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

宫内和幼儿环境对非裔美国青年神经认知和代谢发展的影响：关注肠脑轴

• 批准号: 10004195
• 负责人: PATRICIA A BRENNAN
• 金额: $ 161.99万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-21 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10004195
• 关键词: 5 year old; Affect; African American; Area; Behavior; Biological; Birth; Brain; Chemicals; Child; Child Health; Child Rearing; Collaborations; Complex; DNA Methylation; Data; Demographic Factors; Development; Diet; Dietary Component; Disease; Emotional; Environment; Environmental Exposure; Epigenetic Process; Ethnic Origin; Etiology; Event; Exposure to; Family; Future; Gender; Gene Expression; Genetic Transcription; Geographic Locations; Gestational Age; Gestational Diabetes; Goals; Growth and Development function; Health; Immune response; Infant; Infection; Infectious Agent; Inflammation; Institutes; Lead; Life; Link; Longitudinal Studies; Mediating; Metabolic; Metabolic Diseases; Metabolic Pathway; Metagenomics; Mothers; Neurocognitive; Neurocognitive Deficit; Neurodevelopmental Deficit; Neurosecretory Systems; Nursery Schools; Nutrient; Nutritional; Obesity; Outcome; Oxidative Stress; Pathway interactions; Perinatal; Physical activity; Population; Pregnancy; Premature Birth; Preventive Intervention; Problem behavior; Process; Race; Research; Risk; Risk Factors; Role; Signal Transduction; Socioeconomic Status; Specimen; Stress; Technology; Testing; Toddler; Toxic Environmental Substances; Woman; Youth; aged; autism spectrum disorder; biobehavior; biological adaptation to stress; biopsychosocial; cohort; early childhood; early life exposure; epigenomics; experience; gut microbiome; gut-brain axis; health disparity; immune activation; in utero; insight; maternal stress; metabolomics; microbiome; minority health; neurodevelopment; obesity in children; offspring; perinatal outcomes; postnatal; pregnancy hypertension; pregnant; prenatal; prenatal exposure; protective factors; racial disparity; racism; ranpirnase; sociodemographics; socioeconomics; stressor; toxicant; virtual

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.

项目摘要 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。 AA儿童不成比例地经历的结果包括早产，神经发育， 缺陷和肥胖-所有这些都与环境暴露有关，但由于其病因学而知之甚少 复杂性我们的团队目前正在研究早产和18个月的神经发育， 与出生前后接触环境毒物和生物心理社会风险因素的关系 妊娠AA女性（R 01 NR 014800、R 01 MD 009064）及其婴儿（R 01 MD 009746）和通过我们的P50 儿童中心（P50 ES 026071）与埃默里HERCULES Exposome研究中心合作 (P30 ES 019776）。 通过ECHO，我们建议阐明导致以下问题的暴露和风险途径： 学龄前AA儿童的神经发育缺陷和肥胖：（1）组装亚特兰大ECHO 约440个AA社会经济上不同的母亲-儿童对的队列，结合现有队列， 产前、围产期和幼儿期的环境是或将是特征;（2）完成分析 和亚特兰大ECHO队列的数据合成，以在产前和产后方面描述母婴对的特征。 幼儿期接触（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）;表观遗传和代谢组学特征; 和围产期结局（胎龄，妊娠大小）;（3）测试队列特定的假设， 产前和儿童早期暴露与AA儿童在2，3， 4岁和5岁;（4）参加ECHO范围内的联合研究，以确定风险和保护因素 环境暴露、典型的生长和发育以及不利的 儿童健康成果。我们的队列参与ECHO联盟将有助于生物心理社会 了解儿童健康不良后果的种族内和种族间风险， AA家系的相关保护因素。拟议的研究与以下框架一致： 消除种族差异，承认有必要研究种族内的风险作为至关重要的第一步， 符合国家少数民族健康和健康差异研究所促进理解的目标 在不成比例地影响健康差距人群的条件所涉及的生物机制。