Valproic Acid Concentrations in Mothers, Colostrum and Breastfed Infants during the Early Postpartum Period: Comparison with Concentrations Determined during Delivery and in the Mature Milk Period.

Milan Grundmann,Hana Brozmanova,Ivana Kacirova

doi:10.3390/pharmaceutics13122074

Milan Grundmann, Hana Brozmanova + Show 1 more

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https://doi.org/10.3390/pharmaceutics13122074

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Journal: Pharmaceutics	Publication Date: Dec 3, 2021
Citations: 4	License type: CC BY 4.0

Affiliation: University of Ostrava, University Hospital Ostrava

Abstract

To obtain information on the transport of valproic acid from mothers to colostrum and breastfed infants, in this cohort study, valproic acid concentrations in maternal serum (90 subjects), colostrum and the serum of breastfed infants were analyzed in years 1993–2018, between the 2nd and 5th postnatal days. Valproic acid concentrations ranged from 4.3 to 66.5 mg/L (mean 31.2 ± 13.6 mg/L) in maternal serum, from 0.5 to 5.9 mg/L (mean 1.1 ± 1.2 mg/L) in milk, and from 0.5 to 42.9 mg/L (mean 15.4 ± 9.4 mg/L) in infant serum. The milk/maternal serum concentration ratio ranged from 0.01 to 0.22 (mean 0.04 ± 0.04), and the infant/maternal serum concentration ratio ranged from 0.01 to 1.61 (mean 0.51 ± 0.28). A significant correlation was found between serum concentrations of breastfed infants and milk concentrations, maternal serum concentrations, maternal daily dose, and dose related to maternal body weight. Valproic acid concentrations in milk and infant serum did not reach the lower limit of the reference range used for the general epileptic population, and three-quarters of the concentrations in milk were lower than the lower limit of quantification. Routine monitoring of serum concentrations of breastfed infants is not necessary. If signs of potential adverse reactions are noted, serum concentrations of the infants should be measured.

Highlights

Valproic acid (VPA) has become one of the most widely used antiseizure medications (ASMs) worldwide for the treatment of both generalized and focal seizures
A major concern for VPA use in women is its teratogenic potential, which increases the risk of major congenital malformations (MCMs) 5.69-fold as compared to children of mothers without epilepsy, 3.13-fold for children of mothers with untreated epilepsy, and significantly relative to fetuses exposed to other ASMs
In 2015, we examined the transmission of VPA through the placenta, and in 2019, we examined the transport of VPA from breastfeeding mothers to mature milk and breastfed infants [14,15]

Summary

Introduction

Valproic acid (VPA) has become one of the most widely used antiseizure medications (ASMs) worldwide for the treatment of both generalized and focal seizures. In 2014, the risks of MCM and cognitive delay associated with intrauterine VPA exposure caused regulatory agencies, the U.S Food and Drug Administration (FDA) and the European Medicines Agency (EMA), to restrict usage of VPA in women of fertile age [1,2,3,4]. In 2018, the EMA endorsed new measures to avoid exposure of babies to VPA in the womb, which include a ban on the use of such medicines for migraine or bipolar disorder during pregnancy and a ban on using it to treat epilepsy during pregnancy unless there is no other effective treatment available [5]. Only controversial information is available from clinical practice concerning the magnitude of change that restricting VPA use will achieve regarding fetal malformation rates and seizure disorder control during pregnancy in the same population.

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