Infants with
congenital heart disease are at risk of neurodevelopmental impairments, the origins of which are currently unclear. This study aimed to characterize the relationship between neonatal brain development, cerebral
oxygen delivery and neurodevelopmental outcome in infants with
congenital heart disease. A cohort of infants with serious or critical
congenital heart disease (N = 66; N = 62 born ≥37 weeks) underwent brain MRI before surgery on a 3T scanner situated on the neonatal unit. T2-weighted images were segmented into brain regions using a neonatal-specific algorithm. We generated normative curves of typical volumetric brain development using a data-driven technique applied to 219 healthy infants from the Developing Human Connectome Project (dHCP). Atypicality indices, representing the degree of positive or negative deviation of a regional volume from the normative mean for a given gestational age, sex and postnatal age, were calculated for each infant with
congenital heart disease. Phase contrast angiography was acquired in 53 infants with
congenital heart disease and cerebral
oxygen delivery was calculated. Cognitive and motor abilities were assessed at 22 months (N = 46) using the Bayley scales of Infant and Toddler Development-Third Edition. We assessed the relationship between atypicality indices, cerebral
oxygen delivery and cognitive and motor outcome. Additionally, we examined whether cerebral
oxygen delivery was associated with neurodevelopmental outcome through the mediating effect of brain volume. Negative atypicality indices in deep grey matter were associated with both reduced neonatal cerebral
oxygen delivery and poorer cognitive abilities at 22 months across the whole sample. In infants with
congenital heart disease born ≥37 weeks, negative cortical grey matter and total tissue volume atypicality indices, in addition to deep grey matter structures, were associated with poorer cognition. There was a significant indirect relationship between cerebral
oxygen delivery and cognition through the mediating effect of negative deep grey matter atypicality indices across the whole sample. In infants born ≥37 weeks, cortical grey matter and total tissue volume atypicality indices were also mediators of this relationship. In summary, lower cognitive abilities in toddlers with
congenital heart disease were associated with smaller grey matter volumes before cardiac surgery. The aetiology of poor cognition may encompass poor cerebral
oxygen delivery leading to impaired grey matter growth. Interventions to improve cerebral
oxygen delivery may promote early brain growth and improve cognitive outcomes in infants with
congenital heart disease.