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Managing Pregnancy-Related Issues in Women with Epilepsy

Updated guidelines from the American Academy of Neurology and the American Epilepsy Society

The American Academy of Neurology and the American Epilepsy Society have updated their guidelines about pregnancy-associated risks in women with epilepsy (WWE) who are using antiepileptic drugs (AEDs). Highlights of the new guidelines, which are based on evidence published from 1985 to 2008, are as follows:

PRENATAL EXPOSURE TO AEDS

• Valproate is associated with excess risk for neural tube defects and facial clefts; if possible, this agent should be avoided (particularly in polytherapy), or dosage should be limited during the first trimester.
  
• Compared with AED monotherapy, polytherapy probably increases risk for major congenital malformations (MCMs) when given during the first trimester and for poor cognitive outcomes when given throughout pregnancy; if possible, use of AED polytherapy should be avoided during pregnancy.
  
• Prenatal exposure to valproate is probably associated with poor cognitive outcomes; prenatal exposure to phenytoin or phenobarbital is possibly associated with poor cognitive outcomes. If possible, these AEDs should be avoided during pregnancy.
  

MATERNAL FOLIC ACID SUPPLEMENTATION

• Preconception folic acid supplementation with at least 0.4 mg daily may be considered as it probably lowers risk for MCMs in offspring of WWE, but data are insufficient to determine whether daily doses >0.4 mg offer greater protective benefits.
  

OBSTETRIC COMPLICATIONS

• WWE who smoke might have substantially higher risk for premature delivery than women without epilepsy who smoke; counseling about this risk should be provided.
  
• Pregnancy affects metabolism or clearance of many AEDs; monitoring of serum levels should be considered for some AEDs (e.g., lamotrigine, carbamazepine, and phenytoin) and may be considered for other AEDs (e.g., levetiracetam and oxcarbazepine).
  
• WWE should be counseled that being seizure free for 9 months before conception is probably associated with high rates (84%–92%) of remaining seizure free during pregnancy.
  

NEONATAL COMPLICATIONS

• Compared with offspring of women without epilepsy, offspring of WWE who take AEDs probably have twice the risk for being small for gestational age and possibly for having 1-minute Apgar scores <7; maternal AED use might affect the differential diagnosis of these conditions.
  

BREAST-FEEDING

• WWE who choose to breast-feed should be aware that primidone and levetiracetam probably pass into breast milk in clinically important amounts and that gabapentin, lamotrigine, and topiramate possibly pass into breast milk in clinically important amounts; in contrast, valproate, phenobarbital, phenytoin, and carbamazepine should be considered as probably not passing into breast milk in clinically important amounts.
  

Comment: An estimated one-half million U.S. women with epilepsy are of childbearing age. Overall, these guidelines provide reassurance that issues related to epilepsy can be managed readily during pregnancy. Because AEDs pose varying risks to pregnant WWE and their offspring, clinicians and WWE alike should aim for seizure control with as few medicines as possible before conception to minimize fetal risks and increase the likelihood of remaining seizure free during pregnancy. Maternal folic acid intake is important; no evidence suggests that doses higher than 0.4 mg are harmful, and the American College of Obstetricians and Gynecologists recommends daily supplementation with 4.0 mg of folic acid for women at risk for having offspring with neural tube defects (e.g., WWE who use AEDs). Evidence is insufficient to comment on prenatal vitamin K supplementation in WWE to reduce risk for neonatal hemorrhagic complications; however, all newborns routinely receive vitamin K at birth. WWE who smoke should be strongly urged to quit.

— Wendy S. Biggs, MD

Published in Journal Watch Women's Health June 11, 2009

Citation(s):

Harden CL et al. 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 May 20; [e-pub ahead of print]. (http://dx.doi.org/10.1212/WNL.0b013e3181a6b325)

Harden CL et al. 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 Apr 27; [e-pub ahead of print]. (http://dx.doi.org/10.1212/WNL.0b013e3181a6b2f8)

Harden CL et al. 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 Apr 27; [e-pub ahead of print]. (http://dx.doi.org/10.1212/WNL.0b013e3181a6b312)

Reader Remarks:

Review and add to remarks on this article

• When to switch the AED
  V.R. Quezada, 22 Jun 2009 12:44 PM EST
  Considering that valproate, phenobarbital, and pheytoin are associated with poor cognitive outcomes (and VPA with neural tube defects) and thus... [more]
• Women with epilepsy
  Dr Jude Osa Omoregie, St Jude Medical Centre Jattu, 6 Jul 2009 2:55 PM EST
  I think this report is heart warming and should serve as a guide to all gynaecologists. It is however disheartning... [more]
• Response to "When to switch the AED"
  Kimford J. Meador, MD, Professor of Neurology, Emory University, 15 Sep 2009 3:47 PM EST
  I interpret your query to mean that the woman in question was already receiving valproate, phenobarbital, or phenytoin for her... [more]

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