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：我们对大范围和低收入人群的健康影响的认识存在重大差距 极大地扩大了美国儿童的风险暴露。来自农村地区的儿童尤其 研究不足，但可能会因饮用未受管制的水而暴露于更高的污染物； 木炉造成的家庭空气污染；以及因其农村和不断变化的景观(例如，从 气候变化)。作为ECHO儿科队列应用程序的一部分，我们建议利用 NIEHS/EPA支持的新汉普郡出生队列研究(NHBCS)：农村正在进行的怀孕队列研究 已经积累了1500多个母婴二元组。在本应用程序的UH3阶段开始时， 预计队列规模将为2,000，作为ECHO儿科队列应用程序的一部分，应计金额将为 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、面对面评估和实验室测试。这项研究已经存档了 孕期环境(自来水和室内空气)和生物样本(产妇血液、尿液和 以及出生时获得的生物样本(婴儿脐带血、胎盘和胎粪)以及 儿童时期(尿液、血液、口腔细胞、母乳、脚趾甲和大便)。能够利用这些样本进行 已经演示了广泛的下游分析。对于当前的应用，新兴的假设 将通过以下方式解决令人关切的问题：(1)利用现有的NHBCS执行有针对性和无监督的 1,000份脐带血和250份配对孕妇妊娠血的代谢组学分析 评估暴露、早期生长和婴儿微生物群之间的关系；(2)扩大数据采集， 样本收集和参与者应计，以更准确地表征早期生活的暴露和时机 通过获得尿金属代谢测量和接触组监测数据来获得暴露 妊娠前三个月自然脱落牙齿的空间分析 浓度；以及(3)扩大后续行动，以确定儿童接触污染物的情况(通过 生物标志物和个人监测器)；家庭环境(例如，体力活动和睡眠模式、食物 环境、绿色、蓝色和白色空间以及媒体使用)；以及医疗暴露(例如，处方和 非处方药和手术干预)，与胎儿和儿童的生长、肥胖有关 3岁，5岁时呼吸道感染和哮喘，7.5岁时肺功能数据。 新的统计方法将被用来确定肠道和唾液微生物组作为 这些影响的调停者。来自以下方面的集体专门知识、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儿科队列倡议，以推动 我们在生命早期对环境因素的理解，这些因素推动着儿童和终身健康。

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.