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.
Highlights
Neonatal abstinence syndrome observed in newborns in the neonatal intensive care unit is routinely associated with withdrawal after a prolonged prenatal exposure to opioids
There is a lack of literature available on withdrawal symptoms in infants of mothers treated with antiepileptics and carbamazepine (CBZ) in particular
Recent pharmacoepidemiological studies have shown a prevalence of major malformations of 3.3% after carbamazepine monotherapy in the first trimester with a dose dependent increased risk of spina bifida (0.9% vs. 0.18% in the general population) (Jentink et al, 2010; Tomson et al, 2011; Verrotti et al, 2015) CBZ is excreted in breast milk
Summary
Neonatal abstinence syndrome observed in newborns in the neonatal intensive care unit is routinely associated with withdrawal after a prolonged prenatal exposure to opioids. It is, possible for children to withdraw from additional medications such as antidepressants or benzodiazepines, or from alcohol. CBZ is an iminodibenzyl derivative, structurally similar to tricyclic antidepressants, extensively used in the treatment of epilepsy as Newborn Carbamazepine Withdrawal and CYP2C9 well as neuropathic pain and bipolar disorders. It is one of the most commonly used antiepileptic drugs in Europe among women of childbearing age. Recent pharmacoepidemiological studies have shown a prevalence of major malformations of 3.3% after carbamazepine monotherapy in the first trimester with a dose dependent increased risk of spina bifida (0.9% vs. 0.18% in the general population) (Jentink et al, 2010; Tomson et al, 2011; Verrotti et al, 2015) CBZ is excreted in breast milk
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