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Original Investigation
January 2019

Association of Unintended Pregnancy With Spontaneous Fetal Loss in Women With Epilepsy: Findings of the Epilepsy Birth Control Registry

Author Affiliations
  • 1Harvard Neuroendocrine Unit, Beth Israel Deaconess Medical Center, Boston, Massachusetts
JAMA Neurol. 2019;76(1):50-55. doi:10.1001/jamaneurol.2018.3089
Key Points

Question  Is planned pregnancy associated with spontaneous fetal loss in women with epilepsy?

Findings  In the Epilepsy Birth Control Registry survey study, results indicated that unplanned pregnancy may double the risk of spontaneous fetal loss in women with epilepsy. Interpregnacy interval less than 1 year and conception age younger than 18 years or older than 37 years were also factors.

Meaning  The survey finding that unplanned pregnancy may double the risk for spontaneous fetal loss in women with epilepsy warrants prospective investigation with reliable outcome verification.


Importance  If unintended pregnancy is common among women with epilepsy and is associated with increased risk of spontaneous fetal loss (SFL), it is important to develop guidelines for safe and effective contraception for this community.

Objective  To assess whether planned pregnancy is a determinant of SFL in women with epilepsy.

Design, Setting, and Participants  The Epilepsy Birth Control Registry conducted this web-based, retrospective survey between 2010 and 2014. It gathered demographic, epilepsy, antiepileptic drug (AED), contraceptive, and reproductive data from 1144 women with epilepsy in the community between ages 18 and 47 years. Data were analyzed between March 2018 and May 2018.

Main Outcomes and Measures  The primary outcome was the risk ratio (RR) with 95% confidence intervals for SFL in unplanned vs planned pregnancies. The secondary outcome was the identification of some potentially modifiable variables (maternal age, pregnancy spacing, and AED category) of SFL vs live birth using binary logistic regression.

Results  The participants were proportionally younger (mean [SD] age, 28.5 [6.8] years), and 39.8% had household incomes of $25 000 or less. Minority women represented only 8.7% of the participants. There were 530 of 794 unplanned pregnancies (66.8%) and 264 of 794 planned pregnancies (33.2%). The risk for SFL in 653 unaborted pregnancies in women with epilepsy was greater for unplanned (n = 137 of 391; 35.0%) than planned (n = 43 of 262; 16.4%) pregnancies (RR, 2.14; 95% CI, 1.59-2.90; P < .001). Regression analysis found that the risk for SFL was greater when planning was entered alone (odds ratio [OR], 2.75; 95% CI, 1.87-4.05; P < .001) and more so when adjusted for maternal age, interpregnancy interval, and AED category (OR, 3.57; 95% CI, 1.54-8.78; P = .003). Interpregnancy interval (OR, 2.878; 95% CI, 1.8094-4.5801; P = .008) and maternal age (OR, 0.957; 95% CI, 0.928-0.986 for each year from 18 to 47 years; P = .02), but not AED category, were also associated. The risk was greater when interpregnancy interval was less than 1 year (n = 56 of 122; 45.9%) vs greater than 1 year (n = 56 of 246; 22.8%) (RR, 2.02; 95% CI, 1.49-2.72; P < .001). Relative to the younger than 18 years cohort (n = 15 of 29; 51.7%), the risks were lower for the intermediate older cohort aged 18 to 27 years (n = 118 of 400; 29.5%; RR, 0.57; 95% CI, 0.39-0.84; P < .004) and the cohort aged 28 to 37 years (n = 44 of 212; 20.8%; RR, 0.40; 95% CI, 0.26-0.62; P < .001) but not significantly different for the small number of participants in the aged 38 to 47 years cohort (n = 3 of 12; 25.0%). No individual AED category’s SFL frequency differed significantly from the no AED category.

Conclusions and relevance  The Epilepsy Birth Control Registry retrospective survey finding that unplanned pregnancy in women with epilepsy may double the risk for SFL warrants prospective investigation with outcome verification.