Maternal Cardiac Disease and Congenital Heart Disease Risk in Offspring

Maternal adult congenital heart disease (ACHD) has been associated with increased offspring congenital heart disease (CHD), but evidence from resource-limited regions remains scarce. The association between maternal acquired heart disease (AHD) and offspring CHD is unknown.

To quantify the overall and subtype-specific CHD risk in offspring associated with maternal ACHD and AHD, examine the association of maternal ACHD and AHD with outcomes in offspring with CHD, and identify maternal factors that may modify the associations between maternal cardiac diseases and offspring CHD risk.

This prospective birth cohort study enrolled pregnant women receiving prenatal care between August 1, 2011, and December 31, 2021, at a major cardiac referral center in China. Participants included pregnant women with ACHD, with AHD, or without cardiac disease and were followed up through delivery; their offspring were followed up until 1 year of age. All follow-ups were completed by December 15, 2023. Data were analyzed from April 1, 2024, through April 31, 2025.

Maternal ACHD and AHD, confirmed via the center's electronic medical records.

The main outcome was offspring CHD, which was diagnosed using echocardiography. Log-binomial regression was used to estimate relative risks (risk ratios [RRs]) and 95% CIs. Adverse outcomes were compared using pairwise tests. Stratification analyses identified potential effect modifiers.

A total of 14 336 pregnant women with 15 677 offspring (8480 males [54.1%]) were included. The mean (SD) maternal age and gestational age at enrollment were 31.4 (4.5) years and 16.4 (6.4) weeks, respectively. Both maternal ACHD and AHD were associated with higher CHD risk in offspring (RR, 1.71 [95% CI, 1.26-2.31] and 1.38 [95% CI, 1.02-1.87], respectively). Minor CHDs, particularly septal defects, were the subtypes with the greatest magnitude of associations with maternal ACHD (RR, 2.95; 95% CI, 1.97-4.43) and AHD (RR, 2.28; 95% CI, 1.50-3.45). Right ventricular outflow tract obstruction (RR, 6.17; 95% CI, 3.59-10.60) and valvular heart disease (RR, 1.65; 95% CI, 1.11-2.45) were the key contributors to offspring CHD risk. Preterm birth had higher rates among offspring with CHD and mothers with ACHD as well as offspring with CHD and mothers without ACHD compared with offspring without CHD and mothers without cardiac disease (12 of 39 [30.8%] and 121 of 780 [15.5%] vs 1287 of 14 088 [9.1%]; all P < .001). Higher rates of chromosomal (5 of 39 [12.8%] and 38 of 780 [4.9%] vs 75 of 14 088 [0.5%]; all P < .001) and genetic aberrations (3 of 39 [7.7%] and 16 of 780 [2.1%] vs 57/14 088 [0.4%]; all P < .001) were found among offspring with CHD and mothers with AHD as well as offspring with CHD and mothers without AHCD compared with offspring without CHD and mothers without cardiac disease. Associations between maternal cardiac disease and offspring CHD were robust in primiparous women (ACHD: RR, 2.15 [95% CI, 1.48-3.11], P for interaction < .001; AHD: RR, 1.73 [95% CI, 1.17-2.56], P for interaction = .02) and those with periconceptional exposure to hazardous substances (ACHD: RR, 2.22 [95% CI, 1.56-3.16], P for interaction < .001; AHD: RR, 1.57 [95% CI, 1.05-2.36], P for interaction = .02).

In this cohort study, maternal ACHD and AHD were associated with increased risks and adverse outcomes of offspring CHD. Targeted modification of identified maternal factors could help mitigate offspring CHD risk in this high-risk population.