Valproic acid concentrations in nursing mothers, mature milk, and breastfed infants in monotherapy and combination therapy

Abstract

Valproic acid (VPA) is currently one of the four most often prescribed antiepileptic drugs (AEDs) in pregnancy. However, only a small number of studies have measured suckling infant serum levels of the drug. We studied the transport of VPA from breastfeeding mothers to the mature milk and breastfed infants and the influence of comedication with enzyme-inducing AEDs. The data of 30 nursing women treated by VPA were analyzed retrospectively. Mature milk, maternal, and infant serum levels were collected between the 6th and 32nd postnatal day and measured by gas chromatography during the years 1996–2017.Valproic acid levels varied from 5.4 to 69.0 mg/L (mean: 39.0 ± 16.1 mg/L) in the maternal serum, from <1.0 to 16.7 mg/L (mean: 1.6 ± 3.9 mg/L) in the milk, and from <1.0 to 17.5 mg/L (mean: 4.2 ± 4.3 mg/L) in the infant serum. The milk/maternal serum level ratio ranged from <0.03 to 0.25 (mean: 0.03 ± 0.06) and the infant/maternal serum level ratio from <0.03 to 0.61 (mean: 0.11 ± 0.13). Sixty-seven percent of milk and 33% of infant VPA concentrations were below the limit of quantification. No correlations were observed between maternal serum and milk levels or between maternal and infant serum levels. In conclusion, none of the milk or infant serum VPA levels reached the lower limit of the reference range used for the general population with epilepsy, so the degree of VPA exposure in breastfed infants is less than during gestation. Nevertheless, if signs of potential adverse reactions manifest, infant serum concentrations should be measured.