ECHO Consortium on Perinatal Programming of Neurodevelopment

ECHO 围产期神经发育规划联盟

• 批准号: 10239019
• 负责人: Robert O Wright
• 金额: $ 846.93万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 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/10239019
• 关键词: Address; Affect; Age; Air Pollutants; Air Pollution; Area; Arsenic; Attention; Biological; Biological Markers; Biological Specimen Banks; Birth; Blood; Brain; Cadmium; Carbon; Characteristics; Chemicals; Child; Child Development; Child Health; Childhood; Complex; Complex Mixtures; Coupled; DNA Damage; Data; Data Science; Databases; Development; Disease; Dose; Enrollment; Environment; Environmental Exposure; Environmental Health; Environmental Risk Factor; Epidemiologist; Episodic memory; Equilibrium; Exposure to; Fetal Development; Functional disorder; Future; Genes; Genomics; Goals; Health; Heterogeneity; Human; Hydrocortisone; Infant; Inflammatory; Infrastructure; Interdisciplinary Study; Intervention; Language; Lead; Length; Leukocytes; Life; Life Cycle Stages; Link; Manganese; Measures; Mediating; Mediation; Mediator of activation protein; Memory; Metal exposure; Metals; Methodology; Methods; Mission; Mitochondrial DNA; Modeling; Mothers; Neuraxis; Nitrogen Oxides; Obesity; Outcome; Outcomes Research; Oxidants; Oxidative Stress; Ozone; Pattern; Pediatric Research; Perinatal; Phase; Phenotype; Physiological; Placenta; Play; Predisposition; Pregnancy; Pregnant Women; Process; Production; Psychologist; Psychosocial Stress; Reactive Oxygen Species; Regulation; Research Personnel; Role; Science; Scientist; Sex Differences; Short-Term Memory; Social Change; Source; Statistical Methods; Stress; Sulfur Oxides; Telomere Shortening; Testing; Time; Tooth structure; Toxin; United States National Institutes of Health; Variant; Work; Zinc; ambient air pollution; base; biobank; cohort; data centers; deviant; early childhood; ethnic diversity; executive function; experience; fetal; fine particles; follow-up; gene environment interaction; high dimensionality; in utero; indexing; innovation; molecular marker; neurodevelopment; neuroinflammation; novel; nutrition; pediatrician; postnatal; prenatal; processing speed; programs; prospective; remote sensing; respiratory; respiratory health; response; sex; social; social factors; social stress; spatiotemporal; statistics; stressor; telomere

Environmental interactions with genes, co-occurring environmental factors, sex, and life stage define normal variation and adverse neurodevelopment over the life course. Beginning in utero, the central nervous system (CNS) develops sequentially with network components of distinct functional domains (e.g., attention, memory, etc.) developing at different times. Thus, toxin effects depend both on timing of exposure and dose. The developing fetus and infant are most vulnerable. Moreover, pregnant women and children are not exposed to a single chemical but to complex chemical mixtures. Complex interactions between chemical and non-chemical stressors as well as sex can also influence outcomes. We propose a new ECHO Consortium of 5,000 prenatally enrolled and prospectively followed ethnically diverse mothers and their children to better address these complexities. Our UG3 mission will be to measure environmental exposures across pregnancy and childhood to determine how pro-oxidant environmental factors affect neurodevelopment. We will leverage methodological advances developed by our team including 1) a novel tooth-based biomarker that can objectively ; 2) satellite remote sensing based air pollution models that can reconstruct ; 3) mixtures statistics; and 4) data-driven statistical reconstruct past exposure timing and dose past exposure timing and dose methods to identify vulnerable windows. The Mount Sinai Consortium will also be part of the larger national ECHO synthetic cohort to study the health impacts of chemicals, nutrition, social factors, the biological response to these exposures, and the gene-environment interactions that underlie childhood disease more broadly. We can both meet our UG3 aims and the goals of the ECHO UH3, as our cohorts have extensive biobanking to facilitate expanded exposure assessment and mechanistic studies and our team has the requisite expertise in phenotyping in the four ECHO focus areas, in exposure science, and in cohort management. In this application, we will establish the infrastructure to coordinate, plan, and communicate with the four cohorts that make up our consortium, while performing similar functions within the greater NIH ECHO program, working with the Coordinating Center, the ECHO Data Center, the Pediatric Research Outcomes (PRO) Core, the future Genomics Core, and the CHEAR Exposure Core. Our Consortium will harmonize the databases of our four established cohorts to achieve these goals in tandem with experts in data science from the CHEAR Network Data Center. This proposal links highly experienced environmental health scientists with, statisticians, social epidemiologists, stress researchers, child psychologists, chemists, pediatricians, toxicologists, geneticists, and epigeneticists to build the infrastructure and scientific capacity to create a highly functional, state of the art longitudinal birth cohort consortium that objectively measures human environments that program child health and integrates with the greater NIH ECHO program.

环境与基因的相互作用，共同发生的环境因素，性别和生命阶段定义正常 变异和不利的神经发育在生命过程中。从子宫开始，中枢神经系统 (CNS)与不同功能域的网络组件（例如，注意力、记忆力等） 在不同的时间发展。因此，毒素效应取决于暴露的时间和剂量。发展中 胎儿和婴儿是最脆弱的。此外，孕妇和儿童没有接触到单一的 复杂的化学混合物。化学品和非化学品之间的复杂相互作用 压力源和性别也会影响结果。我们建议成立一个新的ECHO联盟， 产前登记并前瞻性跟踪不同种族的母亲及其子女， 这些复杂性。我们的UG 3使命将是测量怀孕期间的环境暴露， 儿童期，以确定促氧化环境因素如何影响神经发育。我们将利用 我们团队开发的方法学进展包括1）一种新的基于牙齿的生物标志物， 基于卫星遥感的大气污染模型 3）混合统计; 4）数据驱动统计 重建过去的暴露时间和剂量 既往暴露时间和剂量 识别易受攻击的窗口。西奈山财团也将成为更大的国家的一部分， ECHO综合队列研究化学品、营养、社会因素、生物 对这些暴露的反应，以及作为儿童疾病基础的基因-环境相互作用 大致上我们既可以实现我们的UG 3目标，也可以实现ECHO UH 3的目标，因为我们的同伴拥有广泛的 生物库，以促进扩大暴露评估和机制研究，我们的团队有 ECHO四个重点领域的表型分析、暴露科学和队列研究方面的必要专业知识 管理在此应用程序中，我们将建立基础设施，以协调、规划和通信 组成我们联盟的四个队列，同时在更大的NIH ECHO内执行类似的功能 计划，与协调中心，ECHO数据中心，儿科研究成果 (PRO)核心，未来的基因组学核心，和CHEMICAL曝光核心。我们的联盟将协调 我们的四个已建立的队列数据库，以实现这些目标与数据科学专家从 CHEAR网络数据中心。该提案将经验丰富的环境健康科学家与， 统计学家，社会流行病学家，压力研究者，儿童心理学家，化学家，儿科医生， 毒理学家，遗传学家和表观遗传学家建立基础设施和科学能力， 客观测量人类环境的功能性、最先进的纵向出生队列联盟 该计划的儿童健康，并与更大的NIH ECHO计划整合。