Project 1: Molecular Epidemiology Study of Phthalate Exposure and Preterm Birth i

项目总结 早产是一个重大的全球健康挑战，是导致婴儿死亡和长期代价高昂的主要原因 发病率。近几十年来，美国的早产率有所上升，原因仍然是 不确定。波多黎各最近早产的上升尤其令人震惊，那里的早产率 从1997年略高于美国平均水平(12%)上升到2009年的近18%。虽然已知的风险因素 虽然早产未能解释这一增长，但越来越多的证据表明，环境因素可能 发挥关键作用。然而，这些因素仍然没有得到充分的研究和认识。拟议的项目将 应用最先进的分子流行病学方法对1200多名活产儿进行前瞻性队列研究 旨在探索环境、临床、人口统计学、行为和其他因素对 波多黎各的早产风险。该项目还旨在提供有关潜力的迫切需要的信息 早产与环境因素有关的机械性途径，以及重要的 孕妇中邻苯二甲酸盐暴露的预测因素。邻苯二甲酸盐被选为主要污染物 感兴趣，因为它们是波多黎各和其他地方超级基金网站的常见污染物(几个 邻苯二甲酸盐在ATSDR物质优先名单上)，最近的研究表明广泛接触 美国人口中的邻苯二甲酸盐。在我们的初步工作和其他人最近的研究中，多个邻苯二甲酸盐 与早产、胎龄降低和其他可能相关的不良影响有关 早产，如氧化应激、炎症和内分泌紊乱。我们的初步数据也 使用数据和样本表明波多黎各与美国相比接触某些邻苯二甲酸盐的水平更高 由人类受试者和抽样核心(核心C)和数据的招聘工作产生 通过Core D提供的管理集成，我们将收集详细的问卷数据、临床信息、 并在多个时间点检测从孕妇身上收集的尿样中的邻苯二甲酸酯代谢物 怀孕了。我们将评估邻苯二甲酸盐代谢物水平与居住地、水源、水 邻苯二甲酸盐污染，饮食，活动和产品使用，以确定高暴露和 减少暴露战略的机会。利用创新的统计方法，我们将评估 邻苯二甲酸盐暴露与早产风险之间的关系，无论是作为单独的化学品还是AS 邻苯二甲酸盐混合物。我们还将探索邻苯二甲酸盐暴露与氧化生物标记物之间的关系。 在怀孕期间多次测量应激、炎症和内分泌紊乱，以提供有关 可能将环境暴露与早期分娩联系起来的生物途径。拟议的研究将提供 波多黎各关于早产风险因素的急需信息和未来的丰富资源 调查和后续行动。确定早产的可改变的环境风险因素可能有巨大的影响 对公共卫生的影响，因为迄今为止旨在预防早产的干预措施基本上仍然无效。

PROJECT SUMMARY Preterm birth is a significant global health challenge as a leading cause of infant mortality and costly long-term morbidity. Rates of preterm birth in the U.S. have increased in recent decades for reasons that remain uncertain. The recent escalation in preterm births in Puerto Rico is especially alarming, where rates have increased from just above the U.S. average (12%) in 1997 to nearly 18% in 2009. While known risk factors for preterm birth have failed to account for this increase, there is growing evidence that environmental factors may play a key role. However, these factors remain understudied and underappreciated. The proposed project will apply state-of-the-art molecular epidemiological methods to a prospective cohort study of over 1,200 live births designed to explore environmental, clinical, demographic, behavioral and other factors that contribute to preterm birth risk in Puerto Rico. The project also aims to provide much needed information on the potential mechanistic pathways involved in preterm birth as it relates to environmental factors, and data on important predictors of phthalate exposure among pregnant women. Phthalates were chosen as the primary pollutants of interest because they are common contaminants of Superfund sites in Puerto Rico and elsewhere (several phthalates are on the ATSDR Substance Priority List), and recent studies show widespread exposure to phthalates in the U.S. population. In our preliminary work and in recent studies by others, multiple phthalates have been associated with preterm birth, reduced gestational age, and other adverse impacts potentially linked with preterm birth such as oxidative stress, inflammation, and endocrine disruption. Our preliminary data also suggests elevated exposure to certain phthalates in Puerto Rico compared to the U.S. Using data and samples generated by recruitment efforts of the Human Subjects and Sampling Core (Core C) and the Data Management integration provided by Core D, we will collect detailed questionnaire data, clinical information, and measure phthalate metabolites in urine samples collected from pregnant women at multiple time points in pregnancy. We will evaluate phthalate metabolite levels for associations with residence, water sources, water phthalate contamination, diet, activities, and product use to identify determinants of high exposure and opportunities for exposure reduction strategies. Using innovative statistical methods, we will assess the association between exposure to phthalates and risk of preterm birth, both as individual chemicals and as phthalate mixtures. We will also explore relationships between phthalate exposure and biomarkers of oxidative stress, inflammation, and endocrine disruption measured at multiple times during pregnancy to provide data on biologic pathways that may link environmental exposures with early parturition. The proposed study will provide much needed information on preterm birth risk factors in Puerto Rico and a rich resource for future investigations and follow-up. Identifying modifiable environmental risk factors for preterm birth could have huge public health impact since interventions aimed at preventing preterm birth to date remain largely ineffective.