Spontaneous Fetal Loss Risk Doubled for Women with Epilepsy

Unplanned pregnancy in women who have epilepsy may double the risk for spontaneous fetal loss, according to a new study.

Investigators from the Harvard Neuroendocrine Unit at Massachusetts General Hospital in Boston, Massachusetts, examined the Epilepsy Birth Control Registry (EBCR) in order to determine whether a planned pregnancy is a determinant for spontaneous fetal loss in women with epilepsy. They also hoped to assess other risk factors that could potentially be modified, such as maternal age, pregnancy spacing, and antiepileptic drug categories.

The team pulled demographic, epilepsy, antiepileptic drug, contraceptive, and reproductive data from the EBCR between 2010 and 2014 and found 1144 female patients with epilepsy between the ages of 18 and 47 years to include in their analysis.

Further analysis revealed that 65% of pregnancies in women with epilepsy included in the study were unplanned, the investigators wrote. This rate was higher than the 45% to 51% range seen in the general US population between 2001 and 2011. Minority race and younger age were risk factors for both cohorts and a third of the pregnancies occurred when the women were not taking contraception.

European predictions indicate that maternal exposure to antiepileptic drug polytherapy, the presence of major congenital malformation in 1 parent, previous spontaneous fetal loss, and maternal age are risk factors for spontaneous fetal loss.

The investigators used the following predicted risk factors: pregnancy planning, age, and antiepileptic drugs use. Spontaneous fetal loss was the outcome for 180 of 794 pregnancies the investigators studied. The risk of spontaneous fetal loss was greater for unplanned vs planned pregnancies. Furthermore, the risk of spontaneous fetal loss was greater when unplanned pregnancies were entered alone, and when adjusted for maternal age, interpregnancy interval, and antiepileptic drug category. Additionally, maternal age and interpregnancy interval were independent risk factors. The use of antiepileptic drugs was not an independent risk factors, according to the investigators.

Those women younger than 18 years had the highest rate of spontaneous fetal loss while the risks for the other cohorts varied. Women aged 18 to 27 years had a 29% risk; women 28 to 37 years, had a 20% risk; and women 38 to 47 years had a 25% risk.

Of the 368 women with epilepsy who had more than 1 pregnancy, the risk for spontaneous fetal loss was greater when the time between pregnancies was less than 1 year, compared with latencies greater than 1 year, the study authors wrote.

The frequencies of spontaneous fetal loss among women with epilepsy who did and did not use antiepileptic drugs during pregnancies were similar, at 28% and 27%, respectively. About a quarter of women received monotherapy, while another quarter received polytherapy.

Despite practice guidelines suggestions that women with epilepsy achieve seizure control prior to conception—which requires planning—about two-thirds of these pregnancies are unplanned. Thus, the investigators shared that “unplanned pregnancy may increase the risk of spontaneous fetal loss in women with epilepsy and identifies pregnancy planning, maternal age, and interpregnancy interval as significant modifiable variables."

“In view of the finding of increased risk for spontaneous fetal loss in unplanned pregnancies in women with epilepsy, and because a history of spontaneous fetal loss in women with epilepsy may increase the risk that subsequent live-born offspring will develop epilepsy, the finding warrants prospective investigation with medical record verification of pregnancy outcomes,” the authors concluded.

The study “Association of Unintended Pregnancy with Spontaneous Fetal Loss in Women with Epilepsy,” was published in JAMA Neurology.