Maintenance and Enhancement of the Atlanta African American Maternal-Child Cohort: Exposome Profiling via High-resolution Metabolomics and Integration of Microbiome-Metabolome-Epigenome Data

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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) affecting endogenous processes (such as gene regulation and metabolism), which perturb 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 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 Environmental Health Center (P50ES026071) in collaboration with the Emory HERCULES Exposome Research Center (P30 ES019776). We are also evaluating child obesity and neurodevelopment at 2-5 years of age under the Environmental Child Health Outcomes (ECHO) program (UG3OD023318). Through this R24 mechanism, we propose to: (1) Continue to enroll AA women at 8-14 wks' gestation, collect data at three time points during pregnancy, and engage delivered mother-child dyads in on-going postnatal follow-up studies to allow continued investigation of relationships between prenatal and early childhood exposures to chemical and non- chemical stressors and child health outcomes (Cohort Maintenance Aim); (2) Evaluate the performance of high-resolution mass spectrometry coupled with gas chromatography (GC-HRMS) for quantifying persistent organic pollutants (POPs) microliter serum volumes by comparing measured POP concentrations to those measured using conventional targeted analytic chemistry approaches in the same cohort (Resource Infrastructure – Exposure Characterization Aim); and (3) Adapt tools for multi-omic data integration to enable the display, visualization, and integration of comprehensive exposure assessment and biological effect data – to include chemical toxicant concentrations and metabolomic (KEGG pathway), epigenomic (gene methylation and expression), and microbiome data – and the analysis of associations with pregnancy and birth outcomes within our cohort and across cohort collaborations (Resource Infrastructure - Data Preparation Aim). Through this work, we expect to advance environmental health science around the assessment of chemical mixtures (with a focus on POPs) and their adverse preclinical (metabolic and epigenetic) health effects in our own high disparity population of pregnant women and newborns and to support other cohorts and cross-cohort collaborations involving the use of high-dimensional multi-omic data.