Biomarker Epidemiology of In Utero Environmental Exposures and Child Development

子宫内环境暴露和儿童发育的生物标志物流行病学

• 批准号: 8989332
• 负责人: John D. Meeker
• 金额: $ 16.52万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8989332
• 关键词: 4 year old; Address; Air Pollution; Asthma; Behavior; Behavioral; Biological; Biological Markers; Chemical Exposure; Chemicals; Child; Child Development; Child health care; Clinical; Cohort Studies; Communities; Community Outreach; Data; Data Aggregation; Data Set; Databases; Development; Diet; Endocrine disruption; Environmental Exposure; Environmental Pollution; Epidemiology; Exposure to; Fetal Development; Fetal Growth; Funding; Future; Goals; Growth; Health; Human; Hypersensitivity; Incidence; Individual; Infant; Inflammation; Intervention; Island; Life; Link; Measures; Mediating; Mediation; Metals; Modification; Obesity; Outcome Study; Oxidative Stress; Parabens; Parents; Pathway interactions; Perinatal Exposure; Phenols; Policies; Population; Predisposition; Pregnancy; Pregnancy Outcome; Pregnant Women; Premature Birth; Public Health; Puerto Rico; Research; Respiratory physiology; Risk Assessment; Sampling; Services; Socioeconomic Status; Statistical Models; Testing; Time; Toxic effect; Translations; United States National Institutes of Health; Woman; cohort; design; developmental disease; early childhood; early life exposure; effective intervention; environmental chemical; epidemiology study; feeding; fetal; human subject; in utero; innovation; maternal stress; neurodevelopment; novel; parent project; phthalates; pollutant; prenatal exposure; reproductive; reproductive development; screening; social; trend; urinary

PROJECT SUMMARY Incidence rates for a range of adverse child developmental conditions have increased in recent years in the US and elsewhere. There is emerging evidence and concern that exposure to environmental chemicals such as phenols, parabens, and others may contribute to this recent rise in developmental disorders. Additionally, disparities exist in both incidence rates of adverse health conditions and level of pollutant exposure. There are particularly high rates of a number of developmental conditions, as well as elevated exposures to phenols and parabens, in Puerto Rico. Environmental phenols and parabens disrupt endocrine function, induce oxidative stress, and cause other alterations that may result in reduced fetal or child growth, preterm birth, reproductive tract anomalies, neurodevelopmental delays, obesity, allergies/asthma, and other effects. While near- ubiquitous exposures to these chemicals have been documented among pregnant women, well-designed human studies are greatly needed to determine whether developmental impacts are related to early life in utero exposure. In addition, few studies have addressed the real life situation of considering multiple exposures and susceptibility factors individually and together. Our preliminary data show that pregnant women in Puerto Rico may have higher exposures to several of these chemicals than women in the US and elsewhere, significant associations between these chemicals and markers of hypothesized mechanistic pathways, and that certain modifiable behaviors, such as use of specific products during pregnancy, are associated with elevated chemical exposure and suggest effective intervention strategies may be possible. The proposed project is designed to fill these research gaps by leveraging an ongoing NIH-funded pregnancy cohort study in Puerto Rico (P42ES017198) that is building a rich dataset on environmental, clinical, social, demographic, behavioral, dietary and other factors among 1800 pregnant women. The proposed study will follow 600 children born into the cohort through the age of 4 years. Our specific aims are to 1) Investigate the association between prenatal exposure to environmental phenols and parabens, estimated via urinary biomarkers at multiple times during pregnancy, and pregnancy outcomes and child development (including preterm birth, measures of infant feeding, child growth, reproductive development, neurodevelopment, and lung function); 2) Provide evidence for biological mechanisms that may mediate the relationship between early life exposure to environmental phenols or parabens and fetal/child development, including endocrine disruption, inflammation, and oxidative stress; 3) Test effect modification of the relationship between phenols or parabens and fetal/child development by a range of susceptibility factors, including socioeconomic status, maternal stress, and preterm birth; and 4) develop and apply innovative statistical approaches to explore fetal/child development effects of early-life exposure to multi-pollutant mixtures when also incorporating air pollution data that will be collected in Project 1 of this Center, and biomarker data on phthalates and metals being measured as part of the parent study.

项目总结 近年来，在美国，一系列不良儿童发育状况的发病率有所上升 还有其他地方。有新出现的证据和担忧表明，接触环境化学品，如 酚类、对羟基苯甲酸酯和其他物质可能是最近发育障碍上升的原因。另外， 在不良健康状况的发生率和污染物暴露水平方面都存在差异。确实有 特别是一些发育状况的高发生率，以及暴露于酚类和 波多黎各的帕拉本斯。环境中的酚和对羟基苯甲酸酯扰乱内分泌功能，诱导氧化 压力，并引起其他可能导致胎儿或儿童生长发育减慢、早产、生殖 神经束异常、神经发育迟缓、肥胖、过敏/哮喘和其他影响。当接近- 经过精心设计，孕妇普遍暴露于这些化学物质中已有记录 需要大量的人体研究来确定发育影响是否与子宫内的早期生命有关 曝光。此外，很少有研究涉及考虑多次曝光和 单独的和共同的易感因素。我们的初步数据显示，波多黎各的孕妇 可能比美国和其他地方的女性接触到这些化学物质的风险更高，显著 这些化学物质和假想的机械途径的标志物之间的联系，以及某些 可改变的行为，如在怀孕期间使用特定产品，与升高有关 并建议可能采取有效的干预策略。建议的项目是 旨在通过利用正在进行的美国国立卫生研究院资助的波多黎各怀孕队列研究来填补这些研究空白 RICO(P42ES017198)，正在构建关于环境、临床、社会、人口统计、行为 调查1800名孕妇的饮食等因素。这项拟议的研究将跟踪调查600名出生于 该队列已满4岁。我们的具体目标是：1)调查出生前和出生前 接触环境中的苯酚和对羟基苯甲酸酯，通过尿液生物标记物在以下时间多次估计 怀孕、妊娠结局和儿童发展(包括早产、婴儿测量 喂养、儿童生长、生殖发育、神经发育和肺功能)；2)提供证据 寻找可能调节早期生命暴露于环境之间关系的生物学机制 酚或对羟基苯甲酸酯与胎儿/儿童发育，包括内分泌紊乱、炎症和氧化 应激；3)对苯酚或对羟基苯甲酸酯与胎儿/儿童发育关系的测试效果修正 一系列易感因素，包括社会经济地位、母亲压力和早产；以及4) 开发和应用创新的统计方法来探索早期生命对胎儿/儿童发展的影响 在纳入将在项目1中收集的空气污染数据时接触多种污染物混合物 以及作为母研究的一部分正在测量的邻苯二甲酸盐和金属的生物标记物数据。