Polycyclic aromatic hydrocarbons and birth outcomes in Mexico City

描述（由申请人提供）：婴儿出生时的大小和体重是其生存和未来健康的重要决定因素。虽然有多种因素影响出生体重和大小，但最近已探索怀孕期间的空气污染暴露是一个贡献者。数以百万计的妇女暴露在环境空气污染中，发展中国家的污染程度特别高。降低婴儿死亡率是千年发展目标之一，因此了解和尽量减少造成不良出生结果的环境因素对公共卫生至关重要。大多数已发表的流行病学研究是基于人口出生登记，缺乏个人，临床数据和重复的措施，需要阐明可能的生物机制介导的污染和不良出生结果之间的流行病学联系。这项拟议的工作提供了一个独特的机会，可以在居住在墨西哥城不同地区的800名孕妇中研究这些机制，墨西哥城是一个空气污染程度很高的特大城市。我们将研究空气污染和颗粒物中的多环芳烃（PAH）成分如何影响妊娠结局，以及妊娠的某些时期是否代表预防干预的关键时间窗口和机会。我们将从受试者妊娠期间每月提供的血液样本和出生时获得的脐带血中获得与PAH暴露相关的生物标志物（DNA加合物）。我们还将收集有关健康史、临床特征、烟草烟雾暴露、饮食和时间-活动模式的信息。同时，我们将估计空气污染暴露的空间和时间变化，数据来自墨西哥城大都市区（MCMA）空气质量监测网络（PM2.5，PM10，臭氧，二氧化氮，二氧化硫，一氧化碳），与参与者的确切位置相匹配。将使用来自母亲和婴儿的DNA样本对与假设机制相关的遗传多态性（CYP 1A 1、GSTM 1、GSTT 1、GSTP 1、Xrcc 1、XPD）进行分型。我们将评估环境污染和PAH加合物是否与三个结果相关：出生体重，头围和出生身长，控制其他风险因素，以及哪些时间窗口最相关。我们将研究通过摄入抗氧化维生素（E和C）和遗传多态性的影响。最后，我们将补充这项流行病学研究与平行毒理学体外研究，这将涉及收集和表征空气污染颗粒物样品（PM10和PM2.5）每月从MCMA的五个区域，并暴露单核细胞系（J774A.1），以评估PAH加合物。人类和体外证据之间的任何一致性污染和这些加合物之间的机械关联将指导未来的研究。这种多学科的全球卫生合作将使用流行病学和毒理学相结合的新方法，评估不良出生结果的潜在环境决定因素，目标是开发具有深远预防意义的独特知识。

DESCRIPTION (provided by applicant): The size and weight of a baby at birth are important determinants of its survival and future health across the life course. Although multiple factors influence birth weight and size, air pollution exposure during pregnancy has been recently explored as a contributor. Millions of women are exposed to ambient air pollution, and levels can be especially high in developing countries. Reducing infant mortality is one of the Millennium Development Goals, so the public health importance of understanding and minimizing environmental contributors to poor birth outcomes is great. Most published epidemiology studies are based on population birth registries and lack the individual, clinical data and repeated measures needed to elucidate possible biological mechanisms mediating epidemiological associations between pollution and adverse birth outcomes. 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 investigate how air pollution and the polycyclic aromatic hydrocarbon (PAH) component of particles can influence the outcome of pregnancy, and whether certain periods of gestation represent critical time windows and opportunities for preventive intervention. We will obtain biomarkers relevant to PAH exposure (DNA adducts) in blood samples provided by participants monthly during their pregnancies, and umbilical cord blood obtained at birth. We will also collect information on health history, clinical characteristics, tobacco smoke exposure, diet and time-activity patterns. Simultaneously, we will estimate spatial and temporal variability in air pollution exposure with data from the Mexico City Metropolitan Area (MCMA) air quality monitoring network (PM2.5, PM10, ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide), matched to the exact locations of participants' homes. DNA samples from mother and infant will be used to type genetic polymorphisms (CYP1A1, GSTM1, GSTT1, GSTP1, Xrcc1, XPD) relevant to the hypothesized mechanisms. We will evaluate whether ambient pollution and PAH adducts are associated with three outcomes: birth weight, head circumference and birth length, controlling for other risk factors, and which time windows are most relevant. We will examine effect modification by intake of antioxidant vitamins (E and C) and the genetic 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 PAH adducts. Any coherence between the human and in vitro evidence for a mechanistic association between pollution and these adducts will guide future studies. This multi-disciplinary, global health collaboration will evaluate potential environmental determinants of adverse birth outcomes, using a novel approach combining epidemiology and toxicology, with the goal of developing unique knowledge with far-reaching prevention implications.