The Early Life Exposome and Childhood Health - The Colorado Healthy Start 3 Cohort Study

项目摘要 作为对RFA-OD-16-004的回应，我们的首要目标是确定早期生活“麻烦”， 在广泛的暴露（社会，生活方式，营养，化学，物理）和行为 通过生物学途径了解儿童健康结果的综合分析， 考虑到产后因素。我们建议利用现有的，正在进行的出生前队列， 科罗拉多，健康的开始，已经招募并正在跟踪1410对母子 4-5岁（R 01 DK 076648，PI Dabelea）。已经采集了生物样本 在怀孕期间，在出生时，现在在4-5岁时获得。我们的研究建议， 通过实现以下目标来利用这一群体： 目标1：扩大对产前和生命早期环境暴露（空气污染， 建筑环境），并增加已经测量的暴露（社会，生活方式，营养， 化学），以定义暴露模式（干扰体的外部区域）; 目的2：测量与以下相关的生物学特征（干扰素组的内部结构域）： 在具有可用样本的儿童亚群中的产前环境暴露（脐带血， 脐带来源的间充质干细胞和胎盘）; 目的3：继续对队列进行纵向随访，直至7-8岁，重点关注肥胖， 血管、代谢、神经认知和呼吸结果，以及产后社交和 行为因素; 目标4：进行综合分析，以评估多种和联合早期 生活暴露与儿童结果。生物、社会和行为途径和中介 将被探索。 我们的研究准备整合现有的和新测量的估计 产前/生命早期的环境暴露，以及其生物学特性， 签名和可能对发展行为的影响，提供了第一步， 需要全面了解儿童慢性病的病因。若继续 纵向随访科罗拉多健康开始队列，并与更大的 ECHO财团，我们将能够扩大我们的工作范围，通过完善和纳入 问题组的其他组成部分，探讨 随着时间的推移，针对额外的儿童成果，并参与大型 基因-环境交互作用研究

PROJECT SUMMARY In response to RFA-OD-16-004, our overarching goal is to determine the early life “exposome”, across a wide range of exposures (social, lifestyle, nutritional, chemical, physical), and conduct integrative analyses with child health outcomes that are informed by biological pathways and account for postnatal factors. We propose to leverage an existing, ongoing pre-birth cohort in Colorado, Healthy Start, which has recruited and is currently following 1410 mother-child dyads up to age 4-5 years (R01DK076648, PI Dabelea). Biological samples have been collected during pregnancy, at birth, and are now being obtained at age 4-5 years. Our study proposes to leverage this cohort by accomplishing the following aims: AIM 1: Expand the assessment of prenatal and early life environmental exposures (air pollution, built environment) and add to exposures already measured (social, lifestyle, nutritional, chemical) to define exposure patterns (external domain of the exposome); AIM 2: Measure biological signatures (internal domain of the exposome) associated with prenatal environmental exposures in subsets of children with available samples (cord blood, umbilical-derived mesenchymal stem cells, and placentas); AIM 3: Continue the longitudinal follow up of the cohort to age 7-8 years focusing on obesity, vascular, metabolic, neurocognitive and respiratory outcomes, as well as postnatal social and behavioral factors; AIM4: Conduct integrative analyses to assess the relationships of multiple and combined early life exposures with child outcomes. Biological, social and behavioral pathways and mediators will be explored. Our study is poised to integrate estimates of already available and newly measured environmental exposures operating during prenatal/early life, together with their biological signatures and likely effects on developmental behaviors, to provide a first step in the much needed holistic understanding of the etiology of childhood chronic diseases. By continuing to longitudinally follow up the Colorado Healthy Start cohort and collaborating with the larger ECHO consortium we will be able to expand the scope of our work, by refining and incorporating additional components of the exposome, exploring changes in the composition and impact of the exposome over time, targeting additional childhood outcomes, and participating in large gene-environment interaction studies.