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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Practice parameter update: management issues for women with epilepsy - focus on pregnancy (an evidence-based review): obstetrical complications and change in seizure frequency. Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society

CL Harden, J Hopp, TY Ting, PB Pennell, JA French, WA Hauser, S Wiebe, GS Gronseth, D Thurman, KJ Meador, BS Koppel, PW Kaplan, JN Robinson, B Gidal, CA Hovinga, AN Wilner, B Vazquez, L Holmes, A Krumholz, R Finnell, and C Le Guen.

Review published: 2009.

CRD summary

This review concluded that seizure freedom for at least nine months prior to pregnancy in women with epilepsy was probably associated with a high rate of remaining seizure-free during pregnancy, but women with epilepsy who smoke may have a substantially increased risk of premature contractions and premature labour and delivery. Given weaknesses in the evidence, these cautious conclusions appear appropriate.

Authors' objectives

To assess the evidence for management issues related to the care of women with epilepsy during pregnancy, including the risk of complications or other medical problems, change in seizure frequency, risk of status epilepticus, and the rate of remaining seizure-free during pregnancy.

Searching

MEDLINE, Current Contents and BIOSIS Previews databases were searched from December 1985 to June 2007 for relevant studies, published in any language with an English abstract. Hand searches were conducted up to February 2008. Search terms were reported. Bibliographies of reviews and meta-analyses were also examined for relevant publications.

Study selection

Studies that reported the frequency of pregnancy-related or epilepsy-related complications in a cohort of women with epilepsy were eligible for inclusion in the review. Studies were excluded if they related to eclampsia rather than seizures due to epilepsy, or if they related to basic mechanisms such as teratogenesis or placental anti-epileptic drug metabolism, or were otherwise unrelated to the objective.

Among included studies, reported pregnancy-related complications included: caesarean delivery; pre-eclampsia; pregnancy-induced hypertension; premature contractions, labour and delivery; pregnancy-related bleeding complications; and spontaneous abortion. Reported epilepsy outcomes included change in seizure frequency, status epilepticus, and seizure recurrence in previously seizure-free women with epilepsy.

At least two reviewers were involved in the selection of studies for inclusion.

Assessment of study quality

Included studies were classified (from class I to IV) according to pre-specified study design criteria (incorporating sample selection, outcome selection and outcome measurement). A different classification scheme was used for studies evaluating recurrent seizures in seizure-free women with epilepsy than for other outcomes, as the measure of interest was absolute rather than a relative risk.

Four reviewers independently classified the studies with disagreements resolved by discussion and consensus.

Data extraction

Odds ratios (ORs) and related 95% confidence intervals (95% CIs) were extracted from the included studies. If not reported, these values were calculated where possible. The reviewers contacted the authors of one study to obtain additional data.

The authors did not state how many reviewers performed the extraction.

Methods of synthesis

The studies were combined in a narrative synthesis, grouped by outcome. A moderately increased risk was defined by an odds ratio of greater than 1.5 and less than 2.0. An odds ratio greater than 2.0 was considered a substantially increased risk.

Results of the review

Twenty-five studies were included in the review (n=unclear). For pregnancy-related complications, nine studies were class III or higher and summarised in the synthesis. Fourteen studies reporting epilepsy-related complications were included in the synthesis.

Caesarean delivery: One class I and one class II study reported no significant increase in risk of caesarean delivery in women with epilepsy. Three class III studies reported a significant substantial increased risk (p<0.05).

Pre-eclampsia: One class I and two class II studies reported no significant increase in risk of pre-eclampsia in women with epilepsy.

Pregnancy-induced hypertension: One class II study reported a significant increase in risk of pregnancy-induced hypertension in women with epilepsy. Another class II study and two class II studies reported no significant increase in this complication.

Premature contractions, labour and delivery: One class I study showed no substantially increased risk of premature labour and delivery in women with epilepsy taking anti-epileptic drugs. One class II study showed an increased risk for women with epilepsy who were smokers compared with control women who also smoked. Among three class III studies, one also showed an increased risk and two did not. Two further class III studies reported no significant increase in premature births/difference in gestational age in women with epilepsy.

Pregnancy related bleeding complications: One class I and one class III study showed no significant increase in the risk of late bleeding in women with epilepsy.

Spontaneous abortion: One class III study reported a decreased risk of spontaneous abortion in women with epilepsy compared to control groups.

