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

资助ECHO父母补助金摘要（UH 3 OD 023318） 在关键的产前和幼儿期暴露于环境中可能会导致终身健康 后果这些安全-健康关系的机制是复杂的， 暴露（如化学毒物、感染因子、饮食）和内源性过程（如基因 表达、炎症和氧化应激）激活导致不利健康的代谢途径 结果。不良暴露及其健康后果对非洲裔美国人的影响不成比例 (AA)妇女和儿童的健康差距，突出表明健康差距开始在子宫内，并在出生后扩大。之间 AA儿童不成比例地经历的结果是早产，神经发育缺陷， 肥胖-所有这些都与环境暴露有关，但由于其病因的复杂性而知之甚少。我们的团队 目前正在研究早产和18个月的神经发育， AA孕妇队列中环境毒物和生物心理社会危险因素的暴露 （R 01 NR 014800，R 01 MD 009064）和他们的婴儿（R 01 MD 009746），并通过我们的P50儿童中心 （P50 ES 026071）与Emory HERCULES Exposome Research Center（P30 ES 019776）合作。 通过ECHO，我们建议阐明有助于神经发育的暴露和风险途径， 学龄前AA儿童的缺陷和肥胖：（1）收集亚特兰大ECHO队列的~440 AA 社会经济上不同的母亲-儿童对，结合现存的队列，对他们来说，产前，围产期， 幼儿环境的特点，或将其特点;（2）完成分析和综合的数据 从亚特兰大ECHO队列研究中，从产前和幼儿期的角度， 暴露（毒物、应激源和神经内分泌免疫激活，营养和代谢状况， 微生物组和感染，结合和相互作用）;表观遗传和代谢组学概况;围产期 结果（胎龄，妊娠大小）;（3）测试与产前和产后相关的队列特定假设， AA儿童在2、3、4和5岁时的儿童早期暴露和神经发育结局及肥胖 （4）参与ECHO范围内的联合研究，以确定风险和保护因素， 环境暴露、典型的生长和发育与儿童健康不良之间的关系 结果。我们的队列参与ECHO联盟将有助于生物心理社会的理解 种族内和种族间儿童健康不良后果的风险， 与AA家庭有关的因素。拟议的研究与消除种族歧视的框架是一致的。 这种差异认识到需要研究种族内的风险，作为至关重要的第一步， 国家少数民族健康和健康差异研究所的目标是促进对生物多样性的理解， 在不成比例地影响健康差距人口的条件下，

Abstract of Funded ECHO Parent Grant (UH3OD023318) 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.