Fetal loss and malformations in the MONEAD study of pregnant women with epilepsy

Abstract

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.

Clinical characteristics and fetal outcomes in women with epilepsy with planned and unplanned pregnancy: A retrospective study

“…Recent data from the European and International Registry of Antiepileptic Drugs in Pregnancy (EURAP) showed that prevalence of MCMs in offspring exposed prenatally to AED monotherapy ranged from 2.8 % to 10.3 %, depending on the type of AEDs [15]. In the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs study, adverse fetal outcomes including fetal loss and MCMs were significantly more common in WWE than in healthy pregnant women [34].…”

Clinical characteristics and fetal outcomes in women with epilepsy with planned and unplanned pregnancy: a retrospective study

“…15 In the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs study, adverse fetal outcomes including fetal loss and MCMs were significantly more common in WWE than in healthy pregnant women. 33 In our study, the MCM rate was significantly lower in the planned-pregnancy group (1.6%) than in the unplanned-pregnancy group (7.5%). This decrease in MCMs rate could be partly because of the relatively less use of VPA, PB, phenytoin (PHT), CBZ, and topiramate (TPM) in the planned-pregnancy group than in the unplanned group.…”

Comparison of Perinatal Outcomes for Women With and Without Epilepsy

“…There were 45 retrospective 3,[5][6][7][8][9][10][13][14][15]19,20,[22][23][24][25] and 21 prospective 11, [16][17][18]21,26,[60][61][62][63][64][65][66][67][68][69][70][71][72][73][74] cohort studies, 9 case-control studies, 4,12,75-81 and 1 cross-sectional study. 82 Sixty-two articles had a low risk of bias 3-11, 13-16, 18-26, 31-40, 42, 45, 46, 48, 50-60, 62-71,74-77,79 and 14 a high risk of bias 12,17,41,43,44,47,49,61,72,73,78,[80][81][82] (eTable 2 in Supplement 1).…”