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Jaundice comes from the French word “jaune,” meaning yellow. Jaundice refers to the yellow staining of the sclera, mucous membranes, and skin by bilirubin. It is not a disease by itself but rather a manifestation that accompanies different diseases. Jaundice is caused by elevated serum bilirubin levels with subsequent tissue deposition. In infants, it is usually apparent with bilirubin levels above 4–5 mg/dL (68–86 mmol/L). In older children, jaundice can be noted at levels above 2–3 mg/dL (34–51 mmol/L). The color of the sclera and skin varies depending on the serum bilirubin level. Jaundice involves the head first and progresses caudally with higher levels.

Total serum bilirubin is the sum of the unconjugated (or indirect) and conjugated (or direct) bilirubin fractions. The terms direct and conjugated hyperbilirubinemia are often used interchangeably, but this is not always accurate. Direct bilirubin is measured in the laboratory using a diazo dye-binding assay, and, depending on the method used, can include both conjugated bilirubin and delta bilirubin. Delta bilirubin is formed by covalent bond formation between serum conjugated bilirubin and albumin. Clearance of delta bilirubin can therefore be prolonged, reflecting the half-life of albumin, and may lag behind other signs of clinical improvement.

Cholestasis is defined as diminished bile formation or flow, and is manifested by conjugated hyper-bilirubinemia. The guidelines of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN)1 define an abnormal conjugated bilirubin level as:

  • a conjugated bilirubin >1.0 mg/dL, if the total bilirubin is <5 mg/dL, or
  • a conjugated bilirubin level >20% of the total bilirubin, if the total bilirubin is >5 mg/dL.

Neonatal jaundice is common, observed in the first week of life in about 50% of term infants and 80% of preterm infants. This is usually harmless, often related to physiological jaundice or breastfeeding, and is characterized by unconjugated hyperbilirubinemia. Rarely, however, severe unconjugated hyperbilirubinemia can lead to bilirubin encephalopathy or kernicterus.2 On the contrary, cholestasis (or conjugated hyperbilirubinemia) is much less commonly seen but often results from conditions with serious hepatobiliary dysfunction. Cholestatic jaundice affects approximately 1 in every 2500 infants.3 The challenge for physicians is to identify infants with cholestasis who will need additional evaluation and treatment. Early detection of cholestatic jaundice and accurate diagnosis of its etiology are vital for successful treatment and a favorable prognosis.

Bilirubin is the end product of heme moiety metabolism from hemoglobin and other heme-containing proteins (Figure 7–1). After unconjugated bilirubin is formed, it is transported with albumin in blood to the liver. Inside hepatocytes, unconjugated bilirubin is conjugated with glucuronic acid by uridine diphosphate glucuronosyltransferase (UGT) to increase water solubility. Conjugated bilirubin, along with cholesterol, bile acids, and phospholipids, is transported through the bile canalicular system to the gallbladder and later into the small intestine. Conjugated bilirubin cannot be reabsorbed by enterocytes and is degraded by the intestinal flora into colorless urobilinogen, which is excreted ...

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