ArticleEBioMedicine2019
Prospective qualification of early cerebral biomarkers in a randomised trial of treatment with xenon combined with moderate hypothermia after birth asphyxia.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 3 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 3 syntheses or guidelines pooled it, 32 citations in OpenAlex.
- Neonatal encephalopathy: a systematic review of reported treatment outcomes.BMJ paediatrics open · 2024Pooled it
- Comparison of Different Adjuvant Therapies for Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy: A Systematic Review and Network Meta-Analysis.Indian journal of pediatrics · 2024Pooled it
- Efficacy of melatonin in term neonatal models of perinatal hypoxia-ischaemia.Annals of clinical and translational neurology · 2022Pooled it
- MRI and proton MR spectroscopy in neonatal hypoxic-ischemic encephalopathy: a comprehensive imaging review.Japanese journal of radiology · 2026Review
- A reduction in large animal research threatens the perinatal translation research pipeline.Pediatric research · 2026Review
- Magnetic resonance imaging and spectroscopy in neonatal encephalopathy: current consensus position and future opportunities.Pediatric research · 2026Review
- Neonatal encephalopathy and hypoxic-ischemic encephalopathy: the state of the art.Pediatric research · 2025Review
- Article
- Stay cool and keep moving forwards.Pediatric research · 2025Article
- [Research research on the use of melatonin in combination with therapeutic hypothermia for the treatment of neonatal hypoxic-ischemic encephalopathy].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2023Review
- The persistent effects of anaesthesia on the brain.BJA education · 2023Review
- Comparing the efficacy in reducing brain injury of different neuroprotective agents following neonatal hypoxia-ischemia in newborn rats: a multi-drug randomized controlled screening trial.Scientific reports · 2023Article
- Hypothermia combined with neuroprotective adjuvants shortens the duration of hospitalization in infants with hypoxic ischemic encephalopathy: Meta-analysis.Frontiers in pharmacology · 2022Review
- Melatonin for Neonatal Encephalopathy: From Bench to Bedside.International journal of molecular sciences · 2021Review
- Melatonin and/or erythropoietin combined with hypothermia in a piglet model of perinatal asphyxia.Brain communications · 2021Article
- White matter injury after neonatal encephalopathy is associated with thalamic metabolite perturbations.EBioMedicine · 2020Article
- Proton Magnetic Resonance Spectroscopy Lactate/N-Acetylaspartate Within 48 h Predicts Cell Death Following Varied Neuroprotective Interventions in a Piglet Model of Hypoxia-Ischemia With and Without Inflammation-Sensitization.Frontiers in neurology · 2020Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe 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.
methodsOf 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.
resultsFifteen 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.
interpretationThe 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.
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