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Antiepileptic drugs prescribed in pregnancy and prevalence of major congenital malformations: comparative prevalence studies

Authors Petersen I, Collings SL, McCrea RL, Nazareth I, Osborn DP, Cowen PJ, Sammon CJ

Received 28 July 2016

Accepted for publication 1 December 2016

Published 16 February 2017 Volume 2017:9 Pages 95—103

DOI https://doi.org/10.2147/CLEP.S118336

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 4

Editor who approved publication: Professor Vera Ehrenstein


Irene Petersen,1,2 Shuk-Li Collings,1,3 Rachel L McCrea,1 Irwin Nazareth,1 David P Osborn,4 Phil J Cowen,5 Cormac J Sammon1

1Department of Primary Care and Population Health, University College London, London, UK; 2Department of Clinical Epidemiology, Aarhus University, Aarhus N, Denmark; 3OXON Epidemiology, London, UK; 4Division of Psychiatry, University College London, London, UK; 5University Department of Psychiatry, Warneford Hospital, Oxford, UK

Objective: The aim of this study was to examine the prevalence of major congenital malformations associated with antiepileptic drug (AED) treatment in pregnancy.
Patients and methods: Using data from The Health Improvement Network, we identified women who have given live birth and their offspring. Four subgroups were selected based on the AED treatment in early pregnancy, valproate, carbamazepine, lamotrigine and women not receiving AED treatment. We compared the prevalence of major congenital malformations within children of these four groups and estimated prevalence ratios (PRs) using Poisson regression adjusted for maternal age, sex of child, quintiles of Townsend deprivation score and indication for treatment.
Results: In total, 240,071 women were included in the study. A total of 229 women were prescribed valproate in pregnancy, 357 were prescribed lamotrigine and 334 were prescribed carbamazepine and 239,151 women were not prescribed AEDs. Fifteen out of 229 (6.6%) women prescribed valproate gave birth to a child with a major congenital malformation. The figures for lamotrigine, carbamazepine and women not prescribed AEDs were 2.7%, 3.3% and 2.2%, respectively. The prevalence of major congenital malformation was similar for women prescribed lamotrigine or carbamazepine compared to women with no AED treatment in pregnancy. For women prescribed valproate in polytherapy, the prevalence was fourfold higher. After adjustments, the effect of estimates attenuated, but the prevalence remained two- to threefold higher in women prescribed valproate.
Conclusion: The results of our study suggest that lamotrigine and carbamazepine are safer treatment options than valproate in pregnancy and should be considered as alternative treatment options for women of childbearing potential and in pregnancy.

Keywords: pregnancy, valproate, lamotrigine, carbamazepine, adverse drug effects

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