Background and aims The outcome of infants with severe hypoxic-ischaemic encephalopathy (HIE) remains extremely poor. Early identification of these infants could improve patient management and direct care. Our aim was to correlate the metabolomic profile of umbilical cord blood (UCB) with outcome in neonatal HIE.

Methods Full term infants with perinatal asphyxia and healthy matched controls were recruited from 2009 to 2011. All had UCB biobanked at -80°C within 3 h of birth and multichannel electroencephalogram (EEG) recorded in the first 24 h of life. The metabolite profile of UCB was analysed using nuclear magnetic resonance (NMR) spectroscopy. Infant outcome was assessed using the Bayley Scales of Infant and Toddler development at 3 years.

Results The UCB metabolomic profile of 118 infants was described; 59 healthy controls, 34 perinatal asphyxia (no HIE) and 25 HIE defined by Sarnat score and EEG (13 mild, 6 moderate, 6 severe). Of the 6 cases of severe HIE, at 3 years; 4 have died, 1 survived with severe dyskinetic cerebral palsy and 1 had a normal outcome. A characteristic pattern of raised glycerol + succinate occurred in those infants with severe encephalopathy and very low voltage EEG (R² = 0.49, p < 0.001).

Conclusion Alterations in glycerol and succinate at birth reflect critical energy failure in infants with severe neuronal injury. This measurement at birth could help clinicians to identify infants who will not benefit from standard neuroprotection and may need experimental intervention, or limitation of care.