Systematic review and meta-analysis of prenatal risk factors for congenital heart disease: maternal chronic diseases and parental exposures.

Abstract

BackgroundThere is considerable heterogeneity in studies on prenatal risk factors for congenital heart diseases (CHDs). We performed a meta-analyse of all non-genetic factors of CHDs. This report presents results of factors related to maternal chronic diseases and parental exposures. MethodsA systematic search encompassing concepts of CHD and risk factors was used, using the following inclusion criteria: (1) original peer-reviewed articles, (2) quantifying the effects of risk factors for CHDs, (3) between 1989 and 2022. Pooled odds ratios (OR) and 95% confidence interval (CI) were calculated using a random effect model. ResultsInclusion criteria were met for 170 studies. There was an association between being overweight/obese and CHDs (OR 1.26; 95% CI 1.15-1.37), with a dose-effect relationship. Pregestational diabetes (PGDM) was associated with CHDs (OR 3.51; 95% CI 2.86-4.3), without difference between type I and type II PGDM. The effect size of gestational diabetes was less than that of PGDM (OR 1.38;95% CI: 1.18-1.61). There was an association between CHDs and preeclampsia (OR 2.01; 95% CI 1.32-3.05), and paternal smoking (OR 1.32; 95% CI 1.03-1.70) and alcohol use (OR 1.50; 95%CI 1.08-2.08). A smaller association was found with maternal smoking and advanced maternal age. ConclusionsThere exists robust evidence for increased risk of CHD in the presence of obesity, maternal diabetes, maternal smoking and increased maternal age. The effect sizes were relatively modest, except for PGDM. The robustness of the evidence decreased when CHDs were divided into subgroups, or when the analyses were restricted to severe CHDs.