Project 3: Phthalate Exposure and Molecular Epidemiologic Markers of Preterm

近年来，美国的早产率有所上升，原因尚不确定。的 最近在波多黎各早产率的上升尤其令人震惊，自1997年以来， 从略高于美国平均水平（12%）到2005年的近20%。虽然已知的早产风险因素 虽然未能解释这一增长，但越来越多的证据表明，环境因素可能起着重要作用。 关键角色。本拟议项目（项目3）将利用最先进的分子流行病学方法， 探索导致早产风险的环境、遗传、人口统计学和行为因素， 波多黎各，并提供急需的信息的潜在机制途径， 早产与环境因素有关。邻苯二甲酸酯被选为 因为它们是波多黎各和其他地方超级基金场地的常见污染物， 最近的研究表明，邻苯二甲酸酯在美国人口中广泛存在。人类接触到一些 近年来，邻苯二甲酸盐的使用量有所增加，这一趋势与早产儿出生率的增加相一致。 邻苯二甲酸酯被列为SBRP关注的新兴污染物， 胎龄和其他可能与早产相关的影响，包括炎症、内分泌 破坏和氧化应激。利用人力资源部招募工作产生的数据和样本， 以1200名孕妇为研究对象，测定其尿中邻苯二甲酸酯代谢产物。邻苯二甲酸酯代谢物 将评估与居住、水源、活动和产品使用的关联， 高暴露的影响和减少暴露战略的机会。邻苯二甲酸酯代谢物将 然后用于测试与胎龄下降和早产风险增加的相关性，以及 与炎症、内分泌干扰和氧化应激的标志物一起提供生物学途径的数据， 参与了环境暴露和早产之间的联系。多态性分析 候选基因中的等位基因也将在妇女中进行，以探索基因-环境， 基因-基因相互作用，并进一步表征个体的假设表型标记， 基于代谢物比率的邻苯二甲酸酯暴露敏感性。这项研究将提供许多 需要有关波多黎各早产风险因素的信息，以及未来调查的丰富资源

Rates of preterm birth in the U.S. have increased in recent years for reasons that remain uncertain. The recent escalation in preterm births in Puerto Rico is especially alarming, where rates since 1997 have gone from just above the U.S. average (12%) to nearly 20% in 2005. While known risk factors for preterm birth have failed to account for this increase, there is mounting evidence that environmental factors may play a key role. This proposed project (Project 3) will utilize state-of-the-art molecular epidemiological methods to explore environmental, genetic, demographic, and behavioral factors that contribute to preterm birth risk in Puerto Rico, and to provide much needed information on the potential mechanistic pathways involved in preterm birth as it relates to environmental factors. Phthalates were chosen as the primary pollutant of interest because they are common contaminants of Superfund sites in Puerto Rico and elsewhere, and recent studies show widespread exposure to phthalates in the U.S. population. Human exposure to some phthalates have increased in recent years, a trend which coincides with the increased rate of preterm birtti. Phthalates are classified as emerging pollutants of concern to the SBRP and are associated with reduced gestational age and other effects potentially linked with preterm birth, including inflammation, endocrine disruption, and oxidative stress. Utilizing data and samples generated by recruitment efforts of the Human Subjects core, we will measure urinary phthalate metabolites in 1200 pregnant women. Phthalate metabolite levels will be assessed for associations with residence, water sources, activities, and product use to identify influences of high exposure and opportunities for exposure reduction strategies. Phthalate metabolites will then be used to test associations with declined gestational age and increased risk of preterm birth, as well as with markers of inflammation, endocrine disruption, and oxidative stress to provide data on biologic pathways involved in the association between environmental exposures and early parturition. Analysis of polymorphic alleles in candidate genes will also be conducted among the women for exploration of gene-environment and gene-gene interactions, and to further characterize hypothesized phenotypic markers of individual susceptibility to phthalate exposure based on metabolite ratios. The proposed study will provide much needed information on preterm birth risk factors in Puerto Rico and a rich resource for future investigations