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

项目总结 作为对RFA-OD-16-004的回应，我们的首要目标是确定早期生命的“暴露组”， 涉及广泛的暴露(社会、生活方式、营养、化学、物理)和行为 与儿童健康结果的综合分析，这些结果由生物途径和 考虑到出生后的因素。我们建议利用现有的、正在进行的产前队列在 科罗拉多州，Healthy Start，已经招募并目前正在关注1410名母子二人组 4-5岁(R01DK076648，Pi Dabelea)。已经收集了生物样本 在怀孕期间，在出生时，现在是在4-5岁时获得的。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：扩大产前和生命早期环境暴露(空气污染、 建筑环境)，并增加已测量的暴露(社会、生活方式、营养、 化学)以定义曝光图案(曝光体的外部区域)； 目标2：测量与以下相关的生物特征(曝光组的内部结构域) 有可用样本的儿童子组中的产前环境暴露(脐带血， 脐带源间充质干细胞和胎盘)； 目标3：继续队列的纵向随访至7-8岁，重点关注肥胖， 血管、代谢、神经认知和呼吸结果，以及出生后社会和 行为因素； AIM4：进行综合分析，早期评估多项和合并的关系 与孩子的结局有关的生活暴露。生物、社会和行为途径和介体 将会被探索。 我们的研究准备整合已有的和新测量的估计 产前/早期生命中的环境暴露及其生物学 签名和对发育行为的可能影响，以提供许多 需要全面了解儿童慢性病的病因学。通过继续 纵向跟踪科罗拉多州健康启动队列并与更大的 Echo财团我们将能够通过改进和合并来扩大我们的工作范围 曝光体的其他组件，探索组成的变化和影响 随着时间的推移，曝光，目标是额外的童年结果，并参与大型 基因-环境相互作用研究。

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.