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：我们对广泛传播和传播的健康影响的认识存在重大差距。 大大增加了美国儿童的接触机会。尤其是来自农村地区的孩子 尚未得到充分研究，但可能会因饮用不受管制的水而接触到更高的污染物；来自 木火炉造成的家庭空气污染；以及由于他们的农村和不断变化的景观（例如，从 气候变化）。作为 ECHO 儿科队列应用的一部分，我们建议利用 NIEHS/EPA 支持的新罕布什尔州出生队列研究 (NHBCS)：一项农村持续妊娠队列研究 已累积超过1,500对母婴。在本应用的 UH3 阶段开始时， 预期队列规模为 2,000 人，作为 ECHO 儿科队列申请的一部分，应计人数将为 扩大到3000对母婴。临床结果是通过间隔访谈来确定的， 问卷、医疗记录、现场评估和实验室测试。该研究已存档 怀孕期间的环境样本（自来水和室内空气）和生物样本（母体血液、尿液和 头发），以及出生时采集的生物样本（婴儿脐带血、胎盘和胎便）和怀孕期间采集的生物样本 童年（尿液、血液、口腔细胞、母乳、脚趾甲和粪便）。利用这些样本的能力 已经证明了广泛的下游分析。对于当前的应用，新兴的假设 将通过以下方式解决所关注的问题：(1) 利用现有的 NHBCS 来执行有针对性的、无监督的 对 1,000 份脐带血样本和 250 份配对母体妊娠血液样本进行代谢组学分析，以及 评估与暴露、早期生长和婴儿微生物组的关联； (2)扩大数据采集， 样本收集和参与者应计，以更准确地描述早期生活的暴露和时间安排 通过获得尿液金属代谢组学测量值和暴露组监测数据来进行暴露 怀孕前三个月，以及产前金属自然脱落牙齿的空间分析 浓度； (3) 扩大后续行动，以确定儿童接触污染物的情况（通过 生物标记物和个人监测器）；家庭环境（例如身体活动和睡眠模式、食物 环境、绿色、蓝色和白色空间以及媒体使用）；和医疗暴露（例如处方药和 非处方药和手术干预）与胎儿和儿童生长、肥胖有关 3岁时的呼吸道感染和哮喘，5岁时的呼吸道感染和哮喘，以及7.5岁时的肺功能数据。 新的统计方法将用于确定肠道和唾液微生物组的作用 这些影响的中介者。集体的专业知识、方法、数据、样本和初步结果 这项研究将有助于规划更广泛的 ECHO 儿科队列计划，以推进 我们对生命早期影响童年和终生健康的环境因素的了解。

Project Summary/Abstract: Major gaps exist in our knowledge of the health impacts of widespread and dramatically expanding exposures among children in the US. Children from rural regions are particularly understudied, but may experience higher exposures to contaminants by drinking unregulated water; from household air pollution from wood stoves; and consequent to their rural and changing landscape (e.g., from climate change). As part of this ECHO Pediatric Cohorts application, we propose to take advantage of the NIEHS/EPA supported New Hampshire Birth Cohort Study (NHBCS): a rural, ongoing pregnancy cohort that has accrued over 1,500 maternal-infant dyads. By the beginning of the UH3 phase of this application, the anticipated cohort size will be 2,000, and as part of this ECHO Pediatric Cohorts application, accrual will be extended to 3,000 maternal-infant pairs. Clinical outcomes are being ascertained from interval interviews, questionnaires, medical records, in-person assessments and laboratory tests. The study has archived environmental (tap water and indoor air) and biological samples during pregnancy (maternal blood, urine and hair), as well as biological samples acquired at birth (infant cord blood, placenta and meconium) and during childhood (urine, blood, buccal cells, breast milk, toenails and stool). The ability to utilize these samples for a wide range of downstream analyses has been demonstrated. For the current application, emerging hypotheses of concern will be addressed by: (1) leveragingthe extant NHBCS to perform targeted and unsupervised metabolomic analyses of 1,000 cord blood samples and 250 paired maternal gestational blood samples, and assess associations with exposures, early growth, and the infant microbiome; (2) expandingdata acquisition, sample collection and participant accrual to more precisely characterize exposures and timing of early life exposures by obtaining urinary metal metabolomic measurements, and exposome monitoring data from the first trimester of pregnancy, along with spatial analysis of naturally shed teeth for prenatal metal concentrations; and (3) extending follow-up to identify childhood exposures to contaminants (through biomarkers and personal monitors); the home environment (e.g., physical activity and sleep patterns, food environment, green, blue and white space, and media usage); and medical exposures (e.g., prescription and non-prescription medications and surgical interventions) that relate to fetal and childhood growth, obesity at age 3 years, respiratory infection and asthma by age 5 years, and pulmonary function data at age 7.5 years. Novel statistical approaches will be used to determine the role of the intestinal and salivary microbiome as mediators of these effects. The collective expertise, methodologies, data, samples and preliminary results from this study will contribute to the planning of the broader ECHO Pediatric Cohorts initiative in order to advance our understanding of the environmental factors early in life that drive childhood and lifelong health.