How Prenatal Exposures to Endocrine Disrupting Chemicals (EDCs) such as Perfluoroalkyl Substances (PFAS) Adversely Affect Neurodevelopmental Outcomes in Children from Two to Four Years of Age

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Awardee: Patricia Cintora, University of Illinois at Urbana-Champaign
Mentors: Susan Schantz, Sarah Geiger, and Xiaotian Gao
Project Summary: Perfluoroalkyl substances (PFAS), sometimes referred to as “forever chemicals,” are a critical public health concern because of their widespread use, long half-lives, and bioaccumulation in tissues. The prenatal period is a critical time in development during which the brain may be particularly vulnerable to the effects of PFAS. However, the literature to date assessing the association between prenatal exposure to PFAS, and neurodevelopmental outcomes has been inconclusive. Assessments of PFAS-related health outcomes using a mixtures approach are being called for by regulators, given that typical human exposure involves complex combinations of PFAS3. In addition, large prospective studies with diverse samples of children representative of the U.S population are needed to provide for more accurate and consistent data on PFAS-related neurodevelopmental outcomes.

Aim 1: The proposed study would leverage four geographically and demographically diverse ECHO pregnancy cohorts based in Atlanta, GA, San Francisco, CA, Los Angeles, CA, and Urbana-Champaign, IL to investigate the association of prenatal exposure to PFAS with early language development.

Aim 2: The study would apply novel statistical methods to assess the effects of prenatal PFAS as a mixture in a multi-site, multi-racial/ethnic sample of children, using exposure, outcome, and covariate data from the ECHO data platform.

Aim 3: In addition, the study would use more comprehensive data on early language developmental collected at 2 and 4 years of age in the Illinois Kids Development Study (IKIDS) and Chemicals in Our Bodies (CIOB) cohorts to assess the impact of prenatal PFAS exposure on specific language skills.

Predictors of Mental Health and Behaviors in Adolescents in the Longitudinal ReCHARGE Study

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Awardee: Sandra Flores, MPH
Mentors: Dr. Irva Hertz-Picciotto, Dr. Julie Schwartz, and Dr. Julie Dang
Project Summary: Examines whether neighborhood characteristics and parental level exposures of substance use and mental health morbidities are predictors of anxiety and depression in adolescents.

Aim: To identify community and household environments that protect and build resilience against depression and anxiety in adolescents of different race/ethnicity and gender.

Mississippi Environmental Influences on Child Health Outcomes (ECHO) IDeA States Pediatric Trials Network (ISPCTN)

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Awardee: Tre D. Gissandaner, University of Mississippi Medical Center
Mentors: Joseph Majure and Crystal Lim
Project Summary: Examines impact of rurality on family functioning during COVID-19 pandemic, and identifies factors associated with parent willingness to participate in pediatric clinical trials research in Mississippi.

Aim 1: To examine barriers and facilitators of pediatric clinical trials identified by parents in Mississippi.

Aim 2: To increase understanding of the impacts of COVID-19 on families in Mississippi and potential disparities related to geography.

Aim 3: To identify factors associated with parent willingness to have their children participate in vaccine trials in Mississippi.

Associations Among In-Utero Exposure to Metals/Metal Mixtures, Stress/Stress Mixtures, and Internalizing Problems in Early Childhood

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Awardee: Brandon Goldson, BS, Medical Student, Icahn School of Medicine at Mount Sinai ECHO Cohort
Mentors: MPIs Rosalind Wright, MD, MPH and Robert Wright MD, MPH
Project Summary: To examine the influence of complex metal and/or stress mixtures on transdiagnostic (TD) features linked to anxiety and depressive problems in 3-6 year olds.

Aim 1: Examine effects among prenatal metal mixtures (Pb, Cd, As, An, Mn, Hg), stress mixtures [maternal lifetime traumatic/non-traumatic stressors, negative life events and psychological functioning in pregnancy], and TD pathways to internalizing symptoms at ages 3-6 years. We will examine:

Aim 1a. Independent effects of prenatal metals/metal mixtures on TD features including neuroendocrine/behavioral measures of negative valence, arousal/ regulation, and internalizing symptoms (anxiety/depression) at 6 months and 3-6 years.

Aim 1b. Independent effects of prenatal stress/stress mixtures on TD features at 6 months and 3-6 years.

Aim 2:  Examine how associations between prenatal metal mixtures and TD pathways to internalizing symptoms by age 3-6 years, are modified by prenatal stress/stress mixtures.

Environmental Influences on Neurodevelopmental Outcome in Infants Born Very Preterm

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Awardee: Kenyaita Hodge, MPH, Genetics and Molecular Biology, Emory University
Mentor: Todd M. Everson
Project Summary: Approximately 1 in 10 babies are born prematurely each year in the United States, and these neonates are at heightened risk for acute morbidities and early death. While medical advancements have dramatically improved survival for infants born prematurely, survivors, especially if born very preterm (< 30 weeks gestation) have an increased risk for long-term neurodevelopmental impairments. Bronchopulmonary dysplasia (BPD), the most common neonatal morbidity among preterm infants, is a risk factor for future chronic diseases and neurodevelopmental impairments. How BPD and its treatments lead to long-term negative health outcomes requires further study. Altered programming of the HPA axis, which modulates glucocorticoid (GC) activity, has been implicated as one potential mechanism, because infants with BPD are more likely to have been exposed to corticosteroids and BPD itself may activate the stress response system. Others have developed a cross-tissue polyepigenetic predictor, an algorithm that uses DNAm levels at specific sites on the genome, to estimate a score that is associated with exogenous and endogenous GC exposure, which has been associated with maternal anxiety and depression throughout pregnancy and with later mental and behavioral issues. However, this potentially useful biomarker has not been studied within infants that were born very preterm with BPD, who are more likely to have elevated exogenous and endogenous GCs and are at increased risk of neurodevelopmental impairments. To address this gap in our knowledge, we aim to:

