Abstracts

Rationale: In 2008 preliminary data from the UK and Ireland Epilepsy and Pregnancy register highlighted that topiramate was associated with an increased risk of foetal malformation. Similar reports have emerged from other registries. Our aim was to analyse the latest data from the UK and Ireland Epilepsy and Pregnancy register regarding topiramate, to determine the Major Congenital Malformation (MCM) rate for monotherapy and polytherapy. Methods: This study is part of a prospective, observational, registration and follow up study. Suitable cases are women with epilepsy taking topiramate who become pregnant and register before the outcome of the pregnancy is known. The period of the study was from its inception in 1996 through until 31st March 2017. The main outcome measure is the MCM rate.  Results: Through to  31st March 2017, a total of 145 monotherapy registrations were enrolled.  17 uninformative pregnancy losses occurred (11 spontaneous, 4 induced abortions, 0 stillbirths/neonatal deaths, 3 unknown outcomes). This resulted in 127 total informative outcomes. 6 MCMs were recorded and 8 minor malformations were reported. Monotherapy MCM was 4.72 (95% CI 1.97-10.14) Of the MCMs; 2 were hypospadias, and 2 were cleft disorders. 263 polytherapy exposures to topiramate occurred in 52 different combinations of polytherapy.  175 were 2 drug regimes and 70 were in 3 drug regimes regimes. There were 30 uninformative pregnancy losses, with two informative loss which resulted in stillbirth, leaving a total of 235 informative polytherapy outcomes. Polytherapy MCM was 8.09% (19/235) [95% CI 5.17-12.34]. The contribution of valproate was statistically significant (P=0.0016) in predicting MCM and when the combination of topiramate and valproate was assessed it had an MCM of 24.24% (8/33) [95%CI 12.60-41.25], compared with topiramate regimes without valproate which showed an MCM rate of 5.45% (11/202) [95% CI 2.96-9.59]. Regarding temporal trends in topiramate prescribing; the registry has received between 4-18 cases per annum since 2000. It is interesting to note the steady rise in annual referrals to the registry until its peak of 18 in 2007. In 2008 the registry reported its provisional findings regarding topiramate as a potential human teratogen and since then there has been a steady decline in cases reported to the registry.  Conclusions: The original report of the registry topiramate data still remain accurate almost 8 years since publication. At that point we warned that topiramate should ideally not be considered among the first line agents in women with epilepsy of reproductive potential, and this data would suggest this advice should remain as such. The largest reported series of monotherapy topiramate exposures is in the North America AED in pregnancy registry who report a similar MCM rate to us. The teratogenic effects of topiramate have potential implications for its use in other conditions such as migraine and idiopathic intracranial hypertension.   Funding: The first author has not received any direct funding in the preparation of the abstract. The P.I. of the study has received educational grants from Eisai, Glaxo Smith Kline, Novartis, Sanofi-Aventis, Pfizer and UCB for the running of the UK Epilepsy and Pregnancy Register.