Air Pollution Mixture and Folate Status Indicators among Pregnant Women in Canada: Maternal-Infant Research on...

Folic acid (FA) has been reported to modify associations between air pollutants and autism, but no study has investigated whether air pollutants are associated with maternal folate status.

We estimated associations between an air pollution mixture and maternal folate status among pregnant women in Canada.

We enrolled pregnant women (n = 1983) in 10 cities in Canada from 2008 to 2011 in a prospective cohort. We estimated mean daily concentrations of nitrogen dioxide (NO₂), ozone (O₃), fine particulate matter (PM_2.5), and sulfur dioxide (SO₂) at maternal residences for 180 d preceding first and third trimester visits (ranges: 6-14 and 32-34 gestational weeks, respectively). At both visits, we measured plasma 5-methyltetrahydrofolate (5MTHF), unmetabolized FA (UMFA), and nonmethylated folate (NMF) concentrations and proportions (%5MTHF, %UMFA, %NMF). We used Bayesian weighted quantile sum regression to estimate expected differences in folate measures per 1-quartile difference in the air pollution mixture and weights for the mixture components. We stratified by fetal sex and FA supplementation.

Among complete cases in the first and third trimesters (n = 927 and 838, respectively), median (interquartile range) plasma total folate was similar between the first trimester [96.9 (78.6, 119.0) nmol/L] and the third trimester [99.6 (76.0, 135.0) nmol/L]. In the third but not the first trimester, the mixture was positively associated with plasma total folate [12.0 nmol/L per one-quartile increase, 95% confidence interval (CI): 1.5, 22.7 nmol/L], negatively associated with %5MTHF (-2.8, 95% CI: -5.1, -0.70), and positively associated with %UMFA (13.4, 95% CI: 4.4, 23.0). O₃ was the primary component (weights ≥0.4). Associations were stronger for women with female fetuses.

Air pollution was positively associated with total folate concentrations and UMFA proportions and negatively associated with 5MTHF proportions. Associations were strongest in the third trimester and among pregnant women carrying female fetuses. Air pollution may influence maternal folate status during pregnancy.