Exposure to air pollution is associated with congenital anomalies in the population born by in vitro fertilization

Background: Congenital anomalies (CAs) are the leading causes for children's disabilities and mortalities worldwide. The associations between air pollution and CAs are not fully characterized in fetuses born by in vitro fertilization (IVF) who are at high risk of congenital anomalies. Methods: We conducted a cross-sectional study including 16,971 IVF cycles from three hospitals in Hebei Province, China, 2014-2019. Air quality data was obtained from 149 air monitoring stations. Individual average daily concentrations of PM2.5, PM10, NO2, SO2, CO, and O3 were estimated by spatiotemporal kriging method. Exposure windows were divided into 5: preantral follicle period, antral follicle period, germinal period, embryonic period and early fetal period. Logistic generalized estimating equations were used to estimate the associations between air pollutants and overall or organ-system specific congenital anomalies. Negative control exposure method was used to detect and reduce bias of estimation. Results: We found increasing levels of PM2.5 and PM10 were associated with higher risk of overall congenital anomalies during early fetal period, equating gestation 10-12 weeks (OR: 1.05, 95% CI: 1.02-1.09, p = 0.013 for a 10 mu g/m3 increase of PM2.5; OR: 1.03, 95% CI: 1.01-1.06, p = 0.021 for a 10 mu g/m3 increase of PM10). Cleft lip and cleft palate were associated with PM10 in germinal period and early fetal period. The CAs of eye, ear, face and neck were related to CO in preantral follicle stage. We did not find an association between chromosome abnormalities and air pollution exposure. Conclusions: We concluded that ambient air pollution was a risk factor for congenital anomalies in the fetuses conceived through IVF, especially exposure in early fetal period.