The association of congenital heart defects with prenatal exposure to air pollutants: An umbrella review

Abstract

Background and aim: For idiopathic congenital heart defects (CHD), air pollution during fetal development is a potential risk factor. However, findings of previous epidemiological studies and consequently of systematic reviews, have been mixed. We aimed to synthesize and evaluate the extant evidence on associations between gestational exposure to air pollutants and CHD subtypes, using a systematic review of reviews approach ("umbrella review”). Methods: We systematically searched PubMed, Embase, and Epistemonikos for published and unpublished systematic reviews. The search was supplemented by the use of internet search engines and hand-searching of reference lists. The Risk of Bias in Systematic Reviews ("ROBIS”) tool was used to evaluate included systematic reviews. Results: We identified ten systematic reviews, including eight meta-analyses. Moderately strong evidence for an increased risk of coarctation of the aorta following prenatal exposure to NO2 was provided by five reviews, which reported statistically homogeneous pooled odds ratios of 1.10 to 1.20 (95% confidence interval range: 0.99 to 1.41). Also, there was limited evidence for positive associations between SO2 and coarctation of the aorta, PM10 and atrial septal defects, NO2 and pulmonary artery and valve anomalies, and for both, PM2.5 and NO2 and Tetralogy of Fallot. Findings for other pollutant-CHD associations were inconsistent. Based on the ROBIS tool, a high or unclear risk of bias rating was assigned to eight out of ten reviews. Conclusion: Beyond the increased risk of coarctation of the aorta following exposure to NO2, a clear pollutant-outcome pattern was not identified. These incoherent findings may partly be explained by differences in methods used across the reviews (e.g., inclusion criteria) as well as between individual studies (e.g., exposure and outcome assessment methods). Further establishment of and adherence to systematic review methods for environmental exposures and children’s health may improve the validity and consistency of future systematic review findings.