Risk assessment of congenital heart defects based on maternal factors in early pregnancy—a systematic review and meta-analysis

Congenital heart defect (CHD) is a leading cause of neonatal mortality, with early maternal risk factors playing a significant role in its development. This systematic review and meta-analysis investigated the relationship between maternal factors during the first trimester and CHD. The study protocol was registered on PROSPERO (CRD42023476855). MEDLINE, Embase, and Cochrane TRIALS were systematically searched for eligible cohort and case-control studies. The primary outcome was the risk of the fetus developing CHD under the effects of maternal factors. The outcome was estimated by odds ratios (ORs) and 95% confidence interval (CI) using the random-effects model. Seventy-eight studies with 393 534 cases and 29 493 495 controls were included. Maternal pre-pregnancy diabetes (OR 2.91, 95% CI 2.10-4.03), obesity (OR 1.23, 95% CI 1.13-1.33), active (OR 1.28, 95% CI 1.03-1.57) and passive smoking (OR 2.67, 95% CI 1.30-5.46), and chronic hypertension (OR1.39, 95% CI 1.02-1.90) significantly increased the risk of overall CHD in offspring. While underweight was not associated with overall CHD, it showed a slight association with ventricular septal defect (OR 1.10, 95% CI 1.02-1.18). These findings emphasize the importance of optimizing maternal health and lifestyle before and during pregnancy and provide evidence for public health strategies to reduce the risk of CHD.