Spontaneous abortion and the prophylactic effect of folic acid supplementation in epileptic women undergoing antiepileptic therapy

Pittschieler, Sabine; Brezinka, Christoph; Jahn, Beate; Trinka, Eugen; Unterberger, Iris; Dobesberger, Judith; Walser, Gerald; Auckenthaler, Andrea; Embacher, Norbert; Bauer, Gerhard; Luef, Gerhard

doi:10.1007/s00415-008-0029-1

Cited by 65 publications

(37 citation statements)

References 33 publications

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“…Nine fetal losses (9/74 or 11.4%) in the epileptic group in the current study (7 spontaneous abortions and 2 stillbirths) were higher than some previously published data 18,25 . Th omas et al showed a higher rate among women with epilepsy (4%) than in controls (2%).…”

Section: Fetal Losscontrasting

confidence: 71%

“…In the group of women taking VPA as monotherapy, supplementation of FA had signifi cant benefi t. Other examined monotherapies (CBZ, PHE, and PB) known to interfere with FA showed no signifi cant results. Th is study confi rmed the prophylactic eff ect of FA supplementation on spontaneous abortion and the fact that FA supplementation should be included in therapy of every pregnant epileptic woman, especially those treated with VPA 18 . In the NEAD study of children exposed in utero to AED, maternal periconceptional folate intake was associated with higher IQ of their children at the age of six, but the authors concluded that this fi nding should be interpreted with caution because periconceptional folate was one of several confounding variables, and was established by retrospective maternal interview in the study of neurodevelopmental effects of AEDs 19 .…”

Section: Folic Acid Intake and Counseling Of Epileptic Pregnant Womenmentioning

confidence: 75%

“…Th e risk was higher in women on valproate (8%) than in those on other AEDs (1%-6%) 25 . Pittschieler et al report results of a non-randomized, partly retrospective study with 10% of spontaneous abortions in women with epilepsy and a lower range of spontaneous abortion among those using FA supplementation 18 . Our results also suggested a signifi cantly higher risk of spontaneous abortion in epileptic pregnancies as compared to controls.…”

Section: Fetal Lossmentioning

confidence: 99%

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The Croatian Model of Integrative Prospective Management of Epilepsy and Pregnancy

Miškov¹,

Juraški

Mikula³

et al. 2016

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SUMMARY -Epilepsy is the most common neurological complication in pregnancy. Women with epilepsy have a higher risk of complications in pregnancy. In Croatia, women with epilepsy are treated by neurologists at tertiary centers according to the place of residence. We prospectively followed-up pregnancies in women with epilepsy and healthy controls, and analyzed the factors responsible for their delivery outcomes and development of their babies. Healthy pregnant women had a higher level of education and economic status, but pregnant women with epilepsy took folic acid in a higher proportion than controls, possibly due to timely preconception counseling. Complications during pregnancy depended on the number of antiepileptic drugs and epilepsy control. We noticed some behavioral and cognitive aspects in children exposed in utero to valproic acid, which required follow up. Th e rate of congenital malformations was not increased. In conclusion, women with epilepsy should receive preconception counseling about the risk for pregnancy, but also about the possibilities to minimize that risk. We have introduced a model of integrative management of pregnancy and epilepsy based on close collaboration among diff erent clinical experts in Croatia, in order to provide prompt counseling and timely intervention.

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Section: Fetal Losscontrasting

confidence: 71%

Section: Folic Acid Intake and Counseling Of Epileptic Pregnant Womenmentioning

confidence: 75%

Section: Fetal Lossmentioning

confidence: 99%

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The Croatian Model of Integrative Prospective Management of Epilepsy and Pregnancy

Miškov¹,

Juraški

Mikula³

et al. 2016

acc

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“…19 The latter study, however, did not have the power to control for other risk factors. A limitation of our analysis, on the other hand, is the classification of appropriate folate supplementation, which we defined arbitrarily only by exposure time (started at least 3 months before conception and maintained throughout the first trimester irrespective of dose), but similar definitions have been used by others.…”

