Topiramate in pregnancy: preliminary experience from the UK Epilepsy and Pregnancy Register.

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.