ECHO Consortium on Perinatal Programming of Neurodevelopment

ECHO 围产期神经发育规划联盟

• 批准号: 9355705
• 负责人: Robert O Wright
• 金额: $ 863.4万
• 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 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9355705
• 关键词: Address; Affect; Age; Air Pollutants; Air Pollution; Area; Arsenic; Attention; Biological; Biological Markers; Birth; Blood; Brain; Cadmium; Carbon; Characteristics; Chemicals; Child; Child Development; Child health care; 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; Fetus; Functional disorder; Future; Genes; Genomics; Goals; Health; Heterogeneity; Human; Hydrocortisone; Infant; Inflammatory; 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 Infrastructure; Research Personnel; Role; Science; Scientist; Sex Characteristics; Short-Term Memory; Social Change; Source; Specimen; 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; 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 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、同时发生的环境因素、性别和生命阶段定义了正常 生命过程中的变异和不良神经发育。从子宫内开始，中枢神经系统 （中枢神经系统）与不同功能域的网络组件（例如注意力、记忆等）依次发展 不同时期的发展。因此，毒素效应取决于暴露时间和剂量。发展中的 胎儿和婴儿是最脆弱的。此外，孕妇和儿童不接触单一的 化学但复杂的化学混合物。化学和非化学之间复杂的相互作用 压力源和性别也会影响结果。我们提议成立一个由 5,000 人组成的新 ECHO 联盟 产前登记并前瞻性跟踪不同种族的母亲及其子女，以更好地解决 这些复杂性。我们的 UG3 使命是测量怀孕和怀孕期间的环境暴露情况 童年时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) 一种新型的基于牙齿的生物标记物，可以 客观地； 2）基于卫星遥感的空气污染模型 可以重建； 3）混合物统计； 4）数据驱动的统计 重建过去的暴露时间和剂量 过去的暴露时间和剂量 识别易受攻击的窗户的方法。西奈山财团也将成为更大的国家联盟的一部分 ECHO 综合队列研究化学品、营养、社会因素、生物因素对健康的影响 对这些暴露的反应，以及导致儿童疾病的基因-环境相互作用 广泛地说。我们可以实现 UG3 目标和 ECHO UH3 目标，因为我们的队列拥有广泛的 生物样本库以促进扩大暴露评估和机制研究，我们的团队拥有 四个 ECHO 重点领域、暴露科学和队列的表型分析所需的专业知识 管理。在此应用程序中，我们将建立基础设施来协调、规划和沟通 组成我们联盟的四个队列，同时在更大的 NIH ECHO 中执行类似的功能 计划，与协调中心、ECHO 数据中心、儿科研究成果合作 (PRO) Core、未来的 Genomics Core 和 CEAR Exposure Core。我们的联盟将协调 我们四个已建立队列的数据库，与来自数据科学领域的专家合作实现这些目标 CEAR 网络数据中心。该提案将经验丰富的环境健康科学家与以下人员联系起来： 统计学家、社会流行病学家、压力研究人员、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，以创造高度 客观测量人类环境的功能性、最先进的纵向出生队列联盟 该项目儿童健康并与更大的 NIH ECHO 项目相结合。