ARTICLE IN BRIEF
There was a 14-fold increase in birth defects in those taking topiramate with other antiseizure medications.
Although the data are limited, researchers in the United Kingdom have reported a slight increase in birth defects among children born to mothers taking the antiseizure medication topiramate (Topomax), which is also widely prescribed in the US for migraine.
Although the risk for women taking topiramate alone was within the normal range for the population in general, there was a 14-fold increase in those taking it with other antiseizure medications, including valproate, which has been associated with a 20-percent risk of birth defects or fetal death.
Lead author John Craig, MD, a neurologist at the Royal Group of Hospitals in Glasgow, Northern Ireland, and researchers at other centers involved in the UK Epilepsy and Pregnancy Register, reported the findings in the July 22 issue of Neurology.
Among 203 pregnancies and 178 live births, 16 infants had a major congenital malformation; however, only three cases were observed out of 70 topiramate monotherapy exposures. A total of 13 (11.2 percent) were reported in mothers taking topiramate as part of a polytherapy regimen. Of the birth defects, four (2.2 percent) were cleft lips or palates — 11 times higher than in the general population. There were also four cases (5.1 percent) of hypospadia, a defect of the urethra, in 78 male infants — a rate 14 times higher than normal.
The authors emphasized that the data should be interpreted with caution due to the small sample size and limitations in the statistical sampling. They also stressed that women who become pregnant should never discontinue taking topiramate or any antiepileptic drugs without first consulting their physicians.
Monitoring pregnancies in women with migraine exposed to topiramate should also be encouraged, they added.
CONCERNS ABOUT MIGRAINE
At least five major pregnancy registries are examining birth defects associated with medications. Results from two registers in the United States and one in Europe will be published within the year, which should help clarify the findings, experts told Neurology Today.
Stephen D. Silberstein, MD, a neurologist and migraine expert at Thomas Jefferson University Hospital's Jefferson Headache Center, said the new findings should not concern women taking topiramate for migraines.
“The bottom line is that the data state that monotherapy is okay,” he told Neurology Today in a telephone interview. “Topiramate is the number-one drug prescribed for migraine, and I am not convinced that there is anything wrong here — it's only when other drugs are also being used, and we already know that some of these can cause birth defects.”
Figure. Dr. Stephen ...Image Tools
MORE DATA ARE NEEDED
Kimford Meador, MD, the Melvin Greer Professor of Neurology at the University of Florida-Gainesville's McKnight Brain Institute, called the small sample size and wide confidence intervals “problematic,” noting that they prevent drawing any conclusions until data from the larger studies become available.
There is always a balance between risks and benefits associated with any antiseizure medication and pregnancy, Dr. Meador said. “Some mothers with mild, non-convulsive epilepsy might be better off without it, but it is dangerous for others to stop taking epilepsy medication if they become pregnant because seizures pose a much greater risk to mother and fetus.”
Dr. Meador also noted that most children born to these women are normal, and there is some evidence that early childhood behavioral and cognitive development is normal.
Jacqueline A. French, MD, a professor of neurology at New York University, and director of the Clinical Trials Consortium at NYU's Comprehensive Epilepsy Center, said that a far greater concern is that physicians are prescribing newer medications because pregnancy data are not yet available.
“Some doctors believe [a new drug] must be safer than some older medication with a known risk profile just because there is no contradictory information available yet. Others feel pressure to prescribe newer drugs,” she said. “In the long run, this may not turn out to be the best strategy. Consciously selecting a newer drug for a pregnant woman just because you haven't heard anything negative about it is never a good idea.” •
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Craig J, Morrison J, Morrow J, et al. Topiramate in pregnancy: Preliminary experience from the UK Epilepsy and Pregnancy Register. Neurology 2008;71:272–276.