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

Echo家长资助摘要(UH3OD023318) 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。其中 再生障碍性贫血儿童经历的结果不成比例地是早产、神经发育缺陷和 肥胖--都与环境暴露有关，但由于病因的复杂性，人们对其知之甚少。我们的团队 目前正在研究18个月的早产和神经发育与出生前和出生后的关系 再障孕妇队列中环境毒物暴露与生物心理社会危险因素 (R01NR014800，R01MD009064)和他们的婴儿(R01MD009746)，并通过我们的P50儿童中心 (P50ES026071)与Emory Hercules Exposome研究中心合作(P30 ES019776)。 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)收集约440名AA的亚特兰大回声队列 通过结合现有的队列来实现社会经济上多样化的母子对，对这些人来说，产前、围产期和 (2)完成数据的分析和综合 来自亚特兰大回声队列，从产前和早期儿童的角度来描述母子对的特征 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)；表观遗传和代谢组谱；以及围产期 结果(胎龄、孕期大小)；(3)检验与产前和 再生障碍性贫血儿童在2、3、4和5岁时的早期儿童暴露、神经发育结果和肥胖 年龄；(4)参加全回声联盟的研究，以确定适度的风险和保护因素 环境暴露、典型生长发育和不利儿童健康之间的关系 结果。我们在ECHO联盟中的参与将有助于对生物心理社会的理解 对不良儿童健康结果的种族内和种族间风险进行评估，提供对风险和保护的洞察 与再生障碍性贫血家庭相关的因素。拟议的研究与消除种族歧视的框架是一致的 差异，它认识到需要研究种族内部的风险，作为至关重要的第一步，并与 国家少数民族健康和健康差距研究所的目标是促进对生物学 这些机制涉及对健康差距人口造成不成比例影响的情况。

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.