Published online before print April 27, 2009, doi:10.1212/WNL.0b013e3181a6b312)

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NEUROLOGY 2009;73:133-141
© 2009 American Academy of Neurology

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Special Article

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 C. L. Harden, MD, K. J. Meador, MD, P. B. Pennell, MD, W. A. Hauser, MD, G. S. Gronseth, MD, J. A. French, MD, S. Wiebe, MD, D. Thurman, MD, MPH, B. S. Koppel, MD, P. W. Kaplan, MB, FRCP, J. N. Robinson, MD, J. Hopp, MD, T. Y. Ting, MD, B. Gidal, PharmD, C. A. Hovinga, PharmD, A. N. Wilner, MD, B. Vazquez, MD, L. Holmes, MD, A. Krumholz, MD, R. Finnell, PhD, D. Hirtz, MD and C. Le Guen

Authors’ affiliations are listed at the end of the article.
From the University of Miami (C.L.H.), Miami, FL; Emory University (K.J.M., P.B.P.), Atlanta, GA; Columbia University (W.A.H.), New York, NY; Kansas University Medical Center (G.S.G.), Kansas City; New York University School of Medicine (J.A.F.), New York; University of Calgary (S.W.), Alberta, Canada; Centers for Disease Control and Prevention (D.T.), Atlanta, GA; New York Medical College (B.S.K.), New York; Johns Hopkins University (P.W.K.), Baltimore, MD; Harvard Medical School (J.N.R., L.H.), Boston, MA; University of Maryland (J.H., T.Y.T., A.K.), Baltimore; University of Wisconsin–Madison School of Pharmacy (B.G.); University of Tennessee Health Science Center (C.A.H.), Memphis; private practice (A.N.W.), Newport, RI; New York University (B.V.), New York; Texas A&M University Health Science Center (R.F.), Houston; NINDS (D.H.), Bethesda, MD; and University of Pennsylvania (C.L.), Philadelphia.

Address correspondence and reprint requests to the American Academy of Neurology, 1080 Montreal Avenue, St. Paul, MN 55116 guidelines{at}aan.com

Objective: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy.

Methods: Systematic review of relevant articles published between January 1985 and June 2007.

Results: It is highly probable that intrauterine first-trimester valproate (VPA) exposure has higher risk of major congenital malformations (MCMs) compared to carbamazepine and possible compared to phenytoin or lamotrigine. Compared to untreated WWE, it is probable that VPA as part of polytherapy and possible that VPA as monotherapy contribute to the development of MCMs. It is probable that antiepileptic drug (AED) polytherapy as compared to monotherapy regimens contributes to the development of MCMs and to reduced cognitive outcomes. For monotherapy, intrauterine exposure to VPA probably reduces cognitive outcomes. Further, monotherapy exposure to phenytoin or phenobarbital possibly reduces cognitive outcomes. Neonates of WWE taking AEDs probably have an increased risk of being small for gestational age and possibly have an increased risk of a 1-minute Apgar score of <7.

Recommendations: If possible, avoidance of valproate (VPA) and antiepileptic drug (AED) polytherapy during the first trimester of pregnancy should be considered to decrease the risk of major congenital malformations (Level B). If possible, avoidance of VPA and AED polytherapy throughout pregnancy should be considered to prevent reduced cognitive outcomes (Level B). If possible, avoidance of phenytoin and phenobarbital during pregnancy may be considered to prevent reduced cognitive outcomes (Level C). Pregnancy risk stratification should reflect that the offspring of women with epilepsy taking AEDs are probably at increased risk for being small for gestational age (Level B) and possibly at increased risk of 1-minute Apgar scores of <7 (Level C).

Abbreviations: AAN = Academy of Neurology; AED = antiepileptic drug; CBZ = carbamazepine; CI = confidence interval; LTG = lamotrigine; MCM = major congenital malformation; OR = odds ratio; PB = phenobarbital; PHT = phenytoin; RR = relative risk; SGA = small for gestational age; VPA = valproate; WWE = women with epilepsy.

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Supplemental data at www.neurology.org

See pages 126 and 142

e-Pub ahead of print on April 27, 2009, at www.neurology.org.

Published simultaneously in Epilepsia.

The Mission Statements of the Quality Standards Subcommittee (QSS) and Therapeutics and Technology Assessment (TTA) Subcommittee, Conflict of Interest Statement, QSS members, TTA members, AAN classification of evidence, Classification of recommendations (appendices e-1 through e-5), as well as references e1 through e5 and tables e-1 through e-7, are available on the Neurology® Web site at www.neurology.org.

Approved by the Quality Standards Subcommittee April 15, 2008; by the Therapeutics and Technology Assessment Subcommittee December 17, 2007; by the Practice Committee January 25, 2009; and by the AAN Board of Directors March 25, 2009.

Supported by The Milken Family Foundation.

Disclosure: Author disclosures are provided at the end of the article.

Received February 2, 2009. Accepted in final form March 23, 2009.

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