Umbilical Cord, Maternal Milk, and Breastfed Infant Levetiracetam Concentrations Monitoring at Delivery and during Early Postpartum Period

Abstract

(1) To obtain objective information about levetiracetam transplacental passage and its transport into colostrum, mature milk, and breastfed infants, we analyzed data from women treated for epilepsy between October 2006 and January 2021; (2) in this cohort study, maternal, umbilical cord, milk, and infant serum concentrations were measured at delivery, 2–4 days postpartum (colostrum) and 7–31 days postpartum (mature milk). Paired umbilical cord serum, maternal serum, breastfed infant serum, and milk concentrations were used to assess the ratios of umbilical cord/maternal serum, milk/maternal serum, and infant/maternal serum concentrations. The influence of combined treatment with enzyme-inducing antiseizure medication carbamazepine was assessed; (3) the umbilical cord/maternal serum concentration ratio ranged between 0.75 and 1.78 (mean 1.10 ± 0.33), paired maternal and umbilical cord serum concentrations were not significantly different, and a highly significant correlation was found between both concentrations. The mean milk/maternal serum concentration ratio was 1.14 ± 0.27 (2–4 days postpartum) and 1.04 ± 0.24 (7–31 days postpartum) while the mean infant/maternal serum concentration ratio was markedly lower (0.19 ± 0.13 and 0.14 ± 0.05, respectively); (4) levetiracetam was found in the umbilical cord at a concentration similar to those in maternal serum. All of the breastfed infant serum concentrations were below the reference range used for the general epileptic population.

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

“…The paired milk/maternal serum concentration ratio of VPA was found to be much lower than the infant/maternal serum concentration ratio, which is supported by comparing the distribution of these two ratios in Figure 2, in which the infant/maternal serum concentration ratio shifted to higher values (i.e., "to the right"). This result was diametrically different from levetiracetam and topiramate, in which we observed that the mean milk/maternal serum concentration ratio was markedly higher than the mean infant/maternal serum concentration ratio, and that a movement of the infant/maternal serum concentration ratio to lower values (i.e., "to the left") was apparent [35,36]. Paired colostrum and mature milk concentrations of VPA were measured on or under the lower limit of quantification, respectively, and were not significantly different between these two time periods.…”

“…This result corresponds to Figure 3, which presents an almost continuous decrease in VPA-breastfed infant serum concentrations at three time points (delivery-colostrum-mature milk). Different declines in breastfed infant serum concentrations were observed for levetiracetam, in which a rapid decrease in concentrations was found between the delivery and colostrum periods and thereafter the concentrations were stable [35].…”

Breastfeeding while on treatment with antiseizure medications: a systematic review from the ILAE Women Task Force

“…Available information on maternal serum and milk concentrations as well as on serum concentrations in breastfed infants is extensive. Based on 82 published cases, the levetiracetam milk/maternal serum concentration ratios have ranged from 0.58 to 1.79, with averages in most studies in the order of 1.0 [27, 42-45]. Infant/maternal serum concentration ratios were reported in 121 mother‐child pairs, and ranged from below the level of quantification in infant serum to a ratio of 0.71, with a reported average in individual studies in most cases at around 0.1 [14, 27, 42-45].…”

“…Available information on maternal serum and milk concentrations as well as on serum concentrations in breastfed infants is extensive. Based on 82 published cases, the levetiracetam milk/maternal serum concentration ratios have ranged from 0.58 to 1.79, with averages in most studies in the order of 1.0 [27,[42][43][44][45].…”

“…Infant/maternal serum concentration ratios were reported in 121 mother-child pairs, and ranged from below the level of quantification in infant serum to a ratio of 0.71, with a reported average in individual studies in most cases at around 0.1 [14,27,[42][43][44][45].…”