Meta-Analysis of Risk Factors for Congenital Heart Disease: Part 2, Maternal Medication, Reproductive Technologies, and Familial and Fetal Factors

Abstract

BackgroundThe quantitative effects of congenital heart disease (CHD) risk factors are not fully understood. We conducted a meta-analysis of all CHD risk factors. This report explores maternal medication, assisted reproductive technologies (ART), and familial and fetal factors. MethodsRelevant studies were identified using a search strategy encompassing the concepts of CHD and prenatal risk factors with the following inclusion criteria: (1) peer-reviewed articles, (2) quantifying the effects of CHD risk factors, and (3) between 1989 and 2022. Pooled odds ratios (OR) and 95% confidence intervals (CIs) were calculated using a random effect model. ResultsThere were 131 articles that met the inclusion criteria. Associations were found between CHDs and extracardiac anomalies (OR, 3.41; 95% CI, 1.72-6.77), increased nuchal translucency (OR, 6.87; 95% CI, 2.42-19.53), family history of CHD (OR, 2.90; 95% CI, 2.25-3.75), maternal antidepressants (OR, 1.23; 95% CI, 1.09-1.38), and antihypertensives (OR, 2.07; 95% CI, 1.80-2.38). A positive association was observed between severe CHDs and lithium, but with a very wide CI encompassing the null effect. A positive association was observed between severe CHDs and ARTs (OR, 1.98; 95% CI, 1.30-3.02). The data were insufficient for anomalies of the umbilical cord, anticonvulsants, and retinoid medication. ConclusionsThere were strong associations among CHDs and increased nuchal translucency, extracardiac anomalies, and family history of CHD. Effect sizes were modest for maternal medication and ART. Data were scarce and sometimes inconclusive for some risk factors commonly cited as being associated with CHD such as lithium, anomalies of the umbilical cord, anticonvulsants, and retinoid medication.