (1) capturing
the impacts of pollutant exposures that occur through multiple exposure routes and biological pathways
on fetal and early childhood health and development, (2) evaluating how psychosocial risk factors (e.g.
socioeconomic status and maternal stress) may modify these effects, and (3) elucidating biological
mechanisms that may explain mechanistic pathways and mediate these relationships.
KEY RESEARCH FINDINGS: Urinary concentrations of triclosan (TCS) in urine samples collected from the
study participants were higher than among women of reproductive age in the US general population,
with positive associations between TCS concentrations with self-reported use of liquid soap. Further,
findings suggest that exposure to TCS during pregnancy may be related to inflammation, which may
influence birth outcomes and other adverse health effects. These TCS findings are timely for aiding in
preventive public health policy and practice. In September 2017, the U.S. Food and Drug Administration
announced it was prohibiting chemicals, including triclosan, triclocarban, and 17 other chemical
ingredients, in products such as hand soaps and toothpaste.
PRELIMINARY FINDINGS TO BE EXPANDED: In the Center's preliminary data, the Pis have reported
evidence for increased exposures to several phenols compared to women of reproductive age from the
NHANES study. We have also investigated preliminary associations between maternal urinary
concentrations of phenols/para bens and biomarkers of intermediate effect during pregnancy, and found
a significant positive association between TCS and IL-6 (a pro-inflammatory cytokine), significant
associations between numerous phenols/para bens and increased levels of the oxidative stress marker 8-
isoprostane, and several associations between phenols or parabens and altered reproductive or thyroid
hormone levels. CRECE is also examining the association between air pollutant exposures and
development in a cohort of young children living in Puerto Rico, whom they will follow from gestation
through age four. CRECE does so using traditional measures of adverse birth outcomes and development,
such as preterm birth and respiratory and neurodevelopmental evaluations, and using novel
measurements of non-nutritive suck, an established measure of newborn central nervous system
function that has not yet been used to assess neonatal development in environmental epidemiological
studies. By linking these health measures to air pollution exposures, in utero chemical exposures, and
maternal and child characteristics for each child, the Center will examine whether ambient pollution
exposure alters the developing brain, a susceptible organ that is difficult to access in a clinical evaluation.
CFIALLENGES: The implications of Hurricane Maria and staff supporting recovery efforts.
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H EAD LI N ETITLE: Mixtures of Pesticides Used near Homes During Pregnancy Associated with Decreased IQin
Children
SPECIFIC AIMS:
1) To determine whether prenatal exposure to organophosphate pesticides (OPs) and pesticide mixtures
is associated with:
a) Behavior (externalizing and risk-taking behaviors, school failure, delinquency) at age 18 years;
b) Brain function (NIH toolbox, functional near infrared spectroscopy (fNIRS)) at age 18 years;
c) Body mass index (BMI) and metabolic conditions (hypertension, diabetes, fatty liver) at ages 18
and 21 years;
d) Respiratory illness and lung function at ages 18 and 21 years;
2)To determine whether these associations are modified by poorer cognition/attention, or by early life
adversities or protective factors.
3)To determine the contribution of early adversity on the emergence of risk-taking behavior and early puberty.
4)To determine the relationship between paraben and phenol exposure on obesity and metabolic
syndrome, biomarkers of oxidative stress, puberty timing, thyroid function, and lung function.
5)To determine the relationship between phthalate exposure and neurodevelopment, obesity and
metabolic syndrome, biomarkers of oxidative stress, puberty timing, thyroid function, lung function, and
epigenetic changes in blood.
KEY RESEARCH FINDINGS: CERCH has used California's Pesticide Use Reporting (PUR) system to confirm
the associations of in utero organophosphate pesticide exposure with child neurodevelopment that was
observed using urinary dialkyl phosphate (DAP) metabolites, this time using residential proximity to
agricultural pesticide use. This methodology allows researchers to examine other neurotoxic pesticides
besides OPs and also to examine mixtures of many pesticides that are used simultaneously in agriculture.
They observed a decrease of 2.2 points [95% confidence interval (CI): -3.9, -0.5] in Full-Scale IQ and 2.9
points (95% CI: -4.4, -1.3) in Verbal Comprehension for each standard deviation increase in toxicity-
weighted use of organophosphate pesticides, and similar decrements in Full-Scale IQ at 7-years of age
with each standard deviation increase of prenatal use of two organophosphates and three other
neurotoxic pesticide groups. Using Bayesian profile regression, CERCH researchers examined associations
between clustered neurotoxic pesticide use profiles and childhood Full-Scale IQ. Two of the eight distinct
pesticide profile clusters exhibited some of the highest cumulative neurotoxic pesticide use levels and
were associated with deficits in adjusted Full-Scale IQ of -6.9 (95% credible interval: -11.3, -2.2) and -6.4
(95% credible interval: -13.1, 0.49), respectively, when compared with the pesticide profile cluster that
showed the lowest level of pesticides use. CERCH also found that residential proximity to OP and
carbamate pesticide use during pregnancy and both household- and neighborhood-level poverty during
childhood were independently associated with poorer cognitive functioning in children at 10 years of age
and that the previously observed adverse associations between DAP concentrations and IQ were stronger
in children experiencing greater early childhood adversity.
PRELIMINARY FINDINGS TO BE EXPANDED: Prenatal urinary concentrations of chemicals used in personal
care products (specifically monoethyl phthalate (MEP) and triclosan) are associated with earlier puberty
in girls. CERCH researchers found that each doubling of maternal urinary concentrations of triclosan
during pregnancy was associated with a 0.6 month earlier shift in age at menarche. Each doubling of MEP
metabolites in maternal urine during pregnancy was associated with a 1.2 month earlier shift in pubic hair
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development. Models controlled for family income, mother's education, mother's years of residence in
US, and mother's diet quality index in pregnancy.
TITLE: Toxic PCBs Still Harming Children
BACKGROUND: The University of California, Berkeley CIRCLE Children's Center been invested in measuring
children's exposure to polychlorinated biphenyls (PCBs) and assessing the impact of these exposures.
KEY RESEARCH FINDINGS: Despite being banned for several decades, PCBs are still readily detected in the
settled dust of California homes and in the blood of children who live there. Furthermore, CIRCLE
researchers have observed associations between the levels of PCBs in the dust of a child's home and
his/her risk of childhood leukemia.
PRELIMINARY FINDINGS TO BE EXPANDED: In the current cycle, the Center is working to identify the
mechanisms responsible for the observed association between PCB exposure and increased leukemia
risk. Researchers are investigating the relationship between PCB contamination and levels of the
immunomodulatory cytokine, IL-10, at birth - as a marker of abnormal fetal immune development.
CIRCLE researchers are also looking at how PCB contamination in homes might be related to changes in
DNA methylation. Finally, CIRCLE is using a mouse model of childhood leukemia to observe changes in
cytokine levels and DNA methylation after controlled exposure to a mixture of PCBs in utero, to further
elucidate the potential biological mechanisms at play.
TITLE: Ambient Air Pollution Impairs Immune Function, which Impacts Allergy and Asthma
KEY RESEARCH FINDINGS: In earlier work, CHAPS researchers showed that exposure to ambient air
pollution was associated with hypermethylation of the forkhead box protein 3 (FOXP3) locus, impairing
regulatory T-cell (Treg) function and increasing risk of asthma morbidity. In a later follow-up study with a
larger sample size, CHAPS researchers showed that exposure to ambient PAHs in Fresno, CA was
significantly associated with impaired Treg function, increased methylation of FOXP3, and differential
expression of the FOXP3 protein, especially in children with allergies. Methylation was associated with
Treg dysfunction and an increase in total plasma immunoglobulin E (IgE) levels. These findings were
supported by those of another group that reported FOXP3 hypermethylation was associated with diesel
exhaust exposure and risk for childhood asthma. CHAPS researchers have also shown that ambient PAH
exposure is associated with increased respiratory symptoms in children with asthma as well as lower lung
function in children without asthma in Fresno. In addition to exposure to PAHs, CHAPS researchers have
recently shown that short-term and long-term exposures to high levels of carbon monoxide (CO),
nitrogen dioxide (N02), and fine particulate matter (PM2.5) were associated with alterations in CpG site
methylation of FOXP3 and interleukin 10 (IL-10). Collectively, these results demonstrate that increased
exposure to traffic-related air pollution is associated with impaired systemic immunity and epigenetic
modifications in a key locus involved in allergy: FOXP3, with a higher impact on allergic children. The
results suggest that increased exposure to air pollution are linked to increased allergic and asthmatic
symptoms in children.
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TITLE: Neonatal Cytokine Profiles Associated with Autism Spectrum Disorder
SPECIFIC AIMS:
• Leverage the vast research resources generated by the retrospective case-control study, Childhood
Autism Risk from Genes and Environment (CHARGE Study) and the prospective cohort study,
Markers of Autism Risk in Babies-Learning Early Signs (MARBLES Study).
• Build upon our novel 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.
• Develop and apply new biomarkers of autism risk, through analysis of gestational and neonatal
immune dysfunction, genetic susceptibility, and environmental exposures, to best characterize the
potential health effects at various life stages and predict longer-term clinical and behavioral consequences.
CHALLENGES: A challenge was to produce human iPSC-derived neurons with mature phenotypes in a
consistent and robust manner. The Center's response was to develop alternative human cell-based
modes: (1) LUHMES neuronal cell line; (2) differentiation of human epidermal neural crest cells into
neurons.
The Mount Sinai P30 Community Engagement Core (CEC) along with the Region 2 PEHSU has partnered
with the University of Cincinnati P30 CEC and Region 5 PEHSU at Cincinnati Children's Hospital to more
effectively integrate environmental health into clinical practice, using a P30 supplement from NIEHS. This
project incorporates environmental health education into electronic health records and web platforms
which will allow clinicians to: (1) educate, counsel and refer families using evidence-based outreach and
education from local, state and federal agencies including NIEHS CECs as well as the PEHSU national
network, and (2) connect families to needed environmental health services to prevent and reduce
common environmental exposures in the home. Our diverse expert panel includes 4 CECs and 4 PEHSUs
across federal Regions 1,2,3 and 5 (Harvard/Boston Children's, University of Rochester, WEACT, University
of Pennsylvania, Georgetown School of Nursing).
Progress Review Part III
The third Progress Review session included six poster presentations. Abstracts submitted by the centers
for these posters have been provided below. These abstracts and posters reflect the individual views of
meeting participants and centers, none of the statements represent analyses by or positions of EPA.
(12) University of California, San Francisco | Flame Retardants Linked to Lower Child IQ | Tracey
Woodruff, Ph.D., M.P.H.
(13) University of Illinois* | Through the Window of a Baby's Eyes | Susan Schantz, Ph.D.
(14) University of Michigan* | A Tale of Environmental Deflection in Mice and Humans: Toxicant
Exposures and Lifestyle Factors Influence the Rate of Epigenetic Aging | Jaclyn Goodrich, Ph.D.
(15) University of Southern California | Does Air Pollution Cause Childhood Obesity and Increase the
Risk of Diabetes? | Rob Scot McConnell, M.D.
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(16) University of Washington | Longitudinal Exposome Research Reveals Exposure of Agricultural
Families to Over 86 Pesticides, 47 of Which May Impact Neurodevelopment in Young Children |
Elaine Faustman, Ph.D.
(17) PEHSU Region 9 | A Story of Health Multimedia eBook Improves Environmental Health Literacy of
Thousands of Health Professionals | Mark Miller, M.D.
TITLE: Flame Retardants Linked to Lower Child IQ
BACKGROUND: The University of California, San Francisco Children's Center evaluates chemical exposures
during pregnancy and the links to development, whether health effects are enhanced by exposure to
chronic psychosocial stress, and the role of the placenta as an etiologic pathway. The PEEC Center uses
their findings along with those from other Children's Centers to inform the public, clinicians, and policy
decision makers about the science and best approaches to reduce harmful chemical exposures across the
population.
KEY RESEARCH FINDINGS: One of the Center's recent research findings uses systematic review methods,
developed by this program, to conclude that there is sufficient evidence supporting an association
between prenatal exposure to polybrominated diphenyl ether (PBDE) flame retardants and lower child IQ.
A recent report by the National Academies of Sciences endorsed the study and integrated evidence from
animal studies to reach similar conclusions that PBDEs are a "presumed hazard" to intelligence in
humans. As part of the center's aims, researchers will continue to explore and publish data, information,
and resources about exposures in our population, including PDBEs and other chemical exposure, and
what that means for our reproductive health and future.
TITLE: Through the Window of a Baby's Eyes
KEY RESEARCH FINDINGS: The Illinois Children's Center uses a unique approach to assess cognitive
function very early in development. The center is studying the impact of various maternal factors on
infant cognition. These include maternal obesity and prenatal stress, as well as prenatal exposures to a
variety of endocrine disrupting chemicals. Our approach uses infrared eye tracking to record the looking
behavior of infants as they study stimuli and videos displayed on a large-screen high-definition TV. Recent
findings suggest that maternal prenatal stress adversely impacts physical reasoning in 4-month old female
infants, and that higher prenatal bisphenol F (BPF) exposure is associated with poorer visual recognition
memory in 7-month old infants.
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TITLE: A Tale of Environmental Deflection in Mice and Humans: Toxicant Exposures and Lifestyle Factors
Influence the Rate of Epigenetic Aging
BACKGROUND: The overall goals of the University of Michigan Children's Center are to determine
whether in utero and peri-pubertal exposures to endocrine disrupting chemicals (EDCs) affect physical
growth, tempo of sexual maturation, and metabolic homeostasis, and to examine biological mechanisms
underlying these effects in rodent and human models. Epigenetics is one of the mechanisms studied
throughout the center in the agouti mouse model, the Michigan Mother-Infant Pairs (MMIP) cohort, and
the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort. The epigenome is an
alterable regulatory framework that governs the response of cells and tissues to environmental stressors.
DNA methylation is one class of epigenetic modifications that is relatively stable at many loci but known
to change across the lifespan at others. While accelerated epigenetic aging at these loci is associated with
overall mortality, obesity, cancer, and more, few studies have identified specific environmental factors
that influence the rate of change.
SPECIFIC AIMS: 1) Identify loci where DNA methylation changes over time in surrogate tissues from mice
and humans. 2) Determine whether EDC exposures and diet early in life modify the rate of epigenetic
change.
KEY RESEARCH FINDINGS: Recently, investigators published a contemporary review in Toxicological
Sciences introducing the concept of environmental deflection which encompasses toxicant- and nutrient-
mediated shifts away from the baseline rate of epigenetic aging. In the agouti mouse model, center
investigators first examined the influence of perinatal Western high fat diet or Mediterranean high fat
diet with or without concurrent BPA exposure on age-related DNA methylation change in matched tail
and blood DNA samples from 2, 4, and 10 months of age. Results, published in Reproductive Toxicology,
support environmental deflection as perinatal exposure to a Western diet modified the rate of change in
murine tail DNA methylation over time at IAP repetitive elements and Esrl.
PRELIMINARY FINDINGS TO BE EXPANDED: In the ELEMENT birth cohort, the Center is currently
investigating environmental deflection by lead, phthalates, and BPA in matched blood DNA samples from
birth, early adolescence, and late adolescence at genes related to growth and metabolic outcomes as well
as throughout the epigenome using the Infinium MethylationEPIC platform. DNA methylation analysis
was also performed in cord blood samples from the MMIP cohort along with first trimester exposure
assessment. Plans to follow-up MMIP children, funded by the NIH Environmental influences on Child
Health Outcomes (ECHO) program, will provide an opportunity to examine environmental deflection by
prenatal EDC exposures among these young children. Overall, the University of Michigan Center is at the
forefront of identifying early life environmental and lifestyle factors that deflect rates of epigenetic aging
which may ultimately contribute to adverse health outcomes in childhood, adolescence, and adulthood.
TITLE: Does Air Pollution Cause Childhood Obesity and Increase the Risk of Diabetes?
BACKGROUND: The epidemic of childhood obesity threatens the health of a generation of children
because it is a major risk factor for type 2 diabetes, non-alcoholic fatty liver disease and cardiovascular
diseases (CVD).
SPECIFIC AIMS: The University of Southern California Children's Center's integrated program of
population-based, clinical and experimental research addresses the hypothesis that air pollution
contributes to development of childhood obesity and metabolic and inflammatory abnormalities that
increase the risk of type 2 diabetes and cardiovascular disease.
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KEY RESEARCH FINDINGS: Investigators have found that near-roadway air pollution, in synergy with
secondhand tobacco smoke exposure, was associated with a trajectory of increasing BMI over the course
of adolescence. Previous year exposure to ambient PM2.5 was associated in cross-sectional analyses with
25 percent higher fasting insulin, 8.3 percent lower insulin sensitivity, 14.7 percent higher acute insulin
response to glucose and 1.7 percent higher fasting glucose (all p < 0.001) in minority children.
