Brain volumes in congenital heart disease from childhood to adulthood: A pooled neuroimaging study

Complex congenital heart disease (CHD) is associated with reduced brain volumes, but little is known about the brain developmental trajectory in CHD beyond childhood, which is a critical period for brain maturation. This study reports alterations in brain volumes from a large cross-sectional dataset of patients with CHD and controls, with an age range from childhood to young adulthood. Patients and controls underwent 3 T cerebral MRI and overlapping cognitive assessments. Images were processed using Freesurfer 5.3. The dataset comprised 311 participants, 128 CHD and 183 controls aged between 9 and 32 years (male: 52.1%). Associations between the total brain and grey matter, white matter, and cerebrospinal fluid (CSF) volumes and age, sex, group (CHD vs. controls) and maternal education were analysed using linear mixed models. Global and total grey/white matter volumes were smaller in patients with CHD compared to controls ( p < 0.001), whereas CSF volumes did not differ significantly between groups ( p = 0.23). No significant interaction between the group, sex and age was found. Larger global brain volume was associated with higher maternal education ( p < 0.001) and higher IQ ( p < 0.001). Consistent lower brain volume in CHD than in controls throughout childhood and young adulthood suggests that there is no convergence towards healthy peers in CHD brain volumes over time. Functional correlates of smaller brain volumes underscore the importance of longitudinal studies in better understanding the evolution and determinants of impaired brain development in CHD populations.