Clinical Utility of Structural Blood-Based Biomarkers in Pediatric Traumatic Brain Injury: A Focused Review of GFAP, UCH-L1, and S100B

Objective Blood-based biomarkers are becoming increasingly relevant for the diagnosis of acute traumatic brain injury (TBI) in adults, but they remain underutilized in children. There exists the need for high-quality evidence to support their use in defined clinical contexts. Methods This review synthesizes recent evidence on three structural biomarkers cleared for clinical use in adult TBI: glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydroxylase L1 (UCH-L1), and S100 calcium-binding protein B (S100B) for the diagnosis, management, and prognostication in pediatric TBI. Results Notably, plasma/serum biomarker levels in non-injured children were highest in infancy and inversely associated with age, and reference levels for GFAP and S100B across pediatric age groups were higher than those of non-injured adults. Biomarker levels <24 hours post-injury showed acceptable diagnostic performance for clinically-important TBI (area under the receiver-operating characteristic curve (AUC): GFAP=0.75, UCH-L1=0.76, S100B=0.77), and GFAP and UCH-L1 showed strong performance for traumatic intracranial lesions on computed tomography (CT) (overall AUC: GFAP=0.85, UCH-L1=0.83, S100B=0.67; patients aged <5-years: GFAP=1.00, UCH-L1=0.79, S100B=0.62). In European interventional studies, clinical management aided by S100B was associated with reductions in CT utilization by 67-70% and hospitalizations from 54%, underscoring its utility for improving diagnostic efficacy and safety (i.e., decreasing ionizing radiation and time in-hospital). Structural biomarkers predicted death/severe functional disability at 12 months post-injury (AUC: GFAP=1.00, UCH-L1=0.98, S100B=0.96). Conclusions Blood-based biomarkers hold promise for improving pediatric TBI care. Prospective studies incorporating protocolized assessments are needed to validate their diagnostic and prognostic performance and support clinical qualification and implementation.