Prenatal exposure to ambient air pollutants and congenital heart defects: An umbrella review

Background: Prenatal exposure to ambient air pollutants has been linked to congenital heart defects (CHD), but findings of existing systematic reviews have been mixed. Objective: To assess the epidemiological evidence on associations between prenatal exposure to ambient air pollutants and CHD subtypes, based on a systematic overview of reviews ("umbrella review"). Methods: We conducted a systematic search for reviews assessing associations between prenatal exposure to criteria air pollutants and CHD. The risk of bias was evaluated using the Risk of Bias in Systematic Reviews (ROBIS) tool. The certainty of the systematic review findings was graded using the Navigation Guide methodology. Results: We identified eleven systematic reviews, including eight with meta-analyses, assessing in total 35 primary studies of prenatal exposure to criteria air pollutants and various CHD subtypes. The certainty of the findings of four meta-analyses indicating an increased risk for coarctation of the aorta associated with nitrogen dioxide exposure was rated as moderate. The certainty of findings indicating positive, inverse, or null associations for other pollutant-subtype combinations was rated as very low to low, based on low precision and high statistical heterogeneity of summary odds ratios (SOR), substantial inconsistencies between review findings, and methodological limitations of the systematic reviews. Discussion: The inconsistent findings and high statistical heterogeneity of many SOR of the included systematic reviews may partly be traced to differences in methodological approaches, and the risk of bias across included reviews (e.g., inclusion criteria, systematic search strategies, synthesis methods) and primary studies (e.g., exposure assessment, diagnostic criteria). Adherence to appropriate systematic review guidelines for environmental health research, as well as rigorous evaluation of risk of bias in primary studies, are essential for future risk assessments and policy-making. Still, our findings suggest that prenatal exposure to ambient air pollutants may increase risks for at least some CHD subtypes.