TOPIRAMATE THERAPY IN HUMAN PREGNANCY. PRELIMINARY
EXPERIENCE FROM THE UK EPILEPSY AND PREGNANCY REGISTER*
Dr S J Hunt1, Dr J J Craig1, B Irwin1, R Waddell1, Dr A Russell2, Dr W H Smithson3,
Dr L Parsons4, Mr I Robertson5, Prof P J Morrison6 & Dr J I Morrow1.
Affiliations:
1 Department of Neurology, Royal Group of Hospitals, Belfast.
2 Department of Clinical Neurophysiology, Southern General Hospital, Glasgow
3 The Surgery, Escrick, York
4 Department of Neurology, St Albans City Hospital, Waverley Road, St Albans
5 Obstetrics and Gynaecology Department, Lancashire Teaching Hospitals NHS Trust,
Sharoe Green Lane South, Preston
6 Department of Medical Genetics, Belfast City Hospital Trust, Lisburn Road, Belfast, &
School of Biological Sciences, University of Ulster, Coleraine
Objectives
Topiramate is licensed for treatment of generalised tonic clonic seizures or partial
seizures with or without secondary generalisation and for prevention of migraine. The
safety of topiramate in pregnancy is unknown.
Methods
This study is part of a prospective, observational, registration and follow-up study.
Suitable cases are women with epilepsy who become pregnant while taking topiramate
either singly or along with other anti-epileptic drugs, and who are referred before
outcome of the pregnancy is known. The main outcome measure is the major congenital
malformation (MCM) rate.
Results
Full outcome data are available on 179 pregnancies. There were 157 live births. Fifteen
of these had an MCM (9.6%; 95% C.I. 5.9 – 15.2 %). Two MCMs were observed in 56
monotherapy exposures (4.2%; 95% C.I. 1.2 – 14.0 %). Thirteen cases exposed to
topiramate as part of a polytherapy regime had an MCM (11.9%; 95% C.I. 7.1 – 19.3%).
Three MCMs were clefting malformations (1.9%; 95% C.I. 0.7 - 5.5%).
Conclusions
While the number of outcomes of human pregnancies exposed to topiramate is low the
MCM rate observed in the polytherapy group would suggest caution. In particular, the
rate of clefting abnormalities observed is 9.5 times the background rate. Much larger
numbers are required to be more confident about the safety of topiramate in pregnancy.
*Data as of 31st December 2006