“Late” Withdrawal Syndrome after Carbamazepine In Utero Exposure in a CYP2C9 Slow Metabolizer Newborn

Abstract

We report a case of carbamazepine withdrawal syndrome following in utero exposure to carbamazepine related to a pharmacogenetic predisposition factor. The infant was born at 37 1/7 weeks’ gestation by cesarean section to a mother treated for epilepsy with carbamazepine. One hour and thirty minutes after birth, the infant presented a respiratory distress with severe oxygen desaturation requiring intubation 5 h after birth. On the third day of life the infant developed clinical signs of a withdrawal syndrome which resolved progressively after 16 days and symptomatic treatment. The infant genotype analysis showed two low activity CYP2C9 allelic variants (∗2/∗3 heterozygote) predicting a CYP2C9 slow metabolizer phenotype which could explain reduced carbamazepine elimination and a late and long-lasting withdrawal symptoms observed 3 days after birth. The association of a withdrawal syndrome with carbamazepine exposure has not been previously reported and pharmacogenetic tests might therefore be useful in identifying patients at risk.

Emerging trends and knowledge structure of epilepsy during pregnancy research for 2000–2018: a bibliometric analysis

“…Previous studies had focused on MCMs of AEDs in pregnancy and cognitive function after fetal exposure to AEDs. It is noteworthy that there were recent case reports of neonatal abstinence syndrome (NAS) for in utero exposure to carbamazepine (Passia et al, 2017), oxcarbazepine (Chen et al, 2017a; Rolnitsky, Merlob & Klinger, 2013), and gabapentin (Carrasco et al, 2015). NAS was most frequent after in utero exposure to opioids, while recent studies showed that exposure to AEDs during pregnancy may induce NAS.…”