Teratogenic effects of carbamazepine in mice

Abstract

Objectives:The aim of this study was to determine the teratogenic effects of carbamazepine (CBZ) in BALB/c mice.Materials and Methods:Mature female and male BALB/c mice (25–30 g) were used for all experiments. After standardization of administration and dose of CBZ, animals in the CBZ-treated groups (CBZ 450 mg/kg and 600 mg/kg) were fed on medicinal diet. The dams in the control group were mated on the same day as that of the CBZ-treated dams. After cesarean section (CS), fetal viability status and weights were recorded. Gross histopathological examination of fetuses was conducted to identify alterations in morphology and external or internal organs due to in utero exposure of CBZ.Results:Out of the nine female animals (three treated on CBZ 450 mg/kg, three treated on CBZ 600 mg/kg and three controls), seven were pregnant, and two (one each from the two CBZ-treated groups) were nonpregnant. All fetuses of the control group (n = 31) and CBZ 450 mg/kg treated group (n = 24) were live, but eight out of the twenty fetuses (40%) of CBZ 600 mg/kg treated group were dead at CS. The birth weight of the fetuses antenatally exposed to CBZ was drastically reduced (0.71 ± 0.06) when compared to control fetuses (1.67 ± 0.12) (P < 0.0001). All the fetuses of the CBZ-treated groups showed stunted physical development.Conclusion:Although oral administration of CBZ to mice is a convenient model to study the effect of CBZ to pregnancy, higher oral dose was associated with increased fetal loss. Some of the fetuses exposed to CBZ demonstrated structural abnormalities and low body weight.

Prenatal exposure to antiseizure medications and fetal growth: a population-based cohort study from the Nordic countries

“… 3 In addition, studies of prenatal carbamazepine exposure have shown evidence of fetal growth restriction in rodents. 12 , 13 Still, the evidence for an association of fetal growth restriction with prenatal carbamazepine exposure was considered inconclusive before this study, 4 and the risk is not mentioned in the prescribing information for carbamazepine. 24 In two population-based studies based on subsets of data from the current study, prenatal oxcarbazepine exposure was associated with risk of being born SGA, 5 , 25 although fetal growth restriction was not found in a meta-analysis that did not include these two studies.…”

“… 6 , 9 , 10 Chemically, ASMs are heterogeneous drugs that are both related (e.g., oxcarbazepine and carbamazepine) and unrelated (e.g., topiramate and clonazepam). 11 However, in animal studies, prenatal exposure to carbamazepine, 12 , 13 oxarbazepine, 14 clonazepam 15 and topiramate 16 have all been associated with reduced fetal growth. Thus, although animal studies suggest potential harm, the human evidence of some ASMs remains inconclusive.…”