Associations of increased N02 and near-roadway air pollution exposure were also observed with these
outcomes. Higher levels of N02 and PM2.5 were associated with a faster decline in longitudinally collected
measures of insulin sensitivity (SI) and obesity in overweight and obese Latino children, and with a lower
SI at age 18 years. Increased N02 exposure was associated with faster decline in disposition index (Dl) and
a lower Dl at age 18, indicative of adverse effects on B-cell function. Higher levels of N02 and traffic
exposure were associated with increased levels of cytokeratin-18, a marker for hepatic apoptosis. Mice
exposed prenatally to PM had subsequent increased weight gain and fat mass, increased anxiety-like
behavior, disrupted circadian activity patterns, and impaired glucose tolerance in a sexually dimorphic
pattern. Thus, elevated air pollution exposure may cause a metabolic profile characteristic of increased
risk for type 2 diabetes. Innovative infographic and online tools have been developed for communicating
risks and uncertainties to communities and to housing and parks planners and policy makers faced with
balancing the need for these services and reducing residential near-roadway air pollution exposure.
TITLE: Longitudinal Exposome Research Reveals Exposure of Agricultural Families to Over 86 Pesticides, 47
of Which are Identified as Developmental Neurotoxicants
SPECIFIC AIMS:
• Identify cellular, biochemical and molecular mechanisms for the adverse developmental
neurotoxicity of pesticides;
• Identify susceptibility factors for developmental neurotoxicity of pesticides;
• Improve our understanding of risks from children's exposure to pesticides; and to
• Develop interventions to reduce children's exposure to pesticides.
KEY RESEARCH FINDINGS: The theme of the University of Washington Children's Center has been to
understand the mechanisms (molecular, genetic, age, exposure and social factors) that define children's
susceptibility to pesticides, identifying the implications of this susceptibility for development and learning,
and partnering with communities to translate findings into risk communication, risk management and
prevention strategies. This poster shows critical pathways of pesticide exposure for children in
farmworker and non-farm worker families and shows how interventions are shown to reduce children's
exposure to pesticides. The center is organized using a Risk Assessment Framework that facilitates the
incorporation and use of state-of-the-art science to inform risk decisions. A critical premise for the center
is its commitment to Community Based Participatory Research and this commitment allowed
investigators to overcome and investigate the complex patterns of exposure for short-lived and episodic
pesticide use that agricultural communities can experience.
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TITLE: "A Story of Health" Multimedia eBook Improves Environmental Health Literacy of Thousands of
Health Professionals
KEY RESEARCH FINDINGS: Narrative approaches are emerging as powerful health promotion tools that can
increase understanding of the determinants of health and translate complex science. "A Story of Health"
multimedia eBook and continuing education course were designed to harness the power of storytelling to
improve environmental health literacy for health professionals and others. 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. A new chapter on reproductive
health/infertility has just been released. 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. Content was drawn from the collective expertise of the
PEHSU network and the NIEHS/EPA Children's Centers, among others. Each story is enriched with
illustrations, videos, and links to hundreds of online resources and references. Free continuing education
courses are offered through the Centers for Disease Control (CDC) Agency for Toxic Substances and
Disease Registry (ATSDR). 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
8,000 health professionals have registered for the course and evaluations have been overwhelmingly
positive. The "Story of Health" eBook is available online.
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Day 2 - Wednesday, October 25, 2017
i_iBi miing Talks
The second day of the meeting began with a series of five-minute presentations geared toward sharing
successful communication tools and approaches to improve children's environmental health that may be
adaptable for different communities. These presentations were categorized into tools targeted to
different populations, including pregnant women, parents, children, adolescents, and medical and child
care professionals. Following the short presentations, participants broke into small groups to discuss the
tools presented and how they may be adapted for different communities. Abstracts for the lightning talks
have been included below. These abstracts and posters reflect the individual views of meeting
participants and centers, none of the statements represent analyses by or positions of EPA.
Tools Targeted to Pregnant Women and Parents
Moderator: Carmen Marsit, Ph.D., Emory University
(1) Know Better, Live Better: The Development and Implementation of an Environmental Health Social
Impact Campaign for African American Women | Abby Mutic, M.S.N., Emory University
(2) Communication Tools for Parents and Caregivers | Kimberly Burke, M.P.H., Columbia University
(3) Disseminating Pesticide Exposure Results to Farmworker and Nonfarmworker Families in
Agricultural Community, A Community Based Participatory Research Approach | Elaine Faustman,
Ph.D., University of Washington
(4) Toxic Matters | Annemarie Charlesworth, M.A., University of California, San Francisco
(5) NIEHS/EPA Children's Centers Impact Report | Nica Louie, M.S., EPA; Hayley Aja, M.P.H., EPA
Student Contractor; Emily Szwiec, M.P.H., Association of Schools and Programs of Public Health
(ASPPH)/EPA
(1) Know Better, Live Better: The Development and Implementation of an Environmental Health
Social Impact Campaign for African American Women
Abby Mutic, M.S.N., Emory University
The Emory University Children's Center is investigating the influence of environmental exposures on
perinatal outcomes of African American women and children in metro Atlanta. In partnership with
the Stakeholder Advisory Board, the center has developed educational materials for dissemination
through a broader social media campaign, which involved a short documentary introducing the
concept of environmental exposures in a culturally relevant way. As part of the social media
campaign, the center is implementing Hootsuite and Facebook analytic tools to capture quantitative
data on the impact of the messaging campaign within the target audience. This will allow the center
to determine which items attracted the most attention, by whom, and will result in an increased
understanding of viewers. This data will also be used to inform the future direction of the Emory
University Children's Center social media campaign.
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(2) Communication Tools for Parents and Caregivers
Kimberly Burke, M.P.H., Columbia University
The Columbia University Children's Center uses a tiered approach to environmental health
communication with parents through a combination of workshops, tip sheets and promotion of
mobile application tools. The center's research on common urban pollutants are highlighted during
workshops. Tip sheets from the center's "Healthy Home, Healthy Child" campaign are also used to
reinforce holistic methods for reducing exposures to harmful chemicals. The mobile applications are
tested in a focus group with parents from the center's cohort and focus on green cleaning, green tips,
shopping guides for food and for personal care products, as well as climate resiliency/extreme heat.
(3) Disseminating Pesticide Exposure Results to Farmworker and Nonfarmworker Families in an
Agricultural Community, A Community Based Participatory Research Approach
Elaine Faustman, Ph.D., University of Washington
While the University of Washington Children's Center has been committed to returning individual
results of pesticide exposure to study participants, there have been challenges in developing
individual risk messages from complex scientific data. The center worked with the community on new
tools for interpreting exposure and susceptibility. Two town forums were held to identify the best
ways to share the pesticide exposure data, and three types of graphical information for individual
data were tested. The most popular approach was a thermometer that graphically presents the data
using a combination of color gradients and relative values. On follow-up, over 70 percent of
participants recalled the graphic and correctly interpreted the results.
(4) Toxic Matters
Annemarie Charlesworth, M.A., University of California, San Francisco
The University of California, San Francisco Children's Center developed "Toxic Matters" to begin
conversations between clinicians and their patients focused on preventing exposures at home, work,
and in the community, as well as how to become a smart consumer and knowledgeable in
environmental health issues. Additionally, the center worked to embed environmental health in
medical education including in medical textbooks, lectures, electives, and the Life Stages curriculum.
The center also produced a series of short videos, "60 MiNueTs" (available online), that explore the
growing impact of environmental chemicals on children's health - including increasing rates of
asthma, ADHD, autism, and childhood cancer - and interviews with renown medical experts and
scientists.
(5) NIEHS/EPA Children's Centers Impact Report
Nica Louie, M.S., EPA
Hayley Aja, M.P.H., EPA Student Contractor
Emily Szwiec, M.P.H., ASPPH
In October 2017, EPA and NIEHS successfully launched the Children's Centers Impact Report, which is
now available online. The landmark report presents select publications that highlight some of the
important contributions the centers have made toward reducing the burden of environmentally
induced or exacerbated diseases placed on children. The report provides examples of success in the
community in support of public health. It is organized in three sections: health outcomes,
environmental exposures, and hallmark features. The health outcomes section presents scientific
findings from the Children's Centers on several diseases that affect children. The environmental
exposures section presents research findings on chemicals and pollutants children are commonly
exposed to through air, water, and food. The hallmark features section highlights the unique features
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that have facilitated the work of the Children's Centers and advancements in the field. The
presentation included an overview on how the report was developed and a guide for how to navigate
the document. Discussions that followed the presentation focused on ideas for dissemination of the
report.
Tools Targeted to Children and Adolescents
Moderator: Susan Murphy, Ph.D., Duke University
(6) Improving Environmental Health Literacy of Adolescents and Young Adults: Research to Real Life |
Mark Miller, M.D., M.P.H., PEHSU Region 9, University of California, Berkeley CIRCLE
(7) Break the Cycle of Children's Environmental Health Disparities in Poor Communities | Leslie Rubin,
M.D., PEHSU Region 4
(8) Youth Participatory Action Research: Strengthening Community Communication | James Nolan,
M.P.H., University of California, Berkeley CERCH
(9) Empowering Children through Environmental Health Literacy: Moving beyond didactic guest
lectures | Nathan Mutic, M.S., M.A.T., M.Ed., Emory University
(6) Improving Environmental Health Literacy of Adolescents and Young Adults: Research to Real Life
Mark Miller, M.D., M.P.H., PEHSU Region 9, University of California, Berkeley CIRCLE
The University of California, Berkeley CIRCLE COTC collaborated with the Region 9 PEHSU on a project
titled "Improving Environmental Health Literacy of Young Adults". The intent was to create awareness
of the role of pre-conception and prenatal environmental influences on the development of
childhood leukemia and other diseases including developmental disabilities, asthma, and
reproductive health. The video, "Love in the Time of Toxicants" encourages young adults and
prospective parents to learn more about safe products and practices to reduce environmental
exposures and enhance lifelong health for themselves and for their children. Additional outreach
materials include illustrated books, bookmarks, and informational handouts. These outreach
materials are available online.
(7) Break the Cycle of Children's Environmental Health Disparities in Poor Communities
Leslie Rubin, M.D., PEHSU Region 4
Region 4 PEHSU, in collaboration with community and academic partners, has established a program
called "Break the Cycle of Children's Environmental Health Disparities". This is a collaborative,
interdisciplinary research and training program that encourages and inspires university students to
develop creative projects that will reduce or prevent environmental health related illnesses and
disorders of children who live in poor communities. "Break the Cycle" offers a readily replicable and
reasonably inexpensive model for exploring children's environmental health disparities within the
community context, and in cultivating future leaders who will continue to make a positive difference
for the health of children, their families and their communities.
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(8) Youth Participatory Action Research: Strengthening Community Communication
James Nolan, M.P.H., University of California, Berkeley CERCH
The Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) Youth Council
engages CHAMACOS study participants and other high school aged youth in Salinas Valley, California.
The CHAMACOS Youth Council addresses environmental health challenges in the community and
works with CERCH researchers to identify environmental health issues, design and conduct research
projects, and disseminate study results and education materials in their community. In the
CHAMACOS of Salinas Evaluating Chemicals in Homes & Agriculture (COSECHA) study, youth
measured pesticide exposures to adolescent girls in the Salinas Valley using personal monitoring
wristbands, dust samples, and GPS monitoring. The Salinas youth have taken the lead on developing
education and outreach activities. Specific examples include: a radio series for farmworkers on how
to reduce potential pesticide exposures; a bilingual video teaching community members how to learn
what pesticides have been used in the fields near their homes; a bilingual presentation for children of
farmworkers; highlights of their work for local news; and presentations to key stakeholders.
(9) Empowering Children through Environmental Health Literacy: Moving Beyond Didactic Guest
Lectures
Nathan Mutic, M.S., M.A.T., M.Ed., Emory University
Public school systems are an accessible platform for disseminating children's environmental health
education, and the Children's Centers and PEHSUs are uniquely poised to share current research
findings with the children most impacted by their environment. In most modern, digitally-enriched
learning environments, there are a myriad of ways Children's Centers and PEHSUs can enhance the
classroom experience beyond the traditional didactic guest lecturer approach. As many districts are
moving toward non-traditional approaches to curriculum and instruction such as career pathway
models and asynchronous online education, partnerships with universities and other community
stakeholders are becoming increasingly more common as school administrators seek novel and relevant
experiences for their students.
Tools Targeted to Professionals
Moderator: Susan Buchanan, M.D., PEHSU Region 5
(10) Which Environment? Shifting Communication Strategies to Meet Child Care Provider Needs |
Brenda Davis Koester, M.S., University of Illinois
(11) Environmental Health Education for Health Professionals | Carmen Milagros Velez Vega, Ph.D.,
M.S.W., University of Puerto Rico
(12) Environmental Health Screening Tools to be Used by Head Start Teachers | Robin Lee, M.P.H.,
R.D.N., University of Michigan
(13) Children's Environmental Health Basics for Early Intervention and Infant Development Professionals
| Jacqueline Barkoski, Ph.D., M.P.H., University of California, Davis
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(10) Which Environment? Shifting Communication Strategies to Meet Child Care Provider Needs
Brenda Davis Koester, M.S., University of Illinois
It is especially important to focus on child care providers in environmental health education
campaigns, as a majority of children under the age of five are in out-of-home care. In conjunction
with the Community Advisory Board, the center initially developed a public service announcement
(PSA) animated video addressing endocrine disrupting chemicals and children's health. While the
video was very well-received by the child care community, researchers learned through working
with the community that the base knowledge about environmental influences on children's health
is very low, and that the child care community is eager to learn more practical ways they can
implement changes in their day care centers and homes. The center restructured the messaging
campaign to provide more basic overviews of what constitutes children's environmental health and
examples of good practices rather than focus solely on endocrine disruptors, and are now
implementing a variety of messaging tools such as Buzzfeed, Facebook, Twitter, and Pinterest to
complement the PSA video.
(11) Environmental Health Education for Health Professionals
Carmen Milagros Velez Vega, Ph.D., M.S. W., University of Puerto Rico
While health clinic professionals in Puerto Rico are somewhat aware of the specific contaminants
and health effects studied by the Northeastern University Children's Center, they are largely
unaware of the broader relationship between environment and disease. In order to quantify this
observation, center clinic staff conducted surveys to gauge environmental health knowledge of
health providers in Puerto Rico. In order to fill this knowledge gap, center researchers and COTC
staff give formal presentations at clinics and hospitals on current research, teach clinic staff to use
research equipment, present to numerous audiences on Zika prevention, and educate masters
students on environmental health.
(12) Environmental Health Screening Tools to be Used by Head Start Teachers
Robin Lee, M.P.H., R.D.N., University of Michigan
The University of Michigan Children's Center's COTC has worked closely with their Community
Advisory Board in Kent County, Ml, to develop environmental health screening tools to be used by
Head Start teachers during home visits and during parent meetings. One tool is a survey that would
be administered to parents at Head Start Parent Coalition Meetings to understand their level of
concern and knowledge on environmental hazards their children may face in the home setting.
From this survey, researchers can then tailor the resources and information provided to Head Start
teachers to educate parents on environmental hazards in the home. The other tool is an adapted
visual checklist for Head Start teachers to assess environmental health hazards to students during
annual home visits. Teachers can then refer families in high-risk homes to the appropriate
resources, including partner Healthy Homes Coalition of West Michigan. This visual screening tool is
meant to be a quick and simple method for Head Start teachers to evaluate the environmental
health of their students' homes. The center hopes to pilot these tools with Head Start for Kent
County during the 2018-2019 school year, evaluate the processes and effectiveness of these tools,
and adapt the tools to meet the community's needs.
(13) Children's Environmental Health Basics for Early Intervention and Infant Development Professionals
Jacqueline Barkoski, Ph.D., M.P.H., University of California, Davis
The "Children's Environmental Health Basics for Early Intervention and Infant Development" toolkit was
developed by the University of California, Davis Children's Center to serve as a template for future
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outreach and education workshops. This toolkit was designed to help organize workshops for early
intervention service providers and other infant development professionals seeking to increase their
knowledge in environmental risks to neurodevelopment. The workshop template contains
information that is easily modified to fit the varying requirements for different child development
professional training conferences. Contents of the toolkit include workshop proposal, session
outline and learning objectives (2-hour workshop), slide deck (including text, copyright-free images,
imbedded videos), break-out activities and discussion guides, handouts (glossary, resources), and
pre- and post-workshop assessments.
Science Sessions
The afternoon of Day 2 included research findings from the Children's Centers on the effects of
environmental exposures and social stressors on children's health outcomes, including obesity, asthma,
low birth weight, preterm birth, immune function, and the microbiome. Short summaries of these
presentations have been included below. These abstracts reflect the individual views of meeting
participants and centers, none of the statements represent analyses by or positions of EPA.
Obesity
Moderator: Dr. Frederica Perera, Ph.D., Dr.P.H., Columbia University
(1) Does Air Pollution Cause Childhood Obesity and Increased Risk for Diabetes? | Rob McConnell, M.D.,
University of Southern California
(2) Prenatal Phthalate Exposure and Metabolic Risk in Adolescence: Insights from metabolomics | Karen
Peterson, Sc.D., University of Michigan
(3) Obesity as a Susceptibility Factor for Pollution Exposure and Lung Disease | Meredith McCormick,
M.D., M.H.S., Johns Hopkins University
(1) Does Air Pollution Cause Childhood Obesity and Increased Risk for Diabetes?
