Neonatal cholestasis is frequently encountered in infants hospitalized for prematurity, gastrointestinal malformations (such as gastroschisis, omphalocele, short gut syndrome, biliary atresia, Alagille syndrome), infection, hemolytic disorders, endocrinopathies (such as hypothyroidism and hypopituitarism), and metabolic abnormalities (such as alpha-1-antitrypsin deficiency, galactosemia). It is common among preterm infants because of immature hepatobiliary function, associated infections, and exposure to hepatotoxic agents such as parenteral alimentation fluids (TPN). Cholestasis is defined as conjugated hyperbilirubinemia (serum conjugated bilirubin concentration greater than 2 mg/dL) because of diminished bile flow and/or excretion of conjugated bilirubin from the hepatocytes into the duodenum. The conjugated fraction of serum bilirubin is normally no greater than 15% of the total serum bilirubin concentration. The incidence of neonatal cholestasis is approximately 1:2500 live births. Once cholestatic liver disease is identified, prompt diagnosis and treatment are necessary.
Cholestasis is a common complication of long-term parenteral nutrition, especially in VLBW infants. If TPN is administered long-term, management should be focused on preventing occurrence of parenteral nutrition-associated cholestasis (PNAC). In this chapter, causes and strategies for reversal and/or prevention of total parenteral nutritionassociated cholestasis (TPNAC) will be discussed.
Potential causes of TPNAC
TPNAC is the leading cause of neonatal cholestasis and the primary indication for combined liver and intestinal transplantation in children. Within 2 weeks of TPN, biochemical changes in several liver enzymes indicative of hepatic dysfunction appear. Serial measurement of the serum concentration of conjugated bilirubin is necessary to monitor the progression of cholestasis.