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Published online before print April 27, 2009, doi:10.1212/WNL.0b013e3181a6b325)
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Received January 13, 2009
Accepted March 23, 2009

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

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

From the University of Miami (C.L.H.), Miami, FL; Emory University (P.B.P., K.J.M.), Atlanta, GA; New York Medical College (B.S.K.), New York; University of Tennessee Health Science Center (C.A.H.), Memphis; University of Wisconsin–Madison School of Pharmacy (B.G.); University of Maryland (J.H., T.Y.T., A.K.), Baltimore; Columbia University (W.A.H.), New York, NY; Centers for Disease Control and Prevention (D.T.), Atlanta, GA; Johns Hopkins University (P.W.K.), Baltimore, MD; Harvard Medical School (J.N.R., L.H.), Boston, MA; New York University School of Medicine (J.A.F.), New York; University of Calgary (S.W.), Alberta, Canada; private practice (A.N.W.), Newport, RI; New York University (B.V.), New York; Texas A&M University Health Science Center (R.F.), Houston; Beth Israel Deaconess Medical Center (P.O.S.), Boston, MA; and University of Pennsylvania (C.L.), Philadelphia.


Objective: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy, including preconceptional folic acid use, prenatal vitamin K use, risk of hemorrhagic disease of the newborn, clinical implications of placental and breast milk transfer of antiepileptic drugs (AEDs), risks of breastfeeding, and change in AED levels during pregnancy.

Methods: A 20-member committee evaluated the available evidence based on a structured literature review and classification of relevant articles published between 1985 and October 2007.

Results: Preconceptional folic acid supplementation is possibly effective in preventing major congenital malformations in the newborns of WWE taking AEDs. There is inadequate evidence to determine if the newborns of WWE taking AEDs have a substantially increased risk of hemorrhagic complications. Primidone and levetiracetam probably transfer into breast milk in amounts that may be clinically important. Valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts. Pregnancy probably causes an increase in the clearance and a decrease in the concentration of lamotrigine, phenytoin, and to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative.

Recommendations: Supplementing women with epilepsy with at least 0.4 mg of folic acid before they become pregnant may be considered (Level C). Monitoring of lamotrigine, carbamazepine, and phenytoin levels during pregnancy should be considered (Level B) and monitoring of levetiracetam and oxcarbazepine (as monohydroxy derivative) levels may be considered (Level C). A paucity of evidence limited the strength of many recommendations.


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