Retrospective Analysis of Congenital Heart Disease in Saudi Arabian Children Born to Consanguineous Parents: Outcomes and Risk Factors from 2021 to 2025

Abstract Background: Congenital heart disease (CHD) is the most common birth defect in Saudi Arabia, with a notable link to parental consanguinity. This study aimed to assess the prevalence, patterns, outcomes and genetic risk factors of CHD in Saudi children (0–5 years) born to consanguineous parents between January 2021 and January 2025. Methods: A retrospective cohort of 7842 children diagnosed with CHD across 14 tertiary care centres in five regions were analysed. Data included clinical, demographic, genetic and outcome variables. Genetic testing for NKX2.5, GATA4 and TBX5 mutations was performed on 3216 patients. Statistical models identified predictors of CHD severity and adverse outcomes. Results: CHD prevalence was 8.7 per 1000 live births, rising to 12.3 per 1000 in first-cousin unions (adjusted odds ratio [OR]: 2.14, P < 0.001). Common CHD types included ventricular septal defects (28.3%), atrial septal defects (19.7%) and tetralogy of Fallot (11.2%). Pathogenic variants in NKX2.5, GATA4 and TBX5 significantly increased CHD risk. The overall 5-year survival rate was 87.3%, with early surgical intervention improving outcomes (HR: 0.62). Conclusions: Consanguinity and genetic mutations significantly contribute to CHD risk. Targeted public health measures, genetic counselling and early interventions are essential to improving outcomes and reducing the CHD burden in high-risk populations.