Epilepsy Drug May Boost Birth Defect Risk
Women who take topiramate should discuss preconception planning with their doctor
By Steven Reinberg, HealthDay Reporter
Women who take topiramate should discuss preconception planning with their doctor.
MONDAY, July 21 (HealthDay News) -- Pregnant women who use the epilepsy drug topiramate alone or in combination with other epilepsy drugs may be increasing their risk of birth defects, British researchers report.
Topiramate (brand name Topamax) is a common anti-seizure medication used by many with epilepsy. It's also used to treat migraine headaches. Many similar drugs also increase the risk of birth defects, but until this report, the link between birth defects and topiramate had not been well studied.
"More research needs to be done to confirm these results, especially since it was a small study," lead researcher John Craig, of the Royal Group of Hospitals in Belfast, Northern Ireland, said in a news release from the American Academy of Neurology. "But these results should also get the attention of women with migraine and their doctors, since topiramate is also used for preventing migraine, which is an even more common condition that also occurs frequently in women of childbearing age."
The report is published in the July 22 issue of the journal Neurology.
For the study, the researchers collected data on women who became pregnant while taking topiramate alone or in combination with other epilepsy drugs.
Craig's team found that of the 178 babies born, 16 (4.8 percent) suffered from major birth defects. Among the babies with birth defects, three of the mothers were taking topiramate exclusively, while 13 were taking topiramate plus other epilepsy drugs.
Four of the babies had cleft palettes or cleft lips. That's a rate 11 times higher than one would expect among women not taking the drug, the researchers said.
Among male babies, four had genital defects, with two classified as "major defects." That's a rate 14 times higher than normal, the researchers reported.
The incidence of birth defects among women taking topiramate was higher than the rate of birth defects in the general population, which is about 1 percent to 2.5 percent. And there were more birth defects among women taking topiramate along with the epilepsy drug valproate, compared with women taking topiramate and another epilepsy drug.
Despite the risk, it's important that women maintain effective epilepsy control during pregnancy, because seizures can also harm the fetus. The risk of birth defects may be different among women taking topiramate to treat migraines, but these women should be monitored as well, the researchers said.
Dr. Orrin Devinsky, a professor of neurology, neurosurgery and psychiatry, and director of the New York University Epilepsy Center, said this study underscores the need for all women of childbearing years who take antiepileptic drugs to discuss preconception planning with their physician.
"All women should clearly understand the risks and benefits of their therapy," Devinsky said. "Until more information is available, topiramate use in women who plan on conceiving should be restricted to those in whom the drug is definitely needed for seizure control or other indications. Also, the mother should be informed of the potential risks to her child."
Another epilepsy expert, Dr. Edward Barry Bromfield, chief of the Division of Epilepsy at Brigham and Women's Hospital in Boston, agreed that women should be warned about the potential side effects of the drug.
"Women with epilepsy, if they depend on this drug to control their convulsive seizures, they should definitely continue it," Bromfield said. "If they are taking it for migraine prevention, chances are they would want to discontinue it before conception," he said.
For more on epilepsy, visit the U.S. National Library of Medicine.
SOURCES: Orrin Devinsky, M.D., professor of neurology, neurosurgery and psychiatry, and director, New York University Epilepsy Center, New York City; Edward Barry Bromfield, M.D., chief, Division of Epilepsy, Brigham and Women's Hospital, Boston; July 22, 2008, Neurology
Copyright © 2008 ScoutNews, LLC. All rights reserved.
Epilepsy drug Topamax linked to birth defects
A study of 203 pregnant women finds a connection, but experts caution that the group is too small to draw definitive results. Still, they say they aren't surprised.
By Thomas H. Maugh II, Los Angeles Times Staff Writer
July 22, 2008
A widely used anti-epilepsy drug called topiramate raises the risk of birth defects as much as 14-fold when taken by pregnant women, especially in combination with another drug called valproate, British researchers reported today.
Experts were quick to caution, however, that the study involved only 203 women, and thus significant statistical uncertainty remained about the research.
"You can't make any definitive statements from the data," said Dr. Kimford J. Meador of the University of Florida in Gainesville, who was not involved in the study.
But the results are not surprising, experts added, because topiramate -- sold by Johnson & Johnson under the brand name Topamax -- has been shown to cause similar defects in animals.
Other epilepsy drugs that have been studied have also been found to increase the risk of such defects, suggesting that the entire class of drugs may interfere with the reproductive process.
Despite the enormous risks, doctors say that epileptic women cannot stop taking the drugs during pregnancy because seizures can also damage the unborn infant, perhaps even more severely.
But women who are taking the drug to prevent migraines should halt its use if they become pregnant or are planning to do so, said Dr. John Craig of the Royal Group of Hospitals in Belfast, Northern Ireland, who led the research published in the journal Neurology.
Epilepsy, which affects an estimated 2.7 million Americans, is a disorder characterized by powerful seizures. Topamax accounts for about 1 in 5 prescriptions for treatment.
Valproate, which is one of the most common drugs used in treating the disorder, has previously been associated with birth defects or fetal death in about 20% of women who take it.
Craig and his colleagues studied 203 women who became pregnant while taking topiramate on its own or in combination with other epilepsy drugs.
Of the 203 pregnancies, 18 ended in spontaneous abortions, two in stillbirths and five in induced abortions.
Of the 178 babies born, 16 had major birth defects. In three of those cases, the mothers had taken only topiramate, and in the other 13, the mothers had taken it in combination with other drugs.
Four of the babies had cleft palates or lips, a rate 11 times the normal rate of 1 in 500 expected among women not taking epilepsy drugs. Four male babies had genital birth defects, which is 14 times the normal rate of 1 in 300.
The women in the study were part of the U.K. Epilepsy and Pregnancy Register, which was set up to determine the relative safety of such drugs.
Five other registries have also been established, including one in the United States. Results from two of the larger registries may be released later this year.
© 2008 American Academy of Neurology
Topiramate in pregnancy
Preliminary experience from the UK Epilepsy and Pregnancy Register
S. Hunt, MRCP, A. Russell, MRCP, W. H. Smithson, MSc, L. Parsons, MD, I. Robertson, MD, R. Waddell, B. Irwin, P. J. Morrison, MD, J. Morrow, MD and J. Craig, MRCP
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 firstname.lastname@example.org
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.
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