Title : Early post-traumatic seizures in pediatric traumatic brain injury following levetiracetam prophylaxis: A systematic review and meta-analysis
Abstract:
Background: Early post-traumatic seizures (EPTS), defined as seizures occurring within 7 days of injury, are a clinically significant complication of pediatric traumatic brain injury (TBI) associated with increased intracranial pressure, secondary neurological injury, and worse outcomes. Levetiracetam (LVT) has increasingly replaced phenytoin as the preferred prophylactic agent due to its favorable safety profile, ease of administration, and lack of drug interactions. However, robust evidence supporting its efficacy in the pediatric population remains limited and heterogeneous. This systematic review and meta-analysis aimed to determine the pooled incidence of EPTS in pediatric patients with TBI receiving LVT prophylaxis.
Methods: A systematic search was conducted across PubMed, Embase, Cochrane CENTRAL, Scopus, and ClinicalTrials.gov from inception to March 2026. Studies were eligible if they included pediatric patients (0–18 years) with TBI who received LVT specifically as seizure prophylaxis prior to any seizure onset and clearly reported EPTS incidence. Studies where LVT was initiated as treatment for active seizures, or involving patients with pre-existing epilepsy, were excluded. A single-arm proportional meta-analysis was performed using a random-effects model with logit transformation in R. Heterogeneity was assessed using the I² statistic and tau². A leave-one-out sensitivity analysis was conducted to evaluate the robustness of the pooled estimate.
Results: Eight studies met eligibility criteria, comprising 577 pediatric TBI patients who received LVT prophylaxis, of whom 58 developed EPTS. The pooled incidence of EPTS was 10.1% (95% CI: 6.9–14.6%), with a prediction interval of 3.8–24.5%, indicating considerable variability in expected EPTS rates across clinical settings. Moderate heterogeneity was observed (I² = 49.1%; Chi² = 13.76, df = 7, P = 0.056; tau² = 0.155). Leave-one-out sensitivity analysis demonstrated moderate robustness, with pooled estimates ranging from 7.89% (95% CI: 4.40–13.75%) to 11.53% (95% CI: 8.33–15.73%) upon sequential study omission. Omission of Shin et al. 2015, a study with predominantly mild TBI: yielded the highest estimate and the lowest heterogeneity (I² = 22.1%), suggesting this study exerts notable downward influence on the pooled proportion.
Conclusion: Approximately 1 in 10 pediatric TBI patients develops EPTS despite LVT prophylaxis, with the true rate in high-risk clinical settings potentially approaching 24.5% as suggested by the prediction interval. The moderate heterogeneity and influential role of TBI severity across studies highlight the need for prospective, dose-optimized randomized controlled trials specifically in high-risk subgroups including young children and abusive head trauma. Pending stronger evidence, continuous EEG monitoring and individualized clinical vigilance remain essential components of care.
Keywords: Levetiracetam; Pediatric Traumatic Brain Injury; Early Post-Traumatic Seizures; Seizure Prophylaxis; Meta-Analysis
