Association between gestational exposure and risk of congenital heart disease: A systematic review and meta-analysis

Environ Res. 2021 Jun:197:111014. doi: 10.1016/j.envres.2021.111014. Epub 2021 Mar 11.


Congenital heart disease (CHD) is the most common congenital anomaly and one of the leading causes of newborn death. Few studies analyze multiple ambient air pollutants and different congenital heart disease subtypes at the same time. We conducted a meta-analysis to explore the association between gestational air pollution exposure and CHD subtypes. We searched PubMed, Embase, Web of Science from inception till July 31, 2020. Newcastle Ottawa Scale (NOS) was used to evaluate the quality of the literature. Funnel plots and Egger's regression were used to estimate publication bias. Heterogeneity was evaluated by the chi-square test and the coefficient of inconsistency I2 in this study. Finally, we performed a subgroup analysis to find reasons for heterogeneity. In the preliminary analysis, the result shows that the association between air pollutants and congenital heart disease was not statistically significant, except for CO and SO2. There is a positive association between air pollutants and ventricular septal defect (VSD) in our subtype analysis, the OR (95%CI) for PM10, PM2.5, and O3 was 1.057(1.005-1.109), 1.208(1.080-1.337), and 1.205(1.101-1.310), respectively. In addition, we also observed a negative association between SO2 and atrial septal defect (ASD) (OR: 0.817, 95%CI: 0.743-0.890) in subgroup analysis. The source of heterogeneity in our study mainly included study area and exposure time. These findings have implications for researchers to further study the relationship between air pollution and congenital heart disease.

Keywords: Air pollution; Congenital heart disease; Gestational exposure; Meta-analysis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Air Pollutants* / analysis
  • Air Pollutants* / toxicity
  • Air Pollution* / adverse effects
  • Air Pollution* / analysis
  • Environmental Exposure / adverse effects
  • Environmental Exposure / analysis
  • Heart Defects, Congenital* / chemically induced
  • Heart Defects, Congenital* / epidemiology
  • Humans
  • Infant, Newborn
  • Particulate Matter / analysis
  • Particulate Matter / toxicity


  • Air Pollutants
  • Particulate Matter