Antiseizure medications (ASMs) can be detected in breast milk of women with epilepsy and plasma/serum of infants who have consumed breast milk, according to study findings published in Seizure: Journal of Epilepsy.
Global health organizations recommend exclusively breastfeeding infants for at least 6 months. Deciding whether to discontinue ASMs is a serious concern for half of women with epilepsy who are of childbearing age. Many studies have assessed concentrations of ASMs in breast milk of lactating women with epilepsy, but this is the first systematic review of those concentrations.
Researchers searched several databases and Google Scholar to identify English-language observational studies that reported levels of ASMs in lactating women with epilepsy. They found 15 studies (9 cross-sectional 4 prospective cohort 2 case series studies) with generally acceptable quality. Ten studies were published since 2000; 10 studies originated from Germany or Sweden; and each study involved fewer than 50 women with epilepsy.
ASMs 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). Nearly all women in most of the studies received at least 2 ASMs. High-performance liquid chromatography (HPLC) was most frequently used to note ASMs.
Calculated relative infant dose (RID) tended to be less than 10% for ASMs, but lamotrigine, ethosuximide, levetiracetam, and topiramate had higher RID values.
ASMs met 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 through exposure to ASMs via breast milk.
One study reported that 1 of 15 breastfed infants whose mothers took carbamazepine monotherapy had impaired suckling.
Three studies did not report risks exposure to lamotrigine and valproic acid on breastfed infants.
Seven of 8 infants, without clinically significant implications, had higher platelet counts, 1 study of lamotrigine reported. Six infants were sluggish, hypotonic, and suckling poorly in the first 5 days post-birth in a study that reported on women on primidone and its metabolites. After 2 days of deep sedation, 2 infants experienced withdrawal symptoms, including unmotivated sobbing, tremor, and sleep pattern disturbance for a couple of weeks.
Another study reported that infants whose mothers took phenobarbital or primidone had sedative signs and some who had been exposed to primidone experienced withdrawal symptoms in their first 2 weeks after birth.
An ethosuximide study reported 5 infants had withdrawal symptoms and 4 infants experienced sedation, poor sucking, and sleepiness.
Study limitations included exclusion of studies not published in English, qualitative synthesis and absence of meta-analysis, ranges of RIDs of lamotrigine across studies, requirement of reporting concentrations of ASMs, and short follow-up.
“The studies included in this review have shown that many ASMs were excreted into breastmilk in high concentrations,” the researchers said. “However, the majority of these ASMs did not produce significant adverse effects that warrant discontinuation of breastfeeding.”
Shawahna R, Zaid L. Concentrations of antiseizure medications in breast milk of lactating women with epilepsy: a systematic review with qualitative synthesis. Seizure: J Epilepsy. Published online March 27, 2022. doi:10.1016/j.seizure.2022.03.017