Association Between Maternal Hepatitis B Virus Infection and Risk of Cyanotic Congenital Heart Defects in Offspring

Background Maternal hepatitis B virus (HBV) infection has been linked to adverse perinatal outcomes, including congenital anomalies. However, most studies have examined overall congenital heart disease (CHD) without distinguishing subtypes, often including conditions like patent ductus arteriosus that may resolve spontaneously. Clinically severe cyanotic CHDs, which rarely resolve without intervention, have not been specifically assessed. Objective To investigate the association between maternal pre-pregnancy HBV infection and the risk of cyanotic congenital heart defects in offspring using a large, population-based dataset. Methods This retrospective cohort study utilized data from the US National Vital Statistics System from 2021 to 2023. All live births were included. Mothers with pre-pregnancy HBV infection (n = 15,697) were matched 1:4 to uninfected controls (n = 62,788) using propensity score matching based on maternal and neonatal characteristics. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for cyanotic CHDs as the primary outcome and overall congenital anomalies as the secondary outcome. Sensitivity analyses were conducted using 1:1 and 1:2 matching ratios. Results Cyanotic CHDs were identified in 15 of 15,697 infants (0.096%) born to HBV-infected mothers and in 40 of 62,788 infants (0.064%) in the control group (OR, 1.50; 95% CI, 0.83–2.72). Overall congenital anomalies occurred in 50 infants (0.32%) in the HBV group and in 174 infants (0.28%) in the control group (OR, 1.15; 95% CI, 0.84–1.58). Findings were consistent across all sensitivity analyses, with no statistically significant associations observed. Conclusions The association between maternal pre-pregnancy HBV infection and cyanotic CHD in offspring was not statistically significant.