The safety of valproic acid treatment in children with epilepsy: a retrospective real-world research

Background Liver damage, coagulopathy, hyperammonemia, fracture, menstrual disorder and amenorrhea are the most concerned adverse drug reactions of valproic acid (VPA). This study was aimed to retrospectively investigate the incidence of adverse drug reactions of VPA in the real world and its association with the age of patients and duration of treatment in order to obtain the safety data of VPA in children with epilepsy. Methods A total of 1943 patients diagnosed as epilepsy by the Pediatric Neurology Department of Shenzhen Children's Hospital between December 2013 and December 2023, were included in the study. They received VPA as an initial treatment, and had followed up examinations over a time span of at least two years focusing on the adverse drug reactions of VPA. ResultsThere was no significant difference in the incidence of liver damage, coagulation test abnormalities, and nasal bleeding during VPA monotherapy (30-90 days, 90-180 days, and > 2 years). Adolescent female patients (first visit age >= 12 years) showed no significant difference in the incidence of adverse reactions and abnormal ultrasound of the reproductive system pre- versus post-treatment at the first visit, similar for those below 12 years. However, laboratory blood tests revealed significantly age-dependent changes in certain biochemical markers. Two patients stopped VPA treatment due to thrombocytopenia and ovarian cystic mass comorbid with endometrial hyperplasia, recovering after VPA withdrawal. ConclusionsThe initial monotherapy of VPA is generally safe in children with epilepsy of all age ranges. In the real world, VPA does not increase the risk of liver damage, coagulation disorder, elevated blood ammonia, fractures, or low serum sodium, but may significantly decrease the platelet count at 3, 6, 12, and 24 months of treatment. There is no evidence showing that VPA may increase the incidence of impairment of adolescent female reproductive system. Among children under 1 year old, it is recommended to monitor the levels of serum ammonia and aspartate aminotransferase carefully. Trial registrationChiCTR2300075115.