The Impact of the Intrauterine and Early Childhood Environments on Neurocognitive and Metabolic Development in African American Youth: Focus on the Gut-Brain Axis

项目摘要

PROJECT ABSTRACT Environmental exposures during the critical prenatal and early childhood periods can result in lifelong health consequences. Mechanisms underlying these exposure-health relationships are complex, with exogenous exposures (such as chemical toxicants, infectious agents, diet) and endogenous processes (such as gene expression, inflammation and oxidative stress) activating metabolic pathways that lead to adverse health outcomes. Both adverse exposures and their health consequences disproportionately impact African American (AA) women and children, highlighting that health disparities begin in utero and are amplified postnatally. Among outcomes disproportionately experienced by AA children are preterm birth, neurodevelopmental deficits, and obesity – all linked to environmental exposures, yet poorly understood due to their etiologic complexity. Our team is currently investigating preterm birth and neurodevelopment through 18-months in relation to pre- and postnatal exposures to environmental toxicants and biopsychosocial risk factors in cohorts of pregnant AA women (R01NR014800, R01MD009064) and their infants (R01MD009746) and via our P50 Children's Center (P50ES026071) in collaboration with the Emory HERCULES Exposome Research Center (P30 ES019776). Through ECHO, we propose to elucidate exposures and risk pathways that contribute to neurodevelopmental deficits and obesity in preschool aged AA children by: (1) Assembling an Atlanta ECHO cohort of ~440 AA socioeconomically diverse mother-child pairs by combining extant cohorts for whom the prenatal, perinatal, and early childhood environments are, or will be, characterized; (2) Completing the analysis and synthesis of data from the Atlanta ECHO cohort to characterize mother-child pairs in terms of prenatal and early childhood exposures (toxicants, stressors and neuroendocrine-immune activation, nutritional and metabolic status, microbiome and infections, bonding and interaction); epigenetic and metabolomic profiles; and perinatal outcomes (gestational age, size-for-gestation); (3) Testing cohort-specific hypotheses related to prenatal and early childhood exposures and neurodevelopmental outcomes and obesity in AA children at 2, 3, 4, and 5 years of age; (4) Participating in ECHO-wide consortium studies to identify risk and protective factors that moderate associations between environmental exposures, typical growth and development, and adverse child health outcomes. Our cohort's participation in the ECHO consortium will contribute to a biopsychosocial understanding of within- and between-race risk for adverse child health outcomes, providing insight into risk and protective factors relevant to AA families. The proposed research is consistent with frameworks for eliminating racial disparities, which recognize the need to study risks within-race as a vital first step, and is congruent with the National Institute of Minority Health and Health Disparities goal of promoting understanding of the biological mechanisms involved in conditions that disproportionately affect health disparity populations.