Epidemiological Study of Volatile Organic Compounds and Preterm Birth in Detroit

底特律挥发性有机化合物与早产的流行病学研究

• 批准号: 10352966
• 负责人: Andrea E Cassidy-Bushrow
• 金额: $ 34.32万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-08 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10352966
• 关键词: 37 weeks gestation; Address; Affect; Animals; Area; Awareness; Benzene; Biological; Biological Markers; Birth; Birth Rate; Blood; Blood Circulation; Blood specimen; Chronic Disease; Cities; Clinical; Collaborations; Complex; DNA Methylation; Data; Data Analyses; Disease; Engineering; Ensure; Environment; Environmental Exposure; Environmental Health; Environmental Risk Factor; Equilibrium; Exposure to; Failure; Fetal Tissues; Fetus; Frequencies; Gene Expression; Goals; Health; Health system; High Risk Woman; Home; Human; Individual; Industrialization; Infant; Infant Mortality; Inflammation; Inflammatory; Infrastructure; Intervention; Lead; Leadership; Life; Link; Maternal-Fetal Exchange; Measurement; Measures; Mediating; Medical; Methods; Michigan; Minority Women; Mission; Neighborhoods; Nested Case-Control Study; Outcome; Patients; Petroleum; Placenta; Pregnancy; Pregnant Women; Premature Birth; Prevalence; Prevention; Property; Proteins; Public Health; Race; Recording of previous events; Research; Research Project Grants; Resources; Risk; Risk Factors; Sampling; Site; Soil; Source; Specimen; Statistical Data Interpretation; Structure; Superfund; Tetrachloroethylene; Time; Toluene; Trichloroethylene; United States; Urine; Work; Xylene; adduct; adverse pregnancy outcome; black women; case control; cohort; community engagement; cost; data management; epidemiology study; ethylbenzene; ground water; high risk; improved; inflammatory marker; innovation; insight; metropolitan; novel; offspring; prenatal; prenatal exposure; prevent; prospective; racial disparity; recruit; remediation; sex; social determinants; toxicant; urban setting; vapor intrusion; volatile organic compound

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.

底特律在美国所有主要城市中的早产（PTB）率最高。虽然是多因素 疾病，减少PTB的努力尚未完全考虑到环境的复杂相互关系 以及医疗和社会决定者的风险。暴露于挥发性有机化合物（VOC）导致 不良健康结果，包括PTB。被密歇根州视为“重大公共卫生威胁” 环境部，大湖区和能源部，通过蒸气侵入的VOC污染已经存在 在全州范围内确认> 4,000个站点。由于城市恶化，底特律的风险特别高 基础设施，成为制造业的历史以及拥有地下室的大量较老的房屋 - 所有这些都增加了在危险中生活和工作的可能性，以进行VOC暴露。我们关于出生的数据 在底特律表明苯，甲苯，乙烯苯和二甲苯（BTEX）中，在石油中发现的普通VOC 产品与较高的PTB风险有关，并改变了遗物炎症措施中期， 并随着基因表达的变化而变化。探讨我们暴露于VOC的假设 增加PTB风险，我们将在亨利·福特（Henry Ford 密歇根州大都会底特律的卫生系统（HFHS），每年提供> 9,500个婴儿，以经济高效 招募并关注约1,100名孕妇。我们将进行嵌套的病例对照研究（1：1频率 匹配）在这个出生队列中。先前对VOC和PTB的研究是不一致的，并且通过使用 来自单一来源和单个污染物的估计暴露。这项拟议的研究将解决这些问题 通过测量三氯乙烯，四氯乙烯和BTEX代谢产物中的限制（三个 怀孕期间）和苯蛋白加合物中的苯蛋白质中加合物。炎症生物标志物将是 在怀孕和DNA甲基化和基因表达的三个时间点中以三个时间点测量 将在plapeta中进行测量。主要具体目的是：（1）考试如果孕产妇中的VOC代谢水平 尿液（产前暴露）和​​/或苯苯基加合物水平（暴露于Mater-Fetal 界面）与PTB关联； （2）（a）检查VOC水平是否与母体炎症相关或 plapeta中的DNA甲基化/基因表达谱改变，（b）探索母体炎症或 胎盘功能指标可介导VOC暴露与PTB之间的关联； （3）确定来源 与孕产妇尿液和斑点中的VOC水平相关的VOC。项目B3，使用新颖的方法 量化人类的VOC级别，将提供与“明确健康”的总体目标直接相关的数据 VOC暴露的影响，即PTB。值得注意的是，通过确定这些关联的潜在机制 以及潜在的VOC来源，我们将提供数据以清除，这将有助于识别两种生物医学预防 以及环境补救策略，以改善弱势个人的健康，特别是 孕妇和胎儿，并减少与PTB相关的终身健康烧伤。