Rob McConnell, M.D., University of Southern California
This presentation explored results related to air pollution, childhood obesity, and diabetes. The
University of Southern California Children's Center is studying the effects of exposures to regional air
pollutants and near-roadway air pollution on weight and diabetes risk in children. Results show that
markers for near-roadway air pollution were associated with BMI in both boys and girls. Results also
show synergistic associations of secondhand smoke and near-roadway air pollution exposure with
BMI in children. There is compelling evidence that particulate matter exposure causes diabetes in
animal studies and emerging evidence shows robust associations in adult epidemiological studies, but
evidence that the risk is increased in children has not been well studied. To fill this research gap,
center investigators examined associations of N02 and PM2.5 with insulin sensitivity, acute insulin
response to glucose, and disposition index in obese children and adolescents. Exposures to N02 and
PM2.5 were associated with long-term declines in insulin sensitivity and declines in disposition index
((3-celI function). Exposure to PM2.swas also associated with increased acute response to glucose at
age 18 years. These results have a potentially large public health impact. Possible interventions to
lessen this impact include reducing levels of air pollution or mitigating effects of near-roadway air
pollution through local zoning authority.
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(2) Prenatal Phthalate Exposure and Metabolic Risk in Adolescence: Insights from metabolomics
Karen Peterson, Sc.D., University of Michigan
The presentation began by explaining the relationship between phthalates and metabolomics. The
University of Michigan Children's Center examined whether trimester-specific exposures to
phthalates are associated with metabolomics biomarkers among peripubertal youth. This is the first
human study relating untargeted metabolomics during adolescence to in utero exposure to
phthalates. Participants are part of the ELEMENT longitudinal birth cohort study in Mexico City.
Researchers measured nine phthalates in maternal urinary samples from each trimester. A mass-
spectrometry-based untargeted metabolomics platform was used to measure fasting serum
metabolites in the children (ages 8-14 years), yielding data on hundreds of known and unknown
chemical features. Researchers estimated the associations between each urinary phthalate and each
serum metabolite, stratified by sex and adjusted for child age, BMI z-score, and pubertal onset.
Accounting for multiple comparisons using a 10 percent false discovery rate (q<0.1), first trimester
phthalates were not associated with any metabolites in the children. However, exposures during the
second and third trimesters were significantly associated with sets of metabolites with the most
associations observed among girls. Overall, metabolomics biomarkers may reflect sex differences in
response to in utero phthalate exposures manifested during puberty that are not detected in clinical
markers of cardiometabolic risk. The center plans to further explore how these metabolomic
biomarkers relate to health outcomes, such as obesity and pubertal transition, among the children.
(3) Obesity as a Susceptibility F actor for Pollution Exposure and Lung Disease
Meredith McCormick, M.D., M.H.S., Johns Hopkins University
The Johns Hopkins University Children's Center studies how obesity and diet affect the relationship
between indoor air pollution and asthma. Previous studies have shown that children who are obese
or overweight have increased asthma symptoms in response to N02and coarse particulate matter
(PM io). There is also an increased risk of doctor-diagnosed asthma in response to sulfur dioxide (S02)
and PM io. Obesity may alter the asthmatic response to ozone, and may also increase susceptibility to
secondhand smoke. Diet was found to affect asthma symptoms independent of body mass. A
Western diet has been associated with increased risk of wheeze, cough, and phlegm compared to
consumption of a prudent diet. Researchers at Johns Hopkins University are conducting a study to
further characterize the differential susceptibility to air pollution between overweight and obese
children compared to non-obese children with asthma. Using an air purifier intervention study design,
investigators are examining the effects of reduced PM exposure on asthma symptoms in obese versus
non-obese children. They are also identifying potential mediators of susceptibility, including
differences in breathing patterns, inflammatory and oxidative stress responses, and sleep-disordered
breathing.
Cumulative Exposures and Stress
Moderator: Tracey Woodruff, Ph.D., University of California, San Francisco
(4) Assessing the Combined Effects of Environmental and Social Stress: A review of the evidence and
implications for future research | Rachel Morello-Frosch, Ph.D., M.P.H., University of California,
Berkeley
(5) Studying the Impacts of Environmental Exposures and Stress in the Puerto Rico CRECE Study | John
Meeker, Sc.D., M.S., University of Michigan
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(4) Assessing the Combined Effects of Environmental and Social Stress: A review of the evidence
and implications for future research
Rachel Morello-Frosch, Ph.D., M.P.H., University of California, Berkeley
Researchers and communities have become increasingly concerned that variation in chemical
exposures, social vulnerabilities, and biological susceptibility contribute to disparities in mortality and
morbidity. The University of California, San Francisco Children's Center conducted a systematic review
of the toxicology and epidemiological evidence on the combined effects of prenatal exposure to
environmental chemicals and stress on fetal growth and other developmental outcomes. Most of the
studies identified during the systemic review focused on tobacco smoke and air pollution. A meta-
analysis of smoking studies evaluating interactive effects between maternal smoking and
socioeconomic status (SES) found that the odds of low birthweight were significantly higher in low
SES groups compared to high SES groups, indicating likely combined effects of chemical and
psychosocial stressors. Very few human studies exist on other prenatal chemical exposures, such as
endocrine disrupting chemicals, and their combined impacts with psychosocial stress. It is important
to hoiisticaIly measure stress in research, including place-based factors, individual measures,
perceptual measures, and biomarkers. Findings related to cumulative impacts indicate that
community engagement is essential in development of decision-making tools. As community
engagement increases, residents become a more integral part of the research agenda and policy
solutions to advance environmental health.
(5) Studying the Impacts of Environmental Exposures and Stress in the Puerto Rico CRECE Study
John Meeker, Sc.D., M.S., University of Michigan
The Northeastern University Children's Center is testing the modifying effects of SES, maternal stress,
and preterm birth on the relationship between environmental phenols or parabens on pregnancy
outcomes and child development. The CRECE study builds on the previously-established PROTECT
pregnancy cohort in Puerto Rico and observes children born to mothers in the study. Researchers
collect data, including biological and environmental samples, information on product use,
geographical coordinates, and food frequency questionnaires, from mothers starting early in their
pregnancy and continuing until they give birth. Researchers continue to collect data on the children
until age four years. Preliminary analyses show that prenatal exposure to triclocarban resulted in
almost two days-shorter gestational age. Researchers also collected data on maternal stress, then
measured the interactive effect with phenols and parabens on children's health. This center will
continue to interpret these analyses and study the combined effects of chemical and psychosocial
factors.
Immune Function and the Microbiome
Moderator: Catherine Metayer, M.D., Ph.D., University of California, Berkeley
(6) Immune Dysregulation in Autism Spectrum Disorder | Judy Van de Water, Ph.D., University of
California, Davis
(7) In Utero and Infant Arsenic Exposure, Immunity and the Microbiome: Results from the New
Hampshire Birth Cohort Study | Juliette Madan, M.D., Dartmouth College
(8) Intergenerational Transmission of Risk: How the Microbiome Gets Under the Skin* | Anne Dunlop,
M.D., M.P.H., Michelle Wright, Ph.D., R.N., Emory University
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(6) Immune Dysregulation in Autism Spectrum Disorder
Judy Van de Water, Ph.D., M.D., University of California, Davis
The University of California, Davis Children's Center examines the roles of environmental factors,
genes, and the immune system as they relate to autism spectrum disorder (ASD) susceptibility. They
also explore the gestational immune environment in ASD. Disrupted maternal immune function may
be a key factor in the later appearance of certain neurodevelopmental disorders. For example, a viral
infection in early life may increase the risk of autism. Researchers measured maternal cytokines mid-
gestation in the Early Markers of Autism (EMA) study - a case-control prospective study. Results show
that mothers of children with ASD had elevated inflammatory cytokines and chemokines, which are
normally downregulated during mid-gestation. These results suggest atypical immune regulation
during pregnancy. A previously unidentified subtype of autism, Maternal Antibody Related (MAR)
Autism, may be a result of maternal autoantibodies that cross the placenta and bind to their targets
in the developing brain. These autoantibodies change how neurons develop. MAR cases make up
about 20 percent of all ASD cases, and children with MAR autism exhibit more severe behaviors and
pronounced stereotypic behavior. There are multiple points during development at which the
environment can alter neurodevelopment. The environment can affect gestational development and
interfere with neuroimmune interaction, as seen in MAR autism. The environment can also affect
brain and immune system development after birth. Children with ASD also respond differently to
toxicant exposures. For example, T cell cytokine production negatively correlates with total PBDE
body burden in children with ASD. This response is opposite that of neurotypical children. Exploring
differential immune sensitivity to various environmental exposures could provide clues as to the
relationship between immune dysregulation and outcome in ASD.
(7) In Utero and Infant Arsenic Exposure, Immunity and the Microbiome: Results from the New
Hampshire Birth Cohort Study
Juliette Madan, M.D., Dartmouth College
The Dartmouth College Children's Center studies early life exposure to arsenic, immunity, and the
microbiome. The gut microbiome is essential in training the immune system early in life. Toxicants
like arsenic have an antibiotic effect on the microbiome. Antibiotics reduce diversity during a critical
window of metabolic development, and can impact overall health. For example, the proposed
pathway in allergy, asthma, and autoimmune disease is that antibiotics eradicate diversity during
critical windows of immune development. The center is working to determine how maternal gut,
vaginal, and breast milk microbiomes affect the infant microbiome and gut metabolomics. In the New
Hampshire Birth Cohort Study, researchers seek to investigate water and dietary sources of arsenic in
regions with high well-water arsenic concentrations. Researchers follow children from birth and
collect information about diet and biological samples (urine, breast milk) until age 5 years. Results
show that delivery mode has the most substantial impact on infant gut microbiome. Results also
show that the microbiome of children who were fed a mixed diet of formula and breast milk closely
mirrors that of children who were exclusively formula fed. In addition to drinking water, the center
also looks at the potential exposure to arsenic through food. Rice-based products are a food typically
high in arsenic, which is of concern because over 80 percent of infants are introduced to rice cereal in
the first year of life. Impacts of arsenic may occur at lower concentrations than previously known.
Results show dose-related trends in risk of infection and wheeze, with no evidence of a lower
threshold. The center plans to continue investigating the gut microbiome as a mediator of nutrition-
infection associations.
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(8) Intergenerational Transmission of Risk: How the Microbiome Gets Under the Skin
Anne Duniop, M.D., Michelle Wright, Ph.D., R.N., Emory University
The transfer of microbes from mother and newborn starts before birth. The mode of delivery (vaginal
versus Cesarean) and diet (breast milk versus formula) can also affect the infant microbiome.
Changes in the maternal microbiome, preconception and during pregnancy, may initiate a
transgenerational cycle of obesity. Maternal gut dysbiosis may be directly transmitted to the infant
and cause dysbiosis. External influences such as early-life nutrition, mode of delivery, and antibiotic
treatment may also influence the composition of the infant gut microbiome. These changes in gut
microbiome function may result in infants being born large for gestational age with excess adiposity,
both of which place the child at increased risk of obesity and immune dysfunction later in life.
Adulthood obesity during childbearing years may perpetuate the cycle of obesity. With increasing
prevalence of complex chronic disease in children, there has been an emerging focus on the
contributions of early life exposures that lead to chronic health outcomes. Especially important is the
concept of the exposome. Utilization of biological samples to study the exposome will encourage the
discovery of alterations that represent how the exposome "gets under the skin" and contributes to
health outcomes. The relationship between the maternal exposome and health outcomes of the
offspring is complex. The presentation included a model to describe how the preconception and
pregnancy exposome can contribute to high-risk birth outcomes and increased vulnerability to
disease in the offspring throughout the life course. The presenters described how the fetal system
responds through biologically mediated mechanisms to maternal exposures that potentially prime
the body to anticipate similar exposures after birth. While these adaptations may provide short-term
gains, they may also have negative consequences later in life that contribute to adult disease.
Epigenetic mechanisms, such as DNA methylation, contribute to the development of certain
observable characteristics. In addition to the influence of nutrients and diet, the microbiome can
result in changes to DNA methylation and influence fetal health.
Keynote
Science to Policy: Incorporating Children's Health into Decision Making
Gina M. Solomon, M.D., M.P.H., Deputy Secretary for Science and Health, California Environmental
Protection Agency
Dr. Solomon began her presentation by discussing the overall mission and activities of the California
Environmental Protection Agency (CalEPA). She then described the specific role CalEPA serves in
protecting children's health. In 1999, the California legislature created the Children's Environmental
Health Center within CalEPA. The CalEPA Center reviews ambient air quality standards to ensure that they
protect infants and children, establishes a list of toxic air contaminants that may disproportionality affect
children, and revises control measures for these contaminants. Dr. Solomon noted that children face
cumulative stressors, including environmental hazards and social factors, intrinsic biological and
physiological factors, as well as external social vulnerability factors. She then expanded on how these
stressors modify the effects of environmental hazards on children's health and expressed the importance
and value of tools and analytical methods that can accurately assess cumulative stressors. Dr. Solomon
described one such tool, CalEnviroScreen 3.0, which was released in January 2017. CalEnviroScreen,
available online, conducts spatial analysis of relative burdens from pollution and population vulnerability
in California communities. The tool combines 20 different indicators into a single score. These indicators
measure both pollution burden and population characteristics. The final CalEnviroScreen score allows for
comparison of different geographical areas.
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Higher scores mean greater pollution burdens and population vulnerability. Dr. Solomon proceeded to
discuss other efforts by CalEPA, including those focused on investing in and funding projects in
disadvantaged communities. Another CalEPA project identifies gaps in chemicals policy. For example, the
California Safer Consumer Products Program, passed by California legislature in 2008, selects products
and chemicals that may cause harm to human health, evaluates alternatives, and considers possible
responses. Products and chemicals are prioritized for action if there is potential for exposures to
contribute to or cause significant or widespread adverse impacts. Dr. Solomon concluded her
presentation by discussing future policy priorities for CalEPA and thanked the organizers for the
opportunity to share the work of CalEPA.
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Appendices
Appendix A - List of Children's Centers
Appendix B - Meeting Agenda
Appendix C - List of Steering Committee Members
Appendix D - List of Participants
Appendix E - Progress Update Poster Presentations
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Appendix A-List of Participating Children's Centers
Columbia University- NIEHS/EPA Children's Environmental Health Centers; The Columbia Center for
Children's Environmental Health (CCCEH)
Dartmouth College - NIEHS/EPA Children's Environmental Health and Disease Prevention Research
Centers at Dartmouth College
Duke University- NIEHS/EPA Children's Environmental Health Centers Center for Study of
Neurodevelopment and Improving Children's Health Following Environmental Tobacco Smoke Exposure
(NICHES)
Emory University- NIEHS/EPA Children's Environmental Health Centers Center for Children's Health, the
Environment, the Microbiome and Metabolomics (C-CHEM2)
Johns Hopkins University - NIEHS/EPA Children's Environmental Health Centers Center for the Study of
Childhood Asthma in the Urban Environment (CCAUE)
Northeastern University-NIEHS/EPA Children's Environmental Health Centers Center for Research on
Early Childhood Exposure and Development in Puerto Rico (CRECE)
University of California, Berkeley CERCH - NIEHS/EPA Children's Environmental Health Centers Center for
Environmental Research and Children's Health (CERCH)
University of California, Berkeley CIRCLE - NIEHS/EPA Children's Environmental Health Centers Center for
Integrative Research on Childhood Leukemia and the Environment (CIRCLE)
University of California, Berkeley/Stanford University (CHAPS) - NIEHS/EPA Children's Environmental
Health Centers Children's Health and Air Pollution Study - San Joaquin Valley (CHAPS - SJV)
University of California, Davis- NIEHS/EPA Children's Environmental Health Centers UC Davis Center for
Children's Environmental Health and Disease Prevention
University of California, San Francisco - NIEHS/EPA Children's Environmental Health Centers: THE UCSF
Pregnancy Exposures to Environmental Chemicals (PEEC) Children's Center
University of Illinois - NIEHS/EPA Children's Environmental Health Centers: Novel Methods to Assess
Effects of Chemicals on Child Development
University of Michigan - NIEHS/EPA Children's Environmental Health Centers: Lifecourse Exposures &
Diet: Epigenetics, Maturation & Metabolic Syndrome
University of Southern California - NIEHS/EPA Children's Environmental Health Centers: Southern
California Children's Environmental Health Center
University of Washington - NIEHS/EPA Children's Environmental Health Centers Center for Child
Environmental Health Risks Research
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Appendix B - Meeting Agenda
NIEHS/EPA Children's Centers Annua! Meeting
EPA Region 9, 75 Hawthorne Street, San Francisco, CA
October 24-25, 2017
Meeting Goals and Objectives:
• The jointly-funded NIEHS/EPA Children's Centers Annual Meeting provides an opportunity to share
the robust research and scientific analysis that is the foundation of the Children's Centers
program. The 2017 meeting is hosted together with the Pediatric Environmental Health Specialty
Units (PEHSUs).
