Clinical Utility of Structural Blood-Based Biomarkers in Pediatric Traumatic Brain Injury: A Focused Review of Glial Fibrillary Acidic Protein, Ubiquitin C-Terminal Hydrolase L1, and S100 Calcium-Binding Protein B.
Abstract
Background
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 used clinically in adult TBI: glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCH-L1), and S100 calcium-binding protein B (S100 B) for diagnosis, management, and prognostication in pediatric TBI.
Results
Notably, plasma/serum biomarker levels in noninjured children were highest in infancy and inversely associated with age, and reference levels for GFAP and S100 B across pediatric age groups were higher than those of noninjured adults. Biomarker levels <24 hours postinjury showed acceptable diagnostic performance for clinically-important TBI (area under the receiver-operating characteristic curve (AUC): GFAP = 0.75, UCH-L1 = 0.76, S100 B = 0.77), and GFAP and UCH-L1 showed strong performance for traumatic intracranial lesions on computed tomography (overall AUC: GFAP = 0.85, UCH-L1 = 0.83, S100 B = 0.67; patients aged <5 years: GFAP = 1.00, UCH-L1 = 0.79, S100 B = 0.62). In European interventional studies, clinical management aided by S100 B was associated with relative reductions in computed tomography utilization exceeding 30% and hospitalizations by 45-55%, 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 postinjury (AUC: GFAP = 1.00, UCH-L1 = 0.98, S100 B = 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.