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. 2017 Feb 28;15(1):19-27.
doi: 10.9758/cpn.2017.15.1.19.

Teratogenicity of Antiepileptic Drugs

Betül Tekin Güveli  1 , Rasim Özgür Rosti  2 , Alper Güzeltaş  3 , Elif Bahar Tuna  4 , Dilek Ataklı  1 , Serra Sencer  5 , Ensar Yekeler  5 , Hülya Kayserili  2 , Ahmet Dirican  6 , Nerses Bebek  7 , Betül Baykan  7 , Ayşen Gökyiğit  7 , Candan Gürses  7
Affiliations

Teratogenicity of Antiepileptic Drugs

Betül Tekin Güveli et al. Clin Psychopharmacol Neurosci. .

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.

Keywords: Antiepileptic drugs; Congenital malformations; Dental anomalies; Dysmorphic features; Teratogenesis.

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Figures

Fig. 1
Fig. 1
Epicanthic folds, hypertelorism, broad nasal root, short nose, thin upper lip (valproic acid, 500 mg/day).
Fig. 2
Fig. 2
Supernumerary teeth (valproic acid, 600 mg/day).
See this image and copyright information in PMC

References

    1. Fairgrieve SD, Jackson M, Jonas P, Walshaw D, White K, Montgomery TL, et al. Population based, prospective study of the care of women with epilepsy in pregnancy. BMJ. 2000;321:674–675. doi: 10.1136/bmj.321.7262.674. - DOI - PMC - PubMed
    1. Holmes LB. The teratogenicity of anticonvulsant drugs: a progress report. J Med Genet. 2002;39:245–247. doi: 10.1136/jmg.39.4.245. - DOI - PMC - PubMed
    1. Pennell PB. Pregnancy in women who have epilepsy. Neurol Clin. 2004;22:799–820. doi: 10.1016/j.ncl.2004.07.004. - DOI - PubMed
    1. Meador KJ. Effects of in utero antiepileptic drug exposure. Epilepsy Curr. 2008;8:143–147. doi: 10.1111/j.1535-7511.2008.00273.x. - DOI - PMC - PubMed
    1. Battino D, Binelli S, Caccamo ML, Canevini MP, Canger R, Como ML, et al. Malformations in offspring of 305 epileptic women: a prospective study. Acta Neurol Scand. 1992;85:204–207. doi: 10.1111/j.1600-0404.1992.tb04029.x. - DOI - PubMed