• This meeting allows the Children's Centers and PEHSUs to form new collaborations with each
other and with community, state, and federal partners to positively impact public health.
Tuesday, Oct. 24, 2017
8:30 a.m. - 8:40 a.m. Conference Overview
Nica Louie, M.S., Project Officer, U.S. Environmental Protection Agency
(EPA)
Kimberly Gray, Ph.D., Health Science Administrator, National Institute of
Environmental Health Sciences (NIEHS)
8:40 a.m. - 9:00 a.m. Welcoming Remarks
Alexis Strauss, M.A., Acting Regional Administrator, EPA Region 9
Gwen Collman, Ph.D., Director, Division of Extramural Research and
Training, NIEHS
Elaine Cohen Hubal, Ph.D., M.S., Office of Research and Development,
EPA
9:00 a.m. - 10:15 a.m. Progress Review (Part I)
The Children's Centers and PEHSUs will present updates, recent
successes, robust science and scientific analysis aimed at protecting the
health of children. Five-minute presentations will be followed by ten-
minute small group discussions. While this session includes seven
posters, there is time for each participant to visit four posters.
Columbia University, Longitudinal Effects of Prenatal Exposure to
PAHs on Mental, Behavioral, and Emotional Disorders as well as
Obesity in Adolescence
Dartmouth College, Should Rice Cereal be an Infant's First Food?
Duke University, Exposure to Tobacco Smoke During Pregnancy - and
Even During Preconception - Can Alter Baby's Brain Function
Emory University, African American Women in Metro Atlanta Have
Higher Levels of Endocrine Disrupting Plasticizers in Their Bodies Than
Other African American Women
Johns Hopkins University, Obesity and Diet as Susceptibility Factors
to Air Pollution Exposure
10:15 a.m. - 10:30 a.m. Break
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10:30 a.m. - 11:30 a.m. Quick Connections Round I
Through a series of short conversations, participants will identify new
potential collaborators to improve and protect public health. In addition
to networking, participants will also share what makes them passionate
about children's environmental health. Specific directions will be
provided separately.
11:30 a.m. - 12:45 p.m. Lunch (on your own)
12:45 p.m. - 2:00 p.m. Progress Review (Part II)
The Children's Centers and PEHSUs will present updates, recent
successes, robust science and scientific analysis aimed at protecting the
health of children. Five-minute presentations will be followed by ten-
minute small group discussions. While this session includes six posters,
there is time for each participant to visit four posters.
Northeastern University, Exposure to triclosan in pregnancy is
associated with increased inflammation
UC Berkeley (CERCH), Mixtures of Pesticides Used Near Homes
During Pregnancy Associated with Decreased IQ in Children
UC Berkeley (CIRCLE), Toxic PCBs Still Harming Children, Despite
Long-Time Ban
UC Berkeley/Stanford University, Ambient Air Pollution Impairs
Immune Function, which Impacts Allergy and Asthma
UC Davis, Can Newborn Cytokines Predict Autism?
PEHSU Region 2, Effectively Integrate Environmental Health into
Clinical Practice
2:00 p.m. - 3:00 p.m. Quick Connections Round II
Through a series of short conversations, participants will identify new
potential collaborators to improve and protect public health. In addition
to networking, participants will also share what makes them passionate
about children's environmental health. Specific directions will be
provided separately.
3:00 p.m. - 3:15 p.m. Break
3:15 p.m. -4:30 p.m. Progress Review (Part III)
The Children's Centers and PEHSUs will present updates, recent
successes, robust science and scientific analysis aimed at protecting the
health of children. Five-minute presentations will be followed by ten-
minute small group discussions. While this session includes six posters,
there is time for each participant to visit four posters.
UC San Francisco, Flame Retardants Linked to Lower Child IQ
University of Illinois, Through the Window of a Baby's Eyes
University of Michigan, Toxicant Exposures and Lifestyle Factors
Influence the Rate of Epigenetic Aging
University of Southern California, Does Air Pollution Cause Childhood
Obesity and Increase the Risk of Diabetes?
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University of Washington, Longitudinal Exposome Research Reveals
Exposure of Agricultural Families to Over 86 Pesticides, 47 of Which
May Impact Neurodevelopment in Young Children
PEHSU Region 9, A Story of Health Multimedia eBook Improves
Environmental Health Literacy of Thousands of Health Professionals
4:30 p.m. Adjourn
Wednesday, Oct. 25, 2017
8:30 a.m. - 8:40 a.m. Introduction
8:40 a.m. - 12:05 p.m. Lightning Talks
The Children's Centers and PEHSUs will present communication tools and
approaches that educate the community children's environmental health
topics. The objective is to share tools and approaches that other centers
and PEHSUs can adapt for their own communities.
Discussion Questions
1. Identify a partner/stakeholder who would find the tool useful or
educational.
2. What is the best way to disseminate this tool/approach to its target
audience?
3. What suggestions do you have that could improve this tool?
4. Do you have a similar or complimentary tool that you could make
available to others - if so what?
8:40 a.m. - 9:45 a.m. Session I -Tools Targeted to Pregnant Women and Parents
Emory University, 'Know Better, Live Betted Social Media campaign
Columbia University, Communication Tools for Parents and
Caregivers
University of Washington, Communicating with Parents and
Community: Examples for explaining individual and population level
pesticide exposures
UC San Francisco, Toxic Matters
EPA, Children's Centers Impact Report
Moderator: Carmen Marsit, Ph.D., Emory University
9:55 a.m. - 10:55 a.m. Session II -Tools Targeted to Children and Adolescents
UC Berkeley CIRCLE, Improving Environmental Health Literacy of
Adolescents and Young Adults: Research to Real Life
PEHSU Region 4, Break the Cycle of Children's Environmental Health
Disparities in Poor Communities
UC Berkeley CERCH, Youth Participatory Action: A Tool for
Community Communication
Emory University, Empowering children through environmental
health literacy: Moving Beyond Didactic Guest Lectures
Moderator: Susan Murphy, Ph.D., Duke University
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11:05 a.m. - 12:05 p.m. Session III -Tools Targeted to Professionals (medical, childcare, schools)
University of Illinois, Which Environment? Shifting Communication
Strategies to Meet Child Care Provider Needs
Northeastern University, Environmental Health Education for Health
Professionals
University of Michigan, Environmental Health Screening Tools to be
Used by Head Start teachers
UC Davis, Children's Environmental Health Basics for Early
Intervention/Infant Development Professionals
Moderator: Susan Buchanan, M.D., M.P.H., PEHSU Region 5
12:05 p.m. - 1:30 p.m. Lunch (on your own)
1:30 p.m. - 4:30 p.m. Science Seminars
This session provides an overview of environmental factors that may
contribute to multiple health endpoints. The session includes
presentations as well as panel discussions.
1:30 p.m. - 2:35 p.m. Obesity
1:30 p.m. - 1:35 p.m.
1:35 p.m. - 1:50 p.m.
1:50 p.m. - 2:05 p.m.
2:05 p.m. - 2:20 p.m.
2:20 p.m. - 2:35 p.m.
Introduction, Frederica Perera, Ph.D., Columbia
University
Does Air Pollution Cause Childhood Obesity and
Increased Risk for Diabetes, Rob McConnell,
M.D., University of Southern California
Prenatal Phthalate Exposure and Metabolic Risk
in Adolescence: Insights from Metabolomics,
Karen Peterson, Sc.D., University of Michigan
Obesity as a Susceptibility Factor for Pollution
Exposure and Lung Disease, Meredith
McCormack, M.D., M.H.S., Johns Hopkins
University
Discussion
2:35 p.m. - 3:25 p.m. Cumulative Exposures and Stress
2:35 p.m.-2:40 p.m. Introduction, Tracey Woodruff, Ph.D., M.P.H., UC
San Francisco
2:40 p.m. - 2:55 p.m. Cumulative Prenatal Exposure to Exogenous
Chemicals and Psychosocial Stress: A review of
the evidence and implications for future
research, Rachel Morello-Frosch, Ph.D., M.P.H.,
UC Berkeley
2:55 p.m. - 3:10 p.m. Studying the Impacts of Environmental
Exposures and Stress in the Puerto Rico CRECE
study, John Meeker, Sc.D., M.S., University of
Michigan
3:10 p.m. - 3:25 p.m. Discussion
3:25 p.m. - 4:30 p.m. Immune Function and the Microbiome
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3:25 p.m. - 3:30 p.m. Introduction, Catherine Metayer, M.D., Ph.D., UC
Berkeley
3:30 p.m. - 3:45 p.m. Immune Dysregulation in Autism Spectrum
Disorder, Judy Van de Water, Ph.D., UC Davis
3:45 p.m. - 4:00 p.m. In Utero and Infant Arsenic Exposure, Immunity
and the Microbiome: Results from the New
Hampshire Birth Cohort Study, Juliette Madan,
M.D., Dartmouth College
4:00 p.m. - 4:15 p.m. Intergenerational Transmission of Risk: How the
Microbiome Gets Under the Skin, Anne Dunlop,
M.D., M.P.H., Emory University; Michelle Wright,
Ph.D., R.N., Emory University
4:15 p.m. - 4:30 p.m. Discussion
4:30 p.m. - 5:00 p.m. Keynote
Gina Solomon, M.D., M.P.H., Deputy Secretary for Science and Health,
California Environmental Protection Agency
Moderator: Mark Miller, M.D., M.P.H., PEHSU Region 9
5:00 p.m. Adjourn
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Appendix C - List of Steering Committee Members
HayleyAja, EPA Student Contractor
Laura Anderko, PEHSU Region 2
Akram Alshawabkeh, Northeastern University
Children's Center
Martha Berger, EPA
Susan Buchanan, PEHSU Region 5
Annemarie Charlesworth, University of
California, San Francisco Children's Center
Jose Cordero, Northeastern University Children's
Center
Brenda Eskenazi, University of California,
Berkeley CERCH Children's Center
Michael Firestone, EPA
Kenda Freeman, NIEHS
Andrew Geller, EPA
Kimberly Gray, NIEHS
Virginia Guidry, NIEHS
S. Katharine Hammond, University of California,
Berkeley/Stanford University Children's Center
Kim Harley, University of California, Berkeley
CERCH Children's Center
Elaine Cohen Hubal, EPA
Pam Lein, University of California, Davis
Children's Center
Nica Louie, EPA
Carmen Marsit, Dartmouth College Children's
Center
Rob McConnell, University of Southern California
Children's Center
Jacquelyn Menghrajani, EPA Region 9
Catherine Metayer, University of California,
Berkeley CIRLCE Children's Center
Mark Miller, PEHSU Region 9, University of
California, Berkeley CIRCLE Children's Center
Susan Murphy, Duke University Children's
Center
Birgit Puschner, University of California, Davis
Children's Center
Perry Sheffield, PEHSU Region 2
Emily Szwiec, ASPPH
Kelly Widener, EPA
Nsedu Obot Witherspoon, Children's
Environmental Health Network
Tracey Woodruff, University of California, San
Francisco Children's Center
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Appendix D - List of Participants
The 2017 Children's Centers Annual Meeting included 116 total participants, including center
researchers, PEHSUs, EPA labs and centers, EPA regional offices, NIEHS, and CDC.
Angeles Acosta Rodriguez, University of Puerto
Rico/Northeastern University
Andrea Aguilar, University of Illinois
Marcus Aguilar, EPA Region 9
HayleyAja, EPA
Akram Alshawabkeh, Northeastern University
John Balmes, University of California, San
Francisco
Jacqueline Barkoski, University of California,
Davis
Kim Bartels, EPA Region 8
Martha Berger, EPA
Cassie Bernardi, American Academy of Pediatrics
Stephen Borron, PEHSU Region 6
Asa Bradman, University of California, Berkeley
Susan Buchanan, PEHSU Region 5
Kimberly Burke, Columbia University
Rich Campbell, EPA
Annemarie Charlesworth, University of
California, San Francisco
Elaine Cohen Hubal, EPA
JoseCordero, University of Georgia
Mona Dai, EPA
Natalyn Daniels, University of California, San
Francisco
Dana Dolinoy, University of Michigan
Christie Drew, NIEHS
Anne Dunlop, Emory University
Brenda Eskenazi, University of California,
Berkeley
Elaine Faustman, University of Washington
Bryan Fiedorczyk, EPA Region 10
Barbara Fiese, University of Illinois
Jill Franzosa, EPA
Bernard Fuemmeler, Virginia Commonwealth
University
Sam Goldman, University of California, San
Francisco
Jackie Goodrich, University of Michigan
Robert Gould, University of California, San
Francisco
Kimberly Gray, NIEHS
Wendy Gutschow, University of Southern
California
Angela Hackel, EPA
Katharine Hammond, University of California,
Berkeley
Nadia Hansel, Johns Hopkins University
Kim Harley, University of California, Berkeley
Michael Hatcher, Centers for Disease Control
(CDC), Agency for Toxic Substances and Disease
Registry (ATSDR)
Marissa Hauptman, PEHSU Region 1
Irva Hertz-Picciotto, University of California,
Davis
Stephanie Holm, PEHSU Region 9
Karen Huen, University of California, Berkeley
Gredia Huerta-Montanez, Northeastern
University
Brenda Koester, University of Illinois
Susan Korrick, Harvard University
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Patricia Lasley, PEHSU Region 5
Chris Lau, EPA
Robin Lee, University of Michigan
Victoria Leonard, University of California, San
Francisco
Edward Levin, Duke University
Sa Liu, University of California, Berkeley
Nica Louie, EPA
Jennifer Lowry, PEHSU Region 7
Fred Lurmann, Sonoma Technology Inc.
Lisa Lutzker, University of California, Berkeley
Juliette Madan, Dartmouth College
Ehsan Majd, Johns Hopkins University
Melinda Malamoco, PEHSU Region 8
Jennifer Mann, University of California, Berkeley
Carmen Marsit, Emory University
Linda McCauley, Emory University
Rob McConnell, University of Southern California
Meredith McCormack, Johns Hopkins University
John Meeker, University of Michigan
Jaquelyn Menghrajani, EPA Region 9
Mark Miller, University of California, San
Francisco
Rachel Morello-Frosch, University of California,
Berkeley
Susan Murphy, Duke University
Carolyn Murray, Dartmouth College
Nathan Mutic, Emory University
Abby Mutic, Emory University
Kari Nadeau, Stanford University
Andreas Neophytou, University of California,
Berkeley
James Nolan, University of California, Berkeley
Elizabeth Noth, University of California, Berkeley
Liam O'Fallon, NIEHS
Vasantha Padmanabhan, University of Michigan
Amy Padula, University of California, San
Francisco
Frederica Perera, Columbia University
Karen Peterson, University of Michigan
Lillian Prince, University of California, San
Francisco
Kenisha Puckett, University of California, San
Francisco
Danielle Ramos, ASPPH, EPA
Cynthia Rand, Johns Hopkins University
Virginia Rauh, Columbia University
Jamie Rayman, CDC, ATSDR
John Rodgers, EPA
Jeannie Rodriguez, Emory University
Melissa Rose, University of California, Davis
P. Barry Ryan, Emory University
Sheela Sathyanarayana, Seattle Children's
Research Institute
Vicki Sayarath, Dartmouth College
Susan Schantz, University of Illinois
Rebecca Schmidt, University of California, Davis
Sophia Serda, EPA Region 9
Sarah Sharpe, University of California, Berkeley
Perry Sheffield, Icahn School of Medicine at
Mount Sinai, PEHSU Region 2
Veena Singla, University of California, San
Francisco
Gina Solomon, California Environmental
Protection Agency
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Gretchen Stewart, EPA Region 10
Patrice Sutton, University of California, San
Francisco
Emily Szwiec, ASPPH, EPA
Claudia Thompson, NIEHS
GwenTindula, University of California, Berkeley
Judy Van de Water, University of California,
Davis
Julia Varshavsky, University of California, San
Francisco
Julia Vassey, University of California, Berkeley
Carmen Velez Vega, University of Puerto
Rico/Northeastern University
Aolin Wang, University of California, San
Francisco
Lois Wessel, Georgetown University
Todd Whitehead, University of California,
Berkeley
Siobhan Whitlock, EPA Region 4
Patrick Wilson, EPA Region 9
Tracey Woodruff, University of California, San
Francisco
Michelle Wright, Emory University
Marya Zlatnik, University of California, San
Francisco
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Appendix E - Progress Update Poster Presentations
The views expressed in these presentations are those of the authors and do not necessarily represent the views or
policies of EPA.
