RESUMEN
BACKGROUND: The 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. METHODS: Relevant 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, (3) between 1989 and 2022. Pooled odds ratios (OR) and 95% confidence interval (CI) were calculated using a random effect model. RESULTS: 131 articles 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. CONCLUSION: There were strong associations between CHDs and increased nuchal translucency, extracardiac anomalies and family history of CHD. Effect sizes were modest for maternal medication and ART. Data was 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.
RESUMEN
BACKGROUND: There is considerable heterogeneity in studies on prenatal risk factors for congenital heart diseases (CHDs). We performed a meta-analysis of all nongenetic factors of CHDs. This report presents results of factors related to maternal chronic diseases and parental exposures. METHODS: A 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 (ORs) and 95% confidence interval (CI) were calculated using a random-effect model. RESULTS: Inclusion criteria were met for 170 studies. There was an association between being overweight or 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 1 and type 2 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 pre-eclampsia (OR, 2.01; 95% CI, 1.32-3.05), 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. CONCLUSIONS: There 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.