How does levetiracetam compare with other anti-epileptic drugs in terms of congenital malformations in children?

Abstract

Reviewers assessed the incidence of congenital malformations in children associated with levetiracetam versus carbamazepine, gabapentin, lamotrigine, oxycarbazepine, phenobarbital, phenytoin, topiramate, zonisamide, and valproate; no trial compared levetiracetam with primidone. Major malformations were rare, occurring most commonly with phenobarbital (6% of infants; all values on average), valproate (4%), and topiramate (4%); rates for levetiracetam ranged from 0.1% to 2.4% across comparisons. In absolute numbers, the greatest reductions with levetiracetam were observed when compared with phenobarbital (24 vs 55 per 1000 infants), valproate (7 vs 38 per 1000 infants), topiramate (21 vs 42 per 1000 infants), and phenytoin (14 vs 29 per 1000 infants). Reviewers assessed neural tube, cardiac, orofacial cleft/craniofacial, and skeletal/limb malformations separately; similarly, highest rates were observed with valproate, phenytoin, and phenobarbital, although rates were ≤ 2.5% in all groups across all comparisons. It is worth noting that none of the studies were RCTs and all were classified as being at high risk for selection bias and high or unclear risk for blinding of outcome assessment. In addition, details of the regimens used for each antiepileptic drug were not reported, making it difficult to assess the generalizability of results to clinical practice.