Selecting outcome measures to validate prognostic biomarkers of paediatric mild traumatic brain injury: challenges and priorities

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 highli...

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Main Authors: Jonathan E. Attwood, Izabelle Lövgren, Rob Forsyth, Célia Demarchi, Tony Thayanandan, Lara Prisco, Mario Ganau, Rebecca Roberts, Kate Scarff, Julia L. Newton, Gabriele C. DeLuca, Tim Lawrence
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Neurology
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Online Access:https://www.frontiersin.org/articles/10.3389/fneur.2025.1620178/full
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author Jonathan E. Attwood
Jonathan E. Attwood
Izabelle Lövgren
Izabelle Lövgren
Rob Forsyth
Célia Demarchi
Célia Demarchi
Tony Thayanandan
Lara Prisco
Lara Prisco
Lara Prisco
Mario Ganau
Mario Ganau
Rebecca Roberts
Kate Scarff
Julia L. Newton
Gabriele C. DeLuca
Gabriele C. DeLuca
Tim Lawrence
Tim Lawrence
author_facet Jonathan E. Attwood
Jonathan E. Attwood
Izabelle Lövgren
Izabelle Lövgren
Rob Forsyth
Célia Demarchi
Célia Demarchi
Tony Thayanandan
Lara Prisco
Lara Prisco
Lara Prisco
Mario Ganau
Mario Ganau
Rebecca Roberts
Kate Scarff
Julia L. Newton
Gabriele C. DeLuca
Gabriele C. DeLuca
Tim Lawrence
Tim Lawrence
author_sort Jonathan E. Attwood
collection DOAJ
description 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.
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language English
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publisher Frontiers Media S.A.
record_format Article
series Frontiers in Neurology
spelling doaj-art-2c04326514f545899a7b8051bc125d642025-08-20T02:40:48ZengFrontiers Media S.A.Frontiers in Neurology1664-22952025-07-011610.3389/fneur.2025.16201781620178Selecting outcome measures to validate prognostic biomarkers of paediatric mild traumatic brain injury: challenges and prioritiesJonathan E. Attwood0Jonathan E. Attwood1Izabelle Lövgren2Izabelle Lövgren3Rob Forsyth4Célia Demarchi5Célia Demarchi6Tony Thayanandan7Lara Prisco8Lara Prisco9Lara Prisco10Mario Ganau11Mario Ganau12Rebecca Roberts13Kate Scarff14Julia L. Newton15Gabriele C. DeLuca16Gabriele C. DeLuca17Tim Lawrence18Tim Lawrence19Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United KingdomOxford University Hospitals NHS Foundation Trust, Oxford, United KingdomNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United KingdomThe Podium Institute for Sports Medicine and Technology, Department of Engineering Science, University of Oxford, Oxford, United KingdomTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United KingdomDepartment of Brain Sciences, Imperial College London, London, United KingdomChildren’s Neurosciences, Evelina London Children’s Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, United KingdomDepartment of Psychiatry, University of Oxford, Oxford, United KingdomNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United KingdomOxford University Hospitals NHS Foundation Trust, Oxford, United KingdomThe Podium Institute for Sports Medicine and Technology, Department of Engineering Science, University of Oxford, Oxford, United KingdomNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United KingdomOxford University Hospitals NHS Foundation Trust, Oxford, United KingdomOxford University Hospitals NHS Foundation Trust, Oxford, United KingdomOxford University Hospitals NHS Foundation Trust, Oxford, United KingdomOxford University Hospitals NHS Foundation Trust, Oxford, United KingdomNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United KingdomOxford University Hospitals NHS Foundation Trust, Oxford, United KingdomNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United KingdomOxford University Hospitals NHS Foundation Trust, Oxford, United KingdomOutcomes 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.https://www.frontiersin.org/articles/10.3389/fneur.2025.1620178/fullpaediatric mild traumatic brain injuryprognostic biomarkersvalidationoutcomes assessmentneurodevelopment
spellingShingle Jonathan E. Attwood
Jonathan E. Attwood
Izabelle Lövgren
Izabelle Lövgren
Rob Forsyth
Célia Demarchi
Célia Demarchi
Tony Thayanandan
Lara Prisco
Lara Prisco
Lara Prisco
Mario Ganau
Mario Ganau
Rebecca Roberts
Kate Scarff
Julia L. Newton
Gabriele C. DeLuca
Gabriele C. DeLuca
Tim Lawrence
Tim Lawrence
Selecting outcome measures to validate prognostic biomarkers of paediatric mild traumatic brain injury: challenges and priorities
Frontiers in Neurology
paediatric mild traumatic brain injury
prognostic biomarkers
validation
outcomes assessment
neurodevelopment
title Selecting outcome measures to validate prognostic biomarkers of paediatric mild traumatic brain injury: challenges and priorities
title_full Selecting outcome measures to validate prognostic biomarkers of paediatric mild traumatic brain injury: challenges and priorities
title_fullStr Selecting outcome measures to validate prognostic biomarkers of paediatric mild traumatic brain injury: challenges and priorities
title_full_unstemmed Selecting outcome measures to validate prognostic biomarkers of paediatric mild traumatic brain injury: challenges and priorities
title_short Selecting outcome measures to validate prognostic biomarkers of paediatric mild traumatic brain injury: challenges and priorities
title_sort selecting outcome measures to validate prognostic biomarkers of paediatric mild traumatic brain injury challenges and priorities
topic paediatric mild traumatic brain injury
prognostic biomarkers
validation
outcomes assessment
neurodevelopment
url https://www.frontiersin.org/articles/10.3389/fneur.2025.1620178/full
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