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: 9262487
• 负责人: MARGARET Rita KARAGAS
• 金额: $ 132.54万
• 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 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9262487
• 关键词: 3 year old; 5 year old; Accelerometer; Address; Age; Air; Archives; Asthma; Behavioral; Biological; Biological Markers; Birth; Blood; Blood specimen; Cells; Cesarean section; Child; Child Development; Child health care; Childhood; Clinical; Cohort Studies; Complex; Conceptions; DNA; DNA Methylation; Data; Data Collection; Data Element; Diagnosis; Electronics; Elements; Enrollment; Environmental Exposure; 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; Pattern; Persons; Pharmaceutical Preparations; Phase; Physical activity; Physical environment; Placenta; Pregnancy; Prospective Studies; Questionnaires; Records; Research; Respiratory Tract Infections; Role; Rural; Salivary; Sampling; Self-Administered; Sleep; Structure of nail of toe; Techniques; Technology; Test Result; Testing; Time; Tooth structure; Toxic Environmental Substances; Umbilical Cord Blood; Urine; Ursidae Family; Validation; Water; Water Supply; Wood stove; abstracting; air monitoring; biobank; built environment; climate change; cohort; data acquisition; detector; drinking; drinking water; early life exposure; experience; fetal; follow-up; food environment; gut microbiome; improved; in utero; innovation; lifestyle factors; metabolomics; microbiome; neurodevelopment; novel; prenatal; pulmonary function; respiratory; respiratory health; sample collection; sex; social; 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；从 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 怀孕期间收集的环境样本（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 儿童时期（尿液、血液、口腔细胞、母乳、脚趾甲和粪便）。在最先进的支持下 生物样本库，利用这些样本进行广泛的下游分析的能力已经 已被证明可用于 DNA 甲基化阵列、基因表达、微生物组测序、代谢组学和 流式细胞术。对于当前的应用，新出现的令人关注的假设将通过以下方式解决：(1) 利用现有的 NHBCS 对 1,000 份脐带血进行有针对性的、无监督的代谢组学分析 样本和 250 份配对的母亲妊娠血液样本，并评估与早期暴露的关联 生长和婴儿微生物组； (2) 扩大数据采集、样本收集和参与者应计范围 通过获得尿液金属组和 金属代谢组学测量以及妊娠前三个月的暴露组监测数据 对自然脱落的牙齿进行产前金属浓度的空间分析； (3) 延长后续行动 确定儿童时期接触污染物的情况（通过生物标记物和个人监测器）；家 环境（例如身体活动和睡眠模式、饮食环境、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以及手术 与胎儿和儿童生长、3 岁时肥胖、呼吸道感染和哮喘相关的干预措施 5岁时的肺功能数据，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。这 这项研究的集体专业知识、方法、数据、样本和初步结果将有助于 规划更广泛的 ECHO 儿科队列计划，以加深我们对 生命早期的环境因素可促进儿童期和终生健康。