Which anti-seizure medications are safest during pregnancy?

2 minute read

The largest analysis to date singles out three clear winners.

Levetiracetam, oxcarbazepine, and lamotrigine are the anti-seizure medications associated with the lowest incidence of birth defects when taken during pregnancy, a Monash University study has concluded.

Researchers analysed data from more than 9800 pregnancies during which mothers took one of eight common anti-seizure medications. The study ran over 24 years across more than 40 countries.

Valproate ranked as the riskiest, with almost 10% of neonates exposed to it during pregnancy having a major congenital malformation, the researchers reported in JAMA Neurology.

Fetal exposure to topiramate, carbamazepine, phenobarbital and phenytoin resulted in between 4.9% and 6.3%   developing birth defects. Lamotrigine, oxcarbazepine and levetiracetam were associated with the lowest incidence (3.1%, 2.9% and 2.5% respectively).

The study noted that most women with epilepsy needed to continue their medication throughout pregnancy, so therefore this comprehensive data analysis would be helpful for clinicians prescribing for women of childbearing age.

It was noted that the risk of major congenital malformations due to maternal intake of valproate, phenobarbital, and carbamazepine positively correlated with increased dosages. However, even the lowest doses of valproate (less than 650mg daily) were associated with higher teratogenic risk than lamotrigine, oxcarbazepine and levetiracetam.

Overall, the researchers noted there was a shift in the prevalence of major congenital malformations in infants exposed to anti-seizure medications over the duration of the study – down from 6.1% in the 1998-2004 period to 3.7% between 2015-2022.

The authors attributed this to the declining popularity of valproate and carbamazepine and the increased use of levetiracetam and lamotrigine.

“The categories of major congenital malformations that declined most markedly (by at least 50% from first to last period) were neural tube defects, hypospadias, oral clefts, and polydactyly, some of which are associated to a greater extent with valproate and carbamazepine,” they wrote.

JAMA Neurology 2024, online 18 March

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