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

基本信息

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
项目类别：
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

项目摘要

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.

底特律的早产率 (PTB) 是美国所有主要城市中最高的，尽管这是由多种因素造成的。疾病、减少 PTB 的努力没有充分考虑环境之间复杂的相互关系以及风险的医疗和社会决定因素。不良健康后果，包括被密歇根州视为“重大公共卫生威胁”。环境、五大湖和能源部，通过蒸气侵入造成的挥发性有机化合物污染已超过 4,000 个地点证实，由于该市的情况不断恶化，底特律面临着特别高的风险。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挥发性有机化合物暴露风险的结构中生活和工作的可能性。底特律的一项研究表明，石油中常见的 VOC 包括苯、甲苯、乙苯和二甲苯 (BTEX) 产品，与较高的 PTB 风险相关，并且妊娠中期母体炎症指标发生改变，以及胎盘中基因表达的变化来检验我们的假设：暴露于挥发性有机化合物。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大都市的卫生系统 (HFHS) 每年为超过 9,500 名婴儿提供经济高效的服务我们将招募并跟踪约 1,100 名孕妇（频率为 1:1）。在此出生队列中，之前对 VOC 和 PTB 的研究不一致，并且受到使用的限制。这项拟议的研究将解决这些问题。通过测量母体尿液中的三氯乙烯、四氯乙烯和苯系物代谢物（三种怀孕期间的次）和胎盘中的苯蛋白加合物将是炎症生物标志物。在怀孕期间三个时间点的母体血液中进行测量以及 DNA 甲基化和基因表达主要具体目标是：(1) 检查母体中的 VOC 代谢水平。尿液（产前暴露）和/或胎盘中苯加合物水平（母胎暴露） (2) (A) 检查 VOC 水平是否与母体炎症或胎盘中 DNA 甲基化/基因表达谱的改变，以及 (B) 探索母体炎症或胎盘功能测量介导 VOC 暴露与 PTB 之间的关联；(3) 确定来源；项目 B3，使用新方法来研究与母体尿液和胎盘中 VOC 水平相关的 VOC。量化人体 VOC 水平，将提供与 CLEAR 健康总体目标直接相关的数据 VOC 暴露的影响，即与 PTB 的影响，特别是通过确定这些关联的潜在机制。以及 VOC 的潜在来源，我们将向 CLEAR 提供数据，这将有助于确定生物医学预防以及改善弱势个体健康的环境修复策略，特别是，孕妇和胎儿，并减少与 PTB 相关的终生健康负担。