Air Pollution, Inflammation and Preterm Birth: A Mechanistic Study in Mexico City

早产是围产期死亡的主要原因，并与长期不利的健康 对存活婴儿的影响。目前还没有预防早产的有效方法， 早产率上升在美国和世界各地，调查可能的因果机制是一个全球性的问题。 公共卫生优先。医学研究所最近的一份报告指出，空气污染暴露可能是一个 早产的重要原因，但大多数已发表的研究是基于人口出生登记， 个体的临床数据需要阐明可能的生物学机制介导这些 流行病学协会。这项拟议的工作为研究这些机制提供了一个独特的机会 在墨西哥城不同地区的800名孕妇中， 污染水平。我们将通过调查空气污染和 炎症可能共同作用，影响妊娠的结果，以及妊娠的某些时期是否 代表了临床和环境预防干预的关键时间窗口和机会。 我们将获得与炎症和早产相关的生物标志物（IL-1、IL-1 r、IL-6、IL-8、IL-10、TNF-α） 参与者在怀孕期间每月提供的宫颈阴道分泌物中，沿着以下信息 感染、健康史、临床特征、饮食和时间-活动模式。我们将使用最先进的 使用暴露评估技术评估空气污染暴露的空间和时间变异性 来自墨西哥城大都市区（MCMA）空气质量监测网络的数据（PM2.5，PM10，臭氧， 二氧化氮，二氧化硫，一氧化碳），与参与者的家庭位置相匹配。出生时，DNA 来自母亲和婴儿的样本将用于分型三种遗传细胞因子多态性（TNF-α、IL-1 β、IL-10）。 1 r <$）与早产风险增加有关。我们将评估环境污染是否 与早产相关，控制其他风险因素;它们是否与细胞因子相关 在怀孕期间，以及哪些时间窗口是最相关的。我们将通过摄入以下物质来检查效果修改： 抗氧化维生素（E和C）和细胞因子多态性。最后，我们将补充这一流行病学 研究与一项平行的毒理学体外研究，其中将涉及收集和描述空气污染 每月从MCMA的五个区域采集颗粒物样本（PM10和PM2.5），并暴露单核细胞 线（J774A.1），以评估相同细胞因子的表达。人体和体外细胞之间的任何一致性 污染和这些介导分子之间的机械关联的证据将指导未来 问题研究这种多学科的全球卫生合作将评估潜在的环境和临床 早产的决定因素，目标是发展具有深远预防意义的独特知识 影响项目叙述 与公共卫生的相关性：这项研究调查了空气污染如何影响早产风险。 出生，重点是阐明炎症机制的潜在作用。我们的目标是开发 知识支持1）制定和执行保护健康的空气污染标准的政策制定者; 2） 参与多学科研究的科学家了解环境对婴儿健康的贡献， 和3）对预防早产感兴趣的临床医生。

Preterm birth is the leading cause of perinatal mortality and is associated with long-term adverse health consequences for surviving infants. No effective means for prevention of prematurity currently exists, and with preterm birth rates rising in the U.S. and worldwide, investigating possible causal mechanisms is a global public health priority. A recent Institute of Medicine Report notes that air pollution exposure may be a significant cause of prematurity, but most published studies are based on population birth registries and lack the individual, clinical data needed to elucidate possible biological mechanisms mediating these epidemiological associations. This proposed work presents a unique opportunity to study those mechanisms in a new cohort of 800 pregnant women residing in diverse regions of Mexico City, a mega-city with high air pollution levels. We will advance understanding of prematurity by investigating how air pollution and inflammation may act together to influence the outcome of pregnancy, and whether certain periods of gestation represent critical time windows and opportunities for preventive interventions, both clinical and environmental. We will obtain biomarkers relevant to inflammation and preterm delivery (IL-1¿, IL-1r¿, IL-6, IL-8, IL-10, TNF-¿) in cervico-vaginal exudate provided by participants monthly during their pregnancies, along with information on infections, health history, clinical characteristics, diet and time-activity patterns. We will use state-of-the-art exposure assessment techniques to evaluate spatial and temporal variability in air pollution exposure using data from the Mexico City Metropolitan Area (MCMA) air quality monitoring network (PM2.5, PM10, ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide), matched to locations of participants' homes. At birth, DNA samples from mother and infant will be used to type three genetic cytokine polymorphisms (TNF-¿, IL-1¿, IL- 1r¿) that have been associated with enhanced risk of preterm birth. We will evaluate whether ambient pollution is associated with preterm birth, controlling for other risk factors; whether they are associated with cytokines during pregnancy, and which time windows are most relevant. We will examine effect modification by intake of antioxidant vitamins (E and C) and cytokine polymorphisms. Finally, we will complement this epidemiological study with a parallel toxicology in-vitro study which will involve collecting and characterizing air pollution particle samples (PM10 and PM2.5) on a monthly basis from five zones in MCMA and exposing a monocytic cell line (J774A.1) to evaluate expression of the same cytokines. Any coherence between the human and in vitro evidence for a mechanistic association between pollution and these mediating molecules will guide future studies. This multi-disciplinary, global health collaboration will evaluate potential environmental and clinical determinants of preterm delivery, with the goal of developing unique knowledge with far-reaching prevention implications. Project Narrative Relevance to public health: This research investigates how air pollution influences the risk for preterm birth, with a focus on elucidating the potential role for inflammatory mechanisms. The goal is to develop knowledge to support 1) policy-makers who set and enforce health-protective air pollution standards; 2) scientists involved in multi-disciplinary studies to understand environmental contributions to infant health, and 3) clinicians interested in prevention of preterm birth.