Objective: Gingival overgrowth is an important adverse effect of phenytoin (PHT) therapy, occurring in about half of the patients. This study aimed to evaluate the effect of oral folic acid supplementation (0.5 mg/day) for the prevention of PHT-induced gingival overgrowth (PIGO) in children with epilepsy aged 6-15 years on PHT monotherapy for 6 months.
Methods: This was a randomized, double-blind, placebo-controlled trial conducted at a tertiary level hospital from May 2008 to June 2009. Children aged 6-15 years started on PHT monotherapy within last 1 month were eligible for inclusion. Preexisting gingival overgrowth, use of other folic acid antagonists, and macrocytic anemia were exclusion criteria. Trial subjects were randomized to receive either folic acid or placebo. The primary outcome measure was incidence of any degree of gingival overgrowth after 6 months of PHT monotherapy. The trial was registered with clinicaltrials.gov (NCT00781196).
Results: A total of 120 children were recruited, 62 and 58, respectively, in folic acid and placebo arms. The 2 arms were comparable at baseline. Twenty-one percent of patients in the folic acid arm developed PIGO, as compared with 88% receiving placebo (p < 0.001). Absolute risk reduction of PIGO by folic acid was 67% (95% confidence interval 54%-80%), and relative risk reduction was 0.76.
Conclusions: Oral folic acid was found to decrease the incidence of PIGO in children on PHT monotherapy, in a statistically significant and clinically relevant manner.
Classification of evidence: This study provides Class I evidence that folic acid supplementation, 0.5 mg/day, is associated with prevention of gingival overgrowth in children taking PHT monotherapy.