Project 1 - Biomarker Epidemiology of Exposure to Mixtures, Oxidative Stress, and Adverse Pregnancy Outcomes in Puerto Rico

项目总结 早产--怀孕不到37周--是一个重大的全球公共卫生挑战， 美国的早产率比几十年前要高得多。解释 因为这些增长仍然难以捉摸，环境风险因素是一个未被充分研究但潜在的 这是发现可改变的风险因素和高影响干预措施的重要领域。与美国相比 总体而言，波多黎各的早产率要高得多，那里近12%的新生儿是 早产。波多黎各其他不良妊娠结局的发生率也比美国高得多。 波多黎各拥有大量的超级基金和其他危险废物场地，以及可能 导致暴露在环境污染中的风险增加，如飓风、洪水和其他事件。这 该项目建议继续我们对早产和其他新风险因素的前瞻性队列研究 不良妊娠结局，重点是暴露于与超级基金相关的化学品混合物。我们 建议扩大我们的队列，将波多黎各北部的2000名活产婴儿包括在内，并提供详细信息和 在怀孕期间多次采集样本。然后我们将使用最先进的方法来估计 接触化学混合物的生物标记物，以及有效的中间生物标记物，以便 提供波多黎各环境和其他妊娠结局预测因素方面亟需的人类数据 RICO，以及对所涉及的生物途径的见解。到目前为止，我们的研究结果表明，氧化 压力可能是暴露和结果之间的一个重要联系，需要更深入地探讨。这个 研究的目的是开发和纳入用于混合和调解的创新统计技术，并确定 有助于高暴露的条件和活动，可为有效的减少暴露战略提供信息。 我们的具体目标是：1)调查与超级基金相关的一系列化学品(邻苯二甲酸盐， 多环芳烃[多环芳烃]和金属，作为单独的化学品和混合物)和 不良妊娠结局，包括早产、胎儿发育受损(使用重复超声数据 扫描)、出生体重、先兆子痫和妊娠期糖尿病；2)确定人口统计、地理位置、 与较高的暴露生物标记物浓度相关的行为、天气和其他因素，对于 同时使用单个化学品和多种化学品，以便为暴露和降低风险工作提供信息；以及3) 利用最先进的生物标志物和创新的统计方法来发现氧化应激途径 参与化学品暴露与不良妊娠结局之间的关系。预期中的 这项研究的结果是关于艾滋病的规模、来源和影响的新的和迫切需要的信息 在这项研究中，孕妇单独和联合接触与超级基金相关的化学物质 高危人群，以及确定相关生物途径和评估健康的创新方法 暴露在混合物中的影响。我们的发现可能会对公共卫生产生重大的积极影响。

PROJECT SUMMARY Preterm birth – delivery at less than 37 weeks gestation – is a significant global public health challenge, and preterm rates in the United States are considerably higher than they were several decades ago. Explanations for these increases remain elusive, and environmental risk factors are an understudied but potentially important area for discovery of modifiable risk factors and high-impact interventions. Compared to the United States overall, significantly higher rates of preterm birth exist in Puerto Rico, where nearly 12% of all births are preterm. Rates of other adverse pregnancy outcomes are also much higher in Puerto Rico than in the US, and Puerto Rico has a large number of Superfund and other hazardous waste sites, and additional factors that may result in elevated exposures to environmental pollution, such as hurricanes, flooding, and other events. This project proposes to continue our prospective cohort study of novel risk factors for preterm birth and other adverse pregnancy outcomes, with a focus on exposure to mixtures of Superfund-relevant chemicals. We propose to expand our cohort to include 2,000 live births in northern Puerto Rico with detailed information and samples collected at multiple times during pregnancy. We will then utilize state-of-the-art methods to estimate biomarkers of exposure to chemical mixtures, in addition to intermediate biomarkers of effect in order to provide much needed human data on environmental and other predictors of pregnancy outcomes in Puerto Rico, and insights on the biological pathways involved. Results from our study thus far suggest that oxidative stress may be an important link between exposure and outcome that needs to be explored in more depth. The study aims to develop and incorporate innovative statistical techniques for mixtures and mediation, and identify conditions and activities contributing to high exposures that can inform effective exposure reduction strategies. Our specific aims are to: 1) Investigate exposure to a range of Superfund-relevant chemicals (phthalates, polycyclic aromatic hydrocarbons [PAHs], and metals, both as individual chemicals and as mixtures) and adverse pregnancy outcomes, including preterm birth, impaired fetal growth (using data from repeat ultrasound scans), birth weight, preeclampsia, and gestational diabetes; 2) Determine demographic, geographic, behavioral, weather, and other factors associated with higher exposure biomarker concentrations, both for individual chemicals and multiple chemicals concurrently to inform exposure and risk reduction efforts; and 3) Utilize state-of-the-art biomarkers and innovative statistical methods to discover oxidative stress pathways involved in the relationships between chemical exposures and adverse pregnancy outcomes. The expected outcomes of this study are new and much needed information on the magnitude, sources, and impacts of exposure to Superfund-related chemicals, both individually and in combination, among pregnant women in this high-risk population, and innovative methods for identifying relevant biological pathways and assessing health impacts from exposure to mixtures. Our findings are likely to have a significant positive impact on public health.