Early brain development in infants born with congenital heart disease

Student thesis: Doctoral ThesisDoctor of Philosophy


Improving neurodevelopmental outcomes has become one of the biggest remaining challenges for infants born with congenital heart disease (CHD). Despite a dramatic reduction in CHD mortality over the past few decades, there have been comparatively modest improvements in neurodevelopmental outcomes. The burden of the problem is significant, affecting a wide range of developmental domains that impact upon future educational achievement, employability and quality of life for millions of children born with CHD. While it was initially assumed that adverse outcomes were due to brain injury sustained around the time of cardiac surgery, it is now clear that there is a complex interplay between the circulation and brain, involving both fetal and postnatal development. Promising early work has suggested the role of reduced cerebral oxygenation as a key factor in altered early brain development in CHD, although the precise mechanisms through which this is mediated remain unclear.
This thesis aims to test the hypotheses that congenital heart disease is associated with impaired early brain development, and that reduced cerebral oxygen delivery in CHD is associated with impaired cortical development in newborn infants prior to surgery. This is achieved through the study of a new prospective cohort of newborn infants born with major CHD prior to surgery, and the use of both qualitative and quantitative magnetic resonance image analysis of brain tissue macrostructure and microstructure, in order to compare early brain development with age-matched healthy infants.
Evidence is provided that complexity of cortical folding and cortical grey matter volumes are both reduced in newborns with CHD when compared to healthy age-matched controls, and that the degree of impairment is associated with reduced cerebral oxygen delivery. At the microstructural level, fractional anisotropy (FA) is demonstrated to be elevated and cortical orientation dispersion index (ODI) reduced in a number of cortical regions compared to healthy controls, supporting the interpretation that dendritic arborisation in cortical grey matter may be the primary component that is negatively affected. Both findings are convergent with recent animal studies and provide support to the development of future interventional strategies to optimise cerebral oxygenation during early brain development.
Date of Award2018
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorSerena Counsell (Supervisor) & Mary Rutherford (Supervisor)

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