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Columbia Center
For Children's
Environmental
Health
MAILMAN SCHOOL OF PUBLIC HEALTH
Columbia university
Longitudinal Effects of Prenatal Exposure to Polycyclic Aromatic Hydrocarbons (PAH) on
Mental, Behavioural, and Emotional Disorders as well as Obesity in Adolescence
THE COLUMBIA CENTER FOR CHILDREN'S ENVIRONMENTAL HEALTH (CCCEH):
Selected Accomplishments from 2016-17
HYPOTHESIS
Polycyclic Aromatic Hydrocarbons
(PAH)
Neurotoxic pollutants
released from fossil fuels,
tobacco, and other organic
material
Prenatal and
Early Childhood
Exposure
Vuherab e
Period of
Adoescence
Disrupts Development
and Maturation
of Neural Systems
that Support Capacities
for Self-Regulation
Cognitive, Emotional, Behavioural, and
Adiposity Problems
SPECIFIC AIMS
Elevated prenatal PAH exposure is associated with:
1) Adverse effects on self-regulatory processes and clinical
symptoms at age 15-17 years, and distinctive adverse
developmental trajectories from early childhood through
age 15-17 years of age
2) Distinct growth trajectories of body mass index growth and
fat mass index from age 5 to 17 years, and greater
adiposity, higher hedonic eating behavior, sedentary
pursuits, and poorer neuropsychological function at age
15-17 years of age
3) Adverse effects on the structure, function, and metabolism
of neural systems known to support the capacity for self-
regulation at 9-12 years (visualized by MRI), which
mediate the emergence of conduct disturbance, substance
use, depression, the persistence of ADHD symptoms, and
adiposity measures up to 15-17 years of age
KEY RESEARCH FINDINGS
Longitudinal effects of
prenatal exposure
to air pollutants on
self-regulatory capacities
and social competence
Margolis et al, 2016
POPULATION
- Recruited from 1998-2006
- African-American and
Dominican women residing in
Harlem, South Bronx, and
Washington Heights, NY
- Non-active cigarette smokers,
ages 18-35 years, non users of
other tobacco products or illicit
drugs, free of diabetes,
hypertension, or known HIV
MEASURES
Deficient Emotional Self
Regulation (DESR) examines:
~ Anxiety/Depressed
~ Aggressive Behavior
~ Attention Problems
Assessed for children at 3-5, 7,
9, and 11 years of age.
Social Responsiveness Scale
(SRS) examines:
~ Social Awareness
~ Social Cognition
~ Social Communication
~ Social Motivation
~ Autistic Mannerisms
Assessed for children 11 years
of age.
Key Research Finding A
The effects of adducts on DESR were not constant over time (p = 0.05)
- Among those without detectable adducts, the average DESR
score decreased substantially over time (-0.38% per year)
- Among those with detectable adducts, average DESR score
decreases minimally over time (-0.09% per year)
Implication
Developmental trajectory of self-regulatory capacity was delayed in
children exposed to PAH.
© s
5 "
-I--I
CHrtcctaUtoAtKftjcl
n = 462
Mean Time (Year)
Key Research Finding B
- Positive association between presence of PAH-DNA adducts and
problems with social competence (p < 0.04)
- Positive association between level of dysregulation and problems
with social competence (p < 0.0001)
- Evidence that self-regulation mediates the association of
prenatal exposure to PAH with social competence (p < 0.0007)
Implication
Deficits in self-regulatory capacities across early and middle childhood
lead to emerging social problems with real-world consequences for
high-risk adolescent behaviours in this minority urban cohort.
Emotional
Dysregulation
(age 9 years)
n = 262
Sobel test for mediation =
10-23 (p<0.0005)
\
Exposure
Smarter
Maternal PAH-ONA
Adducts
(prenatal)
Clinical Outcome:
Social
Responsiveness
Scale
(age 11 years)
5(PAH) - 9.W. p « 0.02
0(PAH «OJ DESR) - 0.9. p • 0.8
PRELIMINARY FINDINGS
Combined Effects of Prenatal Exposure to
Polycyclic Aromatic Hydrocarbons and Material Hardship
on Child ADHD Behavior Problems
Perera etal, 2017
ADHD symptoms
Estimate
95% CI
p value
ADHD analyzed continuously
ADHD Index
0.42
0.11-0.74
0.01
DSM-IV Inattentive
0.46
0.13-0.79
0.01
DSM-IV Hyperactive-
Impulsive
0.33
0.03-0.62
0.03
DSM-IV Index Total
0.39
0.10-0.68
0.01
ADHD analyzed dichotomously
ADHD Index
1.23
0.12-2.35
0.03
DSM-IV Inattentive
1.77
0.62-2.93
<0.01
DSM-IV Hyperactive-
Impulsive
0.50
-0.61-1.61
0.38
DSM-IV Index Total
1.40
0.35-2.46
0.01
Co-exposure to socioeconomic disadvantage (lack of adequate
food, housing, utilities, and clothing) and prenatal PAH
significantly increases the risk of ADHD behaviour problems,
particularly high PAH and persistent hardship (see table above).
CHALLENGES
\Ne experienced delays in participant recruitment and the
rate of assessment due to the need to refine the MRI protocol
for imaging the brain and abdomen in the same MRI visit.
Solution
By scheduling more visits during the summer months and
weekends, we are on target to achieve our goals.
ACKNOWLEDGEMENTS
Funding was provided by the National Institute for Environmental
Health Sciences (NIEHS) and the U.S. Environmental Protection
Agency (US EPA): NIEHS/EPA P50 ES009600-18.
-------
The Children's environmental
HEALTH & DISEASE PREVENTION
Research Center at Dartmouth
Should Rice Cereal
be an Infant's First Food?
Carolyn Murray, MD, MPH, Juliette Madan, MD, MS, Kathy Cottingham, MS, PhD, Carol Folt, PhD, Diane Gilbert-Diamond, ScD, Brian Jackson, PhD,
Susan Korrick, MD, MPH, Carmen Marsit, PhD, John Moeschler, MD, Kari Nadeau, MD, PhD, Tracy Punshon, PhD, David Robbins, PhD, Vicki Sayarath,
MPH, RD, and Margaret Karagas, MS, PhD
The
New Hampshire
Birth Cohort
Study
Specific Aims
The primary aims of our Center are to identify exposure to common
environmental contaminants such as arsenic during fetal development and
childhood; the impact these exposures have on childhood immunity, growth, and
neurological development and the mechanisms by which they may be operating.
We also are are committed to sharing these findings with key stakeholders which
include parents, pediatric health care providers, policy makers and communities.
j;
t
3
NEW HAMPSHIRE BIRTH COHORT STUDY
Formative Phase
Pregnancy ¦
* Delivery —
~~X NHBCS
1st Follow-up Phase
Months 4-8-12
2nd Follow-up Phase
12-16 Weeks
• Eligibility screen
24-28 Weeks
• Questionnaire
• Maternal blood,
urine, hair, toenail,
tap water
• Maternal diet
(FFQ, diary)
• Prenatal records,
including maternal
infection,
ultrasounds
Birth
Outcomes
Mate ma l/in fan
t health status
Cord blood
Placenta
Meconium/tra
nsition stool
(rrlicrobiome,
metabolmics)
NNNS
—
NHBCS
• Child exposures,
health/respiratory &
growth
• Infant & maternal diet
(FFQ, diary)
• Breast milk
• Infant
n ail s/u ri ne/sto o l/b I oo d
(metals/microbiome
/metabolomics )
• Vaccine response
• P ed i atri c re co rd revi ew
Child exposures,
health/respiratory & growth
Child diet (FFQ/diary, 3 & 5 y )
Child blood/urine/ stool
Neurodevelopment (3 & 5 y)
Anthropometry, BP (5 y)
Pediatric record review
¦ Cohort Location: 2 regions of rural New Hampshire
¦ Inclusion Criteria:
- Pregnant women, ages 18-45 years old;
- Receiving OB care at prenatal clinics;
- Household served by a private water system;
- No plans for moving prior to delivery;
- Singleton pregnancy;
- English speaking, literate, mentally competent.
¦ Subject Recruitment: Eligible women recruited at
~24-28 wks gestation NHBCS; 12 wks gestation ECHO
¦ Year recruitment began: January 2009
¦ Participants recruited to date: 1,741; goal 3,000
¦ Age of oldest children: 8 years
Findings
Exposures
¦ Urinaryarsenic (As) con centrati on s du ri n g pregn an cy rel ate to
both water As & rice intake (Gilbert-Diamond, PNAS, 2011)
¦ Maternal rice intake related to infant As biomarker
concentrations (Davis, JESEE, 2014)
¦ 80% of infants introduced to rice cereal in 1st yr of life
(Karagas, JAMAPeds, 2016)
¦ Breast milk low in As, & breast fed infants
had lower urinary As than formula fed infants
(Carignan, EHP, 2015)
Translation
u New results from work of our CO TC indicate that women who
receive results of elevated well water arsenic levels report less use
of their tap water for drinking, cooking, and for mixing infant formula
than women who received reports of low or no arsenic in their well water.
Mediators
¦ Infant microbiome associated with feeding mode (breast feeding, formula feeding and mixed feeding)
(Madan, JAMA Peds, 2016)
¦ Preliminary data on infant fecal metabolomics profiles
indicate differences by feeding mode (breast milk vs. formula) (Hoen, Unpublished)
Diet during first 6 weeks
Infants' Rice Cereal Introduction
Age (Months) at Introduction of Rice Cereal
Exclusively breast (ed (n^6)
Mixed fed
-------
NiCHES
Exposure To Tobacco During Pregnancy - and Even Preconception -
Can Alter Offspring's Brain Function
Theodore A Slotkin, Ashley Stadler, Samantha Skavicus, Jennifer Card, Jonathan Ruff, Brandon J Hall,
Yael Abreu-Villaca, Shaqif Junaid, Hannah White, Aptin Kiany, Lisa Guo, Zhiqing Huang, Frederic J Seidler and Edward D Levin
Presenter: Susan K Murphy
Overall Specific Aims
Aim 1: To define relevant epigenomic-transcriptomic
changes induced by nicotine exposure.
Aim 2: Examine the effect of exposure timing on
outcome and epigenetic effects.
Aim 3: Determine if methyiation mediates the
relationship between environmental tobacco smoke
exposure and ADHD-related neurobehaviors
Aim 4: Train multidisciplinary researchers to impact
environmental health sciences.
Research Findings
JT
~1
m
Controls
MvF
Pre v
Controls M,
M, F?
(MvF)
Early v
Controls
M, F?
(MvF)
Late v Controls
M, F?
(MvF)
Elevated Plus Maze
(anxiety; time in open arms)
ns
ns
(ns)
ns
(ns)
p<0.05
M + F
(ns)
Figure 8 Apparatus (activity-
adolescent; beam breaks per 5 minutes]
p<0.07
ns
(ns)
ns
(ns)
p<0.025
M + F
(ns)
Figure8 Apparatus (activity-adult;
beam breaks per 5 minutes)
p<0.005
p<0.025
M
ns
0x0.05)
ns
0x0.005)
Figure8 Apparatus (habituation -
adolescence; linear trend 5 min blocks)
ns
p<0.05
M+F
(ns)
ns
(ns)
ns
(ns)
Figure 8 Apparatus (habituation -
adult; linear trend 5 min blocks)
ns
ns
(ns)
ns
(ns)
ns
(ns)
Radial Arm Maze (working memory
errors, fed)
ns
p<0.05
M+F
(ns)
ns
(ns)
ns
(ns)
Radial Arm Maze (working memory
errors, restricted)
ns
ns
(ns)
ns
(ns)
ns
(ns)
Radial Arm Maze (working memory
errors, ted versus restricted)
p<0.005
ns
p<0.05
ns
Attention Task (hits)
ns
ns
p<0.025
M + F
(ns)
p<0.05
M + F
(ns)
Attention Task (correct rejection)
ns
ns
ns
ns
Acetylcholine and
serotonin synaptic
markers
• Original data shown in
(i); collapsed data in (ii)
through (vi).
• Frontal/parietal cortex
(f/p). temporal/occipital
cortex (t/o), midbrain
(mb). brainstem (bs),
hippocampus (hp),
striatum (st)
• 1 male and 1 female
used per litter
™]
Preliminary Research Findings
o*
Tobacco Smoke Exiract
0.2 mg/kg/day
14 days
> Sperm
N=12 per group
Reduced
. Representation
Bisulfite
Sequencing
Possibility of
paternal
transmission?
V 0.6-
£
CpG Sites
FDR<0.05
m
A i
¦n
Controls Exposed
Chromosome:
Nucleotide
Gene
Symbol
Gene Name
FDR
Exposed
vs.
Controls
chrl:222417370
Macrod
macro domain-
0
7.3%
chr1:222417354
1
containing 1
0
-47.4%
chr5:173290694
Mxra8
matrix remodeling
6.3E-07
-47.5%
chr5:173290712
associated 8
1.6E-04
1.0%
chrl 1:38457229
Zfp295
zinc finger protein
295
.4E-06
27.6%
chrl 8:24735001
1.2E-05
-61.7%
chrl 8:24734964
chrl 8:24735036
chrl 8:24734922
Lims2
LIM zinc finger
domain containing 2
1.2E-05
1.2E-05
1.7E-04
-62.1%
-62.1%
-58.0%
chrl 8:24735041
.4E-04
-57.7%
chr5:118348170
Foxd3
forkhead box D3
1.7E-05
-39.1%
Tdrd6
tudor domain
chr9:19923667
containing 6
2.3E-05
-48.6%
chrl 0:93520461
chrl 0:93520484
tetratricopeptide
repeat, ankyrin
repeat and coiled-
coil containing 2
1.2E-03
1.4E-03
-33.1%
-30.5%
Challenges
• Analysis of brain regions mutes effects of
epigenetic alterations in specific cell
types
• Translation to humans
• confounders
• orthologous regions
• difficult to assess preconceptional
exposures
This work is supported by the National Institute of Environmental Health Sciences of the NIH under award number P01ES022831 and by the United States EPA grant RD-83543701-0 and CR-83242401-0. The content is solely the reflection of the grantee and does not
necessarily represent the official views of the NIH or the USEPA. Additional support was provided by Grant Number UL1TR001117 from the National Center for Research Resources (NCRR), a component of the NIH and NIH Roadmap for Medical Research.
m
-------
C-CHEM
American Women in Metro Atlanta Have Higher Levels of Endocrine Disrupting Plasticizers in Their Bodies Than Other African American Women
P. Barry Ryan1, Anne L. Dunlop2, Dana Boyd Barr1, and Linda A. McCauley2
1Emory University Rollins School of Public Health, 2Emory University Nell Hodgson Woodruff School of Nursing
EMORY
UNIVERSITY
CENTER OVERVIEW
Emory University's Center for Children's Health the Environment, the
Microbiome, and Metabolomics (C-CHEM2) involves analysis of a multi-
component, longitudinal birth cohort of African American women and their
offspring in metropolitan Atlanta to evaluate the influence of environmental
exposures on the maternal and infant microbiomes and metabolomes. We
hypothesize that this may ultimately lead to neurodevelopmental sequelae
in children.
RESEARCH FINDINGS
To date, 216 mothers have been enrolled in our birth cohort study and 55
children have been born. We have collected 215 urine and 210 serum
samples at enrollment (8-14 weeks gestation) at the hospital; 101 urine
samples, 101 dust samples and 25 air samples during the home visit at 20-
24 weeks gestation; and 129 urine and 129 serum sample at the second
hospital visit at 24-30 weeks gestation. Postnatal dust samples (N=61) have
also been collected along with infant urine samples at 1 week (N=70), 3
months (N=49), 6 months (N=34), 12 months (N=24) of age, 18 months
(N=13) between C-CHEM2 and the Parent Study.
BIOLOGICAL AND ENVIRONMENTAL SAMPLES COLLECTED AND PROCESSED
Hospital Urine Visit 1
215
Hospital Urine Visit 2
129
Home Urine
101
Serum
108
Prenatal Home Dust
101
Postnatal Home Dust
61
Home Air
25
Baby Urine 1 wk
70
Baby Urine 3 mo
49
Baby Urine 6 mo
34
Baby Urine 12 mo
24
Baby Urine 18 mo
13
SUPPORTIVE RESULTS
We measured urinary BPA and phthalates in 366 urine samples to date. The
geometric mean concentration of urinary mono-ethylphthalate, a
metabolite of diethylphthalate that is used in many personal care products,
was almost 30% higher than the national average for African American
women of reproductive age and nearly 3 times the levels found in non-
African American women in the US population. Note the log scale in the
figure.
MEP
!>
S. iooo
Similarly, mono-butyl phthalate was higher in our population than in African
American or non-African American women in the US population. Notably,
metabolites of di-2-ethylhexylphthalate were about 30% lower in our
population than in the general US population.
