The effect of antiepileptic drugs administered in pregnancy on micronucleus frequency in cord blood lymphocytes.
OBJECTIVE
Epidemiological data indicate that the pregnancies of epileptic women constitute about 1% of all pregnancies. A large group of antiepileptic drugs (AEDs) applied in long-term monotherapy or polytherapy produce toxic metabolites as well as free radicals and reactive oxygen species. The aim of this study was to assess the potential genotoxic effect of AED therapy in pregnancy on DNA structure of umbilical cord blood lymphocytes.


METHODS
The study group were 30 newborns (14 males and 16 females) of mothers receiving long-term AED therapy during pregnancy. The AED considered were carbamazepine, valproic acid, phenyltriazine, benzodiazepine, gamma-aminobutyric acid and sulfonamide analogues. The controls were infants born to mothers not exposed to any medication in pregnancy (n = 20). Positive controls were the same infants, but in this case Nitrogranulogen (Sigma) was added to the collected cord blood samples (n = 11). Micronucleus (MN) assay was used as an indicator of chromosome damage. The frequency (%) of MN/1000 binucleated cells and the nuclear division index (NDI) were calculated.


RESULTS
Mean MN frequency and NDI were respectively 0.110 (+/-0.152), 1.592 (+/-0.206) in the study group and 0.050 (+/-0.061), 1.628 (+/-0.178) in the controls (statistically non-significant difference, p > 0.1).


CONCLUSIONS
The findings did not reveal any genotoxic effect or inhibition of nuclear division in cord blood lymphocytes by AED metabolites. This was reflected by the absence of significant between-group differences in the mean MN frequency and NDI.
Witczak
Monika
M
Department of Biology and Genetics, Medical University of Łódź, Łódź, Poland.
Ferenc
Tomasz
T
Lopaczyńska
Dobrosława
D
Nowakowska
Dorota
D
Kociszewska
Iwona
I
Wilczyński
Jan
J
D000927:Anticonvulsants / Q000009:adverse effects*; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D007231:Infant, Newborn; D008214:Lymphocytes / Q000097:blood / Q000166:cytology / Q000187:drug effects*; D008297:Male; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D015162:Micronucleus Tests; D011247:Pregnancy; D014470:Umbilical Cord / Q000166:cytology
D000927:Anticonvulsants