Neonatal Cholestatic Hepatitis from Carbamazepine Exposure during Pregnancy and Breast Feeding

OBJECTIVE: To report a case of transient cholestatic hepatitis occurring in an infant between the third and seventh weeks of life, most likely due to carbamazepine exposure during pregnancy and breast feeding. CASE SUMMARY: A boy, born to an epileptic mother who had been treated with carbamazepine monotherapy throughout pregnancy and breast feeding, experienced asphyxia at birth with transient hepatic dysfunction in the first week of life. After full recovery from asphyxia, he experienced a second period of liver dysfunction, presenting as cholestatic hepatitis that lasted approximately 5 weeks. Infectious and metabolic etiologies as well as extrahepatic biliary atresia were excluded. DISCUSSION: Carbamazepine is known to induce hepatic damage in children and adults. As the drug crosses the placenta and is excreted into breast milk, infants of mothers taking carbamazepine might also develop liver dysfunction. In addition to the present case, there are 2 well-documented case reports of cholestasis in association with transplacental and transmammary carbamazepine exposure. CONCLUSIONS: Carbamazepine-induced hepatitis may occur in association with prenatal exposure and breast feeding. This may expose infants to unnecessary diagnostic procedures, and should therefore be mentioned in the company's product information.

Transient Hepatic Dysfunction in an Infant of an Epileptic Mother Treated with Carbamazepine during Pregnancy and Breastfeeding

OBJECTIVE: A case is reported of a carbamazepine (CBZ)-treated epileptic mother whose newborn presented with transient hepatic dysfunction characterized by direct hyperbilirubinemia and high concentrations of gamma-glutamyltransferase (GGT). DATA SOURCES: Information was obtained from case reports, clinical trials, and relevant bibliographic laboratory studies. DATA EXTRACTION: Data from case reports were evaluated and compared with those from our patient. The hepatotoxic reactions together with the microsomal enzymatic induction of CBZ were reviewed. DATA SYNTHESIS: A female infant bom to an epileptic mother treated with CBZ throughout pregnancy and breastfeeding presented with transient direct hyperbilirubinemia and high concentrations of GGT. The characteristics of her transient hepatic dysfunction were: early appearance (during the first day of life); discrepancy between the normal liver enzymes and high GGT concentrations; slow decrease of GGT, which nevertheless remained at above-normal concentrations even after the complete disappearance of direct hyperbilirubinemia; and spontaneous resolution in spite of only occasional breastfeeding. The possible explanations of this transient hepatic dysfunction (like enzymatic induction) are discussed. CONCLUSIONS: CBZ-induced hepatic dysfunction in neonates appears to have different clinical expressions. Infants of epileptic mothers treated with CBZ throughout pregnancy and breastfeeding should be carefully monitored for possible adverse effects.