Early Life Exposures and Child Trajectories: Growth and Respiratory Health

项目总结/摘要 在受精、着床前后和怀孕期间的关键发育窗口早期暴露， 对儿童的健康、发育和疾病有长期影响。早期全面评估 暴露需要多方面的评估，包括社区一级的环境 因素（包括空气污染）、化学品暴露（包括内分泌干扰物）、微生物组（包括 与免疫应答相关的病原体和感染因子），以及基因组及其对 环境（包括遗传表观基因组、基因组表达和蛋白质组）。我们目前正在 从两个出生队列中重新入组一个儿科队列，1）犹他州 参与者在全国儿童的研究，和2）参与者在家庭观察围概念 早期生活暴露和儿童轨迹（ELECT）队列。我们也 登记亲生父母和最多一个亲生兄弟姐妹的孩子。在UG 3阶段（前两年），我们 重点是完成整个队列的重新入组，并对创新方法进行评估， 围受孕期关键早期窗口期间已知和新出现的暴露光谱， 早孕。我们评估的暴露将包括微生物组、药物、感染、泛病毒抗体 评估，空气污染物（特别是颗粒污染（PM2.5），还有氮氧化物和臭氧），内分泌 破坏化学物质（特别是双酚A（BPA）和邻苯二甲酸酯），以及牙釉质的矿化不足 作为早期内分泌干扰物暴露的标志。我们也会对一些 健康影响。在UH 3阶段，我们将重点关注这些暴露与后续结果的关联 在两个重点领域：生长（包括胰岛素抵抗和儿童肥胖）和呼吸系统健康（包括 呼吸道感染和哮喘）。我们将与ECHO国家合成 将UCP-ELECT整合到该队列中。我们将协助制定核心措施， 合成ECHO队列并在UCP-ELECT中实施这些。总体而言，该提案侧重于 在整个UG 3和UH 3中，对暴露的新评估可以转换为其他环境， 以可行和具有成本效益的方式，我们特别关注 可在其他队列中回顾性应用的评估，以评估极早期暴露（E.A. 怀孕和早期怀孕）。因此，我们将为ECHO队列1）一个基于人群的儿科 队列（来自500个家庭的950名儿童），具有现存和新的早期生物标本和评估，以及2） 从孕前到妊娠的关键多维麻烦组测量的科学验证 和幼儿期。然后，这些方法将可用于评估整个ECHO合成的儿童 获得妊娠前和妊娠期间暴露的窗口期，并评估其对 哮喘、肥胖和其他结果的发病率。

PROJECT SUMMARY / ABSTRACT Early exposures in critical developmental windows around fertilization, implantation, and during pregnancy can have long-term impact on health, development, and disease in children. A comprehensive assessment of early exposures requires a multidimensional assessment of the exposome, including community-level environmental factors (including air pollution), chemical exposures (including endocrine disruptors), the microbiome (including commensals and infectious agents with associated immune responses), and the genome and its responses to the environment (including the inherited epigenome, genomic expression, and the proteome). We are currently re-enrolling a pediatric cohort from two birth cohorts enrolled peri-conceptionally/prenatally, 1) the Utah participants in the National Children’s Study, and 2) participants in the Home Observation of Peri-conceptional Exposures (HOPE) study, into the Early Life Exposures and Child Trajectories (ELECT) cohort. We are also enrolling biological parents and up to one biological sibling child. In the UG3 phase (the first two years), we focus on completing re-enrollment of the entire cohort, and also on innovative methods for assessment of a spectrum of known and emerging exposures during the key early windows of the peri-conceptional time and early pregnancy. Exposures we assess will include the microbiome, medications, infections, pan-viral antibody assessment, air pollutants (especially particulate pollution (PM2.5), also nitrogen oxides and ozone), endocrine disrupting chemicals (particularly bisphenol-A (BPA) and phthalates), and hypomineralization of dental enamel as a marker for early endocrine disrupting exposure. We will also conduct a preliminary assessment of some health impacts. In UH3 phase, we will focus on the association of these exposures with subsequent outcomes in two focus areas: growth (including insulin resistance and childhood obesity) and respiratory health (including respiratory infections and asthma). We will work completely collaboratively with the ECHO national synthetic cohort to integrate UCP-ELECT into that cohort. We will contribute to the design of the core measures for the synthetic ECHO cohort and implement these within UCP-ELECT. Taken together, this proposal focuses throughout both UG3 and UH3 on novel assessments for exposures that can be translated to other settings of the ECHO synthetic cohort in a feasible and cost-effective manner. We are focused particularly on assessments that can be applied retrospectively in other cohorts to assess very early exposures (peri- conception and early pregnancy). Thus, we will contribute to the ECHO cohort 1) a population-based, pediatric cohort (950 children from 500 families) with extant and new early biospecimens and assessments, and 2) scientific validation of critical multidimensional exposome measurements from preconception through gestation and early childhood. These methods will then be available to assess children across the entire ECHO synthetic cohort to obtain a window on exposures prior to and during gestation, and to assess their impact on the incidence of asthma, obesity, and other outcomes.