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

早产是围产儿死亡的主要原因，并与长期的不良健康有关。 对幸存婴儿的后果。目前尚不存在预防早产的有效手段，而且 在美国和世界范围内，早产率不断上升，调查可能的原因是一个全球性的 公共卫生优先事项。医学研究所最近的一份报告指出，接触空气污染可能是一种 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和缺乏 需要个人的临床数据来阐明调节这些变化的可能生物学机制 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 在居住在墨西哥城不同地区的800名孕妇的新队列中，墨西哥城是一个空气质量很高的超大城市 污染水平。我们将通过调查空气污染和 炎症可能共同作用，影响妊娠结局，以及某些妊娠阶段 代表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-1Rα、IL-6、IL-8、IL-10、肿瘤坏死因子-α) 由参与者在怀孕期间每月提供的宫颈阴道渗出物，以及关于 感染、病史、临床特征、饮食和时间活动模式。我们将使用最先进的 评估空气污染暴露的时空变异性的暴露评估技术 来自墨西哥城大都市区(MCMA)空气质量监测网(PM2.5，PM10，臭氧， 二氧化氮、二氧化硫、一氧化碳)，与参与者住宅的位置相匹配。在出生时，DNA 来自母亲和婴儿的样本将被用来对三种遗传细胞因子基因多态(肿瘤坏死因子-α、白介素1？、白介素1？ 1Rα)与早产风险增加有关。我们将评估环境污染是否 与早产有关，控制其他危险因素；它们是否与细胞因子有关 在怀孕期间，以及哪些时间窗口最相关。我们将研究摄入量的影响修改 抗氧化维生素(E和C)和细胞因子基因多态性。最后，我们将补充这一流行病 与体外毒理学平行的研究，将涉及收集和表征空气污染 每月从MCMA的五个区域采集颗粒物样本(PM10和PM2.5)，暴露出单核细胞 (J774A.1)，检测相同细胞因子的表达。人体和体外之间的任何一致性 污染和这些中介分子之间存在机械联系的证据将指导未来 学习。这一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，目的是发展具有深远预防意义的独特知识 这意味着什么。

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-1ß, IL-1rα, IL-6, IL-8, IL-10, TNF-α) 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-α, IL-1ß, IL- 1rα) 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.