Abstract
BACKGROUND: Despite extensive population-based evidence linking air pollution with adverse birth outcomes, the potential interactive effects of ambient ozone (O₃) and fine particulate matter (PM(2.5)) on low birth weight (LBW) and small for gestational age (SGA) remain largely unstudied. METHODS: We conducted a national retrospective cohort study using approximately 4.07 million birth records being registered in 749 hospitals across 31 provinces of Iran from 2013 to 2018. Gridded estimates of monthly O(3) and PM(2.5) concentrations were obtained from validated spatiotemporal models. Multivariable-adjusted logistic regression models were employed to evaluate the associations between prenatal exposure to O(3) and PM(2.5) and adverse birth outcomes, including LBW, term LBW (TLBW), SGA, and term SGA (TSGA). Stratified analyses were performed to compare O₃-related effects in the lowest and highest tertiles of PM(2.5) groups and PM(2.5)-related effects in lowest and highest tertiles of O₃ groups. The additive interaction effects were testified by introducing 2 × 2 dummy variables to model the joint exposure of O₃ and PM(2.5). Subgroup analyses were performed stratified by maternal age and educational attainment. RESULTS: A total of 3,976,387 singleton live births (6.0% LBW and 11.8% SGA) were included in this study. We observed consistent evidence for intensified effects of maternal O(3) exposure on LBW and SGA under higher PM(2.5) levels. For each 10-ppb increase in O₃ exposure, the estimated odds of LBW increased considerably from 0.99 (95% confidence interval [CI]: 0.96, 1.02) in the lowest tertile of PM(2.5) level to 1.20 (95% CI: 1.16, 1.22) in the highest tertile of PM(2.5) level (P <0.001 for trend), and the estimated odds of SGA parallelly increased from 1.05 (95% CI: 1.03, 1.07) in the lowest PM(2.5) stratum to 1.26 (95% CI: 1.24, 1.28) in the highest PM(2.5) stratum (P <0.001 for trend). Under the scenarios of co-exposure to high O₃ and PM(2.5) levels, the excess odds increased by 8% (95% CI: 6%, 10%) for LBW and 4% (95% CI: 3%, 6%) for SGA, and 7% (95% CI: 5%, 9%) of the odds for LBW and 4% (95% CI: 2%, 5%) for SGA could be attributed to the additive interaction. Subgroup analyses showed more pronounced interactive effects among younger and less-educated mothers. CONCLUSIONS: This nationwide birth cohort evidenced synergistic effects of maternal exposure to O₃ and PM(2.5) during pregnancy in increasing LBW and SGA risks, underscoring the need for coordinated control strategies to effectively reduce the adverse effects of environmental pollution on maternal and infant health. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-025-25579-8.