Modification effects of ambient temperature on associations of ambient ozone exposure before and during pregnancy with adverse birth outcomes: A multicity study in China

Background: Epidemiological studies suggest that both ambient ozone (O₃) and temperature were associated with increased risks of adverse birth outcomes. However, very few studies explored their interaction effects, especially for small for gestational age (SGA) and large for gestational age (LGA). Objectives: To estimate the modification effects of ambient temperature on associations of ambient O₃ exposure before and during pregnancy with preterm birth (PTB), low birth weight (LBW), SGA and LGA based on multicity birth cohorts. Methods: A total of 56,905 singleton pregnant women from three birth cohorts conducted in Tianjin, Beijing and Maoming, China, were included in the study. Maximum daily 8-h average O₃ concentrations of each pregnant woman from the preconception period to delivery for every day were estimated by matching their home addresses with the Tracking Air Pollution in China (TAP) datasets. We first applied the Cox proportional-hazards regression model to evaluate the city-specific effects of O₃ exposure before and during pregnancy on adverse birth outcomes at different temperature levels with adjustment for potential confounders, and then a meta-analysis across three birth cohorts was conducted to calculate the pooled associations. Results: In pooled analysis, significant modification effects of ambient temperature on associations of ambient O₃ with PTB, LBW and LGA were observed (P_interaction < 0.05). For a 10 μg/m³ increase in ambient O₃ exposure at high temperature level (> 75^th percentile), the risk of LBW increased by 28 % (HR: 1.28, 95% CI: 1.13–1.46) during the second trimester and the risk of LGA increased by 116% (HR: 2.16, 95%CI: 1.16–4.00) during the entire pregnancy, while the null or weaker association was observed at corresponding low (≤ 25^th percentile) and medium (> 25^th and ≤ 75^th percentile) temperature levels. Conclusion: This multicity study added new evidence that ambient high temperature may enhance the potential effects of ambient O₃ on adverse birth outcomes.