Aim 1: Investigate whether BPD is associated with neonatal GC scores (as risk factor, and as a response), and

Aim 2: Examine whether the neonatal GC scores are associated with performance on neurodevelopmental assessments at 24 months corrected age, in two ECHO cohorts of infants that were born very preterm (NOVI and ELGAN). These analyses will provide evidence as to whether this epigenetic biomarker is associated with BPD, and will elucidate whether the GC scores may be an early indicator of children that are at increased risk for impairments.

The Role of Racial/Ethnic-Specific Dietary Patterns in Child Birth Outcomes

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Awardee: Luis Enrique Maldonado, University of Southern California (USC)
Mentors: Tracy Bastain
Project Summary: Prenatal diet may contribute to metabolic alterations (e.g., insulin resistance) that could influence fetal programming and, subsequently, birth weight, a known determinant of impaired development, morbidity, and chronic disease risk later in life. Prenatal overall diet, as in a dietary pattern (DP), derived particularly in relevance to fasting plasma glucose, an intermediate variable between diet and birth weight, was found to be associated with birth weight. These findings, however, are specific to predominantly non-Hispanic white women, limiting generalizability of findings to other populations such as Hispanic/Latina women who, compared to non-Hispanic white women, are at greater risk of having adverse birth outcomes and children with childhood obesity. Understanding ethnicity-specific differences in dietary composition may help explain disparities in birth outcomes between non-Hispanic white and Hispanic/Latina women.

Aim 1: Derive prenatal DPs in a racially/ethnically diverse pooled sample from the two cohorts using RRR alternately with GWG and FG as intermediate response variables and characterize resulting DPs based on higher-loading foods;

Aim 2: Identify racial/ethnic differences in DPs by using the RRR approach in Aim 1 in groups stratified by race/ethnicity and compare racial/ethnic-specific DPs with DPs derived in the combined sample;

Aim 3: Determine whether racial/ethnic-specific prenatal DPs (Aim 2), versus those derived in a racially/ethnically diverse pooled sample (Aim 1), better predict birth weight and large-for-gestational age (LGA) by comparing how well they predict the outcomes within these racial/ethnic groups.

Measuring Peripartum Depression Symptoms in Latina and Black Women

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Awardee: Amarelis Raudales, New York State Psychiatric Institute - Columbia University Irving Medical Center
Mentors: Julie Herbstman and Amy Margolis
Project Summary: Within the Columbia Center for Children’s Environmental Health (CCCEH) Environmental influences on Children’s Health Outcmes (ECHO) award (UG3/UH30D023290), we follow three longitudinal pregnancy cohorts comprised primarily of Black and Latina mothers and their children, who were recruited during pregnancy beginning in 1998. At the time of pregnancy, all women reside in/around New York City (NYC) and represent an urban, minority population that is typically under-represented in scientific research.

Aim: The research program in our birth cohorts aims to study the impacts of prenatal chemical and social exposures on children’s health outcomes. In this administrative supplement, which aims to promote diversity within the ECHO consortium workforce, Ms. Amarelis Raudales is our candidate. She is a predoctoral student in clinical psychology and her clinical coursework at the City College of New York (CCNY) will be complemented by practical research experience within the CCCEH ECHO cohorts. The goal of her project is to understand how to better assess peripartum depression (periPD) in ethnic and minority women.

PeriPD is characterized by a major depressive episode during the prenatal period or within four weeks. Depressive symptoms may continue and studies often extend up to one-year postpartum and has been shown to adversely affect children’s health. Latina and Black women are at especially high risk for PeriPD and screening measures for PeriPD are sensitive to the unique experiences of Latina and Black women. Better screening measures are needed for early detection, diagnosis, and treatment. This information will benefit our cohort and the ECHO community, as the ECHO-wide Cohort aims to include representation from multicultural populations.

Evaluation of a HEPA Filter Pilot Project: Formative Data to Support a Future Indoor Air Quality Bronchiolitis Clinical Trial

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Awardee: Madilyn Short, Alaska Native Tribal Health Consortium
Mentors: Rosalyn Singleton and Jenni Dobson
Project Summary: The IDeA States Pediatric Clinical Trials Network (ISPCTN) is developing a protocol for a clinical trial, IAQ bronchiolitis, to evaluate the efficacy of active HEPA filtration units for reducing respiratory symptoms in children hospitalized with bronchiolitis. From 2019-2020, the YK Health Corporation (YKHC) conducted a pilot project to provide HEPA filtration units to households of children with chronic lung conditions in Alaska’s rural YK Delta.

Aim: In this diversity supplement, we will conduct an analysis of data from this pilot to assess the associations between household characteristics and HEPA filtration use. We will mentor Madilyn Short, an Alaska Native (Yup’ik/Inupiat), first-year medical student from the rural YK Delta, in this diversity supplement.