| Summary: | Background: The TOBY-Xe proof of concept randomised trial found no effect of xenon combined with hypothermia after birth asphyxia on the lactate to N-acetyl aspartate ratio (Lac/NAA) in the thalamus and fractional anisotropy (FA) in white matter tracts measured within 15 days of birth. To confirm that these biomarkers are qualified to predict long-term outcome after neural rescue therapy we assessed surviving participants at 2–3 years of age. Methods: Of the 92 infants in TOBY-Xe, one was omitted from the study, 69 survived and we assessed 62 participants, 32 in the hypothermia and xenon and 30 in the hypothermia only groups. We examined the relation between Lac/NAA and FA and the scores of the Bayley Scales of Infant and Toddler Development III and calculated their predictive accuracy for moderate or severe disability or death. Results: Fifteen of 62 participants (24%) developed moderate/severe disability, and 22/92 (24%) died.The Lac/NAA ratio (difference in medians 0.628, 95% CI -0.392 to 4.684) and FA (difference in means −0.055, 95% CI -0.033 to −0.077) differed significantly between participants with or without moderate or severe disability or death and were significantly related with development scores in both groups. Adverse outcomes were correctly identified in 95.65% of cases by Lac/NAA and 78.79% by FA, with adequate mean calibration of the model. Interpretation: The results confirm the qualification of the cerebral magnetic resonance biomarkers employed in the TOBY-Xe study as predictors of outcome after neuroprotective therapy. Fund: The Centre for the Developing Brain, King's College London, UK. Keywords: Encephalopathy, Asphyxia, Biomarkers, Magnetic resonance spectroscopy, Magnetic resonance tensor imaging, Perinatal brain injury
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