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Biomarker-informed prediction of neurosurgical intervention in pediatric traumatic brain injury: a proof-of-concept
Andrew Reisner1,2,3, Ali M Alawieh2, Jacob R Lepard1,2
11Children's Healthcare of Atlanta.
Insights
Blood biomarkers can predict the need for neurosurgical intervention in children with traumatic brain injury (TBI). Glial fibrillary acidic protein (GFAP) showed significant predictive power, aiding clinical decisions.
Area of Science:
- Pediatric Traumatology
- Neurocritical Care
- Biomarker Discovery
Background:
- Traumatic brain injury (TBI) management in children lacks precise diagnostic tools.
- Blood-based biomarkers are emerging as valuable indicators in TBI assessment.
- Current pediatric TBI guidelines have limited integration of these biomarkers.
Purpose of the Study:
- To evaluate the efficacy of a blood biomarker panel in predicting neurosurgical intervention (NSI) in pediatric TBI.
- To assess the diagnostic performance of specific biomarkers like GFAP, UCH-L1, NfL, t-tau, and OPN.
- To determine if biomarkers can improve neurosurgical decision-making in pediatric TBI cases.
Main Methods:
- Prospective cohort study of 425 children (0-17 years) with nonpenetrating TBI.
- Blood samples analyzed for GFAP, UCH-L1, NfL, t-tau, and OPN within 24 hours of injury.
- Logistic regression and AUC analysis used to assess biomarker predictive performance for NSI.
Main Results:
- Neurosurgical intervention (NSI) was required in 14.35% of patients.
- Children needing NSI were younger and had more severe injuries (lower GCS scores).
- Elevated levels of all tested biomarkers were observed in patients requiring NSI (p < 0.001).
- Glial fibrillary acidic protein (GFAP) significantly predicted NSI (AUC 0.83) after controlling for age and GCS.
Conclusions:
- Blood-based biomarkers, particularly GFAP, can predict the need for NSI in pediatric TBI patients.
- Biomarker performance is independent of patient age and initial Glasgow Coma Scale (GCS) score.
- Further research is warranted to integrate these biomarkers into clinical practice and TBI guidelines for improved outcomes.
Objective:
Emerging traumatic brain injury (TBI) guidelines increasingly recognize the role of blood-based biomarkers in improving diagnostic and triage accuracy, yet their integration into pediatric care remains limited and underexplored. This study examined the performance of a blood-based biomarker panel in predicting which pediatric patients with TBI received neurosurgical intervention (NSI).
Methods:
This was a prospective cohort study of 425 children (aged 0-17 years) treated at a pediatric tertiary hospital between March 2017 and June 2021 with nonpenetrating TBI (Glasgow Coma Scale [GCS] score 3-15). Standard of care was rendered. NSI included craniotomy, craniectomy, external ventricular drain (EVD) placement, and intracranial pressure (ICP) monitor placement. Blood samples collected within 24 hours of injury were measured for plasma glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament light (NfL), and total tau (t-tau) with the Quanterix Simoa platform, as well as osteopontin (OPN) quantification via ELISA. Logistic regression and area under the curve (AUC) analysis with 95% confidence intervals (CI) were used to measure predictive discrimination.
Results:
NSI occurred in 14.35% of patients. These children were younger (mean age 6.0 vs 10.1 years) with more severe injury (median GCS score 9.0 vs 15.0) than those who did not require NSI. All median biomarker concentrations were higher in NSI compared with non-NSI patients (p < 0.001). After age and GCS score were controlled for, GFAP significantly predicted NSI (AUC 0.83, 95% CI 0.75-0.90), defining the best predictive model for NSI.
Conclusions:
Blood-based biomarkers predicted NSI following pediatric TBI, independent of age and admission GCS score. These findings support further prospective trials to determine whether integrating blood-based biomarkers into clinical triage algorithms and TBI guidelines can improve neurosurgical decision-making and patient outcomes.