A prospective study of critical environmental exposures in formative early life that impact lifelong health in rural US children: the New Hampshire Birth Cohort Study

项目摘要/摘要。在这次续期申请中，我们将推动环境保护的成功 《对儿童健康结果的影响》项目，该项目旨在“增进世代儿童的健康，以 来“作为怀孕和儿科队列研究网站之一。自2009年以来，新汉普郡出生 队列研究是一项农村前瞻性分子流行病学研究，已收集了关于 孕妇及其子女，目标是6,000个二倍体(包括1,005个新怀孕和2,800个 儿童同意在2023年8月之前加入Echo)。数据和生物武器正被近100人利用 概念提案(每个提案都有一份或多份手稿)，包括机会和基础设施奖，以 早期职业研究人员和新冠肺炎补充剂，还有更多正在筹备中。已经，我们的7440人 由我们的达特茅斯团队领导的Cohort的生物谱系已经致力于11个回声范围的实验室分析 和其他调查人员。这包括大多数参与者参与的ECHO基因组广泛关联研究 正在捐献DNA样本。非DNA生物样本可用或正运往ECHO 生物储存库包括尿液、脚趾甲、头发、血液、胎盘、胎粪、母乳、粪便和牙齿。我们拿到了 参与ECHO计划领导、委员会和工作组，设计和共享协议，以及 制作教学视频和参与者反馈材料。我们回应了对卫生公平的迫切呼吁， 促进劳动力多样化，优先处理公共卫生危机，包括对SARS进行时间敏感的评估- 冠状病毒-2对我们最脆弱的人群。我们致力于在下一阶段加强这些努力。 我们回应了国会和机构利益相关者以及医疗保健提供者和家庭以及 计划提升这种接触，以确保不同的视角和纳入我们的队列，并 对我们工作的影响。我们将再招募1500名孕妇，招募他们的受孕伴侣，招募他们 如果计划再生一个孩子，并跟随先前进入队列的孩子，则进入先入为主的队列 在这个研究阶段新生的。我们将坚持ECHO队列协议，依赖于该计划的RedCap 中央数据库和单一的IRB。我们将继续利用Echo前所未有的数据和样本 来自美国各地的不同人群，以及达特茅斯强大的基础设施和跨学科 专业知识。具体地说，我们将(1)通过描述农村曝光组及其 对儿童健康结果的影响，(2)确定下呼吸道和上呼吸道疾病和其他疾病的早期驱动因素 结果和使用专门暴露措施的发育微生物组的中介作用(例如， 饮食营养毒物成分)和结果(例如，呼吸道感染和疫苗反应)，以及(3) 孕间期肥胖及孕伴因素对儿童生长发育的影响 使用飞行员先入为主的队列。因此，我们的研究站点填补了ECHO计划中的一个关键利基，并将 继续发挥领导和协作作用，支持其总体使命。

Project Summary/Abstract. In this renewal application, we will advance the success of the Environmental Influences on Child Health Outcomes program that seeks to “enhance the health of children for generations to come” as one of the Pregnancy and Pediatric Cohort Study Sites. Since 2009, the New Hampshire Birth Cohort Study, a rural prospective molecular epidemiology study, has accrued data and biologic samples on pregnant people and their children with a goal of 6,000 dyads (including 1,005 new pregnancies and 2,800 children consented into ECHO) by August 2023. Data and biospecimens are being leveraged for nearly 100 Concept Proposals (each with one or more manuscripts), including Opportunity and Infrastructure awards to early career investigators and COVID-19 supplements, and with more in the pipeline. Already, 7,440 of our cohort’s biospecimens have been committed to 11 ECHO-Wide laboratory analyses led by our Dartmouth team and other investigators. This includes the ECHO Genome Wide Association Study to which most participants are contributing DNA samples. Non-DNA biologic samples available or being shipped to the ECHO Biorepository include urine, toenails, hair, blood, placenta, meconium, human milk, stool, and teeth. We took part in ECHO program leadership, committees and working groups, designing and sharing protocols, and creating instructional videos and participant feedback materials. We addressed the urgent call for health equity, fostered workforce diversity, and prioritized public health crises, including time sensitive evaluation of SARS- CoV-2 on our most vulnerable populations. We are committed to strengthening these efforts in the next phase. We responded to congressional and agency stakeholders as well as health care providers and families and plan to elevate this engagement moving forward to ensure diverse perspectives and inclusion in our cohort and impact of our work. We will recruit 1,500 additional pregnant people, enlist their conceiving partner, enroll them into a preconception cohort if planning another child and follow children previously accrued into the cohort and newly born in this study phase. We will adhere to the ECHO Cohort Protocol, rely on the program’s REDCap Central database and single IRB. We will continue to capitalize on ECHO’s unprecedented data and samples from diverse populations across the USA, along with Dartmouth’s robust infrastructure and interdisciplinary expertise. Specifically, we will (1) address rural health inequities by characterizing the rural exposome and its impact on child health outcomes, (2) determine the early drivers of lower and upper airway disease and other outcomes and the mediating role of the developing microbiome using specialized measures of exposures (e.g., dietary nutrient-toxicant composition) and outcomes (e.g., respiratory infections and vaccine response), and (3) investigate the influence of inter-pregnancy adiposity and factors of the conceiving partner on child growth using the pilot preconception cohort. Thus, our study site fills a critical niche in the ECHO program and will continue to provide leadership and collaboration in support of its overall mission.