Teratogenic Effect of Levetiracetam on Albino Mice Placentae

Abstract

Background: Levetiracetam is widely used as a newer antiepileptic drug in women of reproductive age, but data on its teratogenic effects, particularly on the placenta, are limited. This experimental study evaluated dose-related placental changes following prenatal exposure to levetiracetam in albino mice.
Methods: Forty F1-generation pregnant Swiss albino mice were randomly allocated to four groups (n=10 each). Group I received intraperitoneal distilled water (control). Groups II–IV received levetiracetam 600, 1200 and 1800 mg/kg body weight, respectively, from gestational day (GD) 5–11. All dams were sacrificed on GD19. Placentae were weighed, examined grosslyand processed for histology (H&E). Trophoblastic, mucoid and fibrinoid degeneration and presence of dilated vessels were recorded. Data were analysed using one-way ANOVA and chi-square tests.
Results: Mean placental weight differed significantly among groups (F=5.300, p<0.001), being lower in Group II and higher in Groups III and IV compared with controls. Levetiracetam exposure produced marked, dose-related histopathological changes. Trophoblastic degeneration was present in 10% of control placentae versus 93.3%, 84% and 86.96% in Groups II–IV, respectively (p<0.00001). Mucoid degeneration occurred in 1.8% of controls vs 40%, 62% and 91.3% in Groups II–IV. Fibrinoid degeneration was found in 5.5% of controls vs 44.4%, 64%and 87% in Groups II–IV, while dilated vessels were seen in 1.8% of controls vs 2.2%, 20% and 93.5% in Groups II–IV (all p<0.00001).
Conclusion: Prenatal exposure to levetiracetam during organogenesis produced significant, dose-related placental degenerative changes in albino mice. These findings suggest potential teratogenic risk at the placental level and underline the need for cautious use and further mechanistic and clinical studies in pregnancy.