ECHO Consortium on Perinatal Programming of Neurodevelopment

ECHO 围产期神经发育规划联盟

基本信息

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
项目类别：
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

项目摘要

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.

与基因，共发生的环境因素，性别和生命阶段的环境相互作用定义正常生活过程中的变化和不良神经发育。从子宫开始，中枢神经系统（CNS）通过不同功能域的网络组件（例如，注意，记忆等）依次开发。在不同的时间发展。因此，毒素作用既取决于暴露时间和剂量的时间。发展中胎儿和婴儿最脆弱。此外，孕妇和儿童没有接触一次化学，但要进行复杂的化学混合物。化学和非化学之间的复杂相互作用压力源和性别也会影响结果。我们提出了一个新的回声财团5,000 产前招收并前瞻性地跟随种族多样化的母亲及其子女，以更好地解决这些复杂性。我们的UG3任务将是衡量怀孕期间的环境暴露和童年确定促氧化剂环境因素如何影响神经发育。我们将利用我们的团队开发的方法学进步，包括1）一种新型的基于牙齿的生物标志物，可以客观上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曝光时间和剂量过去的曝光时间和剂量识别弱势窗口的方法。西奈山联盟也将成为较大国家的一部分回声合成队列研究化学物质，营养，社会因素，生物学的健康影响对这些暴露的反应，以及儿童疾病基础的基因环境相互作用广泛。我们俩都可以实现我们的UG3目标和Echo UH3的目标，因为我们的同伙有广泛的生物群以促进扩大的接触评估和机械研究，我们的团队拥有在四个回声焦点区域，曝光科学和队列中表型的必要专业知识管理。在此应用程序中，我们将建立以协调，计划和沟通的基础架构构成我们财团的四个队列，同时在更大的NIH中执行相似的功能计划，与协调中心，回声数据中心，儿科研究成果合作（Pro）核心，未来的基因组核心和Chear暴露核心。我们的财团将协调我们四个已建立的同类群体的数据库，以与数据科学专家共同实现这些目标 Chear网络数据中心。该建议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，以创造高度功能性，最先进的纵向出生队列联盟，该联盟客观地衡量人类环境该计划的儿童健康计划与更大的NIH Echo计划集成。