Preconception Folic Acid Supplementation Associated with Attenuated Effects of Air Pollution on Birthweight Outcomes.

Gestational exposure to ambient air pollution has been linked to adverse birth outcomes. Folic acid (FA) supplementation supports fetal development, but the optimal timing for protective effects remains uncertain. This study aims to determine whether maternal FA supplementation prior to conception modifies the association between gestational air pollution exposure and birthweight-related outcomes in a population where most women also took FA during pregnancy. We analyzed data from 10,579 mother-child pairs from a preconception cohort in Shanghai, China. Ambient concentrations of PM2.5, PM10, NO2, and ozone were estimated at a residential level using spatiotemporal models for the preconception period and each trimester. We assessed whether preconception FA supplementation modified the association between air pollution exposure and birth outcomes, including birthweight, birthweight Z-score, small-for-gestational age (SGA), and low birthweight (LBW). Linear and logistic regression models with interaction terms, as well as stratified analyses by FA supplementation status, were applied. Children's sex-specific associations were also explored. Significant interactions between preconception FA supplementation and air pollution exposures were observed for birthweight and SGA. A 10 μg/m3 increase in PM2.5 exposure during pregnancy was associated with a -62.8 g (95% CI: -97.0, -28.6) change in birthweight and a 1.78 (95% CI: 1.16, 2.73) odds ratio for SGA among women without preconception FA supplementation. No such significant associations were found among women receiving preconception FA supplementation, with an estimated change of -1.7 g in birthweight (95% CI: -65.7 to 62.4) and an odds ratio of 0.70 for SGA (95% CI: 0.32-1.44). The protective effect appeared more pronounced for male infants than females. Maternal preconception FA supplementation can attenuate the adverse effects of gestational air pollution exposure on birthweight and SGA risk in women who also received FA supplementation during pregnancy. These findings support the importance of incorporating preconception FA supplementation as a protective measure against gestational exposure to air pollution.