Epidemiological Study of Volatile Organic Compounds and Preterm Birth in Detroit

底特律是美国所有主要城市中早产率（PTB）最高的城市。虽然多因素 尽管结核病是一种常见的疾病，但减少结核病的努力没有充分考虑到环境的复杂相互关系， 以及医疗和社会风险决定因素。暴露于挥发性有机化合物（VOC）会导致 不良的健康后果，包括肺结核。被密歇根州视为“重大公共卫生威胁” 环境部，五大湖，和能源，挥发性有机化合物污染，通过蒸汽入侵已 在全州范围内的4,000多个地点进行了确认。底特律人的风险尤其高，因为城市的恶化 基础设施，作为制造业中心的历史，以及大量带地下室的老房子- 所有这些都增加了在有VOC暴露风险的建筑物中生活和工作的可能性。我们的出生数据 在底特律展示了苯，甲苯，二甲苯和二甲苯（BTEX），这些是石油中常见挥发性有机化合物 产品与较高的PTB风险相关，与妊娠中期母体炎症指标的改变相关， 以及胎盘中基因表达的变化。为了验证我们的假设， 增加PTB风险，我们将利用亨利福特的临床资源建立一个前瞻性出生队列 密歇根州底特律市的卫生系统（HFHS）每年接生9，500多名婴儿， 招募并跟踪约1 100名孕妇。我们将进行巢式病例对照研究（1：1频率 在这个出生队列中匹配。先前对VOCs和PTB的研究不一致，并且受到使用 单一来源和单一污染物的估计暴露量。这项研究将解决这些问题。 通过测量母体尿液中三氯乙烯、四氯乙烯和BTEX代谢物的限制（三个 怀孕期间的时间）和胎盘中的苯蛋白加合物。炎症生物标志物将是 在怀孕期间的三个时间点测量母体血液中的DNA甲基化和基因表达 将在胎盘中测量。主要的具体目标是：（1）检查孕妇体内的VOC代谢物水平， 尿（产前暴露）和/或胎盘中的苯加合物水平（母胎接触） （2）（A）检查VOC水平是否与母体炎症相关， 胎盘中改变的DNA甲基化/基因表达谱和（B）探索母体炎症或 胎盘功能测量介导VOC暴露和PTB之间的关联;（3）确定来源 与母亲尿液和胎盘中VOC水平相关的VOC。项目B3，使用新方法， 量化人体中的挥发性有机化合物水平，将提供与CLEAR的总体健康目标直接相关的数据。 VOC暴露的影响，即与PTB。值得注意的是，通过确定这些关联的潜在机制， 和潜在的挥发性有机化合物的来源，我们将提供数据，以清除，这将有助于确定生物医学预防 和环境补救战略，以改善脆弱个人的健康，特别是， 孕妇和胎儿，并减少与肺结核相关的终身健康负担。

Detroit has the highest preterm birth (PTB) rate of all major United States cities. Although a multifactorial disease, efforts to decrease PTB have not fully considered the complex interrelationships of the environment alongside medical and social determinants of risk. Exposure to volatile organic compounds (VOC) result in adverse health outcomes, including PTB. Considered “a significant public health threat” by the Michigan Department of Environment, Great Lakes, and Energy, VOC contamination via vapor intrusion has been confirmed at >4,000 sites statewide. Detroiters are at particularly high risk because of the city’s deteriorating infrastructure, history of being a manufacturing epicenter, and an abundance of older homes with basements – all which increase the likelihood of living and working in structures at-risk for VOC exposure. Our data on births in Detroit show that benzene, toluene, ethylbenzene, and xylenes (BTEX), common VOCs found in petroleum products, are associated with higher PTB risk, with altered maternal inflammation measures mid-pregnancy, and with gene expression changes in the placenta. To examine our hypothesis that exposure to VOCs increases PTB risk, we will establish a prospective birth cohort leveraging clinical resources at Henry Ford Health System (HFHS) in metropolitan Detroit, MI, which delivers >9,500 babies annually, to cost-effectively recruit and follow ~1,100 pregnant women. We will conduct a nested case-control study (1:1 frequency matched) within this birth cohort. Prior studies of VOCs and PTB have been inconsistent and limited by use of estimated exposures from single sources and single contaminants. This proposed study will address these limitations by measuring trichloroethylene, tetrachloroethylene, and BTEX metabolites in maternal urine (three times during pregnancy) and benzene protein adducts in the placenta. Inflammatory biomarkers will be measured in maternal blood at three time points over pregnancy and DNA methylation and gene expression will be measured in the placenta. Key specific aims are to: (1) examine if VOC metabolite levels in maternal urine (prenatal exposure), and/or benzene adduct levels in the placenta (exposure at the maternal-fetal interface) are associated with PTB; (2) (A) examine if VOC levels are associated with maternal inflammation or altered DNA methylation/gene expression profiles in the placenta and (B) explore if maternal inflammation or placental functional measures mediate associations between VOC exposure and PTB; and (3) identify sources of VOCs associated with VOC levels in maternal urine and the placenta. Project B3, using novel methods to quantify VOC levels in humans, will provide data directly relevant to the overall goal of CLEAR on health effects of VOC exposure, namely with PTB. Notably, by identifying potential mechanisms of these associations and potential sources of VOCs, we will provide data to CLEAR that will help identify both biomedical prevention and environmental remediation strategies to improve the health of vulnerable individuals, in particular, pregnant women and fetuses, and reduce life-long health burdens associated with PTB.