While it is well-established that several of the older anticonvulsants, including valproate (Depakote), carry a significant teratogenic risk, less is known about the reproductive safety of the newer antiepileptic drugs (AEDs).  A new report from the U.K. and Ireland Epilepsy and Pregnancy Registers suggests that the risk of malformations associated with levetiracetam (LVT, Keppra) use during pregnancy is low.

These prospective, observational registries were established to determine the risk of congenital malformations associated with AED use in pregnancy. Women were enrolled before any diagnosis of malformation, typically in the first trimester.

The registry included 671 pregnancies exposed to levetiracetam (LVT) and reported on malformation rates and neonatal outcomes. The rates of major malformations were described in the following groups:

  • LVT monotherapy (n=304): Rate of major malformations was 0.70%.
  • LVT in combination with another AED (n=367): 6.47%.
  • LVT with another AED, rates of malformations were
    • 1.8% with lamotrigine
    • 6.9% with valproate
    • 9.4% with carbamazepine
  • Use of folic acid supplements did not affect the rate of MCMs.
  • LVT dose was unrelated to birth weight or gestational age.

This report indicates that with levetiracetam monotherapy, the rate of major malformations was low, but with polytherapy, rates were significantly higher.  This parallels studies with other AEDs, such as lamotrigine, where polytherapy was associated with a higher risk.  It is a bit different in that in other studies it was polytherapy with valproic acid that carried the greatest risk.

At 0.7% this rate of malformations is lower than previously reported by the North American AED Pregnancy Registry (2.4%) and the UCB Antiepileptic Drug Pregnancy Registry (4.7%). Even though it appears that these other registries reported higher rates of malformations with LVT, it appears that the risk of malformation with LVT monotherapy is lower than that observed with the older anticonvulsants, such as valproic acid.

Ruta Nonacs, MD PhD

Mawhinney E, et al. Levetiracetam in pregnancy: Results from the UK and Ireland epilepsy and pregnancy registers. Neurology 2013 Jan 22; 80:400-405.