ObjectiveTo examine occurrence of severe adverse fetal outcomes (SAO), including fetal loss and major congenital malformations (MCMs), in pregnant women with epilepsy (PWWE) vs healthy pregnant women (HPW).MethodsThe Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is an NIH-funded, prospective, observational, multicenter investigation of pregnancy outcomes for both mother and child, which enrolled women December 2012 through January 2016.ResultsThe 351 PWWE had 365 conceptions, and 105 HPW had 109 conceptions. SAOs occurred more often in PWWE (7.9%) vs HPW (1.9%) (p = 0.025) with odds ratio (OR) 4.45 (95% confidence intervals [CI] 1.04-19.01). There were no significant differences for fetal loss (2.8% vs 0%, p = 0.126) or MCMs (5.2% vs 1.9%, p = 0.185; OR 2.86, 95% CI 0.65-12.53) individually. No fetal losses in PWWE appeared to be related to acute seizures. Outcomes were not affected by periconceptional folate, unplanned/unwanted pregnancies, prior maternal pregnancy history, or antiepileptic drug (AED) blood levels, except for an AED level effect for fetal loss that appeared to be due to polytherapy. Combined maternal or paternal family history of MCM was marginally associated with increased SAOs (p = 0.046).ConclusionsThe findings provide additional information on risks of SAOs in PWWE, assessing effects of both AED levels and periconceptional folate. Group differences in average enrollment gestational age could have affected fetal loss results. Analyses are limited by small sample sizes as the MONEAD study was not powered for these secondary outcomes. The large majority of pregnancies in women with epilepsy do not have SOAs.
Bibliographical noteFunding Information:
Epilepsy Foundation and for consulting work on behalf of the Epilepsy Study Consortium for Acorda, Adamas, Alexza, Anavex, Axcella Health, Biogen, BioPharm Solutions, Cavion, Cerecor, Concert Pharmaceuticals, Engage, Eisai, Glaxo Smith-Kline, GW Pharma, Marinus, Nestle-Health Science, Neurelis, Novartis, Pfizer, Pfizer-Neusentis, Otzuka, Ovid, Sage Therapeutics, SK Life Sciences, Sunovion, Takeda, UCB Inc., Upsher Smith, Xenon Pharmaceuticals, Zogenix, and Zynerba. J. French has also received research grants from Acorda, Alexza, Eisai Medical Research, LCGH, Lundbeck, Pfizer, SK Life Sciences, Sunovion, Takeda, and UCB, as well as grants from the Epilepsy Research Foundation, Epilepsy Study Consortium, Epilepsy Therapy Project, and NINDS. She is on the Scientific Advisory Board of Ovid, Sage Therapeutics, and Blackfynn. She is on the editorial board of Lancet Neurology, Neurology Today, and Epileptic Disorders. She is scientific officer for the Epilepsy Foundation for which NYU receives salary support. She has received travel reimbursement related to research, advisory meetings, or presentation of results at scientific meetings from the Epilepsy Study Consortium, the Epilepsy Foundation, Eisai, GW Pharma, Mar-inus, Nestle Life Sciences, Novartis, Pfizer, Sage, SK life Sciences, Takeda, UCB, Upsher-Smith, Zogenix, and Zynerba. S. Hwang reports no disclosures relevant to the manuscript. A. Pack received royalties for the UpToDate website. M. Sam reports no disclosures relevant to the manuscript. A. Birnbaum reports research support from the NIH and Veloxis Pharmaceuticals. R. Finnell receives research support from the NIH. Go to Neurology.org/N for full disclosures.
This work was supported by NIH NINDS, NICHD U01-NS038455 (K.J.M., P.B.P.), U01-NS050659 (R.C.M.), and 2U01-NS038455 (K.J.M., P.B.P., R.C.M.). The funding source had no role in the analyses, writing the manuscript, or the decision to submit for publication.
and honoraria and travel support from American Epilepsy Society, American Academy of Neurology, Epilepsy Foundation, NIH, and academic institutions for CME lectures. R. May reports no disclosures relevant to the manuscript. L. Van Mater has received support from Shire Pharmaceuticals (now Takeda) for travel to several investigator meetings. F. McEl-rath has received research support from the NIH, Abbott Diagnostics, and NxPrenatal. C. Brown reports no disclosures relevant to the manuscript. E. Gerard received research support from Sage Pharmaceuticals and Sunovion Pharmaceuticals and received speaker and travel funds from UCB Pharma. L. Kalayjian and E. Gedzelman report no disclosures relevant to the manuscript. P. Penovich received consulting fees for SK Biosciences and Neuralis and has served on speakers bureaus for Eisai, Sunovian, GW Pharmaceuticals, Aquestive Therapeutics, and UCB. J. Cavitt received research support from NINDS (MONEAD) and from GW Pharmaceuticals. J. French receives NYU salary support from the
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