Short-Term Increases in NO₂ and O₃ Concentrations during Pregnancy and Stillbirth Risk in the U.S. A Time-Stratified Case-Crossover Study

Associations between gaseous pollutant exposure and stillbirth have focused on exposures averaged over trimesters or gestation. We investigated the association between short-term increases in nitrogen dioxide (NO₂) and ozone (O₃) concentrations and stillbirth risk among a national sample of 116 788 Medicaid enrollees from 2000 to 2014. A time-stratified case-crossover design was used to estimate distributed (lag 0-lag 6) and cumulative lag effects, which were adjusted for PM_2.5 concentration and temperature. Effect modification by race/ethnicity and proximity to hydraulic fracturing (fracking) wells was assessed. Short-term increases in the NO₂ and O₃ concentrations were not associated with stillbirth in the overall sample. Among American Indian individuals (n = 1694), a 10 ppb increase in NO₂ concentrations was associated with increased stillbirth odds at lag 0 (5.66%, 95%CI: [0.57%, 11.01%], p = 0.03) and lag 1 (4.08%, 95%CI: [0.22%, 8.09%], p = 0.04) but not lag 0-6 (7.12%, 95%CI: [−9.83%, 27.27%], p = 0.43). Among participants living in zip codes within 15 km of active fracking wells (n = 9486), a 10 ppb increase in NO₂ concentration was associated with increased stillbirth odds in single-day lags (2.42%, 95%CI: [0.37%, 4.52%], p = 0.02 for lag 0 and 1.83%, 95%CI: [0.25%, 3.43%], p = 0.03 for lag 1) but not the cumulative lag (lag 0-6) (4.62%, 95%CI: [−2.75%, 12.55%], p = 0.22). Odds ratios were close to the null in zip codes distant from fracking wells. Future studies should investigate the role of air pollutants emitted from fracking and potential racial disparities in the relationship between short-term increases in NO₂ concentrations and stillbirth.