Case ReportOld and new antiepileptic drugs during pregnancy and lactation – report of a case
Introduction
Three to five of 1000 births are reported from women with epilepsy (WWE) [1], [2]. Close monitoring at frequent intervals is essential for WWE, as antiepileptic drug (AED) treatment might be associated with an increased risk for an abnormal pregnancy outcome. There is a mounting wall of literature reporting on transfer of AEDs into breast milk in an inverse proportion to their extent of protein binding [3] (Table 1). However, with the exception of barbiturates (bearing the risk of sedation), plasma concentrations in the breastfed infant are usually lower than those the fetus is exposed to via placental transfer during pregnancy [4]. Of note and as described in 1988 by Kuhnz and co-workers, withdrawal symptoms were observed in phenobarbital (PB)- and primidone (PRM)-exposed neonates of mothers who refrained from breastfeeding (PB is a metabolite of PRM), whereas in nursed infants no such symptoms occurred possibly because of slower elimination [4].
With the growing number of so-called “new” drugs (e.g., levetiracetam [LEV]), possible adverse effects on newborns ingesting AEDs via breast milk might produce anxiety. Data concerning new AEDs and breastfeeding are sparse and often misinterpreted, and as a consequence, the increasing number of WWE treated with “old” and “new” AEDs in combination leads to uncertainty.
We describe the case of a woman with epilepsy treated with PRM/PB (so-called “old” AED) and LEV (so-called “new” AED) who was discouraged from breastfeeding, resulting in clinically significant withdrawal seizures in her newborn.
Section snippets
Case report
A 30-year-old woman known to have juvenile myoclonic epilepsy since the age of 14 was referred for delivery to the Department of Gynaecology, Medical University Innsbruck, Innsbruck, Austria. Long-term anticonvulsive therapy comprised PRM 187.5 mg per day (2.5 mg/kg body wt per day) for 10 years and LEV 3000 mg per day (40 mg/kg body wt per day) for 3 years. Initially, seizure semiology (and EEG) was uniform, including typical myoclonias of the arms and generalized tonic–clonic seizures with low
Discussion
The benefits of breastfeeding to mother and infant are not to be called into question, and there are only a few reasons justifying advice against nursing by WWE on long-term AED treatment. This is the first case demonstrating the complexity of recommendations for WWE resulting from the growing number of patients treated with combinations of so-called “new” AEDs and so-called “old” AEDs.
Although the overwhelming majority of AEDs are known to be transferred from maternal plasma to breast milk and
Conflict of interest statement
The authors report no conflicts of interest.
References (12)
- et al.
Descriptive epidemiology of epilepsy: contributions of population-based studies from Rochester, Minnesota
Mayo Clin Proc
(1996) - et al.
Infantile spasms on weaning from breast milk containing anticonvulsants
Lancet
(1987) - et al.
Pregnancy and epilepsy: what should we tell our patients?
J Neurol
(2009) Antiepileptic drug pharmacokinetics during pregnancy and lactation
Neurology
(2003)- et al.
Primidone and phenobarbital during lactation period in epileptic women: total and free drug serum levels in the nursed infants and their effects on neonatal behavior
Dev Pharmacol Ther
(1988) Gender aspects of pharmacokinetics of new and old AEDs: pregnancy and breast-feeding
Ther Drug Monit
(2005)
Cited by (11)
Breastfeeding recommendations for women taking anti-seizure medications
2022, Epilepsy and BehaviorCitation Excerpt :Accurate determination of infant’s drug exposure via breastmilk is challenging. There are several factors that need to be considered such the ASM’s physiochemical properties (e.g., molecular weight, protein binding capacity, and pKA level), maternal drug serum concentration, infant’s level of absorption, maturation of infant’s drug metabolism system, and drug clearance [18,19]. One should also consider the drug distribution gradient in breastmilk which is a measure of drug concentration from foremilk to hindmilk [19].
Epilepsy and recommendations for breastfeeding
2015, SeizureCitation Excerpt :Some even argue that AEDs via breastmilk could have a beneficial tapering effect for the infant that has already been exposed in utero, minimizing the child's total experience of side effects over time. Discontinued breastfeeding has been associated with withdrawal symptoms in neonates of mothers taking high dose barbiturates [78]. Two prospective studies have evaluated the risk of adverse development in children exposed to AEDs via breastmilk [33,36,75].
Antiepileptics
2015, Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment: Third EditionThe Postpartum Period in Women with Epilepsy
2012, Neurologic ClinicsCitation Excerpt :Children born to mothers taking high-dose barbiturates, such as primidone or phenobarbital, and benzodiazepines are potentially vulnerable to withdrawal and may need observation, but this should be evaluated on a case-by-case basis. One case report suggested that breastfeeding may minimize withdrawal symptoms, suggesting that over time the child experiences less medication.5 There are few criteria for withdrawal in neonates, and there is usually greater scrutiny in offspring of WWE, biasing observation of potential withdrawal symptoms.
Neonatal abstinence syndrome due to prenatal levetiracetam exposure
2023, No To Hattatsu