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

AIM: 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. METHOD: 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). RESULTS: 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). INTERPRETATION: Children who underwent therapeutic hypothermia have reduced whole‐brain grey and white‐matter volumes, with associations between hippocampal and thalamic volumes and functional outcomes.