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决定其整个生命过程中生存和未来健康的重要决定因素。尽管影响出生体重和体型的因素很多，但最近人们发现，孕期暴露在空气污染中也是一个因素。数以百万计的妇女暴露在环境空气污染中，在发展中国家，污染水平可能特别高。降低婴儿死亡率是千年发展目标之一，因此，了解和尽量减少导致不良出生结果的环境因素对公共卫生的重要性是巨大的。大多数已发表的流行病学研究都是基于人口出生登记，缺乏个人、临床数据和必要的重复措施，以阐明可能的生物学机制，调解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名孕妇的新队列中研究这些机制。墨西哥城是一个空气污染水平很高的特大城市。我们将调查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，以及某些妊娠期是否代表着预防干预的关键时间窗口和机会。我们将获取参与者在怀孕期间每月提供的血液样本中与PAH暴露相关的生物标志物(DNA加合物)，以及出生时获得的脐带血。我们还将收集有关健康史、临床特征、吸烟暴露、饮食和时间活动模式的信息。同时，我们将利用墨西哥城大都会地区(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)的数据，与参与者住宅的确切位置匹配，估计空气污染暴露的空间和时间变异性。母亲和婴儿的DNA样本将被用来对与假设机制相关的遗传多态(CYP1A1、GSTM1、GSTT1、GSTP1、Xrcc1、XPD)进行分型。我们将评估环境污染和多环芳烃加合物是否与三种结果相关：出生体重、头围和出生长度，控制其他危险因素，以及哪些时间窗最相关。我们将研究摄入抗氧化剂维生素(E和C)的效果改变和遗传多态。最后，我们将通过一项平行的体外毒理学研究来补充这项流行病学研究，该研究将涉及每月从MCMA的五个区域收集和表征空气污染颗粒物样本(PM10和PM2.5)，并暴露单核细胞株(J774A.1)以评估多环芳烃加合物。人类和体外证据之间的任何一致性，证明污染和这些加合物之间存在机械联系，都将指导未来的研究。这项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，评估不良生育结果的潜在环境决定因素，目的是发展具有深远预防意义的独特知识。公共卫生相关性这项研究调查了空气污染如何影响不良生育结果的风险，重点是了解暴露的机制和关键时间窗口。其目标是开发知识，以支持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，以了解环境对婴儿健康的贡献；以及3)对预防不良生育结果感兴趣的临床医生。

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. PUBLIC HEALTH RELEVANCE This research investigates how air pollution influences the risk of adverse birth outcomes, with a focus on understanding mechanisms and critical time windows of exposure. 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 adverse birth outcomes.