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Is breastfeeding safe for infants of women with epilepsy taking anticonvulsant drugs?

According to the results of a study published in Seizure: Epilepsy Journal.

World health organizations recommend exclusively breastfeeding infants for at least 6 months. Deciding whether or not to stop ASM is a serious concern for half of women epilepsy who are of childbearing age. Many studies have assessed ASM concentrations in the breast milk of lactating women with epilepsy, but this is the first systematic review of such concentrations.

The researchers searched several databases and Google Scholar to identify observational studies in English that reported levels of ASM in breastfeeding women with epilepsy. They found 15 studies (9 cross-sectional studies 4 prospective cohort studies 2 case series) with generally acceptable quality. Ten studies have been published since 2000; 10 studies were from Germany or Sweden; and each study involved fewer than 50 women with epilepsy.


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The MSAs quantified were carbamazepine (2 studies), lamotrigine (5 studies), primidone and its metabolites (2 studies), levetiracetam (2 studies), ethosuximide (1 study), topiramate (1 study), gabapentin (1 study) and valproic. acid (1 study). Almost all women in most studies received at least 2 ASMs. High-performance liquid chromatography (HPLC) has been most frequently used to score ASMs.

The calculated relative infant dose (RID) tended to be less than 10% for ASM, but lamotrigine, ethosuximide, levetiracetam, and topiramate had higher RID values.

ASMs complied with Lipinski’s rule of 5, had sufficient oral bioavailability and could cross the blood-brain barrier. Most breastfed infants did not experience clinically significant adverse effects from exposure to ASM via breast milk.

One study reported that 1 of 15 breastfed infants whose mothers took carbamazepine monotherapy had difficulty suckling.

Three studies did not report the risks of exposure to lamotrigine and valproic acid in breastfed infants.

Seven of 8 infants, with no clinically significant implications, had higher platelet counts, 1 lamotrigine study reported. Six infants were sluggish, hypotonic, and suckled poorly during the first 5 days after birth in a study of women on primidone and its metabolites. After 2 days of deep sedation, 2 infants experienced withdrawal symptoms including unmotivated sobbing, tremors and sleep disturbances for a few weeks.

Another study reported that infants whose mothers took phenobarbital or primidone showed signs of sedation and some who had been exposed to primidone showed withdrawal symptoms during the first 2 weeks after birth.

A study of ethosuximide reported that 5 infants had withdrawal symptoms and 4 infants had sedation, poor sucking and drowsiness.

Study limitations included exclusion of unpublished studies in English, qualitative synthesis and lack of meta-analysis, lamotrigine RID ranges in studies, requirement to report ASM concentrations and a short follow-up.

“The studies included in this review showed that many ASMs were excreted in breast milk at high concentrations,” the researchers said. “However, the majority of these ASMs did not produce significant adverse effects that warranted discontinuation of breastfeeding.”

Reference

Shawahna R, Zaid L. Concentrations of anticonvulsant drugs in the breast milk of lactating women with epilepsy: a systematic review with qualitative synthesis. Entry: J Epilepsy. Published online March 27, 2022. doi:10.1016/j.seizure.2022.03.017

This article originally appeared on Neurology Advisor