Combined effects of ambient temperature and ozone exposure before and during pregnancy on hypertensive disorders of pregnancy in 568 Chinese healthcare facilities.

Hypertensive disorders in pregnancy (HDP) are a major contributor of maternal and perinatal mortality and morbidity. Although ambient ozone (O3) and temperature have been individually associated with increased HDP risk, their combined effects remain unclear. In this multicenter retrospective cohort study involving 173,644 women, we assessed the independent and interactive relationships of O3 and temperature on HDP risk using logistic regression and distributed lag non-linear models (DLNM). Temperature was categorized by percentiles as extreme cold (≤5th), moderate cold (>5th to ≤10th), moderate (>10th to ≤90th), moderate hot (>90th to ≤95th), and extreme hot (>95th). For DLNM analyses, the 10th and 90th percentiles of temperature were used to represent low and high temperature, respectively. Compared with moderate temperatures, preconception exposure to extreme cold conditions (OR: 1.37, 95 % CI: 1.21-1.54) and moderate hot during the first 20 weeks of pregnancy (OR: 1.14, 95 % CI: 1.01-1.29) were associated with higher HDP risk. Each 10 μg/m3 increase in O3 concentration elevated HDP risk during the 13 weeks before pregnancy (OR: 1.10, 95 % CI: 1.08-1.12) and the first 20 weeks of pregnancy (OR: 1.04, 95 % CI: 1.01-1.07). Temperature-related HDP risk increased significantly at O3 concentrations above 60 μg/m3 and was markedly amplified beyond 110 μg/m3, where extreme temperatures nearly doubled the risk (OR: 2.00, 95 % CI: 1.35-2.96). Critical susceptibility windows were identified at weeks 9-12 before pregnancy for O3 exposure and gestational weeks 13-20 for high temperature. These findings provide novel evidence of pre-pregnancy O3-sensitivity windows, stage-specific bidirectional temperature associations, and significant O3-temperature interactions, underscoring the need for targeted environmental interventions during preconception and early pregnancy.