The short-term effect of ozone on pregnancy loss modified by temperature: Findings from a nationwide epidemiological study in the contiguous United States

Abstract

BackgroundPregnancy loss, a major health issue that affects human sustainability, has been linked to short-term exposure to ground-surface ozone (O3). However, the association is inconsistent, possibly because of the co-occurrence of O3 and heat episodes, as increased temperature is a risk factor for pregnancy loss. To explain this inconsistency, the effect of O3 on pregnancy loss needs to be examined jointly with that of high temperature. MethodsA total of 247,305 pregnancy losses during the warm season were extracted from fetal death certificates from the 386 counties in contiguous United States from 1989 to 2005. We assessed environmental exposure based on the daily maximum 8 h average of O3 from Air Quality System monitors and the 24 h average temperature from the North American Regional Reanalysis product. We conducted a bidirectional, time-stratified case-crossover study of the association between pregnancy loss and exposures to O3 and temperature and their multiplicative interaction. The main time window for the exposure assessment was the day of case occurrence and the preceding 3 days. To estimate the association, we used conditional logistic regression with adjustment for relative humidity, height of the planetary boundary layer, and holidays. Sensitivity analyses were performed on the lagged structure, nonlinearity, and between-subpopulation heterogeneity of the estimated joint effect. ResultsThe joint effect was first estimated by the regression against categorical exposure by tertile. Compared to the low-low exposure group (O3 ≤ 78 μg/m3 and temperature ≤ 18 °C), the odds of pregnancy loss was significantly higher by 6.0 % (95 % confidence interval [CI] 2.4–9.7 %), 9.8 % (6.1–13.8 %), and 7.5 % (4.7–10.3 %) in the high-low (>104 μg/m3 and ≤18 °C), low-high (≤78 μg/m3 and >23 °C), and high-high (>104 μg/m3 and >23 °C) groups. The model of linear exposure and the multiplicative interaction yielded similar results. Each increment of 10 μg/m3 in O3 and 1 °C in temperature was associated with a 3.0 % (2.0 %–4.0 %) and 3.9 % (3.5 %–4.3 %), respectively, increase in the odds of pregnancy loss. A decrease in odds of 0.2 % (0.1 %–0.2 %) was associated with the temperature × O3 interaction. The finding of an antagonistic interaction between temperature and O3 was confirmed by models parametrizing the joint exposure as alternative nonlinear terms (i.e., a two-dimensional spline term or a varying-coefficient term) and was robust to a variety of exposure lags and stratifications. Therefore, the marginal effect of O3 was estimated to vary by climate zone. A significant association between O3 and pregnancy loss was observed in the northern, but not southern, United States. ConclusionJoint exposure to O3 and high temperature can increase the risk for pregnancy loss. The adverse effect of O3 is potentially modified by ambient temperature. In high-latitude cities, controlling for O3 pollution could protect maternal health.