Role of Folic acid on the reduction of topiramate- induced craniofacial deformities in Balb/c mic fetuses

Topiramate is an anti-epilepsy drug and its Consumption during pregnancy may induce skeletal and craniofacial malformations. The aim of this study was to evaluate the protective effect of folic acid on the reduction of topiramate- induced anomalies in Balb/c mice. In this study, 72 Balb/c timed-pregnant mice were divided into 6 experimental and 2 control groups. Experimental groups I,II and III received daily oral gavages of topiramate (50,100 and 200 mg/kg, respectively) and experimental groups IV, V and VI received similar doses of topiramate with 3 mg/kg/day folic acid supplement by gavage route. Control negative and positive groups received normal saline and folic acid, respectively. Oral gavages were done during GD6-GD15. Gavage of folic acid was done from 10 days before pregnancy to day 15th of pregnancy. Dams underwent Cesarean section on GD18 and were investigated by microscopic tools, and after determination of weight and crown- rump length, external examination was done and fetuses were stained with Alizarin red S and Alcian blue staining. The mean weight and crown-rump length of the fetuses in three experimental groups I, II and III were significantly reduced compared with control groups (P < 0.05). Orofacial deformities such as mandibular hypoplasia and open mouth were detected in experimental groups I, II and III. A significant decrease was seen in the incidence of these deformities in fetuses of groups IV, V and VI that received folic acid-topiramate co-administrations. Findings of this study showed that using topiramate during pregnancy may induce fetus malformations and consumption of folic acid can reduce topiramate- induced birth defects.