title: Antiepileptic drugs prescribed in pregnancy and prevalence of major congenital malformations: comparative prevalence studies.
abstract: OBJECTIVE
  The aim of this study was to examine the prevalence of major congenital malformations associated with antiepileptic drug (AED) treatment in pregnancy.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Primary Care and Population Health, University College London, London, UK; Department of Clinical Epidemiology, Aarhus University, Aarhus N, Denmark.
authors.forename: Irene
authors.initials: I
authors.lastname: Petersen
authors.affiliation: Department of Primary Care and Population Health, University College London, London, UK; OXON Epidemiology, London, UK.
authors.forename: Shuk-Li
authors.initials: SL
authors.lastname: Collings
authors.affiliation: Department of Primary Care and Population Health, University College London, London, UK.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: McCrea
authors.affiliation: Department of Primary Care and Population Health, University College London, London, UK.
authors.forename: Irwin
authors.initials: I
authors.lastname: Nazareth
authors.affiliation: Division of Psychiatry, University College London, London, UK.
authors.forename: David P
authors.initials: DP
authors.lastname: Osborn
authors.affiliation: University Department of Psychiatry, Warneford Hospital, Oxford, UK.
authors.forename: Phil J
authors.initials: PJ
authors.lastname: Cowen
authors.affiliation: Department of Primary Care and Population Health, University College London, London, UK.
authors.forename: Cormac J
authors.initials: CJ
authors.lastname: Sammon
keywords: adverse drug effects; carbamazepine; lamotrigine; pregnancy; valproate