Most Congenital Heart Disease (CHD) arises from combined genetic and environmental influences, with emerging data suggesting polygenic inheritance in complex phenotypes. This linked-data study published in the Maternal and Child Health Journal examined associations between prenatal factors, maternal chronic health conditions and CHD severity. Patients from the Kids Heart BioBank (n = 2,389) were linked to the NSW Perinatal Data

Collection and the NSW Admitted Patient Data Collection. CHD cases were stratified by severity: complex CHD requiring neonatal intervention (n = 581) and other CHD requiring intervention after the neonatal period (n = 1,808). Healthy controls (n = 58,624) were included for comparison. Prenatal factors and maternal chronic conditions were coded using ICD-10-AM classifications. Analyses were adjusted for socioeconomic status, smoking, maternal age at pregnancy, gestational age and year of birth.

Preexisting diabetes mellitus (p = 0.003) and urinary tract infections (p = 0.01) were significantly increased in mothers of infants with complex CHD compared with other CHD. In contrast, circulatory system disorders (p = 0.01) and preeclampsia/gestational hypertension (p = 0.06) were reduced in mothers of infants with complex CHD compared with other CHD. These associations persisted after adjustment for confounders.

The findings suggest an important role for prenatal factors and maternal chronic health conditions in CHD severity. Results align with polygenic models incorporating environmental contributors to complex disease expression.