Ozone exposure during early pregnancy and preterm birth: A systematic review and meta-analysis

Exposure to ozone has been linked to reproductive outcomes, including preterm birth. In this systematic review, we summarize published epidemiologic cohort and case-control studies examining ozone exposures (estimated on a continuous scale) in early pregnancy (1st and 2nd trimesters (T1, T2)) and preterm birth using ratio measures, and perform a meta-analysis to evaluate the potential relationship between them. Studies were identified by searching PubMed and Web of Science, screened according to predefined inclusion/exclusion criteria, and evaluated for study quality. We extracted study data including effect estimates, confidence limits, study location, study years, ozone exposure assessment method, and mean or median ozone concentrations. Nineteen studies were identified and included, of which 18 examined T1 exposure (17 reported effect estimates), and 15 examined T2 exposure. Random effects meta-analysis was performed in the metafor package, R 3.5.3. The pooled OR (95% CI) for a 10 ppb increase in ozone exposure in T1 was 1.06 (1.03, 1.10) with a 95% prediction interval of 0.95, 1.19; for T2 it was 1.05 (1.02, 1.08) with a 95% prediction interval of 0.95, 1.16. Effect estimates for both exposure periods showed high heterogeneity. In meta-regression analyses of study characteristics, study location (continent) explained some (~20%) heterogeneity for T1 exposure studies, but no characteristic explained a substantial amount of heterogeneity for T2 exposure studies. Increased ozone exposure during early pregnancy is associated with preterm birth across studies.