Evaluation of chromosome aberrations, sister chromatid exchange and micronuclei in cultured cord-blood lymphocytes of newborns of women treated for epilepsy during pregnancy

Abstract

Epidemiological data indicate that pregnancies of epileptic women constitute about 1% of all pregnancies. Newborns of mothers exposed to anti-epileptic drugs (AEDs) are at increased risk for major congenital malformations, cognitive impairment and fetal death. Cord-blood lymphocytes of the newborns whose mothers received long-term AEDs therapy during pregnancy were used in this study. There were 37 newborns (Group A), divided into two subgroups, i.e. from mothers receiving mono-therapy (A1) and from those receiving poly-therapy (A2). The major drugs given to the pregnant women with epilepsy in mono-therapy were valproic acid (VPA) and carbamazepine (CBZ) analogues. In poly-therapy, besides VPA and CBZ derivatives also phenyltriazine, sulphanamide, benzodiazepines and gamma-aminobutyric acid (GABA) derivatives were administered. Three kinds of in vitro cytogenetic test were applied: the chromosome aberration (CA) assay, the sister chromatid exchange (SCE) assay, and the cytokinesis-block micronucleus assay (CBMN). In addition, the mitotic index (MI), the replication index (RI) and the nuclear division index (NDI) were determined. The mean number of CA/cell (excluding gaps) for group A did not differ statistically significantly from the negative controls (p>0.1), nor did the mean MI value (p>0.1). In group A, the mean number of SCE/cell was statistically significantly higher compared with the negative control (p<0.05). The mean RI value for group A did not demonstrate statistically significant differences (p>0.1). The mean MN number for group A was higher than in the negative control, but this difference was on the border of statistical significance (p=0.07). The value of NDI for group A did not differ significantly from the value in the negative control (p>0.1). The anti-epileptic drugs given to epileptic women in mono- and poly-therapy during pregnancy evoked potentially clastogenic and genotoxic effects in cord-blood lymphocytes. These drugs did not exert a cytotoxic effect, neither did they inhibit the cell-division kinetics of cord-blood lymphocytes.