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  • Jaundice within the first 24 hours of life is NEVER normal.
  • Urinary tract infections can be associated with the onset of unconjugated hyperbilirubinemia after a week of age.
  • Conjugated hyperbilirubinemia is never normal at any age and mandates consultation with a pediatric gastroenterologist.
  • The treatment of breast milk jaundice is not the cessation of breast-feeding.
  • Consider exchange transfusion if levels >20 mg/dL.
  • Consider hemolytic disease with unconjugated hyperbilirubinemia beyond the neonatal period.
  • Postexposure prophylaxis is available for some types of hepatitis.
  • RUQ pain can be an important clue to the recognition and diagnosis of hepatic dysfunction.
  • Normal serum liver transaminases do not rule out liver failure.
  • Always think of biliary atresia in an infant younger than 2 months with direct hyperbilirubinemia.
  • Acute cholangitis should be suspected in any patient with fever and jaundice who has had surgical correction of biliary atresia.
  • Think of choledochal cyst when presented with a patient with history of recurrent jaundice.
  • Cholesterol stones account for up to 90% of gallstones in adolescents.
  • Gallbladder hydrops does not occur in isolation; look for the underlying cause.


Hemoglobin is released from red blood cells, broken down into heme, and ultimately reduced to unconjugated bilirubin, which is then bound to serum albumin. Unconjugated (indirect) bilirubin is converted into conjugated (direct) bilirubin in the liver and stored in the gallbladder. Bile is released into the intestines to assist in digestion and cholesterol metabolism as well as absorption of lipids and fat-soluble vitamins. Hyperbilirubinemia indicates either increased production of or impaired excretion of bilirubin and is the result of numerous etiologies, some pathologic and some physiologic. Increased red blood cell destruction may lead to unconjugated hyperbilirubinemia. Impairment of bile secretion from the liver or excretion from the gallbladder may lead to conjugated hyperbilirubinemia.


The patient's age and the type of hyperbilirubinemia, whether direct or indirect, are important factors in determining the cause and treatment. Hyperbilirubinemia within the first day of life is never normal and can be concerning within the first week of life. Multiple etiologies, including serious bacterial infection, must be considered with prompt diagnosis and treatment imperative for the prevention of serious side effects. Hyperbilirubinemia in older children and adolescents is concerning for hemolysis, extrahepatic obstruction, or hepatocellular injury.


Neonatal Hyperbilirubinemia, Unconjugated


The most common causes of indirect hyperbilirubinemia in the first week of life are physiologic jaundice, breast milk jaundice, and hemolysis. Associated conditions increasing the risk for development of hyperbilirubinemia include infection, prematurity, maternal diabetes, breast-feeding, infant hypothyroidism, and poor feeding leading to delayed intestinal transit. Physiologic jaundice is self-limited with bilirubin levels peaking by the third day of life and returning to normal over the next 2 weeks. These infants are well with no risk factors or associated conditions. Breast milk jaundice is thought to be caused by decreased hepatic excretion and intestinal resorption of unconjugated bilirubin. Bilirubin levels are initially normal and increase to a peak at 2 to 3 ...

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