Women with epilepsy, who are childbearing potential, and their physicians face difficult decisions about the risks and benefits of antiepileptic drug (AED) use during pregnancy. These decisions need to be addressed prior to pregnancy, as about half of the pregnancies in the USA are not planned. Effective seizure control for the potential mother is extremely important, but often difficult to maintain during pregnancy as a result of unpredictable metabolic changes during pregnancy. The need for seizure control must be balanced against possible serious adverse outcomes for the child exposed to AED medications during gestation and/or breastfeeding.
In the last decade, pregnancy registries have begun to identify differential risks across AEDs. In particular, their results have indicated that valproate poses the highest risk for major congenital malformations (10.7% of children exposed to valproate during their mother’s pregnancy). Other drugs with noted risks of malformations include phenobarbital (about 6.5%) and topiramate (about 4.8% overall and 1.4% for cleft lip/palate defects). Lower risks near the general population are seen for carbamazepine and lamotrigine, but even these AEDs, as well as phenobarbital and valproate, have demonstrated dose dependent risks (i.e., more malformations with higher AED dose). Although less information is available, levetiracetam also appears to have a low risk for malformations. The malformation risks for many other AEDs remain uncertain.
In 2011, the FDA added a new warning for risk of cognitive impairments for children who had fetal exposure to valproate. The primary basis for this warning was findings from the NEAD Study, which has found that children exposed in utero to valproate have IQs which are 7-10 points lower than other commonly used AEDs. This study found deficits not only in IQ but also in many other cognitive functions. All of these adverse effects were worse at higher doses of valproate. Recently, a study from Denmark reported an increase risk of autism in children exposed to valproate during their mother’s pregnancy.
However, the risks of many AEDs remain uncertain for malformations, cognitive deficits and behavioral problems in the children, as well as many other pregnancy outcomes. In 2009, the American Academy of Neurology and the American Epilepsy Society identified multiple areas in the clinical management of women with epilepsy for which evidence is inconclusive or lacking.
The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) Study (previously known as NEAD Study) seeks to improve our knowledge and the care of women with epilepsy. The MONEAD Study now seeks to determine if: 1) seizures increase during pregnancy; 2) obstetrical complications (e.g., C-sections) are increased; depression is increased during pregnancy/post-partum compared to healthy women; 4) fetal AED exposure has adverse effects on intellectual abilities and behavior of the children; 5) adverse neonatal outcomes (e.g., small for gestation age) are increased; 6) breastfeeding when taking AEDs is safe. The study will determine if risks are higher for certain AEDs and delineate contributing factors such as differences in AED metabolism during pregnancy. The MONEAD Study is now enrolling 350 pregnant women with epilepsy at 19 different sites across the USA. In addition, two comparison groups are being enrolled including100 non-pregnant women with epilepsy and 100 healthy pregnant women. The clinical sites are listed below. For more information see www.moneadstudy.org.
MONEAD Clinical Sites
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Atlanta, Georgia
Emory University
Investigator: Kimford Meador, M.D.
Project Manager: Gene Moore
Contact: Melanee Newman
[email protected]
Augusta, Georgia
Georgia Reagents University
Investigator: Suzanne Strockland
Contact: Patty Ray
[email protected]
Baltimore, Maryland
Johns Hopkins Bayview Medical Center
Investigator: Peter Kaplan
Contact: TBD
Birmingham, Alabama
University of Alabama
Investigator: Jennifer DeWolfe
Contact: Cheryl Hall
[email protected]
Boston, Massachusetts
Brigham & Womens Hospital
Investigator: Page Pennell
Contact: Rutendo Kashambwa
[email protected]
Chicago, Illinois
Northwestern University
Investigator: Elizabeth Gerard
Contact: Irena Garic
[email protected]
Cincinnati, Ohio
University of Cincinnati
Investigator: Michael Privitera, MD
contact: Lucy Mendoza
[email protected]
Danville, Pennsylvania
Geisinger Medical Center
Investigator: Frank Gilliam
Contact: Laura Snavely
[email protected]
Detroit, Michigan
Henry Ford Hospital
Investigator: Gregory Barkley, MD
Contact: Carla M. Sandles
[email protected]
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Los Angeles, California
University of Southern California
Investigator: Laura Kalayjian, MD
Contact: Guadalupe Corral-Leyva
[email protected]
Manhasset, New York
Feinstein Institute for Medical Research NSLIJ Health System
Investigator: Cynthia Harden
Contact: Connie Lau
[email protected]
Miami, Florida
University of Miami
Investigator: Enrique Serrano
Contact: Pedro Figueredo
[email protected]
New York, New York
Columbia University
Investigator: Alison Pack, MD
Contact: Elizabeth Baez
[email protected]
New York, New York
New York University
Investigator: Jacqueline French
Contact: Benny Kaufman
[email protected]
Pittsburgh, Pennsylvania
University of Pittsburgh
Contact: Katherine Kniseley
[email protected]
Seattle, Washington
University of Washington
Investigator: John Miller, MD
Contact: Samantha Coleman
[email protected]
St. Paul, Minnesota
Minnesota Epilepsy Group
Investigator: Patricia Penovich, MD
Contact: Geraldine Pira
[email protected]
Tucson, Arizona
University of Arizona Health Sciences
Investigator: David Labiner, MD
contact: Susan Merski
[email protected]
Winston-Salem, North Carolina
Wake Forest University
Investigator: Maria Sam, MD
Contact: Janet Hutchins
[email protected]
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[success]This article was written by Dr. Kimford J Meador.[/success]
