Vitamin K, Folic Acid, Blood Levels, and Breastfeeding
Dr. Harden and coauthors also analyzed articles published between 1985 and October 2007 to assess the evidence for management issues related to preconceptional folic acid use, risk of hemorrhage of the newborn, prenatal vitamin K use, transfer of AEDs through the placenta and breast milk, and change in AED levels during pregnancy.
The authors recommended that physicians consider supplementing women with a minimum of 0.4 folic acid before they become pregnant in order to reduce the newborn’s risk for major congenital malformations. “There has long been a concern about decreased folic acid being a mechanism of increased birth defects in the population we treat, because many of the medicines we use do have an antifolate mechanism,” said Dr. Hopp, an Assistant Professor of Neurology at the University of Maryland in Baltimore. “However, we haven’t found that folate acid supplementation completely mitigates the risk of birth defects in our specific population.”
The association between neonatal hemorrhage and enzyme-inducing AEDs was not significant, but a substantial risk could not be excluded. “It was found that the enzyme-inhibiting AEDs likely do not increase the risk of hemorrhage in newborns who get vitamin K intramuscularly at birth, but the evidence was not conclusive,” Dr. Hopp stated.
The committee reported that primidone and levetiracetam are transferred into breast milk in what may be considered clinically important amounts, but valproate, phenobarbital, phenytoin, and carbamazepine are not. In addition, significant amounts of most antiseizure medications were found to cross the placenta.
Dr. Harden and coauthors recommended that physicians consider monitoring blood levels of lamotrigine, carbamazepine, phenytoin, levetiracetam, and oxcarbazepine during pregnancy. Although there was a lack of evidence regarding changes in phenobarbital, valproate, primidone, and ethosuximide, the authors do not infer that blood levels of these drugs should not be monitored as well.
Emerging Data
The update was prompted by a plethora of new data regarding best management of women with epilepsy and emerging information about risks of AEDs related to reproductive issues,” Dr. Harden stated. “Further, the previous practice parameters did not employ the current, more rigorous evidence-based analysis of the data, since it had not been developed at that time.” New information from pregnancy registries is expected to emerge in the next year, as are data from various industry-sponsored registries. “Very soon, we should have more ballpark estimates for the risks of some of the most widely used AEDs, such as levetiracetam, topiramate, gabapentin, oxcarbazepine, and pregabalin,” Dr. Harden said.
—Laura Sassano