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 在关键的产前和幼儿期接触环境可导致终生健康 后果。这些暴露-健康关系背后的机制是复杂的，外源 暴露(如化学毒物、感染剂、饮食)和内源性过程(如基因 表达、炎症和氧化应激)激活代谢途径，从而导致不利的健康 结果。不良暴露及其健康后果对非裔美国人的影响不成比例 (Aa)妇女和儿童，强调健康差距始于子宫，并在出生后扩大。 再生障碍性贫血儿童经历的不成比例的后果包括早产、神经发育 缺陷和肥胖--都与环境暴露有关，但由于其病因尚不清楚 复杂性。我们的团队目前正在研究18个月的早产和神经发育 队列中出生前和出生后暴露于环境毒物和生物、心理、社会危险因素的关系 怀孕的AA妇女(R01NR014800，R01MD009064)及其婴儿(R01MD009746)和通过我们的P50 儿童中心(P50ES026071)，与Emory Hercules Exposome研究中心合作 (第30页ES019776)。 通过ECHO，我们建议阐明暴露和风险途径，这些途径有助于 学龄前AA儿童的神经发育缺陷和肥胖：(1)组装亚特兰大回声 约440对社会经济上不同的母子对通过结合现有的队列 产前、围产期和儿童早期环境已经或将被描述；(2)完成分析 和来自亚特兰大回声队列的数据的合成，以根据产前和 儿童早期暴露(毒物、应激源和神经内分泌免疫激活、营养和 代谢状态、微生物组和感染、结合和相互作用)；表观遗传学和代谢组学； 和围产儿结局(胎龄、孕期大小)；(3)测试与以下相关的队列特定假设 AA儿童出生前和儿童早期暴露与神经发育结局和肥胖的关系 4岁和5岁；(4)参加全回声联盟研究，以确定风险和保护因素 环境暴露、典型的生长和发育以及不利因素之间的适度联系 儿童健康结果。我们在ECHO财团中的参与将有助于生物心理社会 了解不良儿童健康结局的种族内和种族间风险，提供对风险的洞察 与再生障碍性贫血家庭相关的保护因素。拟议的研究与以下框架一致 消除种族差异，认识到有必要研究种族内部的风险，这是至关重要的第一步，并正在 与国家少数民族健康和健康差距研究所促进了解的目标一致 对不成比例地影响健康差距人群的条件所涉及的生物学机制。

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.