Maternal Exposure to PM 2.5 and the Risk of Congenital Heart Defects in 1.4 Million Births: A Nationwide Surveillance-Based Study

Background: Evidence remains limited about the association of maternal exposure to ambient fine particulate matter (airborne particles with an aerodynamic diameter ≤2.5 µm [PM 2.5 ]) with fetal congenital heart defects (CHDs) in highly polluted regions, and few studies have focused on preconception exposure. Methods: Using a nationwide surveillance-based case-control design in China, we examined the association between maternal exposure to PM 2.5 during periconception (defined as 3 months before conception until 3 months into pregnancy) and risk of CHD in offspring. The study included 1 434 998 births involving 7335 CHDs from 2014 through 2017 on the basis of the National Population-Based Birth Defects Surveillance System, covering 30 provinces, municipalities, or municipal districts in China. We assigned maternal PM 2.5 exposure during the periconception period to each participant using satellite-based PM 2.5 concentrations at 1-km spatial resolution. Multilevel logistic regression models were used to calculate the multivariable-adjusted odds ratio and 95% CI for CHDs in offspring associated with maternal PM 2.5 exposure, and the exposure–response association was investigated using restricted cubic spline analysis. Subgroup or sensitivity analyses were conducted to identify factors that may modify the association. Results: The average maternal exposure to PM 2.5 levels across all participants was 56.51 μg/m 3 (range, 10.95 to 182.13 μg/m 3 ). For each 10 μg/m³ increase in maternal PM 2.5 exposure, the risk of CHDs in offspring was increased by 2% (odds ratio, 1.02 [95% CI, 1.00 to 1.05]), and septal defect was the most influenced subtype (odds ratio, 1.04 [95% CI, 1.01 to 1.08]). The effect of PM 2.5 on CHD risk was more pronounced during the preconception period. Mothers <35 years of age, those living in northern China, and those living in low-income areas were more susceptible to PM 2.5 exposure than their counterparts (all P <0.05). PM 2.5 exposure showed a linear association with total CHDs or specific CHD types. Conclusions: High maternal PM 2.5 exposure, especially during the preconception period, increases risk of certain types of CHD in offspring. These findings are useful for CHD prevention and highlight the public health benefits of improving air quality in China and other highly polluted regions.