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News from the American Epilepsy Society Annual Meeting
Study Finds High Rate of Unintended Pregnancies in Women with Epilepsy

ARTICLE IN BRIEF

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IN ALL, 78.9 percent of the women reported having at least one unintended pregnancy, including 65 percent of 804 pregnancies reported in the study.

Women with epilepsy have an unusually high rate of unintended pregnancy, which varies sharply based on the choice of contraception and category of antiepileptic drug.

HOUSTON—Women with epilepsy have an unusually high rate of unintended pregnancy, which varies sharply based on the choice of contraception and category of antiepileptic drug (AED), according to a large retrospective study presented at the American Epilepsy Society meeting here.

The findings highlight the need for neurologists treating women with epilepsy to discuss contraception and the need to avoid unintended pregnancy, the study authors and other neurologists agreed.

“We hope this finding will affect practice,” said the first author of the poster, Andrew G. Herzog, MD, FAAN, director of the Harvard Neuroendocrine Unit at Beth Israel Deaconess Medical Center in Boston and professor of neurology at Harvard Medical School. “Neurologists need to do a better job of discussing contraception with this population.”

In a paper published in Epilepsia last April, Dr. Herzog reports that only 25.7 percent of women with epilepsy said they had consulted their neurologists regarding their selection of contraceptive method, even though neurologists are their primary point of contact with a health caregiver and the women listed AED interaction as their most important consideration in contraceptive selection.

Those results, and the new findings presented here, were based on information from the Epilepsy Birth Control Registry, a web-based survey of 1,144 women with epilepsy in the community, aged 18 to 47, who provided demographic, epilepsy, AED and contraceptive data.

The failure rate of systemic hormonal contraceptives was among the highest of any method, with a relative risk of unplanned pregnancy 4.94 times higher than for IUD (2.35-10.39, p<0.001).

That increased risk, however, varied greatly by the subcategories of hormonal contraceptive as combined with AEDs. Oral forms of hormonal contraceptives failed at a rate 2.89 times higher than did non-oral forms (95% confidence interval: 1.95-4.28, p<0.0001). But only when hormone treatment was combined with enzyme-inducing AEDs did it have a substantially and significantly greater failure rate compared to hormones when no AED was being taken (RR=2.70 [1.51-4.82, p=0.0008]).

“It's really the women using enzyme-inducing AEDs who have a greater risk of unintended pregnancies on hormonal contraception than women using barrier [methods],” Dr. Herzog said. “The enzyme-inducing drugs are known to break down the contraceptive hormones.”

Enzyme-inducing AEDs include phenobarbital, phenytoin, carbamazepine, felbamate, oxcarbazepine, and topiramate. Non-enzyme-inducing AEDs include valproic acid, benzodiazepines, gabapentin and zonisamide.

In all, 78.9 percent of the women reported having at least one unintended pregnancy, including 65 percent of 804 pregnancies reported in the study. Women who had a history of generalized convulsions were at greater risk as compared to those who had only partial seizures (RR = 1.20 [1.03-1.39]; p=0.017). By comparison, he said, about half of all pregnancies among women in the general population are unintended.

Of the 804 pregnancies, 175 occurred on no contraception. Intrauterine devices (IUDs) had the lowest failure rate of any method of reversible contraception, at 3.1 percent. Relative to IUD, barrier methods had a relative risk of 3.89 [1.83-8.29], p= 0.0004; hormonal had a relative risk of 4.94 [2.35-10.39], p< 0.0001 and withdrawal had a relative risk of 5.74 [2.67-12.31], p< 0.0001.

EXPERTS COMMENT

Jacqueline A. French, MD, FAAN, professor of neurology and director of translational research and clinical trials at the Comprehensive Epilepsy Center at New York University Langone Medical Center, said that one reason for the higher rate of unintended pregnancies among women with epilepsy is that some of them may be getting inaccurate information from their internists.

“I have had many women tell me their doctor said that if they have epilepsy, they can't take an oral contraceptive,” Dr. French said. “So they end up on a barrier method, which is less effective. When I tell them they can take an oral contraceptive, because they are on an AED that does not interact, they are surprised to say the least.”

Michael R. Sperling, MD, FAAN, professor of neurology and director of the Jefferson Comprehensive Epilepsy Center at Thomas Jefferson University in Philadelphia, said that the study was well designed and that the findings make sense based on what is known about the pharmacokinetics of enzyme-inducing AEDs. But given that the study population is self-selecting, he said, “I would be afraid to put too much stock in the exact numbers given for relative risks.”

Dr. Herzog agreed that the potential for bias in the self-selecting group is real, which is why he is launching a prospective study that should provide more accurate relative risk numbers. Even so, he emphasized, “The data line up very well with what we would expect from basic pharmacological data.”

Page B. Pennell, MD, director of research for the division of epilepsy in the department of neurology at Brigham and Women's Hospital in Boston and professor of neurology at Harvard Medical School, agreed with Dr. Herzog that the numbers are likely representative and need to be taken seriously, even while awaiting results from a prospective study.

“The message is quite clear,” Dr. Pennell said. “Ideally, this group of women should have a lower than average rate of unintended pregnancies, because of the risk of birth defects and neurodevelopmental delays that can be higher when the AED regimen is not optimized prior to pregnancy. Instead their rate of unintended pregnancies is higher. That's very concerning.”

Neurologists who prescribe AEDs for any reason, Dr. Pennell said, “whether for epilepsy, migraine or neuropathic pain, need to make sure these discussions occur. The burden is on us.”

While it is important to educate patients that the IUD is the most effective method to prevent an unintended pregnancy, Dr. Pennell noted: “A lot of women would just prefer not to have an IUD. Then you have to explain that taking an oral hormonal contraceptive while taking an enzyme-inducing AED put them at the highest relative risk of an unintended pregnancy.”

Conversations between a neurologist and a woman with epilepsy about pregnancy and contraception can never come too soon, Dr. French said.

“Let's say a woman comes into my office, she's 18, says she doesn't have a boyfriend, isn't sexually active,” Dr. French said. “I might not see her for another year, when she could be taking a potentially ineffective birth control by then. I always discuss that the stakes are higher for a woman with epilepsy. That's the last person you want to have an unplanned pregnancy.”

Indeed, she went on, “I always tell my female patients, if they become pregnant, I'm the first person they need to tell after their husband or boyfriend.”

Dr. Sperling agreed. “Neurologists need to sit down with patients to talk about the most effective means of contraception,” he said, “or they can talk with their gynecology colleagues about it.”

LINK UP FOR MORE INFORMATION:

• Herzog AG, Mandle H, Cahill K, et al.AES Abstract 1.207: Predictors of unintended pregnancy in women with epilepsy. http://bit.ly/NT-UnintendedPregnancyEpilepsy
    • Herzog AG, Mandle HB, Cahill KE, et al. Contraceptive practices of women with epilepsy: Findings of the epilepsy birth control registry http://onlinelibrary.wiley.com/doi/10.1111/epi.13320/full. Epilepsia 2016; 57(4):630–637.