Polycyclic aromatic hydrocarbons and birth outcomes in Mexico City

墨西哥城的多环芳烃和出生结果

• 批准号: 7563098
• 负责人: Marie Sylvia O'Neill
• 金额: $ 33.28万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7563098
• 关键词: Accounting; Address; Age; Air; Air Pollutants; Air Pollution; Antioxidants; Area; Aromatic Polycyclic Hydrocarbons; Attenuated; Biological; Biological Markers; Birth; Birth Weight; Birth length; Blood; Blood specimen; CYP1A1 gene; Carbon; Carbon Monoxide; Cell Line; Characteristics; Child health care; Cities; Clinical; Clinical Data; Collaborations; Complement; Cotinine; DNA; DNA Adducts; DNA Repair; Data; Developed Countries; Developing Countries; Development; Diet; Dietary intake; Dose; Education; Endotoxins; Environmental Exposure; Environmental Health; Epidemiologic Studies; Epidemiology; Etiology; Exposure to; Food; Future; GSTM1 gene; GSTP1 gene; GSTT1 gene; Genetic Polymorphism; Gestational Age; Goals; Growth; Head circumference; Health; Height; Home environment; Human; In Vitro; Individual; Infant; Infant Health; Infant Mortality; Intake; Knowledge; Length; Life Cycle Stages; Location; Marital Status; Measures; Mediating; Metals; Methods; Mexico; Modification; Molecular Biology; Monitor; Mothers; National Institute of Environmental Health Sciences; Nitrogen Dioxide; Nutritional status; Outcome; Oxidants; Ozone; Participant; Particle Size; Particulate; Patient Self-Report; Pattern; Personal Satisfaction; Policy Maker; Pollution; Population; Pregnancy; Pregnancy Outcome; Pregnant Women; Prevention; Preventive Intervention; Public Health; Publishing; Recording of previous events; Registries; Research; Risk; Risk Factors; Sampling; Scientist; Seasons; Site; Source; Sulfur Dioxide; Time; Tobacco smoke; Toxicology; Umbilical Cord Blood; Vitamin E; Vitamins; Weight; Woman; Work; Xenobiotic Metabolism; adduct; base; cohort; epidemiology study; genetic profiling; global environment; improved; in vivo; interest; metropolitan; novel strategies; parity; particle; particle exposure; pollutant; prenatal exposure; public health relevance; trafficking

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.

描述（由申请人提供）：婴儿出生时的体型和体重是其一生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有多种，但最近人们已经探讨了怀孕期间的空气污染暴露是一个因素。数以百万计的妇女受到环境空气污染的影响，发展中国家的空气污染水平尤其高。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于公共卫生至关重要。大多数已发表的流行病学研究都是基于人口出生登记，缺乏阐明介导污染与不良出生结果之间流行病学关联的可能生物学机制所需的个体临床数据和重复测量。这项拟议的工作提供了一个独特的机会来研究居住在墨西哥城不同地区的 800 名孕妇的这些机制，墨西哥城是一个空气污染水平很高的大城市。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果，以及某些妊娠期是否代表关键的时间窗口和预防性干预的机会。我们将在参与者怀孕期间每月提供的血液样本以及出生时获取的脐带血中获取与 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，我们将利用墨西哥城大都市区 (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）的数据来估计空气污染暴露的空间和时间变化，并与参与者家中的确切位置相匹配。母亲和婴儿的 DNA 样本将用于分析与假设机制相关的遗传多态性（CYP1A1、GSTM1、GSTT1、GSTP1、Xrcc1、XPD）。我们将评估环境污染和多环芳烃加合物是否与以下三种结果相关：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。我们将检查抗氧化维生素（E 和 C）的摄入和遗传多态性的影响修改。最后，我们将通过平行毒理学体外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​​污染颗粒样本（PM10 和 PM2.5），并暴露单核细胞系 (J774A.1) 以评估 PAH 加合物。污染与这些加合物之间存在机械关联的人类和体外证据之间的任何一致性都将指导未来的研究。这项多学科的全球卫生合作将采用流行病学和毒理学相结合的新方法来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。公共卫生相关性 这项研究调查了空气污染如何影响不良出生结果的风险，重点是了解空气污染的机制和关键的暴露时间窗口。目标是开发知识来支持：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影响；3) 对预防不良分娩结果感兴趣的临床医生。