Pediatric neurology · 2026
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.
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Fu Allen Y, Elguindy Mahmoud M, Tang-Tan Angela, Caldwell David J, Letchuman Vijay, Gotthardt Christine J, Haddad Alexander F, Chung Jason E, Aabedi Alexander A, van Essen Thomas A, Sun Peter P, Kobeissy Firas H, Eagle Shawn R, Wang Kevin K W, Manley Geoffrey T, Yue John K
Аннотация
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.
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.