NEONATAL CHOLESTASIS - DEVELOPMENTAL ASPECTS AND CURRENT CONCEPTS

The vectorial transport into bile of bile acids, bilirubin, oxidized glutathione, metals such as copper and iron together with polar, biotransformed compounds, including drugs and sex hormones, is a major hepatic function. In utero, hepatic function is uniquely adapted to the in utero environment in order to facilitate the placental removal of these compounds. Immediately following birth, numerous and dramatic shifts must occur in the hepatic blood flow, the hormonal milieu, and in the structural and functional organization of the liver, the intestine, and the other components of the enterohepatic circulation. This period of adaptation imposes a 'physiologic cholestasis' in the infant, providing an atavistic glimpse into the process of bile formation and the mechanisms of hepatic injury. This article will consider the distinctive features of fetal and neonatal bile acid metabolism from several aspects: the first is to characterize the fetal and neonatal features of the enterohepatic circulation, including the process of bile formation, the second is to explore the distinctive features of fetal and neonatal bile acid metabolism, and the third is to characterize in part many of the neonatal cholestatic syndromes and their potential for therapy.