Critical Congenital Heart Disease Beyond HLHS and TGA: Neonatal Brain Injury and Early Neurodevelopment

BACKGROUND: Characterization of brain injury and neurodevelopmental (ND) outcomes in critical congenital heart disease (cCHD) has primarily focused on hypoplastic left heart syndrome (HLHS) and transposition of the great arteries (TGA). This study reports brain injury and ND outcomes among patients with heterogeneous cCHD diagnoses beyond HLHS and TGA. METHODS: This prospective cohort study included infants with HLHS, TGA, or heterogenous “Other cCHD” including left- or right-sided obstructive lesions, anomalous pulmonary venous return, and truncus arteriosus. Brain injury on perioperative brain MRI and ND outcomes on the Bayley-II at 30 months were compared. RESULTS: A total of 218 participants were included (HLHS=60; TGA=118; “Other cCHD”=40, including 8 with genetic syndromes). Pre-operative (n=209) and post-operative (n=189) MRI showed similarly high brain injury rates across groups, regardless of cardiopulmonary bypass exposure. At 30 months, participants with “Other cCHD” had lower cognitive scores (p=0.035) compared to those with HLHS and TGA, though worse ND outcome in this group was driven by those with genetic disorders. CONCLUSION: Frequency of brain injury and neurodevelopmental delay among patients with “Other cCHD” is similar to those with HLHS or TGA. Patients with all cCHD lesions are at risk for impaired outcomes; developmental and genetic screening is indicated.