Brain volumes and functional outcomes in children without cerebral palsy after therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy.

Abstract

To investigate whether brain volumes were reduced in children aged 6 to 8 years without cerebral palsy, who underwent therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy (patients), and matched controls, and to examine the relation between subcortical volumes and functional outcome. We measured regional brain volumes in 31 patients and 32 controls (median age 7 years and 7 years 2 months respectively) from T1-weighted magnetic resonance imaging (MRI). We assessed cognition using the Wechsler Intelligence Scales for Children, Fourth Edition and motor ability using the Movement Assessment Battery for Children, Second Edition (MABC-2). Patients had lower volume of whole-brain grey matter, white matter, pallidi, hippocampi, and thalami than controls (false discovery rate-corrected p < 0.05). Differences in subcortical grey-matter volumes were not independent of total brain volume (TBV). In patients, hippocampal and thalamic volumes correlated with full-scale IQ (hippocampi, r=0.477, p=0.010; thalami, r=0.452, p=0.016) and MABC-2 total score (hippocampi, r=0.526, p=0.004; thalami, r=0.505, p=0.006) independent of age, sex, and TBV. No significant correlations were found in controls. In patients, cortical injury on neonatal MRI was associated with reduced volumes of hippocampi (p=0.001), thalami (p=0.002), grey matter (p=0.015), and white matter (p=0.013). Children who underwent therapeutic hypothermia have reduced whole-brain grey and white-matter volumes, with associations between hippocampal and thalamic volumes and functional outcomes.