Epidemiological Study of Volatile Organic Compounds and Preterm Birth in Detroit

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.

Grant Number: 5P42ES030991-04
NIH Institute/Center: NIH
Principal Investigator: Andrea Cassidy-Bushrow