The cumulative impact of clinical risk on brain networks and associations with executive function impairments in adolescents with congenital heart disease

Congenital heart disease (CHD) is known to negatively affect brain development. Individual clinical factors have been identified to contribute to this detrimental effect, however, the cumulative effect of these factors on brain development and neurodevelopmental outcomes are not fully understood. Our study utilized structural brain connectomics as an indicator of brain development to investigate the potential combined impact of clinical risk factors and family-environmental factors in adolescents with CHD. We developed a cumulative clinical risk (CCR) score by summing up binary risk factors (neonatal, cardiac, neurologic) based on clinically relevant thresholds and further investigated the role of family-environmental factors (parental education, parental mental health, and family function). Brain development in 53 adolescents with CHD who underwent infant open-heart surgery, and 75 healthy controls was studied by diffusion MRI connectomic analysis and neuropsychological assessments. The CCR score explains a great variability of the structural brain connectome. A higher CCR score was associated with lower network segregation, edge strength, and executive functioning. Edge strength was particularly reduced in an inter-frontal and fronto-parietal-thalamic network. There was no association with family-environmental factors. Poorer executive functioning was associated with lower network integration and segregation. Our results provide evidence for persisting alterations of network connectivity in adolescents with CHD – particularly in those patients who face a cumulative exposure to multiple clinical risk over time. Quantifying the cumulative load of risk early in life, may help to better predict trajectories of brain development in order to identify and support the most vulnerable patients as early as possible.