Section: Methodsmentioning

confidence: 97%

Antiepileptic drugs and intrauterine death

et al. 2015

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Objective: To compare the risk of spontaneous abortions and stillbirth associated with maternal use of different antiepileptic drugs (AEDs). Methods:The EURAP registry is an observational international cohort study primarily designed to determine the risk of major congenital malformations (MCMs) after prenatal AED exposure. Using EURAP data, we prospectively monitored pregnancies exposed to the 6 most common AED monotherapies and to polytherapy. Intrauterine death (spontaneous abortion and stillbirth combined) was the primary endpoint.Results: Of 7,055 pregnancies exposed to monotherapy with lamotrigine (n 5 1,910), carbamazepine (n 5 1,713), valproic acid (n 5 1,171), levetiracetam (n 5 324), oxcarbazepine (n 5 262), or phenobarbital (n 5 260), and to polytherapy (n 5 1,415), 632 ended in intrauterine deaths (592 spontaneous abortions and 40 stillbirths). Rates of intrauterine death were similar across the different monotherapies (8.2%; 95% confidence interval [CI] 7.5%-8.9%), higher with polytherapy (12.1%; 95% CI 10.5%-13.9%), but showed no relationship with AED dose in monotherapy at conception. Multivariable analysis including 11 covariates in addition to the different AED exposures showed that the risk was greater with polytherapy vs monotherapy (risk ratio [RR] 1.38; 95% CI 1.14-1.66), parental history of MCMs (RR 1.92; 1.20-3.07), maternal age (RR 1.06; 1.04-1.07), and number of previous intrauterine deaths (RR 1.09; 1.00-1.19). The risk was greater with early enrollment and decreased with later gestational week at enrollment (RR 0.84; 0.82-0.86). Conclusions:The most important risk factors for intrauterine death in pregnancies of women with epilepsy include maternal exposure to AED polytherapy and the presence of MCMs in at least one of the parents. Neurology ® 2015;85:580-588 GLOSSARY AED 5 antiepileptic drug; CBZ 5 carbamazepine; CI 5 confidence interval; EURAP 5 International Registry of Antiepileptic Drugs and Pregnancy; LTG 5 lamotrigine; MCM 5 major congenital malformation; RR 5 risk ratio; VPA 5 valproic acid.Ever since the first report of major congenital malformations (MCMs) in the offspring of women taking antiepileptic drugs (AEDs) in pregnancy, 1 research has been dedicated to the assessment of teratogenic risks associated with AEDs. Concerns focused primarily on the risk of MCMs 2,3 and, more recently, on impaired cognitive and behavioral development after prenatal AED exposure. 4,5 Registries set up in the late 1990s have enrolled thousands of pregnancies and enabled comparisons of MCM rates between different AEDs at different dose levels. [6][7][8][9] Other observational studies have revealed differences in postnatal cognitive development.5 For both *These authors contributed equally to this work.

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“…However recent evidence fails to support the same. Many reports [18][19][20] demonstrated no decrease in the risk of NTD of valproate by supplementation of folatets.…”

Section: Discussionmentioning

confidence: 99%

Maternal and Fetal Outcomes of Women with Epilepsy: Study from a Tertiary Care Center in India

Chawla¹

2015

OGIJ

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Spontaneous abortion and the prophylactic effect of folic acid supplementation in epileptic women undergoing antiepileptic therapy

Abstract: This study confirms the prophylactic effect of folic acid supplementation on spontaneous abortion. For AED therapy, folic acid supplementation should be part of the therapy of every pregnant epileptic woman, especially for those treated with VPA.

Cited by 65 publications

References 33 publications

The Croatian Model of Integrative Prospective Management of Epilepsy and Pregnancy

The Croatian Model of Integrative Prospective Management of Epilepsy and Pregnancy

Antiepileptic drugs and intrauterine death

Maternal and Fetal Outcomes of Women with Epilepsy: Study from a Tertiary Care Center in India

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