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

项目摘要 早产是一个重大的全球健康挑战，是婴儿死亡的主要原因， 发病率。近几十年来，美国的早产率有所上升，原因仍然存在。 不确定最近在波多黎各早产率的上升尤其令人震惊， 从1997年的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 早产未能解释这种增长，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研究和重视。拟议项目将 将最先进的分子流行病学方法应用于对1，200多名活产婴儿的前瞻性队列研究 旨在探索环境、临床、人口统计、行为和其他因素 波多黎各的早产风险。该项目还旨在提供急需的信息， 与环境因素有关的早产机制途径，以及关于重要的 孕妇邻苯二甲酸酯暴露的预测因素。邻苯二甲酸酯被选为 感兴趣，因为它们是波多黎各和其他地方（几个 邻苯二甲酸盐在ATSDR物质优先列表上），最近的研究表明， 邻苯二甲酸酯在美国人口中的比例在我们的初步工作和其他人最近的研究中， 与早产、胎龄减少和其他潜在的不良影响有关 与早产有关，如氧化应激、炎症和内分泌失调。我们的初步数据还 表明与美国相比，波多黎各某些邻苯二甲酸酯的暴露量较高。 由人类受试者招募工作和采样核心（核心C）和数据生成 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， 并测量在多个时间点从孕妇收集的尿样中的邻苯二甲酸酯代谢物， 怀孕我们将评估邻苯二甲酸酯代谢物水平与住宅，水源，水 邻苯二甲酸酯污染、饮食、活动和产品使用，以确定高暴露的决定因素， 减少暴露的战略机会。通过创新的统计方法，我们将评估 邻苯二甲酸酯暴露与早产风险之间的关联，无论是作为单独的化学品还是作为 邻苯二甲酸酯混合物。我们还将探讨邻苯二甲酸酯暴露与氧化应激生物标志物之间的关系。 在怀孕期间多次测量压力、炎症和内分泌干扰，以提供以下数据： 可能将环境暴露与早产联系起来的生物途径。这项研究将提供 急需的关于波多黎各早产风险因素的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会产生巨大的 由于旨在预防早产的干预措施迄今为止基本上仍然无效，因此对公共卫生的影响不大。

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.