Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Feb 16:9:95-103.
doi: 10.2147/CLEP.S118336. eCollection 2017.

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

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

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

Irene Petersen et al. Clin Epidemiol. .

Abstract

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: adverse drug effects; carbamazepine; lamotrigine; pregnancy; valproate.

PubMed Disclaimer

Conflict of interest statement

Disclosure PJC has in the last three years been a paid member of an advisory boards of Lundbeck. CJS has received funding for research from Novartis Vaccines and Diagnostics. IP supervises a PhD student who is sponsored by Novo Nordisk. IN is currently member of the NIHR HTA commissioning board. The other authors report no conflicts of interest in this work.

References

    1. Tomson T, Battino D. Teratogenic effects of antiepileptic drugs. Lancet Neurol. 2012;11(9):803–813. - PubMed
    1. Galbally M, Roberts M, Buist A, Perinatal Psychotropic Review Group Mood stabilizers in pregnancy: a systematic review. Aust N Z J Psychiatry. 2010;44(11):967–977. - PubMed
    1. Meador K, Reynolds MW, Crean S, Fahrbach K, Probst C. Pregnancy outcomes in women with epilepsy: a systematic review and meta-analysis of published pregnancy registries and cohorts. Epilepsy Res. 2008;81(1):1–13. - PMC - PubMed
    1. Jentink J, Loane MA, Dolk H, et al. Valproic acid monotherapy in pregnancy and major congenital malformations. N Engl J Med. 2010;362(23):2185–2193. - PubMed
    1. Dolk H, Jentink J, Loane M, Morris J, de Jong-van den Berg LTW. EUROCAT Antiepileptic Drug Working Group Does lamotrigine use in pregnancy increase orofacial cleft risk relative to other malformations? Neurology. 2008;71(10):714–722. - PubMed

LinkOut - more resources