Fertility, Birth Rates the Same in Women With, Without Epilepsy

Batya Swift Yasgur, MA, LSW

May 10, 2018

Women with epilepsy are just as likely to become pregnant and deliver live babies as their counterparts without epilepsy, new research shows.

Investigators compared WWE to a group of control women and found that the number of women who achieved pregnancy, the median times to pregnancy, and number of live births were virtually identical in both groups.

"There are myths that fertility rates are lower for women with epilepsy, that it takes longer for them to conceive, and there are higher rates of miscarriage," lead author, Page B. Pennell, professor of neurology, Harvard Medical School and director of epilepsy research, Brigham and Women's Hospital, Boston, Massachusetts, told Medscape Medical News.

"Our study showed that the groups were the same, with regard to all three, and this will be very helpful in allowing us to dispel the old myths and better counsel these women with epilepsy who are of childbearing years," she said.

The study was published online April 30 in JAMA Neurology.

Decision-Making

Most previous studies suggest low birth rates in women with epilepsy, with birth rates of only 36% to 88% of those among other groups, the authors write.

However, "when we looked at previous studies, we saw that these statistics were not sufficiently based on data," Pennell reported.

"While it is true that the number of children that women with epilepsy had was lower than their peers, these studies did not take into account the choices that the women were making regarding becoming pregnant and starting a family," she explained.

"Since many women had been discouraged from becoming pregnant, we felt that the lower rates of pregnancy might be attributed to social factors and decision-making on the part of the women rather than whether they could actually become pregnant," she said.

For this reason, the investigators conducted an observational study called Women With Epilepsy: Pregnancy Outcomes and Deliveries.

"We decided to design a study that enrolled women with epilepsy and without a history of infertility, who wanted to become pregnant and get off birth control, and also to enroll women without epilepsy who served as controls, and seeing if there were any differences in fertility and birth outcomes."

Given that the population-based estimate of pregnancy rate over 3 menstrual cycles is approximately 55%, the researchers estimated that the rate among women with epilepsy was expected to be approximately 36%.

Participants were required to be aged 18 to 40 years, to have expressed a desire to conceive, to be free of contraceptive use for 6 months before the beginning of the study, to have no history of infertility or hormonal or pituitary disease, and to smoke fewer than 10 cigarettes per day.

Women whose partners had forms of male infertility were also excluded.

The researchers collected demographic information as well as medical history, including results of ancillary studies, seizure types and epilepsy treatment, and fertility.

Women were required to complete a daily diary, via use of an app, a web-based interface, or paper diary, to track menses and sexual intercourse, as well as medication use and seizures for those with epilepsy.

Participants had monthly visits  in person or via telephone to review the diary. If menses did not begin by day 35 of their cycle, they were required to conduct a home pregnancy test.

If the test result was positive, they had an initial pregnancy visit and a 1-month postpartum visit, with pregnancy losses (eg, ectopic pregnancy, miscarriage, fetal death, and abortions) included in the "positive" group.

The researchers additionally conducted hormonal testing using blood serum samples within a day of menstrual day 21 for up to two cycles.

"We treated both groups of the women the same way, in terms of daily diaries, finding out about menstrual bleeding, sexual activity, and all medications and vitamins, as well as how long it took to become pregnant, and we followed all women until delivery to see pregnancy outcomes," Pennell reported.

"Pleasant Surprise"

The study included 197 participants: 89 women with epilepsy and 108 control women (mean age [SD], 31.9 [3.5] and 31.1 [4.2] years, respectively).

After controlling for key covariates, the researchers found no differences between the women with epilepsy and the controls in the proportion who achieved pregnancy (60.7% [54 of 89] vs 60.2% [65 of 108] respectively; c2 = 0.28; P = .60)

Median times to pregnancy in the women with epilepsy and the controls were 6.0 months (95% CI, 3.8 - 10.1 months) and 9.0 months (95% CI, 6.5 - 11.2 months; P = .30), respectively.

Women who had features of higher parity, were white, and were married were more likely to achieve pregnancy, while women with a higher age at enrollment were less likely.

After controlling for parity, race/ethnicity, marital status, age, and body mass index, the researchers found no difference between the groups in time to pregnancy.

There were an identical number of pregnancy outcomes (81.5% live births) for both groups, and similar miscarriage rates (14% in women with epilepsy vs 18.5% in control women).

Among the women with epilepsy, there were one ectopic pregnancy and one therapeutic abortion.

Sexual activity rates did not differ between groups, and the relationship between ovulation and study group was not found to be significant.

The presence of active seizure in the prior 9 months did not influence the likelihood of pregnancy.

Women with epilepsy who used enzyme-inducing antiepileptic drugs (EIAEDs) were less likely to achieve pregnancy than were women taking other antiepileptic drugs, "a signal that did not turn out to be statistically significant," Pennell reported.

However, the impact of EIAEDs requires further research because of "the small number of women in our study who were taking EIAEDs," she suggested.

She acknowledged being "pleasantly surprised although not shocked" by the findings.

"We designed the study with the hypothesis that women with epilepsy would have lower rates of pregnancy, although we would not have done the study if we had not realized the limitations of the previous studies," she said.

Unplanned Pregnancy Risk

Commenting on the study for Medscape Medical News, David Ficker, MD, professor of neurology, University of Cincinnati College of Medicine,  Ohio, and chair elect, Professional Advisory Board, who was not involved with the study, called it "well done," noting that "the control population added strength to the study."

He stated that the finding accords with his clinical experience in young women with epilepsy who "haven't had difficulty becoming pregnant and having healthy, normal children."

The study has important take-home message for clinicians counseling these patients.

"Beyond dispelling myths about lower fertility rates, these findings have implications for women of childbearing age who may not be planning pregnancy, which is that their pregnancy rate is similar to women without epilepsy, so we need to take appropriate steps to reduce the risk of unplanned pregnancies."

This includes counseling women about contraception and also about taking folic acid if they are using antiseizure medications, he advised.

Pennell agreed. "As people treating these women, we should remember that women with epilepsy are equally fertile, so we need to address contraception until they are ready to start a family."

For example, she warned, "Valproic acid has a high risk of birth defects and lower IQ, and a female of reproductive age taking it has to be on very clear birth control."

The Milken Family Foundation, Epilepsy Therapy Project, and Epilepsy Foundation provided financial support for the Women With Epilepsy: Pregnancy Outcomes and Deliveries study. Study data were collected and managed using REDCap (Research Electronic Data Capture) tools hosted at Brigham and Women's Hospital. Pennell received grants from the Milken Family Foundation, the Epilepsy Therapy Project, and the Epilepsy Foundation, and the National Institutes of Health during the conduct of the study as well as honoraria and travel reimbursements from the American Academy of Neurology, American Epilepsy Society, National Institutes of Health, academic universities, Peru Ministry of Health, and Indian Academy of Neurology. The other authors' disclosures are listed with the original study. Ficker has disclosed no relevant financial relationships.

JAMA Neurol. Published online April 30, 2018. Abstract

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