Advances on associations of exposure to air pollutants during pregnancy with congenital heart disease in offspring

Congenital heart disease (CHD) is the most common birth defect and one of the major causes of neonatal death, with an average prevalence of 9.4‰ worldwide. We reviewed recent epidemiological studies and found that exposure to air pollutants is associated with increased CHD risks, but the associations are inconsistent between exposure to air pollutants and different subtypes of CHD due to developmental and etiological heterogeneity among different subtypes of CHD. It has been reported that air pollutants are associated with increased risks of ventricular septal defect, patent ductus arteriosus, pulmonary stenosis, tetralogy of Fallot, and transposition of the great arteries. However, associations between maternal exposure to air pollutants and atrial septal defect (ASD) are contradictory, with significantly positive associations of inhalable particulate matter and nitrogen dioxide exposure, negative associations of fine particulate matter and carbon monoxide, and mixed associations of sulfur dioxide. Adverse effects of air pollutant on cardiac development cover a wide time window beyond 3-8 weeks during gestation; particulate matter and nitrogen oxide are more likely to affect fetal heart in early pregnancy, while the association strength of carbon monoxide shows a trough in early pregnancy, and sulfur dioxide and ozone affect cardiac health throughout pregnancy. In addition, we discussed the limitations of previous studies on the associations between maternal air pollutant exposure and CHD, and highlighted the application of precise assessment on exposure to air pollutants, the performance of prospective cohort studies and longitudinal studies, and the necessity of studies on CHD subtypes, in order to provide scientific evidence to control exposure to environmental pollutants and CHD occurrence.