Association between maternal exposure to gaseous pollutants and atrial septal defect in China: A nationwide population-based study

The association between maternal exposure to gaseous air pollutants and congenital heart defects (CHD) remains unclear. The concentration-response relationship and the time windows of susceptibility to gaseous pollutants may vary by pollutant species and CHD subtypes.We aimed to examine the relationship between maternal exposures to four species of gaseous pollutants (NO2, O3, SO2, and CO) and atrial septal defect (ASD), which is a common subtype of CHD, and to determine the critical time windows of susceptibility for each gaseous pollutant.Among 1,253,633 infants born between October 1, 2013 and December 31, 2016 in China, 1937 newborns were diagnosed with isolated ASD, a prevalence of 1.55‰. Maternal exposures to the gaseous pollutants were estimated by matching the geocoded maternal addresses with the gridded ambient concentrations. The adjusted odds ratios (aOR) between exposures and ASD were quantified by using mixed-effects logistic regression models.We found significantly positive associations between ASD and maternal exposures to NO2, O3, SO2, and CO during entire pregnancy, first-, second-, and third-trimester. However, no statistically significant association was found between maternal exposure to PM2.5, PM2.5-10 and ASD risk (P > 0.05). In the fully adjusted model with respect to average exposure over entire pregnancy, the adjusted odds ratios (aOR) for each 10 μg/m3 increment of NO2, O3, SO2 were 1.33 (95% CI: 1.22-1.45), 1.13 (95% CI: 1.10-1.16), 1.28 (95% CI: 1.20-1.35), respectively; the aOR for each 100 μg/m3 increment of CO was 1.10 (95% CI: 1.06-1.15). The observed concentration-response relationships varied by exposure periods and pollutants, with the strongest association for NO2 during the 1st-8th embryology weeks, for O3 during the third trimester, for SO2 during the second trimester, and for CO without obvious variation.The findings suggest an increased risk of ASD in association with maternal exposures to four common gaseous pollutants. From the perspective of birth defects prevention and ASD risk mitigation, it is critical to reduce maternal exposure to gaseous pollutants especially during the most susceptible time windows.