Reducing risks: have the changing antiepileptic drug prescribing habits in pregnancy resulted in an improvement in pregnancy outcomes between 1995 and 2010?

Abstract

Purpose: The risk of major congenital malformations (MCM) with in utero exposure to valproate used in monotherapy (6.2%; 95% CI 4.1–7.8) or in polytherapy (7.8%; 95%CI 5.6–10.7) has previously been shown to be greater than the risk due to exposure to carbamazepine (2.6%; 95%CI 1.9–3.5) or lamotrigine (2.3%; 95%CI 1.6–3.2). (Morrow JI, et al. J Neurol Neurosurg Psychiatry 2006; 77:193–198) The awareness of this association has increased over the past 10–15 years. This current study sought to assess the impact on prescribing habits and onMCMrate. Method: An analysis of the UK Epilepsy and Pregnancy register, which now encompasses more than 8000 registrations, allows for review of prescribing habits and for calculation ofMCMrates from 1995 to 2010. Results: There was no change in the ratio of monotherapy, polytherapy and no drug exposures, but sodium valproate prescription fell from 31.2 to 23.25% of monotherapy exposures during the study period. This was associated with a trend towards reducing MCM in the pregnancies of women with epilepsy from 4.3% (95% CI 3.5–5.4%) to 3.2% (95%CI 2.6–3.9%). Conclusion: The MCM rate has fallen by approximately a quarter during the study period, this equates to 26 less children born with MCM per annum. Given the spectrum of MCMs seen with valproate and their cost to the Health Service this may represent an extrapolated direct health cost saving in the order of £2–3 million per annum in the UK.