Maternal exposure to ambient ozone and fetal congenital heart defects: a national multicenter study in China.

Background: Ambient O₃ has demonstrated an aggravated increasing trend in the context of global warming. The available evidence of maternal exposure to ambient O₃ on fetal congenital heart defects (CHD) is still limited, especially in high polluted areas.

Objective: To examine associations of maternal exposure to ambient O₃ during early pregnancy with fetal CHDs.

Methods: We conducted a national multicenter study in 1313 hospitals from 26 provinces in China and collected a total of 27,817 participants at high risk of CHD from 2013 to 2021. Exposure to ambient O₃ during the embryonic period, preconception, the first trimester and periconception was assessed by extracting daily concentrations from a validated grid dataset at each subject's residential district. CHDs were diagnosed based on fetal echocardiography.

Results: Each 10 µg/m³ increase of exposure to ambient O₃ during the embryonic period was approximately linearly associated with a 12.7% (odds ratio [OR]: 1.127, 95% confidence interval [CI]: 1.098, 1.155) increase in odds of pooled CHD (p < 0.001). The associations remain robust after adjusting for ambient PM_2.5 and NO₂ exposure. The odds of different types of CHD in association with ambient O₃ exposure varied greatly. We observed significant association of ambient O₃ exposure with ventricular septal defect (VSD), tetralogy of Fallot (TOF); pulmonary stenosis (PS), pulmonary atresia (PA), transposition of great arteries (TGA) and persistent left superior vena cava (PLSVC), with TOF demonstrating the strongest estimates (OR: 1.194, 95% CI:1.107, 1.288). The estimates for preconception, the first trimester and periconception demonstrate consistent findings with the main analyses, indicating stronger associations of ambient O₃ exposure during the periconception period.

Impact: Our study provides evidence that higher ambient O₃ during early pregnancy was significantly associated with increased odds of fetal CHD. Our findings suggest that pregnant women, clinical practitioners, and policy makers need to pay more attention to the exposure to higher ambient O₃ during early pregnancy to reduce the risk of developing CHD and to improve outcomes across the life span.