Management issues for women with epilepsy—Focus on pregnancy (an evidence‐based review): III. Vitamin K, folic acid, blood levels, and breast‐feeding: Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the American Epilepsy Society
Open accessAbstract
Summary: A committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including preconceptional folic acid and prenatal vitamin K use and the clinical implications of placental and breast‐milk transfer of antiepileptic drugs (AEDs). The committee evaluated the available evidence based on a structured literature review and classification of relevant articles. 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 clinically important amounts. 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 concentrations of lamotrigine, phenytoin, and, to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative (MHD). Supplementing WWE with at least 0.4 mg of folic acid before pregnancy may be considered. Monitoring of lamotrigine, carbamazepine, and phenytoin levels during pregnancy should be considered, and monitoring of levetiracetam and oxcarbazepine (as MHD) levels may be considered. A paucity of evidence limited the strength of many recommendations.
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AED use during pregnancy is associated with adverse neurodevelopment outcomes in children.
“AED use during pregnancy is associated with risks to the fetus as these drugs can cross the placenta or may be transferred to the infant through breast feeding and may be associated with adverse neurodevelopment outcomes.2–4”
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- Authors
- Harden, C. L., Pennell, P. B., Koppel, B. S., Hovinga, C. A., Gidal, B., Meador, K. J., Hopp, J., Ting, T. Y., Hauser, W. A., Thurman, D., Kaplan, P. W., Robinson, J. N., French, J. A., Wiebe, S., Wilner, A. N., Vazquez, B., Holmes, L., Krumholz, A., Finnell, R., Shafer, P. O., & Le Guen, C. L.
- Affiliations
- University of Miami (US)
- Emory University (US)
- New York Medical College (US)
- University of Tennessee Health Science Center (US)
- University of Wisconsin–Madison (US)
- University of Maryland, Baltimore (US)
- Columbia University (US)
- Centers for Disease Control and Prevention (US)
- Johns Hopkins University (US)
- Harvard University (US)
- New York University (US)
- University of Calgary (CA)
- Texas A&M University (US)
- Beth Israel Deaconess Medical Center (US)
- ORCID
- Venue
- Epilepsia
- Publisher
- Wiley
- Published
- 2009-05
- Volume
- 50
- Issue
- 5
- Pages
- 1247-1255
- ISSN
- 0013-9580 (ISSN-L)
- 1528-1167
- OpenAlex
- W2072538443
- Cited by
- 170
- References
- 45
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 5 · 2023: 9 · 2022: 4 · 2021: 4 · 2020: 6 · 2019: 9 · 2018: 8 · 2017: 6 · 2016: 13 · 2015: 17 · 2014: 16 · 2013: 11 · 2012: 19
- FWCI
- 15.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Epilepsia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Milken Family Foundation
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
- Keywords
- women with epilepsy, pregnancy, antiepileptic drugs, placental transfer, breast milk transfer, congenital malformations, bleeding complications, lamotrigine, phenytoin, carbamazepine, levetiracetam, oxcarbazepine, therapeutic drug monitoring, primidone, valproic acid
- MeSH terms
- Congenital Abnormalities, Anticonvulsants, Breast Feeding, Epilepsy, Female, Folic Acid, Vitamin K Deficiency Bleeding, Humans, Infant, Newborn, Milk, Human, Placenta, Pregnancy, Pregnancy Complications, Risk, Vitamin K
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