PERSPECTIVE article
Front. Neurol.
Sec. Neurotrauma
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1620178
Selecting outcome measures to validate prognostic biomarkers of paediatric mild traumatic brain injury: challenges and priorities
Provisionally accepted
Jonathan E Attwood1,2*
Izabelle Lövgren1,3
Rob Forsyth4Célia Demarchi5,6
Tony Thayanandan7
Lara Prisco1,2
Mario Ganau1,2Rebecca Roberts2Kate Scarff2Julia L Newton2
Gabriele Carmine DeLuca1,2Tim Lawrence1,2- 1Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, United Kingdom
- 2Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
- 3Podium Institute for Sports Medicine and Technology, Department of Engineering Science, University of Oxford, Oxford, United Kingdom
- 4Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
- 5Department of Brain Sciences, Imperial College London, London, United Kingdom
- 6Children’s Neurosciences, Evelina London Children’s Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom
- 7Department of Psychiatry, University of Oxford, Oxford, United Kingdom
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Outcomes following paediatric mild traumatic brain injury (mTBI) are extremely heterogenous. While emerging biomarkers promise enhanced prognostic accuracy, a critical question remains unanswered -which outcome measures provide the most accurate assessment of injury impact? In this article, we highlight barriers to selecting appropriate outcome measures, including variability in how outcomes are defined and the wide range of assessment tools used. With reference to the most recent literature, we summarise current evidence of adverse outcomes following paediatric mTBI and highlight emerging candidate biomarkers of these outcomes. We emphasise the unique challenges associated with interpreting outcome measures in younger patients, from the impact of developmental stage and assessment timing to the influence of injury-independent factors. We assert the need to consider these obstacles when designing and interpreting mTBI biomarker studies. To realise the potential of prognostic biomarkers, future research should prioritise establishing consensus definitions, compiling a set of accessible and comprehensive outcome measures, and capturing injury-independent factors through longitudinal study designs.
Keywords: Prognostic biomarkers, Validation, Outcomes Assessment, neurodevelopment, paediatric mild traumatic brain injury
Received: 29 Apr 2025; Accepted: 08 Jul 2025.
Copyright: © 2025 Attwood, Lövgren, Forsyth, Demarchi, Thayanandan, Prisco, Ganau, Roberts, Scarff, Newton, DeLuca and Lawrence. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jonathan E Attwood, Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, United Kingdom
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