Alterations in serum zinc, copper, and selenium levels in children with drug-resistant epilepsy: A systematic review and meta-analysis.

BACKGROUND: Drug-resistant epilepsy (DRE) affects around one-third of children with epilepsy and is associated with high morbidity and mortality. Trace elements such as zinc (Zn), copper (Cu), and selenium (Se) play important roles in neuronal excitability, oxidative stress regulation, and enzymatic antioxidant defense. OBJECTIVE: To systematically evaluate and synthesize the available evidence on serum zinc, copper, and selenium levels in children with DRE. METHODS: A systematic review and meta-analysis was conducted following PRISMA guidelines. PubMed, Scopus, ScienceDirect, and Google Scholar were searched from inception to December 31, 2025. Studies reported serum zinc, copper, or selenium levels in children with DRE and comparator groups were included. Data were pooled using standardized mean differences (SMDs) with 95% confidence intervals (CIs). Heterogeneity was measured by I2 statistic. Study quality was appraised using Newcastle-Ottawa Scale. RESULTS: Seven studies met the inclusion criteria. Serum zinc levels were significantly lower in children with DRE than in healthy controls (SMD: -0.68; 95% CI: [-1.32, -0.05]; p = 0.04) and drug-controlled epilepsy patients (SMD: -0.44; 95% CI: [-0.78, -0.10]; p = 0.01). Serum selenium levels were also significantly lower in children with DRE compared with healthy controls (SMD: -1.06; 95% CI: [-1.67, -0.44]; p = 0.0007) and drug-controlled epilepsy patients (SMD: -0.54; 95% CI: [-0.84, -0.25]; p = 0.0003). Serum copper levels showed a borderline reduction in children with DRE compared with healthy controls (SMD: -0.33; 95% CI: [-0.67, -0.01]; p = 0.05). However, no significant difference was observed when compared with drug-controlled epilepsy patients (SMD: -0.08; 95% CI: [-0.29, 0.13]; p = 0.48). Substantial heterogeneity was observed in several analyses, particularly in comparisons involving zinc and selenium with healthy controls. CONCLUSION: Children with DRE exhibit significantly lower serum zinc and selenium levels, while association with copper levels remains inconsistent. Larger randomized controlled trials are needed to determine causality and evaluate the potential role of trace element supplementation in DRE.