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

项目1：邻苯二甲酸盐暴露与早产的分子流行病学研究i

• 批准号: 9308319
• 负责人: John D. Meeker
• 金额: $ 85万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-12 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9308319
• 关键词: Accounting; Age; Area; Behavior; Behavioral; Biological; Biological Markers; Birth; Birth Rate; Chemicals; Classification; Clinical; Clinical Data; Cohort Studies; Data; Diet; Dietary Practices; Endocrine Disruptors; Endocrine disruption; Environmental Exposure; Environmental Pollution; Environmental Risk Factor; Epidemiologic Methods; Etiology; Exposure to; Future; Gestational Age; Hazardous Waste Sites; Health; Hormones; Individual; Infant Mortality; Inflammation; Intervention; Investigation; Island; Lead; Link; Live Birth; Measures; Mediator of activation protein; Methods; Mexico; Molecular; Molecular Epidemiology; Morbidity - disease rate; Other Genetics; Outcome Study; Oxidative Stress; Pathway interactions; Patient Self-Report; Plasma; Play; Population; Pregnancy; Pregnant Women; Premature Birth; Prevention strategy; Prospective Studies; Public Health; Puerto Rico; Questionnaires; Resources; Risk; Risk Factors; Risk Reduction; Sampling; Serum; Source; Statistical Methods; Stratification; Techniques; Testing; Time; Urine; Water; Woman; Work; cohort; data management; demographics; design; drinking water; environmental agent; epidemiology study; follow-up; global health; high risk; human data; human subject; innovation; interest; modifiable risk; novel; personal care products; phthalates; pollutant; prevent; prospective; psychosocial; reproductive; residence; superfund site; urinary

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.

项目概要 早产是一项重大的全球健康挑战，是婴儿死亡的主要原因，且长期费用高昂。 发病率。近几十年来，美国的早产率有所上升，其原因仍然存在 不确定。波多黎各最近早产率的上升尤其令人震惊，该地区的早产率已经上升 从 1997 年略高于美国平均水平 (12%) 上升到 2009 年的近 18%。 早产未能解释这种增加，越来越多的证据表明环境因素可能 发挥关键作用。然而，这些因素仍未得到充分研究和认识。拟议的项目将 应用最先进的分子流行病学方法对 1,200 多名活产婴儿进行前瞻性队列研究 旨在探索环境、临床、人口、行为和其他有助于 波多黎各的早产风险。该项目还旨在提供有关潜在潜力的急需信息 早产的机制途径，因为它与环境因素有关，以及重要的数据 孕妇接触邻苯二甲酸盐的预测因素。邻苯二甲酸盐被选定为主要污染物 兴趣，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（几个 邻苯二甲酸盐已列入 ATSDR 物质优先列表），最近的研究表明广泛接触 美国人口中的邻苯二甲酸盐。在我们的前期工作和其他人最近的研究中，多种邻苯二甲酸盐 与早产、胎龄缩短以及其他可能相关的不利影响有关 与早产有关，如氧化应激、炎症和内分泌干扰。我们的初步数据还 使用数据和样本表明，与美国相比，波多黎各某些邻苯二甲酸盐的暴露量更高 由人类受试者和采样核心（核心 C）和数据的招募工作产生 由Core D提供的管理整合，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液样本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居住地、水源、水源的关系 邻苯二甲酸盐污染、饮食、活动和产品使用，以确定高接触和邻苯二甲酸盐污染的决定因素 减少暴露策略的机会。我们将使用创新的统计方法来评估 接触邻苯二甲酸盐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盐暴露与氧化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，以提供相关数据 可能将环境暴露与早产联系起来的生物途径。拟议的研究将提供 关于波多黎各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。识别早产的可改变的环境风险因素可能会产生巨大的影响 由于迄今为止旨在预防早产的干预措施基本上仍然无效，因此对公共卫生产生了影响。