Abstract
BACKGROUND: Studies show that an impaired maternal-fetal environment (iMFE) increases the mortality risk in children with single-ventricle congenital heart defects (CHDs). We investigated the impact of an iMFE on death in children with various surgically corrected CHDs. METHODS AND RESULTS: In this nationwide register-based study, we examined the association between an iMFE (including preeclampsia, gestational hypertension, gestational diabetes, maternal smoking during pregnancy) and death in a large cohort of children with surgically corrected CHDs in Denmark (1994-2018). Survival analysis was done using Cox regression, adjusted for confounding and mediating covariates. The cohort included 3304 children: 1662 (50.3%) with minor CHD and 1642 (49.7%) with major CHD. Among them, 792 (24%) children were exposed to an iMFE. During the study, there were 290 deaths: 71 (9.3%) in children exposed to an iMFE and 219 (8.7%) in those unexposed. There were no differences in mortality risk between children with CHD exposed to an iMFE and those unexposed (hazard ratio [HR], 1.12 [95% CI, 0.86-1.47]; P=0.4). This was consistent across subgroups, including minor CHD (HR, 0.76 [95% CI, 0.39-1.47]; P=0.4), major CHD (HR, 1.23 [95% CI, 0.92-1.64]; P=0.2), and hypoplastic left heart syndrome/univentricular heart (HR, 1.08 [95% CI, 0.64-1.85]; P=0.8). CONCLUSIONS: Impairment of the maternal-fetal environment did not impact the mortality rate in children with CHD undergoing operation in Denmark from 1994 to 2018. We believe the cause of these discrepant findings to previous studies may be due to differences in the composition of CHD and prenatal maternal health care and health status of the population.