Early Life Exposure to Endocrine Disrupting Chemicals and Child Growth, Adiposity, and Neurodevelopment

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PROJECT SUMMARY/ABSTRACT We propose continued follow-up of our large, racially/ethnically diverse ECHO ELEGANT cohort (n=2130) and to lead collaborative ECHO Cohort science. Our scientific aims focus on child obesity and adverse neurodevelopment, two common and increasingly prevalent conditions. Our comprehensive planned analyses take advantage of the core longitudinal data collected via the ECHO Cohort Protocol during the initial phase and the new phase. In Aim 1, we will assess the role of in-utero exposure to endocrine disrupting compounds (EDC) on child growth (growth trajectory), adiposity (body fat mass), obesity (body mass index [BMI]) and neurodevelopment (autism, autism-related traits, and emotional-behavioral development [ND]), by addressing solution oriented scientific questions that may promote precision interventions, practice recommendations and policies. We will clarify the effects of two understudied classes of EDCs (perfluoroalkyl substances (PFAS) and contemporary organophosphate ester flame retardants (OPE)) and increase understanding of real-world exposure scenarios by examining individual and joint effects. In Aim 2, we will clarify the joint effects of multiple maternal prenatal overnutrition factors (high dietary energy intake/poor diet quality, high pre- conception BMI, excessive gestational weight gain, gestational diabetes/diabetes) on child growth, adiposity, obesity, and ND. While likely to co-occur, human studies on their joint effects on childhood obesity and ND are sparse. Since child growth and development are dynamic processes, we will address the proposed associations at different ages of the child. Our hypotheses are that prenatal exposure to EDCs and maternal overnutrition factors adversely affect child growth, adiposity, obesity and ND by mechanistic pathways (metabolomics, DNA methylation), and that maternal prenatal and child lifestyle behaviors, psychosocial factors, social determinants of health, and sex assigned at birth may moderate these effects. In Aim 3 we will maximize retention of our existing ECHO participants by implementing evidence-based strategies focused on engaging diverse groups in clinical research and implementing the ECHO Cohort Protocol applying systematic quality control approaches and best practices. Our experienced research team is very diverse, including investigators from historically underrepresented racial and ethnic groups, disadvantaged backgrounds, different career stages, multiple scientific fields, geographic locations, and institutions. We are committed to providing equitable opportunities for all members of our research team to contribute to all aspects of our proposed project and assure that they will have equal opportunity to be involved in the new ECHO phase. Our continued involvement in ECHO provides an unparalleled opportunity to further understanding of the developmental origins of child obesity and neurodevelopment and inform future interventions, prevention strategies and policies to reduce the burden of these common and costly childhood disorders and possibly their long-term impact on health across the lifespan.