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最高的城市。虽然是多因素的 疾病，减少肺结核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。接触挥发性有机化合物(VOC)会导致 不利的健康后果，包括肺结核。被密歇根州《密歇根州人报》认为是对公众健康的重大威胁 环境、五大湖和能源部，通过蒸汽入侵造成的VOC污染已经被 在全州范围内确认了AT&GT；4000个地点。底特律人面临着特别高的风险，因为城市的恶化 基础设施，作为制造业中心的历史，以及大量带有地下室的老房子- 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 底特律的研究表明，石油中常见的挥发性有机化合物苯、甲苯、乙苯和二甲苯(BTEX) 产品，与更高的肺结核风险相关，与怀孕中期母亲炎症措施的改变有关， 以及胎盘中基因表达的变化。来检验我们的假设，接触VOCs 增加肺结核风险，我们将利用亨利福特的临床资源建立一个预期出生队列 密歇根州底特律大都市的医疗系统(HFHS)，每年接生9,500名婴儿，以经济高效的方式 招募和跟踪约1100名孕妇。我们将进行嵌套病例对照研究(1：1频率 匹配的)在这个出生队列中。以前对VOCs和PTB的研究一直不一致，而且受到使用的限制 单一来源和单一污染物的估计暴露量。这项拟议的研究将解决这些问题 测量母体尿液中的三氯乙烯、四氯乙烯和苯系物的局限性(三种 孕期)和胎盘中的苯蛋白加合物。炎性生物标志物将是 孕期三个时间点母血中DNA甲基化和基因表达的测定 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 尿液(产前暴露)和/或胎盘中的苯加合物水平(母婴暴露 (2)(A)检查VOC水平是否与母体炎症或 胎盘中DNA甲基化/基因表达的改变和(B)探索母体炎症或 胎盘功能测量在VOC暴露和肺结核之间起中介作用；以及(3)确定来源 与母亲尿液和胎盘中的VOC水平有关的VOCs。项目B3，使用新方法来 量化人体内的VOC水平，将提供与Clear on Health总体目标直接相关的数据 VOC暴露的影响，即与肺结核有关。值得注意的是，通过确定这些关联的潜在机制 和VOCs的潜在来源，我们将提供数据来清除，这将有助于识别生物医学预防 和环境补救战略，以改善弱势个人的健康，特别是， 减少与肺结核相关的终生健康负担。

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.