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 (PM2.5) 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 O3 and PM2.5 concentrations were obtained from validated spatiotemporal models. Multivariable-adjusted logistic regression models were employed to evaluate the associations between prenatal exposure to O3 and PM2.5 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 PM2.5 groups and PM2.5-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 PM2.5. 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 O3 exposure on LBW and SGA under higher PM2.5 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 PM2.5 level to 1.20 (95% CI: 1.16, 1.22) in the highest tertile of PM2.5 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 PM2.5 stratum to 1.26 (95% CI: 1.24, 1.28) in the highest PM2.5 stratum (P <0.001 for trend). Under the scenarios of co-exposure to high O₃ and PM2.5 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 PM2.5 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.

Interactive and joint associations of prenatal ozone and PM_2.5 exposure with fetal growth restriction: an Iranian nationwide birth cohort study

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2025年12月18日

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Ling Tong,
Yixiang Wang,
Yuqian Huang,
Yalin Zhang,
Fatemeh Mayvaneh,
Yunquan Zhang

摘要

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 O₃ 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 O₃ 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 O₃ 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.

Interactive and joint associations of prenatal ozone and PM2.5 exposure with fetal growth restriction: an Iranian nationwide birth cohort study

摘要

Interactive and joint associations of prenatal ozone and PM_2.5 exposure with fetal growth restriction: an Iranian nationwide birth cohort study