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

一项关于影响美国农村儿童终身健康的生命形成早期关键环境暴露的前瞻性研究：新罕布什尔州出生队列研究

• 批准号: 10241453
• 负责人: MARGARET Rita KARAGAS
• 金额: $ 525.52万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-21 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10241453
• 关键词: 3 year old; 5 year old; Accelerometer; Address; Age; Air; Archives; Asthma; Behavioral; Bioinformatics; Biological; Biological Markers; Birth; Blood; Blood specimen; Cells; Cesarean section; Child; Child Development; Child Health; Childhood; Clinical; Cohort Studies; Complex; Conceptions; Cryopreservation; DNA; DNA Methylation; Data; Data Collection; Data Element; Diagnosis; Elements; Enrollment; Environmental Exposure; Environmental Impact; Environmental Pollution; Environmental Risk Factor; Exposure to; Feces; First Pregnancy Trimester; Flow Cytometry; Gene Expression; Growth; Hair; Health; Home environment; Hospitalization; Household Air Pollution; Human; Human Milk; Infant; Intervention; Interview; Intestines; Knowledge; Laboratories; Life; Lymphocyte; Measurement; Meconium; Mediator of activation protein; Medical; Medical Records; Metals; Methodology; Monitor; Mothers; National Institute of Environmental Health Sciences; New Hampshire; Non-Prescription Drugs; Obesity; Operative Surgical Procedures; Outcome; Outcome Assessment; Participant; Pediatric cohort; Persons; Phase; Physical activity; Physical environment; Placenta; Pregnancy; Prospective Studies; Questionnaires; Records; Research; Respiratory Tract Infections; Role; Rural; Salivary; Sampling; Self Administration; Structure of nail of toe; Techniques; Technology; Testing; Time; Tooth structure; Toxic Environmental Substances; Umbilical Cord Blood; Urine; Ursidae Family; Validation; Water; Water Supply; Wood stove; air monitoring; biobank; built environment; climate change; cohort; data acquisition; detector; drinking; drinking water; early life exposure; experience; feasibility testing; fetal; follow-up; food environment; gut microbiome; improved; in utero; innovation; lifestyle factors; metabolomics; microbiome; microbiome sequencing; neurodevelopment; novel; prenatal; pulmonary function; respiratory; respiratory health; rural area; rural setting; sample collection; sex; sleep pattern; social; stool sample; urinary; vaccine response; wood smoke

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 collected 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). With support of a state-of-the-art biorepository, the ability to utilize these samples for a wide range of downstream analyses has been demonstrated, e.g., for DNA methylation arrays, gene expression, microbiome sequencing, metabolomics and flow cytometry. For the current application, emerging hypotheses of concern will be addressed by: (1) leveraging the 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) expanding data acquisition, sample collection and participant accrual to more precisely characterize exposures and timing of early life exposures by obtaining urinary metallome and 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. Additionally, 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.

项目摘要/摘要：我们对广泛和广泛的健康影响的认识存在重大差距， 在美国儿童中的暴露量急剧增加。农村地区的儿童尤其 研究不足，但可能会经历更高的暴露于污染物饮用不受管制的水; 家庭空气污染的木材炉灶;和随之而来的农村和不断变化的景观（例如，从 气候变化）。作为ECHO儿科队列应用程序的一部分，我们建议利用 NIEHS/EPA支持的新罕布什尔州出生队列研究（NHBCS）：一项农村正在进行的妊娠队列研究， 已经累积了超过1,500对母婴。在本申请的UH 3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， 扩展到3,000对母婴。临床结果正在从间隔访谈中确定， 调查问卷、医疗记录、亲自评估和实验室检测。该研究已存档 在怀孕期间收集的环境（自来水和室内空气）和生物样品（母体血液， 尿液和毛发），以及出生时采集的生物样本（婴儿脐带血、胎盘和胎粪）， 儿童期（尿液、血液、口腔细胞、母乳、脚趾甲和粪便）。在最先进的 生物储存库，利用这些样品进行广泛的下游分析的能力已经得到了提高。 例如，用于DNA甲基化阵列、基因表达、微生物组测序、代谢组学和 流式细胞仪对于当前的应用程序，将通过以下方式解决新出现的关注假设：（1） 利用现有的NHBCS对1,000份脐带血进行有针对性的和无人监督的代谢组学分析 样本和250对孕妇妊娠期血液样本，并评估与暴露，早期 生长和婴儿微生物组;（2）扩大数据采集，样本收集和参与者增加， 通过获得尿金属组，更精确地表征生命早期暴露的暴露和时间， 金属代谢组学测量和妊娠前三个月的代谢组学监测数据，沿着 对自然脱落的牙齿进行产前金属浓度的空间分析;（3）延长随访时间， 确定儿童期接触污染物的情况（通过生物标志物和个人监测器）; 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）;以及医疗暴露（例如，处方药和非处方药以及外科手术 干预），这些干预与胎儿和儿童生长、3岁肥胖、呼吸道感染和哮喘有关 5岁时，以及7.5岁时的肺功能数据。此外，新的统计方法将 用于确定肠道和唾液微生物组作为这些效应的介质的作用。的 这项研究的集体专门知识、方法、数据、样本和初步结果将有助于 计划更广泛的ECHO儿科队列计划，以促进我们对 生命早期的环境因素，推动儿童和终身健康。