Investigating the Association Between Volatile Organic Compounds and Preterm Birth in Detroit, Michigan: Protocol for the Center for Leadership in Environmental Awareness and Research Birth Cohort Study.

Background: Preterm birth (PTB), or birth before 37 weeks of gestation, remains a significant public health issue in the United States, particularly in Detroit, Michigan. Growing evidence suggests that volatile organic compounds (VOCs), aromatic or chlorinated organic compounds that vaporize readily, may influence PTB risk. However, much of this prior work is limited by indirect VOC exposure estimates (eg, assignment based on maternal residential address), single-point or cumulative exposure estimates during pregnancy, or limited consideration of potential mechanistic factors. Objective: The Center for Leadership in Environmental Awareness and Research (CLEAR) birth cohort has been designed to test the hypotheses that prenatal VOC exposures, measured as VOC metabolites in maternal urine, increase the risk of PTB; that VOC exposures are associated with maternal inflammation and placental function measures; that associations between prenatal VOC exposures and PTB may be mediated by these maternal inflammation and placental function measures; and that there are neighborhood-level factors that may increase the risk of VOC exposure during pregnancy. Methods: A prospective cohort of 1075 pregnant patients receiving prenatal care at Henry Ford Health will be recruited. Pregnant patients residing in Detroit or receiving prenatal care at a Detroit-based Henry Ford Health women's health clinic are eligible. Pregnant patients are followed until delivery. Up to 3 urine and blood samples (collected during early, mid, and late pregnancy) are obtained for measurement of VOC metabolites and inflammatory biomarkers, respectively. The placenta is obtained after delivery for epigenomic and transcriptomic measurement. Surveys are administered to pregnant participants to assess a variety of lifestyle, psychosocial, medical, residential, and other factors. Address information collected from both surveys and electronic medical records across pregnancy will be used to identify potential sources of VOC exposure. The electronic medical record is used to obtain medical and delivery data, including infant sex, date of delivery, and gestational age (GA) at delivery. PTB, the primary study outcome, is defined as GA at delivery <37 weeks. A nested case-control approach (frequency matching PTB cases 1:1 with full-term controls [GA at delivery ≥37 weeks] based on infant sex and maternal race) will be applied. Statistical methods, including logistic regression, linear mixed methods, and geographically weighted regression models, as well as chemical mixture approaches, will be used. Results: Funding began September 2022 and recruitment commenced November 2023. Through April 22, 2026, a total of 468 pregnant patients have consented to participate in the CLEAR birth cohort, and recruitment is ongoing. Conclusions: The CLEAR cohort will provide novel data on the role of VOCs during pregnancy in the risk of PTB. Additionally, the role of VOC exposures during pregnancy in maternal inflammation and placental function will be examined. Finally, potential sources of VOC exposures, which could be targets for environmental remediation, will be identified.