TOPLINE:

Concentrations of most antiseizure medications (ASMs) were similar in maternal and umbilical cord blood at delivery in pregnant women with epilepsy in a new study, which researchers said suggests significant placental passage and fetal exposure.

METHODOLOGY:

• Researchers analyzed blood samples from 199 pregnant women aged 14-45 years with epilepsy who received ASM monotherapy or polytherapy at delivery, along with umbilical cord blood from 207 infants (including eight pairs of twins) across 20 sites in the US as part of the MONEAD study.
• Participants were enrolled from 2012 to 2016, excluding women with an intelligence quotient < 70, major medical illnesses, substance use, poor treatment adherence, or pregnancies of < 20 weeks’ gestation.
• ASM concentrations in 305 paired maternal and umbilical cord samples were measured using liquid chromatography-mass spectrometry. The assessed ASMs were carbamazepine, gabapentin, lacosamide, levetiracetam, lamotrigine, oxcarbazepine, topiramate, pregabalin, phenobarbital, phenytoin, valproic acid, and zonisamide. Both total and unbound drug concentrations were assessed for select ASMs.
• Researchers determined the mean ratios of ASM concentrations in the umbilical cord to maternal plasma at birth as a measure of fetal exposure to ASMs. Paired and maternal cord samples were collected at delivery to assess placental transfer at the time of birth.

TAKEAWAY:

• A significant correlation was observed between ASM concentrations in the cord and maternal plasma for total and unbound carbamazepine, total and unbound carbamazepine epoxide, gabapentin, lamotrigine, levetiracetam, total and unbound oxcarbazepine, and zonisamide (P < .05 for all), accounting for more than 90% of maternal-cord concentration pairs analyzed.
• The mean ratios of ASM concentrations in the cord to maternal plasma were variable but close to 1, indicating significant placental transfer and fetal exposure.
• The mean ratio was highest for gabapentin (1.56), suggesting possible fetal accumulation, although this was only based on three maternal-cord pairs.

IN PRACTICE:

“A high level of correlation between maternal and umbilical cord blood concentrations is indicative of substantial drug transfer through the placenta,” the investigators wrote.

“Larger sample size studies in individuals on less frequently prescribed ASMs and on newer ASMs approved by the US Food and Drug Administration in the past decade need to be conducted,” they added.

SOURCE:

This study was led by Charul Avachat, MS, University of Minnesota, Minneapolis. It was published online on May 28 in Epilepsia.

LIMITATIONS:

Cord blood collection may have represented a mixture of maternal and infant blood and may not have been reflective of only fetal/infant drug exposure. The number of individuals on certain ASMs other than lamotrigine and levetiracetam was small. Additionally, a high variability was observed in concentrations of valproic acid possibly due to a lower sample size.

DISCLOSURES:

This study was funded by the National Institute of Neurological Disorders and Stroke, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the University of Minnesota’s Doctoral Dissertation Fellowship. Disclosure information for study investigators is available in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.