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.

Volatile organic compounds (VOCs) contaminate shallow soils and groundwater at Superfund, residential, commercial, and industrial properties, leading to exposures via vapor intrusion; available data suggests that VOCs are associated with higher risk for preterm birth (PTB). The Center for Leadership in Environmental Awareness and Research (CLEAR) is dedicated to understanding and mitigating this serious environmental health problem. CLEAR Project B3 will specifically address the impact of VOCs on PTB risk through an epidemiologic study of pregnant women in metropolitan Detroit; additionally, B3 will examine if VOCs are associated with altered maternal inflammation or placental function (DNA methylation, gene expression) and potential sources of VOC exposure, which may yield insights into interventions to prevent adverse pregnancy outcomes and/or areas to target for VOC remediation.