Number of
Samples
Mean
Standard Deviation
Minimum
Maximum
LOD
BPA MEP MBP MiBP MBzP MEHP MEOHP MEHHP MECPP
366 288 287 278 287 267 287 286 288
2.34 422.53 24.75 16.18 15.56 4.36 6.67 8.78 10.67
7.7347603.83 38.38 20.31 27.67 6.67 10.05 13.76 14.18
0.2 4.97 0.43 0.08 0.09 0.07 0.06 0.38 0.28
139.69 1443.26 374.29 136.37 222.66 58.2 112.97 169.55 114.58
0.02 0.2 0.2 0.1 0.1 0.1 0.2 0.2 2.5
OTHER FINDINGS
In addition to phthalates and alkylphenols, we have measured PBDEs,
cotinine and pesticide metabolites in a subset of our population to survey
exposures. PBDE 47 was detectable in 100% of the samples analysed with
frequent detection of PBDEs 99 and 100. Urinary cotinine levels were
higher than expected as few women report smoking during pregnancy.
Despite the self-report of not smoking, about 30% of the samples tested
fell within the range of smokers. Pesticides metabolite levels were higher
than US population levels likely reflecting more prevalent use of pesticides
in the Southeast.
CHALLENGES
Developing a messaging protocol to report study findings to participants
has been challenging. Participants have been very engaged in the study
and are very interested in their personal results and in the overall study
results. However, developing a message that is accurate, informative and
contextual has proven difficult. We are developing several templates for
reporting results and plan to seek community advisory board input on the
more effective format to use. Please see our COTC Presentation.
ACKNOWLEDGEMENTS
This work was supported by NIEHS: P50ES026071 and EPA: 3615301.
m
Ln
-------
A
BREATHE
CENTER
AIRWEICHS
~ JOHNS HOPKINS
4
CSTS W CJIDHQQOASTHW ft T-l 15S4M 9uP:WE>T
MtAfHaWH OK • MIAIMHf* W,
K) IIJJ «V«M» |WJ 3771?J7| #
Obesity and Diet as Susceptibility Factors to Air Pollution Exposure
Meredith McCormack MD MHS, Greg Diette MD MHS, Jessica Rice, MD, Vsevolod Polotsky MD, Laura Paulin MD MHS, Emily Brigham, MD MHS,
Michelle Eakin PhD, Cynthia Rand PhD, David Wu MD, Ashraf Fawzy, MD, Nirupama Putcha MD MHS, Kirsten Koehler, PhD, Nadia Hansel, MD MPH
INTRODUCTION
The Center for Childhood Asthma in the Urban Environment is currently investigating the role of obesity and diet as determinants of susceptibility to air pollution among children
with asthma. This is a key step in achieving the Center's overall goal of developing strategies to reduce susceptibility and exposure to the harms of indoor air pollution.
Obesity Modifies the Effects on Secondhand
Smoke on Pediatric Asthma Symptoms
Omega-3 and Omega-6 Intake Modify the Effects
of Indoor PM on Pediatric Asthma Symptoms
Obesity leads to the development of Airway Hyper-
responsiveness in Mice
METHODS
Two independent cohorts of 150 Mouse Allergen Asthma Cohort
Study and 162 in the DISCOVER study of children with asthma
Both cohorts included children in Baltimore city with active asthma.
Atopic status determined by skin or RAST
Week-long environmental at baseline, 3, 6, 9, and 12 months;
• Airborne nicotine and PM2.5
Spirometry, fractional exhaled nitric oxide (FeNO), height, weight
measured at each assessment period. Urine at 0,6,9 months
Associations between SHS and asthma outcomes were modeled
by GEE, and effect modification by BMI category was tested.
METHODS
137 inner-city children with asthma enrolled in the Asthma Diet Study
Home air monitoring for one week at baseline, 3, and 6 months
Dietary intake assessed at each monitoring period via a Baltimore-specific food
frequency questionnaire (FFQ).
• Average daily intake of omega-3 and omega-6 derived from FFQ.
Daily symptom diary each week-long period. Presence of trouble breathing,
bothered by asthma, activity limited by asthma dichotomized to present/absent.
Associations between indoor PM and asthma outcomes were modeled by
GEE, and effect modification by omega 3 and 6 intake was tested
Models adjusted for age, gender, BMI, asthma severity, caloric intake,
caregiver education level, ICS use, and season.
RESULTS
RESULTS
METHODS
64 C57BL/6J male mice (Jackson Labs), 6-8 weeks old, were studied.
n=32 for the obese mice group, n=32 for the food restriction group
8 mice in each group were fed with either chow diet (CD), high fat diet (HFD), high
fat diet with 30% fructose (HFD+ HFr) or high trans-fat diet with 30% fructose
(HTFD+ HFr). In food restricted group, all mice were weight matched to CD mice
and provided limited amount of food twice a day.
After 8 weeks of exposure to different diets mice were anesthetized with
intraperitoneal ketamine and succinylcholine. Tracheostomy was performed and
mice were attached to computer controlled ventilator (Flexivent) to calculate
airway hyper-responsiveness (AHR). Lung resistance (Rrs) was measured at
baseline and after methacholine aerosol challenge (1,3,10,30 mg/ml).
Mice euthanized and bronchoalveolar lavage (BAL) was performed and IL-1 (3 were
measured . Blood was then collected and lungs were harvested.
• 48% of all participants were overweight/obese.
• 49% had SHS exposure based on urine cotinine (MAACS) and 73% had
detectable home air nicotine (both studies)
• Overweight/obesity modified associations between SHS and asthma morbidity
• SHS exposure in MAACS associated with greater odds of asthma-limiting
activity among obese (2.69 [1.23-5.85]) and overweight (3.25 [1.17-9.03])
compared to normal weight children (1.13 [0.66-1.91])
• SHS exposure in Discover associated with greater trouble breathing among
obese (aOR 1.43 [95% CI 1.01-2.01]) compared to overweight (1.35 [0.81-
2.25]) or normal weight children (0.85 [0.61-1.21]) (p-interactions<0.1).
Figure 1. The association between increasing urine cotinine concentration and
predicted days of maximum asthma symptoms per two, stratified by BMI category.
Normal Weight
Ovefwe*ght
Obese
10 100
Urint Cotinine (ng/ml)
Challenges and Implications
Mean age 9.5 years (SD 2.2), 64% female, 96% African-American, majority
had public insurance (91%)
Mean omega-6 levels [5.2 g (SD 4.1 g)] and and omega-3 [0.36 g (SD 0.19)].
Mean PM2.5 level 34 |jg/m3 (SD 32)
Increasing omega-3 intake associated with reduced effect of indoor PM25 on
daytime symptoms (p-interaction <0.05)
Increasing omega-6 intake associated with increased effect of indoor PM25 on
daytime symptoms (p-interaction <0.05)
Figure 2. Conditional marginal effects of indoor PM2.5 on daytime symptoms varies
by intake level of omega-3 and omega-6 fatty acids among children with asthma.
The Effect of Indoor P Ms,* on Daytime Symptoms Varies
\»tth Omega-3 and Omega-6 Fatty Acid Hake
Reported Daily Fatty And htaka
RESULTS
IL-1 (3 gene expression was increased in lung tissue of obese mice on hypercaloric
diets, whereas no increase was seen in food restricted mice (P-value<0.05) (Fig 3A
and B). In food restriction group there was no difference in AHR in all diets. However in
obese group, there was significant increase in AHR at 30 mg of methacholine in all
hypercaloric diets. The Rrs was 7.1 cmH20.s/mL in HFD, 6.8 cmH20.s/mL in HFD +
HFr, 6.24 cmH20.s/mL in HTFD + HFr and 4.59 cmH20.s/mL in CD (p-value >0.05).
The AHR in all diets was normalized to CD. (Fig 3C and D).
Figure 3: Obesity increases IL-1 (3 gene expression and AHR regardless of the type
of hypercaloric diet consumed (Fig B and D). High fat diet had no effect on IL-1 (3
gene expression or AHR if calorie restricted and not leading to obesity (Fig A and C)
I . .
O 4
c i:
Methacholine dose (mg/mL)
Methacholine dose (mg/mL)
Conducting home based environmental research requires building trust and ensuring two way communication. The work of our community outreach core with the input of the
Community Research Advisory Council has built bridges and fostered trust that has enabled us to successfully complete these projects.
The study of diet, obesity, and indoor pollution is complex. We have used unique study designs, including dietary feeding studies and air pollution reduction strategies in
ongoing work, to perform studies that will have the ability to build an evidence base supporting causality.
-------
Center for Research on Early Childhood Exposure and
Development in Puerto Rico (CRECE)
RECE
John Meeker, Jose Cordero, Deb Watkins, Zaira Rosario,
Carmen Velez, Gredia Huerta-Montanez, Emily Zimmerman,
Phil Brown, Helen Suh, April Gu, Akram Alshawabkeh
Presented by:
(IT
Northeastern
UJPR earths^ft
The University ofGeorgia o
\ SILENT SPRING INSTITUTE
Center Description
CRECE is a Children's Environmental Health Center that studies how mixtures of environmental
exposures and other factors affect the health and development of infants and children living in the
heavily-contaminated island of Puerto Rico—an underserved, highly-exposed, and low-income
population with significant health disparities. CRECE recognizes that many exposures including air
quality, water quality, consumer product use, and psychosocial dynamics that can combine to
create adverse health effects during infancy and childhood. CRECE is using a holistic strategy known
as the "exposome" that captures the totality of the environment. As a multi-project Center, CRECE
will couple air-pollution epidemiology (Project 1), high throughput toxicity screening of multi-
media pollutant mixtures (Project 2), and biomarker epidemiology (Project 3) to analyze the
impacts of early life exposure on fetal/child health and development, taking into account
environmental, clinical, social, demographic, behavioral, dietary, and other factors. CRECE's mission
is to be a vital and informative children's environmental health resource for researchers, cohort
articipants, the broader underserved Puerto Rican community, and beyond.
Low income, Latino
population
CRECE Integrated
Knowledge
Data Analysis
> 200 hazardous
waste sites,
16 Superfund |
sites,
high air pollution
Highest rate (16.5%) of childhood
asthma in the U.S. (vs. 7.9% for
Hispanic children on the mainland);
High preterm birth rate;
Similarly autism and child obesity.
rKUJtn
10®
@0©
I
Exposure to Triclosan in
Pregnancy is Associated with
Increased Inflammation
Air Pollution and Development
200
Multiple Chemical
Mechanistic Screening
3 ©O©
®©
Lab Analysis
CECs and Development
Human
Subjects
Core
OG
©CD C)0
Community and
Translation Core
As part of the PROTECT cohort study, pregnant women were recruited early in pregnancy
(<20 weeks gestation) between 2010 and 2012 in 7 prenatal clinics and hospitals in Northern
Puerto Rico. At the initial study visit (Visit 1; 16-20 weeks gestation) women provided urine
and blood samples and filled out detailed questionnaires. At Visit 2 (20-24 weeks) a second
urine sample was collected, and at Visit 3 (24-28 weeks) both urine and blood samples were
collected again. Women were followed until delivery and birth outcome data was recorded.
All urine samples were analyzed via LC-MS/MS at the National Center for Environmental
Health of the CDC for five phenols: bisphenol A (BPA), triclosan (TCS), benzophenone-3 (BP-3),
2,4-dichlorophenol (2,4-DCP), and 2,5-dichlorophenol (2,5-DCP); and three parabens (butyl
paraben (B-PB), methyl para ben (M-PB), propyl paraben (PPB). Specific gravity was also
measured in each sample to account for urinary dilution.
For 120 subjects, plasma samples (N=215 total samples) from visits 1 (N=119) and 3 (N=96)
were available for measurement of C-reactive protein (CRP) as well as 4 cytokines (IL-1|3, IL-6,
IL-10, and TNF-a). For 58 subjects, urine samples (N=162 total) from visits 1 (N=58), 2 (N=54),
and 3 (N=50) were analyzed for 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane as
indicators of oxidative stress. Linear mixed models were used to estimate associations
between exposure and inflammation markers, adjusting for visit number, maternal pre-
pregnancy BMI, education, and specific gravity.
| KEY:
«Ss?rnp*«: O©W"5 (J)B012 0°~"onr,""
. /Tf\ Reproductive Development
Biom«rk« (gjj pt^, Growth
PROTECT Data _
and Samples: Q Water
(|Q) Data Questionnaires
Comparison of exposure biomarker concentrations to NHANES Product use in relation to exposure biomarker concentrations
Exposure
Biomarker
Product used in
previous 48 hours
Yes, ng/rr
(Geo Me
L No, ng/m
n) (Geo Me
L P-value
in)
Triclosan
Liquid Soap
36.7
18.5
0.06
Hair Spray
50.0
27.5
0.05
BP-3
Sunscreen
503
49.8
0.001
Hand/Body Lotion
62.7
30.1
0.05
Mou thwa sh
75.5
37.2
0.03
Change in inflammation or oxidative stress marker in relation to interquartile range increase in exposure biomarker
95% ci
8.05, 59.9
19.9,13.1
7.76. 29.1
TherfftECE Center is jointly supported by Award Number P50ES026049 from the National Institute of Environmental Health Sciences and Assistance Agreement Number 83615501 from the
U.S."^Vivi ran mental Protection Agency. The content and views expressed here are the sole responsibility of the authors and do not necessarily represent the official views of the EPA, NIEHS,
or the National Institutes of Health. CRECE has not been formally reviewed by the EPA, and the EPA does not endorse any products or commercial services mentioned here.
Other Preliminary Research Findinss:
Follow-up of children is ongoing, we are collecting data on:
Health Measure
Study Visits
Prenatal (week)
Birrtv
Post-
Delwery
Child (age in years)
18-20
30-24
24-29
0
1
2
3
•
Demographic
/
/
/
~
/
/
/
/
Medical Record*
/
/
~
~
~
/
~
Maternal Suess
/
~
~
/
~
~
/
~
'
Birth Outcomes
/
NNS
~
Developmental
Measure*
~
~
~
~
~
~
Respiratory Symptoms
~
/
/
~
~
'
Challenge: Hurricane Maria
Hurricane Maria left a devastating path of destruction throughout the
island that continues to be an extremely serious humanitarian and
public health crisis. Lack of electricity and access to clean water and
other resources remains a huge concern. CRECE researchers and staff
in Puerto Rico have been on the front lines of these recovery efforts.
Photo Credits: Gredia Huerta-Montanez, Carmen Velez, Colleen Murphy
!Sf
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~ riortheastern.edu/crece
-------
"All the Research
That's Fit to Publish"
tllje Circle I)o5t-€>teeito'
EARLY EDITION
Today, sunny, high 80.
Tonight, clouds, low 54.
Tomorrow, still really nice,
welcome to the Bay.
VOL. 50 No. 18172
©2017 The Circle Post-Observer
BERKELEY, TUESDAY, OCTOBER 24, 2017
$2,00
Toxic PCBs Still Threaten Children
Despite long-time bans, California homes remain
polluted with PCBs-posing cancer risk for kids
This article was written by the Center
for Integrative Research on Childhood
Leukemia and the Environment.
BERKELEY, CA - During the 1970s
polychlorinated biphenyls, the erstwhile
industrial wonder-compounds, were
banned from production in the U.S.
due to concerns over possible toxicity,
persistence in the environment, and
bioaccumulation within the food chain.
Like Frankenstein's monster, "PCBs"
turned on their creators - with their
engineered properties, initially so
useful, ultimately becoming monstrous.
Now, forty years later, PCBs are still
"ALIVE!"and we, the pitch-fork wielding
villagers, are still reluctantly chasing the
menace away from our children.
Researchers from the University of
California-Berkeley sampled dust from
the floors of local residences and found
that PCB pollution remains widespread
- with the toxins detected in each of
the nearly 300 participating homes.
Subsequent research revealed that
PCBs were also present in the blood of
children with leukemia, in proportion to
the levels observed in the house dust.
After noting that PCB levels were
elevated in dust from the homes of
leukemia patients, the investigators
deduced the cancer-causing effect of
Continued on Page A2
A Stiff Chemical Cocktail
PCBs sold in "aroclor" mixtures,
found alongside other pollutants -
implicating one culprit is difficult
DURHAM, NC- R.J. Reynolds, American
Tobacco Company, Liggett & Myers -
all of the country's biggest cigarette
makers, the purveyors of the stiffest
toxic cocktails in the world - have their
shops on Tobacco Road. It was here in
2015, at the birthplace of so many icky
chemical concoctions, that NIEHS
convened a think-tank of experts to
find the best way to assess the impact
of these mixtures in health studies.
Today, CIRCLE uses new approaches
- weighted quantile sum regression,
targeted machine learning, dimension
reduction - to account for groups of
Continued on Page A3
CIRCLE investigators are taking aim on cancer. Pl credit Dr Catherine Metayer
Aims for the 2nd cycle of CIRCLE, a Children's Environmental Health Center in Berkeley CA.
Immune
1^1 Development
Find links between
in utero exposures,
fetal immune
development, and
'childhood leukemia.
Exposomics
Discover in utero
exposures that
, cause childhood
leukemia using
meta bolomics
and adductomics.
Epigenetics
Assess the impact
of environmental
changes to DNA
methylation on
childhood
leukemia risk.
Yuck!
