HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Correspondence: Submit a response Correspondence: View responses Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Hunt, S. Articles by Craig, J. PubMed PubMed Citation Articles by Hunt, S. Articles by Craig, J. Related Collections Clinical trials Observational study (Cohort, Case control) All Epilepsy/Seizures Antiepileptic drugs

Topiramate in pregnancy

Preliminary experience from the UK Epilepsy and Pregnancy Register

From the Department of Neurology (S.H., J.M., J.C.) and Bostock House (R.W., B.I.), Royal Group of Hospitals, Belfast; Department of Clinical Neurophysiology (A.R.), Southern General Hospital, Glasgow; The Surgery (W.H.S.), Escrick, York; Department of Neurology (L.P.), St Albans City Hospital, Herts; Obstetrics and Gynaecology Department (I.R.), Lancashire Teaching Hospitals NHS Trust, Preston; and Department of Medical Genetics (P.J.M.), Belfast City Hospital Trust, and School of Biological Sciences, University of Ulster, Coleraine, UK.

Address correspondence and reprint requests to Dr. John Craig, Department of Neurology, Royal Group of Hospitals, Grosvenor Road, Belfast, BT12 6BA, UK john.craig{at}belfasttrust.hscni.net

Objectives: Topiramate (Topamax®) is licensed to be used, either in monotherapy or as adjunctive treatment, for generalized tonic clonic seizures or partial seizures with or without secondary generalization and for prevention of migraine. The safety of topiramate in human pregnancy is largely unknown. Here we report on our experience of pregnancies exposed to topiramate.

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 antiepileptic drugs (AEDs), and who are referred before outcome of the pregnancy is known. The main outcome measure is the major congenital malformation (MCM) rate. Secondary outcomes include risk of specific MCM, minor malformation rate, birthweight, and gestational age at delivery.

Results: Full outcome data are available on 203 pregnancies. Of these, 178 resulted in live birth; 16 had an MCM (9.0%; 95% CI 5.6% to 14.1%). Three MCMs were observed in 70 monotherapy exposures (4.8%; 95% CI 1.7% to 13.3%) and 13 in cases exposed to topiramate as part of a polytherapy regimen (11.2%; 95% CI 6.7% to 18.2%). Four of the MCMs were oral clefts (2.2%; 95% CI 0.9% to 5.6%). Four cases of hypospadias were reported (5.1%; 95% CI 0.2% to 10.1%) among 78 known live male births of which two were classified as major malformations.

Conclusions: The number of outcomes of human pregnancies exposed to topiramate is low, but the major congenital malformation rate for topiramate polytherapy raises some concerns. Overall, the rate of oral clefts observed was 11 times the background rate. Although the present data provide new information, they should be interpreted with caution due to the sample size and wide confidence intervals.

Abbreviations: AED = antiepileptic drug; MCM = major congenital malformation; SGA = small for gestational age.

Disclosure: The study was made possible by a research grant from the Epilepsy Research Foundation and a number of unrestricted educational grants from pharmaceutical companies (Glaxo-Smith-Kline, Sanofi-Aventis, UCB-Pharma, Janssen-Cilag, Pfizer, Eisai). An Internet-based Web site detailing the aims of the UK Epilepsy and Pregnancy Register was made possible by a grant from Glaxo-Smith-Kline. Over the lifetime of the register, these grants have exceeded $10,000 from each company/grant awarding body. S.H., J.C., A.R., W.H.S., L.P., P.M., R.W., B.I., and J.M. have attended meetings with the support of various pharmaceutical companies, including Janssen-Cilag. J.C., L.P., P.M., and J.M. have given lectures at the bequest of pharmaceutical companies, including Janssen-Cilag, for which they have received honoraria. No individual has received personal compensation in excess of $10,000. I.R. reports no conflicts of interest.

Received November 19, 2007. Accepted in final form April 2, 2008.

This article has been cited by other articles:

				Topiramate Use During Pregnancy and Risk for Birth Defects Journal Watch Neurology, October 7, 2008; 2008(1007): 1 - 1. [Full Text]

				Topiramate: Another Concern About Teratogenicity Journal Watch Psychiatry, August 18, 2008; 2008(818): 6 - 6. [Full Text]

				Topiramate: Another Concern About Teratogenicity Journal Watch Pediatrics and Adolescent Medicine, August 13, 2008; 2008(813): 5 - 5. [Full Text]

Correspondence: