Saturday, September 7, 2024
9/7/2024
PROJECT SUMMARY/ABSTRACT The rapid rise in childhood obesity and neurodevelopment disorders (NDDs) in children has occurred over a period of increased manufacturing and exposure to endocrine disrupting compounds (EDCs), suggesting a possible etiologic role for these environmental exposures. EDCss of interest include perfluoroalkyl substances (PFASs), polybrominated diphenyl ethers (PBDEs), and contemporary organophosphate flame retardants (OPFRs). Despite their widespread detection, few studies have characterized the effects of in-utero exposure to these EDCs in humans, and even fewer have investigated associated mechanistic pathways. We will leverage and expand two large extant racially and ethnically diverse pregnancy cohorts to prospectively investigate the role of in-utero exposure to EDCs in relation to child obesity and NDDs. The first of these cohorts (PETALS) has enrolled 1,800 women since 2013 to investigate phenol exposure in relation to gestational diabetes and excessive fetal growth. The second (KPRB-PC) has enrolled ~22,000 women since 2010 to create a resource for studies related to women's and children's health. The NIH Environmental Influences on Child Health Outcomes (ECHO) provides an opportunity to extend follow-up and to expand the work of these two cohorts. During the UG3 phase, we will re-contact and consent study participants, pilot test our proposed data collection protocol, and work with ECHO partners to develop the multi-site protocol. During the UH3 phase, we will follow 1,600 mother-child pairs, hereafter referred to as the ELEGANT cohort. We will assess in-utero EDC exposures in biospecimens of 1,600 pregnant women and clinically evaluate their children at age 4 years for growth, adiposity, and neurodevelopment. Our hypothesis is that in-utero exposure to EDCs (i.e., PFASs, PBDEs, OPFRs), individually or in combination, have adverse effects on child growth (i.e. BMI), adiposity (i.e. fat mass), and neurodevelopment, possibly through common pathways. In our Aims, we propose to: 1. evaluate whether in-utero exposures to EDCs, individually or in combination are associated with child growth, adiposity, and neurodevelopment, and whether these associations vary by child sex; 2. evaluate whether overnutrition (high dietary energy intake, high pregravid BMI, high gestational weight gain and gestational diabetes) modifies the associations of in-utero exposure to EDCs and child growth, adiposity and neurodevelopment; 3. evaluate whether in-utero EDC exposures are associated with metabolic factors (pregnancy levels of glucose, insulin, leptin and thyroid hormones) and whether these factors mediate the association between in-utero exposure to EDCs and child growth, adiposity, and neurodevelopment; and 4. measure genome-wide methylation in child DNA, to develop sensitive and specific child DNA methylation markers of prenatal EDC exposure, and to illuminate potential mechanistic roles of child DNA methylation. Our contemporary pregnancy cohorts and follow-up of their children represent a valuable addition to the ECHO consortium and will enhance knowledge of the origins of childhood obesity and NDDs.
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