Change in seizure frequency: Among five class IV (uncontrolled) studies, seizure frequency was unchanged from baseline in 54 to 80% of women with epilepsy. The rate of seizure decrease ranged from 3 to 24%. The rate of seizure increase ranged from 14 to 32%.

Status epilepticus: Three class IV studies reported a frequency of status epilepticus in women with epilepsy during pregnancy ranging from 0 to 1.3%.

Seizure recurrence in previously seizure-free women with epilepsy: Two class II articles reported that for women with epilepsy who were seizure-free nine months prior to pregnancy, 84 to 92% remained seizure-free during pregnancy.

Authors' conclusions

Women with epilepsy should be counselled that seizure freedom for at least nine months prior to pregnancy was probably associated with a high rate of remaining seizure-free during pregnancy. However, women with epilepsy who smoke should be advised that they may have a substantially increased risk of premature contractions, and premature labour and delivery.

CRD commentary

The review question was defined in terms of the participants, outcomes and study designs of interest. Attempts were made to identify relevant evidence from multiple sources, regardless of language. With the exception of data extraction, the authors reported attempts to minimise bias at each stage of the review process.

Validity of studies was broadly assessed using established criteria; this assessment was incorporated into the synthesis. The use of a narrative synthesis appeared appropriate, given the apparent heterogeneity of the included studies; although the number of studies referred to in the synthesis did not appear to always match that presented in the data extraction tables.

Given the weakness of the available evidence, the authors' cautiousness about their conclusions appears appropriate.

Implications of the review for practice and research

Practice: The authors did not state any additional implications for practice.

Research: The authors stated that evidence from large, prospective studies, with well matched control groups, is needed to establish the risks of pre-eclampsia, pregnancy-induced hypertension, and spontaneous abortion in women with epilepsy. They added that the effects of anti-epileptic drugs could be investigated further, as could the risks of seizure increase during pregnancy.

Funding

The Milken Family Foundation.

Bibliographic details

Harden CL, Hopp J, Ting TY, Pennell PB, French JA, Hauser WA, Wiebe S, Gronseth GS, Thurman D, Meador KJ, Koppel BS, Kaplan PW, Robinson JN, Gidal B, Hovinga CA, Wilner AN, Vazquez B, Holmes L, Krumholz A, Finnell R, Le Guen C. Practice parameter update: management issues for women with epilepsy - focus on pregnancy (an evidence-based review): obstetrical complications and change in seizure frequency. Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society Neurology 2009; 73(2): 126-132. [PMC free article: PMC3475195] [PubMed: 19398682]

Other publications of related interest

Harden CL, Meador KJ, Pennell PB, Hauser WA, Gronseth GS, French JA, Wiebe S, Thurman D, Koppel BS, Kaplan PW, Robinson JN, Hopp J, Ting TY, Gidal B, Hovinga CA, Wilner AN, Vazquez B, Holmes L, Krumholz A, Finnell R, Hirtz D, Le Guen C. Practice parameter update: management issues for women with epilepsy - focus on pregnancy (an evidence-based review): teratogenesis and perinatal outcomes. Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology 2009;73(2):133-141.

Harden CL, Pennell PB, Koppel BS, Hovinga CA, Gidal B, Meador KJ, Hopp J, Ting TY, Hauser WA, Thurman D, Kaplan PW, Robinson JN, French JA, Wiebe S, Wilner AN, Vazquez B, Holmes L, Krumholz A, Finnell R, Shafer PO, Le Guen C. Practice parameter update: management issues for women with epilepsy - focus on pregnancy (an evidence-based review): vitamin K, folic acid, blood levels, and breastfeeding. Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology 2009;73(2):142-149.

Indexing Status

Subject indexing assigned by NLM

MeSH

Abortion, Spontaneous /epidemiology; Anticonvulsants /therapeutic use; Cesarean Section; Epilepsy /drug therapy /epidemiology; Female; Humans; Hypertension /epidemiology; Obstetric Labor, Premature /epidemiology; Odds Ratio; Pre-Eclampsia /epidemiology; Pregnancy; Pregnancy Complications /drug therapy /epidemiology; Recurrence; Risk; Smoking /epidemiology; Status Epilepticus /drug therapy /epidemiology; Uterine Hemorrhage /epidemiology

AccessionNumber

12009107455

Database entry date

15/09/2010

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 19398682

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