Objective To systematically evaluate the safety profiles of anti-seizure medications (ASMs) regarding metabolic adverse events in the pediatric population, identify risk signals across different age stages, and provide evidence-based support for clinical individualized medication and pharmacovigilance. MethodsData from the Food and Drug Administration (FDA) adverse event reporting system (FAERS) spanning Q1 2013 to Q3 2024 were analyzed. Reports involving metabolic adverse events in patients aged 0~18 years after ASMs use were screened. Data mining methods, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Bayesian Confidence Propagation Neural Network (BCPNN), were applied. Standardized classification was performed using the Medical Dictionary for Regulatory Activities (MedDRA) v26.1 to analyze adverse reaction signals across metabolic pathways, including glucose, lipids, proteins/amino acids, and bone/calcium/phosphorus/magnesium, as well as trace metals. Stratified safety evaluations were conducted across four age groups: infants (0~2 years), toddlers (2~6 years), children (6~2 years), and adolescents (12~18 years). ResultsA total of 2,356 metabolic adverse event reports were included. Significant signals were observed for protein and amino acid metabolism disorders (ROR=5.44), bone/calcium/magnesium/phosphorus metabolism disorders (ROR=1.59), and iron/trace metal metabolism disorders (ROR=1.83), with some signals being specific to the pediatric population. Several drugs, including valproate, topiramate, levetiracetam, and gabapentin, showed strong risk signals across multiple metabolic pathways, primarily manifesting as hyperammonemia, hypocalcemia, and hypomagnesemia. Risk profiles varied significantly by age group: lacosamide showed prominent signals for bone metabolism disorders in the 0~2 years group; perampanel showed significant signals for amino acid metabolism disorders in the 2~6 years group; and in the 12~18 years group, clonazepam and gabapentin showed extremely high ROR values (>48) for iron/trace metal metabolism disorders. The median onset time for metabolic adverse events associated with novel ASMs was significantly later than that of traditional ASMs (38 days vs. 8 days), suggesting a relatively delayed but prolonged metabolic toxicity for newer agents. ConclusionThe use of ASMs in minors can trigger multi-system metabolic disturbances, with significant differences in risk profiles across different drugs and age groups. We recommend strengthening the dynamic monitoring of metabolic parameters during treatment, with particular attention to the potential toxicity of high-risk drugs within specific age windows, thereby promoting the establishment of precision dosing and early intervention strategies.
