Biomarker Epidemiology of In Utero Environmental Exposures and Child Development

项目摘要 近年来，在美国，一系列不良儿童发育状况的发病率有所增加 和其他地方。有新的证据和关注，暴露于环境化学品， 酚类、对羟基苯甲酸酯类和其他物质可能是导致最近发育障碍增加的原因。此外，本发明还 在不良健康状况的发生率和污染物暴露水平方面存在差异。有 特别是一些发育条件的高比率，以及对酚类的高暴露， 对羟基苯甲酸酯，在波多黎各。环境中的酚类和对羟基苯甲酸酯会破坏内分泌功能， 压力，并导致其他可能导致胎儿或儿童生长减少，早产，生殖 道异常、神经发育迟缓、肥胖、过敏/哮喘和其他影响。虽然近- 孕妇普遍暴露于这些化学物质， 非常需要对人类进行研究，以确定发育影响是否与子宫内的早期生命有关。 exposure.此外，很少有研究涉及考虑多次暴露的真实的生活情况， 单独和共同的易感性因素。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更容易接触到这些化学物质， 这些化学物质和假设的机械途径的标记之间的关联， 可改变的行为，如在怀孕期间使用特定产品， 化学品暴露和建议有效的干预策略可能是可能的。拟建项目 旨在通过利用正在进行的NIH资助的波多黎各妊娠队列研究来填补这些研究空白 Rico（P42 ES 017198）正在建立一个关于环境、临床、社会、人口统计、行为 1800名孕妇的饮食和其他因素。这项研究将追踪600名出生在 这群人一直到4岁。我们的具体目标是：1）调查产前 暴露于环境酚类和对羟基苯甲酸酯，通过尿液生物标志物在多个时间估计， 妊娠、妊娠结局和儿童发育（包括早产、婴儿 喂养、儿童生长、生殖发育、神经发育和肺功能）; 2）提供证据 对于可能介导生命早期暴露于环境之间关系的生物机制， 酚类或对羟基苯甲酸酯和胎儿/儿童发育，包括内分泌干扰，炎症和氧化 压力; 3）酚类或对羟基苯甲酸酯与胎儿/儿童发育之间关系的测试效果修改 受一系列易感因素影响，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，探索早期生命对胎儿/儿童发育的影响 同时纳入项目1中收集的空气污染数据时， 邻苯二甲酸盐和金属的生物标志物数据作为母研究的一部分进行测量。

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.