Transplacental genotoxicity of antiepileptic drugs: animal model and pilot study on mother/newborn cohort

Reprod Toxicol. 2010 Dec;30(4):613-8. doi: 10.1016/j.reprotox.2010.08.008. Epub 2010 Oct 16.

Abstract

Antiepileptic drugs (AED) as transplacental agents are known to have adverse effects on fetal development. Genotoxicity of AEDs is still not fully understood. The aim of present study was to investigate the transplacental genotoxicity of valproate on animal model and in 21 mothers and their newborns receiving AED. In both studies, in vivo micronucleus (MN) assay was used. Pregnant dams were exposed to Na-valproate (100mg/kg) on gestational days 12-14. Dams and pups receiving Na-valproate showed a significantly increased MN frequency (5.17 ± 1.17/1000; 5.20 ± 1.48/1000) compared to the control (1.0 ± 0.58/1000; 1.67 ± 1.03/1000). In mother/newborn study a significant increase of MN frequency was detected in newborns of mothers taking AEDs (3.09 ± 0.49/10,000) compared to the referent newborns (1.56 ± 0.22/10,000). The results of this study suggest that AEDs may act as transplacental genotoxins. Launching the mother/newborn cohorts for genotoxicological monitoring may give a significant new insight in health effects of AEDs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Animals, Newborn
  • Anticonvulsants / adverse effects*
  • Anticonvulsants / toxicity*
  • Cohort Studies
  • Epilepsy / blood
  • Epilepsy / drug therapy*
  • Female
  • Humans
  • Infant, Newborn
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Micronucleus Tests
  • Mutagens / adverse effects*
  • Mutagens / toxicity*
  • Pilot Projects
  • Pregnancy
  • Pregnancy Complications / blood
  • Pregnancy Complications / drug therapy*
  • Prenatal Exposure Delayed Effects / blood*
  • Reticulocytes / drug effects
  • Valproic Acid / adverse effects
  • Valproic Acid / toxicity
  • Young Adult

Substances

  • Anticonvulsants
  • Mutagens
  • Valproic Acid