Environmental influences on Child Health Outcomes - The Colorado ECHO Pediatric Cohort

项目总结/摘要 慢性疾病，如肥胖，哮喘，抑郁症和发育障碍，正在增加， 世界各地的儿童。此外，许多此类疾病的诊断年龄正在下降，指向早期生命 起源.健康和疾病的发展起源（DOHaD）范式假定， 子宫内和生命早期的经历会影响表型和生理以及行为， 终身健康。DOHaD现象的流行病学研究历来集中在单一的疾病-健康 结果关联，尽管呼吁采取更全面的方法来捕捉暴露的总体情况及其 因果路径先前工作的其他重要限制包括同质研究样本减少 普遍性和有限的机会，以确定差异和不经常或缺乏粒度的评估 个体发育过程中的暴露和健康结果。总之，这些限制阻碍了识别何时 以及生命早期的风险因素和风险因素组合如何最终导致慢性病。这项建议 通过利用环境对儿童健康结果的影响（ECHO）解决上述差距 计划调查广泛的早期生活暴露，从社会到生物学，与儿科有关 约50，000对子代-后代的健康结果。科罗拉多团队将实施ECHO的核心， 健康开端研究的专门方案，这是一项科罗拉多的出生前队列研究，招募并随访了1250名 母子二人组在该队列中，收集了妊娠期间与ECHO相关的暴露和结局， 出生时、婴儿期和学步期以及幼儿期（4-5岁）。在第一个ECHO周期中， 科罗拉多研究小组跟踪了765名儿童，到目前为止，通过童年中期（8-12岁）和转移现存的数据 从怀孕到ECHO平台。响应RFA-OD-22-019并与其他 ECHO组件，我们的团队将实施ECHO队列数据和生物标本采集方案， 高保真度和使用社区参与的保留策略，以跟踪900名年龄在11-19岁之间的不同参与者 实现两个科学目标：（1）描述结构、化学和物理暴露的模式 在子宫内时期和幼儿期，通过以下方式预测主要ECHO结局的共同发生集群 青春期;（2）检查暴露于子宫内营养过剩和儿童期心理社会的联合影响 儿童肥胖症的专业结果的逆境。拟议的工作将促进全面的 了解生命早期暴露和经历的总体情况如何影响儿童患慢性病的风险; 检查潜在的可改变的生物机制（DNA甲基化）的参与;并提供 深入了解预防行动的多层次目标，包括家庭和个人层面的因素， 面对不利的早期风险的弹性。科罗拉多团队为ECHO带来了一个多元化的团队， 研究人员谁是独特的准备领导创新的团队科学，以引导解决方案为导向的研究。

PROJECT SUMMARY/ABSTRACT Chronic conditions, such as obesity, asthma, depression, and developmental disabilities, are increasing among children worldwide. Further, the age at diagnosis for many such conditions is decreasing, pointing to early-life origins. The developmental origins of health and disease (DOHaD) paradigm posits that exposures and experiences in utero and during early life influence phenotype and physiology as well as behaviors that shape lifelong health. Epidemiologic studies of DOHaD phenomena have historically focused on single exposure-health outcome associations, despite calls for more holistic approaches to capture the totality of exposures and their causal pathways. Other important limitations of prior work include homogenous study samples that diminish generalizability and limit opportunities to identify disparities and infrequent or lack of granularity in assessment of exposures and health outcomes across ontogeny. Together, these limitations hamper identification of when and how risk factors and combinations of risk factors across early life culminate in chronic disease. This proposal addresses the above gaps by leveraging the Environmental influences on Child Health Outcomes (ECHO) Program to investigate a broad range of early-life exposures, from society to biology, in relation to pediatric health outcomes among ~50,000 caregiver-offspring pairs. The Colorado team will implement ECHO’s Core and Specialized Protocols in the Healthy Start Study, a Colorado pre-birth cohort that recruited and followed 1,250 mother-child dyads. In this cohort, exposures, and outcomes relevant to ECHO were collected during pregnancy, at birth, during infancy and the toddler years, and in early childhood (4-5 years). In the first ECHO Cycle, the Colorado team followed 765 children, to date, through middle childhood (8-12 years) and transferred extant data from pregnancy onward to the ECHO platform. In response to RFA-OD-22-019 and in collaboration with other ECHO components, our team will implement the ECHO Cohort Data and Biospecimen Collection Protocol with high fidelity and use community-engaged retention strategies to follow 900 diverse participants aged 11-19 years to achieve two scientific objectives: (1) characterize patterns of structural, chemical, and physical exposures during the in utero period and early childhood that predict co-occurring clusters of major ECHO outcomes through adolescence; and (2) examine joint effects of exposure to in utero overnutrition and childhood psychosocial adversity on the Specialized Outcome of pediatric obesity. The work proposed will facilitate a holistic understanding of how the totality of early-life exposures and experiences shape chronic disease risk in children; examine the involvement of a potentially modifiable biological mechanism (DNA methylation); and provide insights into multi-level targets for preventive action, including family- and individual-level factors that build resiliency in the face of unfavorable early exposures. The Colorado team brings to ECHO a diverse group of investigators who are uniquely poised to lead innovative team science to steer solution-oriented research.