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Individualized brain development and cognitive outcome in infants with congenital heart disease
Alexandra F Bonthrone1, Ralica Dimitrova1,2, Andrew Chew1
1Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, London SE1 7EH, UK.
Insights
Infants with congenital heart disease often experience neurodevelopmental issues. This study found that smaller grey matter volumes in newborns with congenital heart disease correlate with poorer cognitive abilities later on, possibly due to reduced cerebral oxygen delivery.
Area of Science:
- Neuroscience
- Pediatrics
- Medical Imaging
Background:
- Infants with congenital heart disease (CHD) are susceptible to neurodevelopmental impairments.
- The underlying causes of these impairments, particularly the interplay between brain development and oxygenation, remain unclear.
Purpose of the Study:
- To investigate the relationship between neonatal brain development, cerebral oxygen delivery, and neurodevelopmental outcomes in infants with CHD.
- To characterize how brain volume deviations and oxygen delivery impact cognitive and motor abilities.
Main Methods:
- Brain MRI was performed on infants with serious or critical CHD before surgery to assess brain volumes.
- Normative brain development curves were generated using data from healthy infants.
- Atypicality indices were calculated to quantify deviations from typical brain development.
- Cerebral oxygen delivery was measured using phase contrast angiography.
- Cognitive and motor abilities were assessed at 22 months using the Bayley Scales of Infant and Toddler Development.
Main Results:
- Negative atypicality indices in deep grey matter were linked to reduced cerebral oxygen delivery and poorer cognitive function at 22 months.
- In term-born infants with CHD, smaller cortical grey matter and total tissue volumes also correlated with poorer cognition.
- Cerebral oxygen delivery indirectly influenced cognition through its effect on deep grey matter volume.
Conclusions:
- Lower cognitive abilities in toddlers with CHD are associated with reduced grey matter volumes detected before surgery.
- Impaired cerebral oxygen delivery may lead to diminished grey matter growth, contributing to cognitive deficits.
- Interventions aimed at improving cerebral oxygen delivery could potentially enhance early brain growth and improve cognitive outcomes in infants with CHD.
Abstract:
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.
