Breastfeeding while on treatment with antiseizure medications: a systematic review from the ILAE Women Task Force

Abstract

We carried out a systematic review of published information on transfer of antiseizure medications (ASMs) into breastmilk, ASM serum concentrations in breastfed infants, and the wellbeing of infants breastfed by mothers on ASM treatment. Information was extracted from 85 relevant articles. No data on ASM levels in breastmilk or in breastfed infants was identified for cannabidiol, cenobamate, clobazam, eslicarbazepine-acetate, everolimus, felbamate, fenfluramine, retigabine, rufinamide, stiripentol, tiagabine, and vigabatrin. For ASMs, with available information on levels in breastfed infants, very low concentrations (in the order of 10% or less of maternal serum concentrations) were reported for carbamazepine, gabapentin, levetiracetam, oxcarbazepine, phenytoin, valproate, and clonazepam. Slightly higher levels (up to approximately 30% of maternal serum concentrations) have been observed with lamotrigine and topiramate, and in single case reports for brivaracetam, lacosamide, and perampanel. High infant levels (30% up to 100% of maternal serum concentrations) have been reported with ethosuximide, phenobarbital and zonisamide. Adverse infant effects during breastfeeding by mothers on ASMs appear to be rare regardless of the type of ASM, but systematic study is limited. Prospective long-term follow-up studies of developmental outcomes among children who have been breastfed by mothers taking ASMs are sparse and have mainly involved children whose mothers were taking carbamazepine, lamotrigine, levetiracetam, phenytoin or valproate as monotherapy while breastfeeding. Although these studies have not indicated poorer outcome among breastfed children compared with those who were not breastfed, further data on long-term outcomes are needed to draw firm conclusions. It is concluded that breastfeeding should in general be encouraged in women taking ASMs, given the well-established benefits of breastfeeding with regard to both short-and long-term infant health in the general population. Counselling needs to be individualized including information on the current knowledge regarding the woman's specific ASM treatment.

Management of epilepsy during pregnancy and lactation

“…Some experts have recommended breastfeeding with caution for women with epilepsy taking phenobarbital, primidone, clobazam, and clonazepam, with close monitoring of the infant for lethargy, hypotonia, poor suck, or apneas 106. Breastfeeding for women with epilepsy taking felbamate is generally avoided owing to lack of safety evidence for the infant and known risks of acute hepatic failure and aplastic anemia in adults 107108. Another notable feature of the NEAD and MONEAD studies is that antiseizure medication exposure in utero preceded exposure during breastfeeding.…”

Management of epilepsy in pregnancy: What we still need to learn

“…Another important lesson learned is that some ASMs, notably phenobarbital, probably lamotrigine and zonisamide, are extensively transferred into breastmilk but also that immediate or long-term adverse effects of breastfeeding are rare [14] , [15] , [16] . Given the benefits of breastfeeding to both mother and child, breastfeeding should be encouraged for women with epilepsy taking ASMs.…”

“…When known, ASM concentrations in children breastfed by mothers on treatment are generally very low. However, for some ASMs, notably phenobarbital and ethosuximide, the serum concentrations in the breastfed infant may reach levels comparable to those in the treated mother [14] . Data for lamotrigine have been variable, with ratios lower to 0.2 and higher to nearly 1 [14] , [24] , [25] .…”

“…However, for some ASMs, notably phenobarbital and ethosuximide, the serum concentrations in the breastfed infant may reach levels comparable to those in the treated mother [14] . Data for lamotrigine have been variable, with ratios lower to 0.2 and higher to nearly 1 [14] , [24] , [25] . However, the average ratio is about 0.3.…”

Lacosamide use during breastfeeding: A case report and a literature review

“…Women with epilepsy are less likely to breastfeed compared to healthy women [1]. This is partly due to concerns from mothers, their healthcare providers, or both, who worry about anti‐seizure medication (ASM) passing into breast milk, resulting in potential negative risks for the infants [1]. Lacosamide, a voltage‐gated sodium channel inhibitor, is an ASM from the age of 4.…”