Pediatric brain trauma outcome prediction using paired serum levels of inflammatory mediators and brain-specific proteins
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Updated: Jun 25, 2026
Systems Analysis of the Neuroinflammatory and Hemodynamic Response to Traumatic Brain Injury
Published on: May 27, 2022
Tsz-Yan M Lo1, Patricia A Jones, Robert A Minns
1Child Life and Health, University of Edinburgh, Edinburgh, United Kingdom. mils.lo@doctors.org.uk
Insights
Combining two serum biomarkers significantly improves prediction of unfavorable outcomes after childhood brain trauma. Pairs of biomarkers, including S100b protein and either L-selectin or IL-6, demonstrated high accuracy in predicting outcomes.
Area of Science:
- Neuroscience
- Biomarker Discovery
- Pediatric Critical Care
Background:
- Numerous biomarkers for brain trauma exist, but their combined predictive value for patient outcomes remains underexplored.
- Accurate prediction of outcomes following pediatric brain trauma is crucial for guiding clinical management and therapeutic interventions.
Purpose of the Study:
- To evaluate the outcome predictive capabilities of individual serum biomarkers and their combinations.
- To determine if paired biomarkers offer superior prediction accuracy compared to single markers for childhood brain trauma.
Main Methods:
- A prospective observational study involving 28 pediatric patients with brain trauma.
- Quantification of eight serum biomarkers (S100b, NSE, IL-6, IL-8, IL-10, SICAM, L-selectin, endothelin) on Day 1 post-injury using ELISA.
- Global outcome assessment at 6 months using the Glasgow Outcome Score (GOS); analysis via ROC and Multivariate ROC (MultiROC).
Main Results:
- No single biomarker achieved an Area Under the ROC Curve (AUC) > 0.95 for unfavorable outcome prediction.
- Five out of 20 biomarker pairs demonstrated high predictive value (AUC > 0.95).
- Two specific combinations (S100b with L-selectin or IL-6) achieved an AUC of 0.98, with 96% specificity and 100% sensitivity for unfavorable outcomes.
Conclusions:
- Prognostic pairs of serum biomarkers, integrating inflammatory mediators and brain-specific proteins, significantly enhance the prediction of unfavorable outcomes in childhood brain trauma.
- Combined biomarker analysis offers superior predictive power compared to individual marker assessment for pediatric brain trauma prognosis.
Abstract:
Many potential brain trauma biomarkers have been reported, but no previous study has described outcome prediction using combinations of biomarker levels. We aimed to investigate the outcome predictive values of multiple biomarkers from different mediator families and to determine whether combinations of two serum biomarkers may achieve higher outcome predictive values than individual biomarker levels. A prospective observational study was conducted involving 28 children requiring intensive care management following brain trauma. Day 1 post-injury serum concentrations of eight different biomarkers--S100b protein (S100b), neuron-specific enolase (NSE), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), soluble intracellular adhesion molecule (SICAM), L-selectin, and endothelin--were quantified using enzyme-linked immunosorbent assay (ELISA). Global outcome was assessed at 6 months post-injury using the Glasgow Outcome Score (GOS). Receiver operator characteristic curve (ROC) analysis and its multivariate extension, Multivariate ROC (MultiROC), were used to assess the outcome predictive values of the individual and the paired biomarkers. None of the eight biomarkers assessed individually achieved an area under the ROC curve (AUC) of more than 0.95 for predicting unfavorable outcome, but five of the 20 biomarker pairs assessed had this high degree of outcome predictability. Two combinations using S100b as the "screening marker" and either L-selectin or IL-6 as the "varying marker" achieved an AUC of 0.98, and their specificity and sensitivity for unfavorable outcome prediction were 96% and 100%, respectively. Prognostic pairs combining serum levels of two biomarkers (inflammatory mediators and brain-specific proteins) offer better outcome predictive values for unfavorable outcome after childhood brain trauma than may be achieved using individual marker levels.
