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

项目摘要 早产-妊娠不足37周时分娩-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高得多。解释 因为这些增加仍然难以捉摸，环境风险因素研究不足，但可能 这是发现可改变的风险因素和高效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%的新生儿是在 早产儿波多黎各其他不良妊娠结局的发生率也远高于美国， 波多黎各有大量的超级基金和其他危险废物场地， 导致暴露于环境污染的风险增加，例如飓风、洪水和其他事件。这 项目建议继续我们的前瞻性队列研究的新的风险因素早产和其他 不良妊娠结局，重点是接触超级基金相关化学品的混合物。我们 我建议扩大我们的队列，包括北方波多黎各的2 000名活产婴儿，并提供详细信息， 在怀孕期间多次采集样本。然后我们将利用最先进的方法来估计 接触化学混合物的生物标志物，以及影响的中间生物标志物， 提供波多黎各急需的关于环境和其他妊娠结局预测因素的人类数据 里科，以及对所涉及的生物学途径的见解。从我们的研究结果到目前为止表明，氧化 压力可能是暴露和结果之间重要联系，需要更深入地探讨。的 研究旨在开发和采用混合物和调解的创新统计技术，并确定 可为有效减少接触战略提供信息的导致高接触的条件和活动。 我们的具体目标是：1）调查接触一系列超级基金相关化学品（邻苯二甲酸酯， 多环芳烃[PAH]和金属，包括单独的化学品和混合物）， 不良妊娠结局，包括早产、胎儿生长受损（使用重复超声数据 扫描）、出生体重、先兆子痫和妊娠糖尿病; 2）确定人口统计学、地理、 行为、天气和其他与较高暴露生物标志物浓度相关的因素， 同时使用单个化学品和多种化学品，为接触和风险降低工作提供信息;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 参与化学品暴露和不良妊娠结果之间的关系。预期 这项研究的结果是新的和急需的信息的规模，来源和影响， 孕妇接触超级基金相关的化学品，无论是单独还是组合，在这方面， 高风险人群，以及确定相关生物途径和评估健康的创新方法 混合物的影响。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.