Toxic industrial
New Research To Prevent Future Cancer Cases
CIRCLE investigators evaluating abnormal immune development,
epigenetic changes as causes of PCB-induced childhood leukemia
By Todd Whitehead
SAN FRANCISCO, CA - Nestled below
Pacific Heights (one of the city's most
affluent neighborhoods) - there is a
family of mice that, by all appearances,
lives in the lap of luxury. Unlimited
cheese snacks, top-notch veterinary
care, clean cages, and NO CATS!
The bad news? The mice have been
bred to harbor a genetic weakness for
cancer and the food is laced with PCBs.
They live at the Mouse Pathology
Core of the UCSF Helen Diller Family
Comprehensive Cancer Center and they
do important work - helping to prevent
future children (the human kind) from
being diagnosed with leukemia.
By exposing the mice to PCBs
prenatally and tracking their health,
CIRCLE investigators learn more about
how chemicals cause leukemia in utero.
Findings from the controlled rodent
experiments will be corroborated by
observational studies of humans, with
the Center investigating two potential
cancer-causing mechanisms in CA kids
- abnormal fetal immune development
and in utero epigenetic perturbations.
To help gauge the status of a child's
immune development, the researchers
are turning their attention to IL-10, a
"cytokine" (or signaling protein) that
helps immune cells communicate. They
will measure this biomarker of immune
health in a single blood drop collected
at birth and determine the causes and
consequences of stilted development.
Preliminary evidence points to a
suspicious link between prenatal PCB
exposures and IL-10 levels at birth.
In the same blood drop, researchers
will measure DNA methylation and test
whether PCBs can flip the epigenetic
Continued on Page A6
fiber—are
Protected from y
the elements, A
PCBs are very *
persistent indoors.
Dust particles—trapped under
dense forests of carpet
reservoirs
for chemicals.
Photo Credit Doira Krug
chemicals are lurking deep within the carpet under your feet.
-------
[JCSF Fres
no
577
Ambient Air Pollution Impairs Immune Function which Impacts Allergy and Asthma
SK Hammond, JR Balmes, GM Shaw, K Nadeau, FW Lurmann, E Eisen, JK Mann, EM Noth, John Capitman
University of California, Berkeley; Stanford University; Fresno State; Sonoma Technology, inc.; UCSF-Fresno
CHAPS
V*/
jn Study
ABSTRACT
In earlier work, we showed that exposure to ambient air pollution
was associated with hypermethylation of the forkhead box protein 3
(FOXP3) locus, impairing regulatory T-cell (Treg) function and
increasing risk of asthma morbidity. In a later follow-up study with a
larger sample size we showed that exposure to ambient polycyclic
aromatic hydrocarbons (PAHs) in Fresno, CA was significantly
associated with impaired Treg function, increased methylation of
FOXP3, and differential expression of the FoxP3 protein, especially in
children with allergies. Methylation was associated with Treg
dysfunction and an increase in total plasma IgE levels. Our findings
were supported by those of another group that reported FOXP3
hype rmethylat ion was associated with diesel exhaust exposure and
risk for childhood asthma. We have also shown that ambient PAH
exposure is associated with increased respiratory symptoms in
children with asthma as well as lower lung function in children
without asthma in Fresno. In addition to exposure to PAHs, we have
recently shown that short-term and long-term exposures to high
levels of CO, N02, and PM25 were associated with alterations in CpG
site methylation of FOXP3 and IL-10. Collectively, these results
demonstrate that increased exposure to traffic-related air pollution
is associated with impaired systemic immunity and epigenetic
modifications in a key locus involved in allergy: FOXP3, with a higher
impact on allergic children. The results suggest that increased
exposure to air pollution is linked to increased allergic and asthmatic
symptoms in children.
AIMS
Project 1; To advance scientific understanding of the potential
contribution of social and environmental etiologies of birth defects and
preterm birth.
Project 2: To determine the molecular mechanisms by which immune
dysregulation leads to human disease, specifically the atopic diseases
of food allergy, allergic rhinitis, allergic conjunctivitis and allergic
asthma in children exposed to high levels of PAHs (polycyclic aromatic
hydrocarbons).
Project 3: To assess whether exposure to outdoor air pollution during
childhood contributes to the development of the metabolic syndrome
in adults.
Project 4: To test the hypothesis that neighborhood characteristics
have a direct and quantifiable relationship with an individual's transit
patterns which affect personal exposures to traffic related air pollution
(PAHs, PM25, and BC).
CHAPS STUDY QUESTIONS
Fig 1. The Directed Acyclic graph (DAG) shows how our four projects
link together as an overarching hypothesis. Immune modulation of the
part of the immune system that reflects t-regulatory cell activity is the
centerpiece of all of our study questions.
RESULTS
Immunologic Modulation
2. Obesity & Glucose
Dysregulation
3. Allergy/Asthma/Atopy
4. Pulmonary Function
Air pollution
Neighborhood
Initial Hypothesis
CHAPS/P20
CHAPS/P01
Fig 2. Hew et al.,
2015: Methylation
was associated
with Treg
dysfunction and an
increase in total
plasma IgE levels.
Protein expression
of IL-10 decreased
and IFN-
y increased as the
extent of PAH
¦
Fig 2. Nadeau et al., 2010: Exposure to
ambient air pollution, specifically PAHs, is
associated with hyper-m ethyl at ion of the
FOXP3 locus, impairing Treg cell function
and increasing asthma morbidity.
Air Pollution/Exposure Assessment
Exposure Study in Bakers field, CA (Noth et al., 2016)
• To update our model to estimate subject specific PAH
concentrations, 96-hour integrated PAH samples (n=58) were
collected during four time periods at 14 locations from
November 2010 to January 2011 in Bakersfield, CA.
• individual exposures to PAHs and EC are higher near high
traffic roadways and rail lines (see Figure 5)
Preliminary: Long term trends in air pollution concentrations.
• Observed a long-term declining trend in PAH concentrations
in Fresno from 2000-2017. The most intense decline was
from 2000-2004 (see Figure 5). Similar declines seen with
NO, and BC.
Obesity/Glucose Dysregulation
Preliminary Results:
In the child cohort at baseline (ages 6to 8, n=221):
• BMI percentile was positively associated with 6-month average N02, NOx, and PAH among boys.
• 3-month average PAH and PM2 5 associated with elevations of HbAlc (%) .
• PAH, EC, N02, 03 and PM2 5 associated with elevated 8-isoprostane levels over many averaging
times.
• 3-month average N02 was associated with an increase in 13.7 mm Hg systolic blood pressure.
Look at effects
across 3 cohorts:
• infants
• Children (6-8)
• Adolescents/
Young Adults
Updated PAH
models
Study Obesity/
Glucose
Dysregulation
Fig 3. Prunicki et al.
(submitted): Both short-term and
long-term exposures to high levels of
CO, 03, N02, and PMZS are
associated with alterations in CpG
site methylation of FOXP3 and IL-10.
Birth Outcomes
Neural Tube Defects in Children with Hispanic Mothers
(Padtila et al., 2017)
• Increased odds of neural tube defects (NTDs),
particularly spina bifida, in children born in the San
Joaquin Valley (1997 to 2006) whose mothers had high
exposures to CO, NO, or N02 and lived in
neighborhoods that were more acculturated.
• Conversely, there were increased odds of NTDs for
those who had high prenatal exposure to PM10 and
lived in neighborhoods that were less acculturated.
• CO, NO, and N02 exposures were more strongly
associated with NTDs among U.S.-born vs. foreign-
born Hispanic mothers.
Genetic variation in biotransformation enzymes, air
pollution exposures, and risk of spina bifida (Padula et
a!., submitted)
• We evaluated the role of air pollution exposure during
pregnancy and gene variants of biotransformation
enzymes from bloodspots and buccal cells in a case-
control study (86 spina bifida and 208 nonmalformed
controls).
• Observed several gene-environment interactions
between pollutants and gene variants.
SES/Neiqhborhood
Lessard et al., 2016
• Neighborhood exposure to traffic pollution as well as neighborhood segregation and poverty predict risk for avoidable hospitalization and ER use
among children 1-14. Children under 5 are at greatest risk for these events.
Preliminary Result:
• Neighborhood social disorganization and walkability predict asthma hospitalization and ER visits among children 1-14.
• Parents of infants and young children reported low income, food insecurity, severe crowding and inability to live on income at follow-up visits.
CHALLENGE
In 2015 we began to use mass cytomtery (CyTOF) instead of flow
cytometry because of CYTOF's ability to measure more cell surface
markers, increased sensitivity and cell recovery rates. However, the large
volume of data obtained with CyTOF required us to obtain statistical
expertise to employ analytical approaches such as clustering,
dimensionality reduction, and predictive modeling.
REFERENCES
Lessard, L.N. Alcala, E. Capitman, J.A. (2016). Pollution, poverty, and
potentially preventable childhood morbidity in Central California. J
Pediatr; 168:198-204.
Noth, E.M., Lurmann, F., Northcross, A., Perrino, C., Vaughn, D., Hammond,
S.K. (2016) Spatial and temporal distribution of polycyclic aromatic
hydrocarbons and elemental carbon in Bakersfield, California. Air Quality
Atmosphere and Health ; 9(8): 899-908. doi:10.1007/sll869-016-0399-y
Padula AM, Yang W, Carmichael SL, Lurmann F, Balmes J, Hammond SK,
Shaw GM. Air pollution, neighborhood acculturation factors, and neural
tube defects among Hispanic women in California. Birth Defects Res. 2017
Apr 3;109(6):403-422. doi: 10.1002/bdra.23602. Epub 2017 Feb 21
Nadeau K., McDonald-Hyman C, Noth EM, Pratt B, Hammond SK, Balmes J
et al. (2010). Ambient air pollution impairs regulatory T-cell function in
asthma. J Allergy Clin Immunol. 126(4), 845-852 e810.
doi:10:1016j.jaci.2010.08.008
Hew, K.M., Walker, A.L., Kohli, A., Garcia, M., Syed, A., McDonald-Hyman,
C., Noth, E.M., Mann, J.K., Pratt, B., Balmes, J., Hammond, S.K., Eisen, E.A.,
Nadeau, K.C. (2015). Childhood exposure to ambient polycyclic aromatic
hydrocarbons is linked to epigenetic modifications and impaired systemic
immunity in t-cells. Clin Exp Allergy. Jan;45(l):238-48. doi:
10.1111/cea.12377.
Prunicki M, de Planell-Saguer M, Lucas RW, Hammond SK, Balmes JR,
Zhou X, PaglinoT, Sabatti C; Miller RL; Nadeau KC. Exposure to N02, CO
and PM2.5 is linked to regional DNA methylation differences in asthma,
(submitted)
Padula AM, Yang W, Schultz K, Lee C, Lurmann F, Hammond SK, Shaw GM.
Genetic variation in biotransformation enzymes, air pollution exposures,
and risk of spina bifida, (submitted)
ACKNOWLEDGMENTS
The authors gratefully acknowledge the funders of this research, which was
performed as part of the University of California, Berkeley/Stanford Children's
Environmental Health Center funded by NIEHS 1P01ES022849 and EPA
RD83543501 This work was also supported by the National Institute for
Environmental Health Science (R21ESO14891; P20ES018173; K99ES021470) and
the March of Dimes Prematurity Center at Stanford University. This publication
was made possible by US EPA STAR Grants RD83459601 and RD83543501. Its
contents are solely the responsibility of the grantee and do not necessarily
represent the official views of the US EPA. Further, the US EPA does not endorse
the purchase of any commercial products or services mentioned in the
publication.
y
Notional Institute of Environmental Health Science*
-------
UC Davis Center for Children's Environmental Health
Judy Van de Water, PhD, Director
¦ Leverage the vast research resou rces generated by the retrospective
case-control study. Childhood Autism Risk from Genes and Environment
(CHARGE Study) and the prospective cohort study. Markers of Autism Risk
in Babies-Learning Early Signs (MARBLES Study).
• Build upon our novel findings of calcium deregulation in cultured neurons
and Immune cells in the context of understanding the eplgenetic effects
and ramifications of toxicant exposure on gene pathways and Immune
function.
• Develop and apply nw blomarkers of autism risk, through analysis of
gestational and neonatal Immune dysfunction, genetic susceptibility, and
environmental exposures, to best characterize the potential health effects
at various life stages and predict longer-term clinical and behavioral
consequences.
CAN CYTOKINES PREDICT AUTISM?
Neonatal Cytokine Profiles Associated with Autism Spectrum
Disorder Paula Krakowlak, Paula E. Golnes, Daniel J. TancredL Paul Ashwood,
Robin L Hansen, Irva Hertz-Plcclotto, Judy Van de Water
BACKGROUND: Autism spectrum disorder (ASD) is a complex
neurodevelopmental condition that can be reliably diagnosed at 24 months.
Immunological phenomena, Including stewed cytokine production, have been
observed among children with ASD. Little Is known about whether immune
dysregulation Is present before diagnosis of ASD.
METHODS: The authors examined neonatal blood spots from 214 children
with ASD (141 severe, 73 mild/moderate), 62 children with typical
development; and 27 children with developmental delay as control subjects
who participated In the CHARGE Study. Levels of 17 cytokines and chemoldnes
Were compared and In relation to developmental and behatvoral domains.
RESULTS
RESULTS: Interieukln (IL)-1S and IL-4 were Independently associated with ASD
compared with typical development although these relationships varied by
ASD symptom intensity. Elevated IL-4 was associated with Increased odds of
severe ASD (OR=1.40,95H CI, 1.03,1.91, whereas IL-1B was associated with
increased odds of mild/moderate ASD (OR=3.02,95% CI, 1.43,636).
Additionally, IL-4 was associated with a higher likelihood of severe ASD versus
mild/moderate ASD (0R=135,95% a, 1.04,1.75). In many children with ASD,
IL-4 was negatively associated with nonverbal cognitive ability (fl=-3,63.
SE-1.33,p=.04).
«h
192
M? Id I6 W.W Ml ((41, « \»i >«l
1.B ilM ITS) IN 140 Il.tmih Ml I# on
<1 HIAfDlw
CHALLENGE & RESPONSE
Challenge; Produce human IPSC-derived neurons with mature phenotypes
In a consistent and robust manner
Response: Develop alternative human cell-based modes: (1) LUHMES
neuronal cell line; (2) differentiation of human epidermal neural crest cells
Into neurons
PRELIMINARY FINDINGS
Effects of Autlsm-Relevartt Inflammatory Cytokines on Neurlte
Outgrowth and Toxicity in the Human LUHMES Neuronal Cell
Line Lauren Matelsla, Ana Cristina Grodzki, Judy Van de Water, Pamela Lein
Nuclear factor kappa-llght-chaln-enhancer of activated B cells (NF-kB) is a
protein found In almost all cell types and mediates regulation of Immune
response by Inducing the expression of Inflammatory cytokines and
chemoldnes, establishing a feedback mechanism that can produce chronic or
excessive Inflammation.
Differentiation Day 6
TNP-u
[a
=7-8 wotts: *"p<0 0001 vs vehicle control (V)
ine-way AT J OVA wflh Ounnett's ies! for multiple eomMMon
NF4(B P65, Mtl III TUBO, and
These data suggest that Inflammatory cytokines such as are seen In
maternal Immune activation have a direct effect on the development of
neurons.
Future Studies: We will repeat the LUHMES cell work, as well as
add concomitant toxicant exposure to determine if
the effects are additive.
ACKNOWLEDGEMENTS
This work Is funded by the US Environmental Protection Agency (Grant
#93543201), the National Institute of Environmental Health Sciences (Grant
#P01 ES011269, Grant #R01 ES015359, Grant #R21 -ES021330), the UC Davis
School of Medicine, School of Veterinary Medldne, and the MIND Institute. We
gratefully acknowledge and thank the many families who generously donated
their time to participate in the CHARGE Study.
[}opt Decsrtaxytoe (DDQ and
-------
©
Program on Reproductive
Health and the Environment
Flame Retardants Linked to Lower Child IQ
The University of California, San Francisco (UCSF) Pregnancy Exposures to Environmental Chemicals Children's Center
October 24 - 26, 2017 NIEHS/USEPA Annual Children's Centers Meeting, San Francisco, CA
UCsf
University of California
San Francisco
I. Abbreviated Center Aims
Study Question
Understand how EDCS, like PBDE affect biological pathways in placenta development.
Evaluate relationship between prenatal EDC exposures to adverse pregnancy outcomes,
such as low birth weight.
Assess how chronic psychosocial stress in pregnant women modify the
chemical/pregnancy outcome associations
Communicate the science and , harness the evolving science to healthcare, and advance
prevention-based public policy.
Exposure to flame retardant chemicals is associated with cancer, reproductive, and developmental toxicity.
2
Study Question: Does developmental exposure to PBDEs in humans affect quantitative measures of intelligence?
