Clin Psychopharmacol Neurosci.  2017 Feb;15(1):19-27. 10.9758/cpn.2017.15.1.19.

Teratogenicity of Antiepileptic Drugs

Affiliations
  • 1Department of Neurology, Bakirkoy Research and Training Hospital for Psychiatry, Neurology, and Neurosurgery, Istanbul University, Istanbul, Turkey. betultekin2013@gmail.com
  • 2Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
  • 3Department of Radiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
  • 4Department of Biostatistics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
  • 5Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
  • 6Department of Pediatric Cardiology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
  • 7Department of Pedodonty, Faculty of Dentistry, Istanbul University, Istanbul, Turkey.

Abstract

OBJECTIVE: Antiepileptic drugs (AED) have chronic teratogenic effects, the most common of which are congenital heart disease, cleft lip/palate, urogenital and neural tube defects. The aim of our study is to examine teratogenic effects of AED and the correlation between these malformations and AED in single or multiple pregnancies.
METHODS
This is a retrospective study of malformations in children born to mothers currently followed up by our outpatient clinics who used or discontinued AED during their pregnancy. Their children were then investigated using echocardiography, urinary ultrasound, cranial magnetic resonance image, and examined by geneticists and pediatric dentists.
RESULTS
One hundred and seventeen children were included in the study. Ninety one of these children were exposed to AED during pregnancy. The most commonly used AED were valproic acid and carbamazepine in monotherapy. The percentage of major anomaly was 6.8% in all children. Dysmorphic features and dental anomalies were observed more in children exposed especially to valproic acid. There were 26 mothers with two and four mothers with three pregnancies from the same fathers. No correlation was found between the distribution of malformations in recurring pregnancies and AED usage.
CONCLUSION
Our study has the highest number of dysmorphism examined in literature, found in all the children exposed to valproic acid, which may account for the higher rate of facial dysmorphism and dental anomalies. On lower doses of valproic acid, major malformations are not seen, although the risk increases with polytherapy. Our data also indicate possible effects of genetic and environmental factors on malformations.

Keyword

Dysmorphic features; Dental anomalies; Congenital malformations; Antiepileptic drugs; Teratogenesis
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