Elucidating metabolic effects of hypoxic-ischaemic encephalopathy (HIE) may reveal
early biomarkers of injury and new treatment targets. This study uses untargeted metabolomics
to examine early metabolic alterations in a carefully defined neonatal population.
Infants with perinatal asphyxia who were resuscitated at birth and recovered (PA group),
those who developed HIE (HIE group) and healthy controls were all recruited at birth.
Metabolomic analysis of cord blood was performed using direct infusion FT-ICR mass
spectrometry. For each reproducibly detected metabolic feature, mean fold differences
were calculated HIE vs. controls (Delta HIE) and PA vs. controls (Delta PA). Putative
metabolite annotations were assigned and pathway analysis was performed. Twenty-nine
putatively annotated metabolic features were significantly different in Delta PA after
false discovery correction (q < 0.05), with eight of these also significantly altered
in Delta HIE. Altered putative metabolites included; melatonin, leucine, kynurenine
and 3-hydroxydodecanoic acid which differentiated between infant groups (Delta PA
and Delta HIE); and D-erythrose-phosphate, acetone, 3-oxotetradecanoic acid and methylglutarylcarnitine
which differentiated across severity grades of HIE. Pathway analysis revealed Delta
HIE was associated with a 50% and 75% perturbation of tryptophan and pyrimidine metabolism,
respectively. We have identified perturbed metabolic pathways and potential biomarkers
specific to PA and HIE, which measured at birth, may help direct treatment.