II. Research Findings
Our "BIG" result/finding from our Children's Center is from our systematic review examining PBDEs and IQ
Internal Validity (Risk of Bias) Ratings for Studies
l»i I nitron* data
MlfMM rif«W|
riMMiil [Mlht »1 alortl
* Highlighted »tucties were thote included in tl
Meta-Analysis for PBDE exposure for IQ outcome
assessed in children between 48-84 months
Eskenaaetai 2013
Chen el al 2014
Gascon ol at 2011
-2691-92a. 3.89}
-3801-8 30, 0 70]
-4.171-890, 0 56}
-3 10 (-17.63, 11 43}
-3.701-6.56, -083}
-20 -10 0 10
Observed Outcome
Nine studies measured IQ; most
were "low" or "probably low"
risk of bias and the evidence was
"moderate" quality,
meta-analysis found
-3.7 IQ points (95%
CI: -6.56, -0.83) per 10-
fold increase in PBDE
exposure
range:
-------
of parks to highways, Los Angeles County
Parks. Pollution
and Obesity
I.IFE IN I ri:i:\vay
DANC.KR ZONES
• nPM
-O Control
Does air pollution cause childhood obesity and increase the risk of diabetes? .
Keck
School of
Medicine
of USC
Studies in Mice
XRP (i i I'M) and body composition In mire
Rob McConnell, Frank Gilliland, Hooman Allayee, Wendy Gutschow. Jill Johnston
University of Southern California
Research questions
Does in utero and childhood near-roadway air pollution (NRP) exposure cause:
•Childhood obesity?
•Metabolic syndrome?
•Visceral fat redistribution, ectopic fat and adipose tissue inflammation?
Are NRP effects on metabolic outcomes mediated by fat distribution and adipose
tissue inflammation?
CEHC
Studies in Children and Young Adults
Synergistic associations of NRP and SHS with BMI
• SHS trO NRP
• SMS Or*
• HgftNRPOrty
Early life NRP and BME Age 5-10 years
BMI Growth per Year |
BMI at Age 10 Years)
N02 and PM2.5 exposure was
associated with declines in [3-cell
function (DI)
s
-6% I 16
:B
t T 6
I-6
1 i -3
1 T i 16
¦ L
# -v
1 24
i E
no2 pm(5
no2 pm25
1-SDd
fference in N02 (5 ppb) and PM25
4 pg/m3) with 95% CI.
T-reg counts by lifetime average ozone
exposure in high and low Teff count groups
Community Outreach & Translation
Bridging worlds of obesity prevention, urban design and air pollution.
Fostering dialogue between scientists and weight loss community-based
organizations, parks and housing advocates, and policy makers.
Infographics developed in partnership with community organizations to promote
dialogue on risks and benefits.
Designing an online StoryMap tool to visualize the landscape of green space, near-
roadway exposure and health disparities.
ICS
Fasting glucose was associated with
increased lifetime NRP
Dispersion Modeled NOx
Clinical Fasting Glucose
0.19
0.10
0.07
Fasting Insulin*
-0.004
0.01
0.60
Insulin AUC
-0.32
0.71
0.66
HOMA-IR*
-0.002
0.01
0.85
HOMA-p*
-0.01
0.01
0.11
Matsuda
-0.001
0.07
0.99
Impaired glucose tolerance
Perturbed metabolic gene expression
only in adipose tissue
"p<0.05 ™ nr,vl
¦ Control
ill lit fcilh
Insr Irs1 Irs2 Insr Irs1 Irs2 Insr Irs1 Irs2
Adipose Liver Skeletal Muscle
Proximity
Exposure in Southern California
PUJ.i Annual Avaraga ai CHS ComuiniM
-------
Longitudinal exposome research reveals exposure of agricultural families to over 86 pesticides, 47 of
4 j ~ which are identified as developmental neurotoxicants
Beti Thompson, Rachel Ceballos, Tomomi Workman, Marissa Smith, Breana Bennett, Bill Griffith and Elaine Faustman
Fred Hutchinson Cancer Research Center and University of Washington, School of Public Health, Seattle, WA
FRED HUTCH
Abstract
The theme of the Center for Child Environmental Health Risks Research has
been to understand the mechanisms (molecular, genetic, age, exposure, and
social factors) that define children's susceptibility to pesticides, identifying
the implications of this susceptibility for development and learning, and
partnering with our communities to translate our findings into risk
communication, risk management, and prevention strategies. This poster
shows critical pathways of pesticide exposure for children in farmworker
and non-farmworker families and shows how interventions are shown to
reduce children's exposure to pesticides. The Center is organized using a
Risk Assessment Framework that facilitates the incorporation and use of
state of the art science to inform risk decisions. A critical premise for the
Center is its commitment to Community Based Participatory Research and
this commitment allowed us to overcome and investigate the complex
patterns of exposure for short-lived and episodic pesticide use that
agricultural communities can experience.
Mission and Objectives
Center Organization
Work in the Center is organized around the Public Health paradigm "V-
diagram," which connects occurrence of disease in humans to the original
source of the problem. Along the pathway from source/stressor to
disease, the diagram identifies intermediate processes (which may be
subject to Public Health intervention) and conditions (which may be
observable for public health monitoring and hypothesis testing
ar P01-ES009601 frc
Center Study Design
ChUd Health CentM Lon(Ku*ul Cohort Muit» 0*4(«
taw iwi Moilfctrtni'tomiMW
tJ V
ill" •!
Our Center study design
sampled farmworker and non-
farmworker households over
multiple days for three seasons
and three different study years.
Overall, the Center has worked
with 800 families from the "Para
Ninos Saludables" Cohort since
Pesticide Measurement Using LC-MS
Pesti cid e Type Pe stici de Class
Pesticide
Organophosphate
1) Improve our understanding of critical pathways of pesticide exposure for
children;
2) Intervene to reduce children's exposure to pesticides;
3) Identify susceptibility factors for developmental neurotoxicity of
pesticides;
4) Identify cellular, biochemical and molecular mechanisms for the
developmental neurotoxicity of pesticides;
5) Provide core support for the development and application of risk
assessment methods;
6) Foster partnerships and dialogue between academic researchers and the
community.
Azinphosmethyl
Chi orpyrifos
Coumaphos
Diazinon
Dichlorvos
Mai at hi on
Methamidophos
Phosmet
Tetrachlorvinphos
Carbaryl
N-Methyl Carbamate
Methomyl
Propoxur
Acetamiprid
Neonicotinoid
Clothianidin
Imidacloprid
Cyphenothrin
Imiprothrin
Pyrethroid
S-Bioallethrin
Sumithrin
Tetramethrin
Insect Growth Regulator
Hexythiazox
Pyriproxyfen
Urea/Insect Growth Regulator
Novaluron
Macro cyclic Lactone
Spinosyn A
Spinosyn D
Synergist
Piperonyl Butoxide
Pesticide Type
Pesticide Class
Pesticide
Myclobutanil
Azole
Tebuconazole
Azole (Benzimidazole)
Thi ophan atem ethyl
Fungicides
Azole (Imidazole)
Triflumizole
Strobin
Azoxy strobin
Trifloxy strobin
Guanidine
Dodine
Anilide
Boscalid
Quinonline
Quinoxyfen
Urea
Diuron
Chlorophenoxy acid or est
2,4-D
:er MCPA
Herbicides
MCPP
2,6-Dinitro aniline
Pendimethalin
Pyridazinone
Norflurazon
Pyridaben
Microbiocides
Chlorophenol
Triclosan
Phenol
Na o-phenylphenate
References
m
Linking Exposure with Biomarkers of Response
ethylalkylphosph
ITOl/ I'l
nmol/g)
Tamaro et. al. (2017)
Connecting Seasonal Work with Cortisol
J
Classification for pesticides detected in
household dust. For dust analysis, 86/145
candidate pesticides were successfully
measured using LC-MS. Table above shows
pesticide type (e.g., insecticide, herbicide,
etc.), classification (e.g., pyrethroid, azole,
etc.), and name. Modified from Bennett et.
Our Center has also
characterized chronic stress
biomarkers in a nested cohort
(n = 27) of mothers. The figures
show average daily Cortisol
fluctuations for two consecutive
days for both the summer and
fall seasons for our nested
cohort.
Smith et. al. (2015)
Community Outreach & Return of Results
Work in the Center is influenced by our commitment to Community Based
Participatory Research (CBPR). We have disseminated research results to
our study participants through the use of a thermometer graphic (below), as
chosen by community members. These evaluations were conducted at a
town forum. On follow-up, over 70% of participants recalled the graphic and
correctly interpreted the results. This follow-up also demonstrates the
effectiveness of using a CBPR approach throughout the entire research
process.
Bennett, B., Workman, T., Smith, M., Griffith, W.C., Thompson, B., Faustman, E.M. (2017).
Defining the pesticide exposome: Characterizing longitudinal seasonal and occupational
trends of pesticides in house dust. In progress.
Tamaro, C. M., Smith, M. N., Workman, T., Griffith, W. C., Thompson, B., & Faustman, E.M.
(2017). Characterization of Organophosphate Pesticides in Urine and Home Environment Dust
in an Agricultural Community. Biomarkers, 1-35. (Epub ahead of Print)
Smith, M. N., Wilder, C. S., Griffith, W. C., Workman, T., Thompson, B., Dills, R.,... &
Faustman, E. M. (2015). Seasonal variation in Cortisol biomarkers in Hispanic
mothers living in an agricultural region. Biomarkers, 20(5), 299-305.
Thompson, B., Carosso, E., Griffith, W., Workman, T., Hohl, S., & Faustman, E. (2017).
Disseminating pesticide exposure results to farmworker and nonfarmworker families in
an agricultural community: A community-based participatory research
approach. Journal of occupational and environmental medicine, 59(10), 982-987.
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NEW!
Using storytelling to translate
science for health promotion,
disease prevention
The Power of Personal Stories:
Cased-based learning has long been used in medical education. Our
eBook grounds the science of health in stories of fictional people,
their families, and communities to enable readers to explore the
collection of risk factors for increasingly
common illnesses that are a serious
problem for the health of our nation.
Examples:
"Brett is a nine year old boy.H-1
who lives with his mother in an
urban area. Like many children,
Brett suffersfromasthma..." d
interactions,
in this example fi
the asthma story, can
have dramatic effects.
interactions:
"...For example, prenatal
and early life exposure to
social stressors, such as
violence, can increase the
risk of asthma as well as
respiratory heafth from
allergens, air pollution, and
tobacco smoke."
A Story of Health
A Multi-media eBook
Reunion I Asthma I Cancer I Learning/ I Diabetes I Infertility I Cognitive I References
Home | | (Childhood | Developmental | | | Decline |
Leukemia) Disabilities
Mark Miller MD MPH, Ted Schettler MD MPH, Brian Tencza MEd,
Maria Valenti, Victoria Leonard RN PhD, Marya Zlatnik MD
V
Using the setting of a family reunion as a backdrop,
we explore how multiple environments influence
our health across the lifespan.
'Stephen is a
^ > Toshio and Reiko
are a couple in their
early 30's who have been trying
unsuccessfully to have a child...
3-year-old
boy in treatment
for childhood
leukemia..."
BB/GYNs lack
Estimated U.S. fertility
statistics - 2006-2010
environments
health training
Early life exposures contribute
to lifelong effects
Q. Do you routinely
discuss this issu
f cren
Genetics increase Susceptibility
to Air Polluti
Amelia is a
13-year-old. Like
one in six young people
in America, Amelia
has a developmental
disability..."
Environmental exposures can affect
ovarian function
Life cycle of an ovarian follicle
10% routinely
PRENATAL HEALTHY CARE
A Rationale for Thyroid
Screening Before or
During Pregnancy
©Thyroid disrupti
technical diagram
a
Multiple environmental contributors
to reproductive health
Although not an exhaustive
account, the eBook is a
presentation of current scientific
evidence to help readers make
informed decisions and take
actions to promote health
"idividuals and Tamilies are progressively
nested within communities, societies, cultures
id ecosystems. Each of these levels
significant influences on the oth
each can influence levels of
The ecological
health framework
also extends to th
b-cellular level
biologic marlcers
matory mediators or stress hormones
that can be measured in beople's blood
Ecological
Health Framework
this an ECOLOGICAL FRAMEWORK
because it recognizes the contribution of each
to the health status of individuals, families
ecosyste
stA wm
Stress affects our health. Watch this
video by Dr. Rosalind Wright to see
how soaal stressors, along with
environmental factors,
can be linked
to asthma. (5min.)
Multiple factors influence health
Our individual stories
highlight the many ways our
health is influenced by the
complex environments where
we live, eat, work, exercise,
gather and socialize.
A Story of Health Continuing
Education (CE) Course via
CDC Receives High Marks
CDC
I l 'enter* fcn Pi*
Dbase nrhl Prevention i
CE Registrations at 10.31.16: 4,989
Total Credit Hours: 8,919
CE Registrant Feedback
Overwhelmingly Positive
Training and Continuing EAkjiims Online
RESPONSE:
AVERAGE OF
3 STORIES
SoVtqi
Th* Story of NMtth AaUvn* - Swi'i Story (W*b-
Com IVMr MB231T
STRONGLY AGREE
+ AGREE =
TOTAL IN %
"The content and learning materials
addressed a need or a gap in my
knowledge or skills."
"I will be able to apply the knowledge/ QAO/
skills gained from this activity to develop vV/0
strategies/provide interventions."
97%
COMMENTS FROM COURSE TAKERS
Anticipated changes after
taking the course:
"Applying knowledge to nursing practice
and in community with children/friends
with asthma."
"Better able to educate patients."
"More guidance for patients in the precon-
ception phase."
Feedback from a Q2/201S CE summary
Free Continuing Education credits offered through the
Centers for Disease Control and Prevention/ATSDR available
for physicians, nurses, health educators and others. Visit
www. atsdr. cdc.gov/em es/health_prof essi onals/index. html.
WHAT COLLEAGUES ARE SAYING
HEALTH PROFESSIONALS RECOMMEND A STORY OF HEALTH
Downloads
Story of Health at S
http://wspehsu.ucsf.edu/for-clinical-professionals/ fflwsrrtf
training/a-story-of-health-a-multi-media-ebook/
A Story of Health is a new eBook on how to
promote health and prevent disease.
Pop-up graphics and
rollover functions
reveal key concepts,
relevant graphics
and links to videos
presented by
researchers -
in-depth information
tectiicai ship this
details section
for health
professionals
A Story of Health is written by health experts with content
relevant to a wide audience, from clinidans, to health advocates,
to policy makers.
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.
Our goal: Improve the
health of individuals,
families, communities
and patients.
Watch: Dr. Mark Millet
Barker hypothesis (1:40 min.)
Acknowledgements: A Story of Health is a collaboration among the
Agency for Toxic Substances and Disease Registry (ATSDR), the Collaborative on
Health and the Environment (CHE), the Office of Environmental Health Hazard
Assessment California Environmental Protection Agency (OEHHA), the Science
and Environmental Health Network (SEHN), and the Western States Pediatric
Environmental Health Specialty Unit(PEHSU) and has been supported by a
range of public and private funding as well as significant in-kind contributions
acknowledged in the eBook.
The U.S. Environmental Protection Agency (EPA) supports the PEHSU by providing
partial funding to ATSDR under Inter-Agency Agreement number DW- 75- 92301301.
This work was also supported with funds from NIH Grant No. 1P01ES018172 and
USE PA Grant No. RD83451101 to CIRCLE, P.I. C. Metayer PhD. Neither EPA nor ATSDR
endorse the purchase of any commercial products or services mentioned in PEHSU
publications. The findings and conclusions in this presentation have not been
formally disseminated by the Agency for Toxic Substances and Disease Registry and
should not be construed to represent an agency determination or policy.
For more information contact: Maria Valenti, mvalenti@iac.ora or Brian Tencza,
bht1@cdc.gov.
"Brilliant! The focus on a family and on each
of their health challenges weaving in the
environmental factors is masterful and I believe
very effective. It is a wonderful format - and
very cleverly done with a compelling story and
interactive elements."
-Leslie Rubin, MD, Co director. Southeast Pediatric
Environmental Health Specialty Unit, Emory University;
Medical Director, Developmental Pediatrics Specialists;
Research Associate Professor, Department of Pediatrics,
Morehouse School of Medicine
"This is a really innovative addition to the
existing textbooks on children's environmental
health and could truly generate in depth
learning on this complex issue. The chapter on
leukemia brings together in a really cohesive
way the multiple risk factors that come into
play in the etiology of childhood cancer. The
case based approach is particularly engaging
for diverse audiences. Kudos!
-Maida P. Galvez, MD, Associate Professor Preventive
Medicine, Associate Professor Pediatrics, Mount Sinai
Hospital"
"It [SOH] should be required for all
medical students in curriculum that ties
into a life cycle approach to health...
Many medical school deans and
educators are looking for off the shelf
materials that can be used for teaching.
This is perfect."
-Robert Harrison, MD, MPH, chief of the Occupa-
tional Health Surveillance and Evaluation Program
(OHSEP) in the Occupational Health Branch of the
California Department of Public Health
Finally, a resource
that clearly explains
the multiple factors
that influence our
health across the
lifespan - the natural,
built, chemical, food,
economic, and social
environments - and
how they interact
with genetics and
each other.
About the eBook:
An interactive document with
multiple chapters features prompts
for embedded information and
links to online resources.
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