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Jaundice, a yellow discoloration of the skin and sclerae resulting from bilirubin deposition in tissues arises when the rate of bilirubin production exceeds the rate of its elimination. Newborn infants have a rate of bilirubin formation that is 2 to 3 times higher than that of adults due to the higher hematocrit and the shorter lifespan of the red blood cells. The decrease in bilirubin elimination results from the limited ability of the newborn liver to conjugate bilirubin and the increased enterohepatic circulation. Although jaundice can result from an increase in either unconjugated (indirect) or conjugated (direct) bilirubin, a rise in the indirect fraction is the most common cause of newborn jaundice and is the focus of this chapter.


Bilirubin is derived from the catabolism of heme. Approximately 75% of bilirubin is derived from the breakdown of hemoglobin from senescent red blood cells and the rest from ineffective erythropoiesis and breakdown of hemoproteins, such as cytochromes, myoglobin, nitric oxide synthase, glutathione peroxidase, and catalase (Fig. 56-1).

Figure 56-1

Bile pigment metabolism in the newborn. RBC, red blood cells; R.E. system, reticulo-endothelial system. (Adapted with permission from MacDonald MG, Mullett MD, Seshia M: Avery’s Neonatology: Pathophysiology and Management of the Newborn, 6th ed. Philadelphia: Lippincot Williams & Wilkins; 2005.)

Heme is degraded in a 2-step process by the enzyme heme oxygenase resulting in formation of biliverdin and carbon monoxide in equimolar amounts. Carbon monoxide, which diffuses from the cell, binds to hemoglobin in circulating red blood cells to form carboxyhemoglobin (COHb) and is eventually excreted during exhalation (measurable as end-tidal carbon monoxide). Bilirubin is produced from biliverdin by the action of biliverdin reductase, and on entering the circulation, bilirubin binds to albumin and is transported to the liver. Fat-soluble, nonpolar bilirubin crosses the plasma membrane of the hepatocyte and binds to cytoplasmic ligandin, for transport to the endoplasmic reticulum. Conjugation with glucuronic acid in a reaction catalyzed by uridine diphosphate glucuronosyltransferase (UGT) transforms bilirubin into a water-soluble form, bilirubin glucuronide, which is easily excretable. Distribution of bilirubin into tissues depends on its binding to albumin and the serum pH. The greater the binding to albumin is and the more alkaline the pH is, the more likely it is that bilirubin will remain in circulation until it enters the liver. Conjugated bilirubin is excreted into the intestine via the bile, where it is either deconjugated by the enzyme μ-glucuronidase and reabsorbed into the circulation (enterohepatic circulation), or converted by bacteria to nonabsorbable breakdown products. Because the newborn infant has few intestinal bacteria, the enterohepatic circulation of bilirubin is active in the newborn and contributes to the increased propensity for jaundice.

Although not all full-term infants become visibly jaundiced, nearly all have a higher total serum bilirubin (TSB) concentration (hyperbilirubinemia > 1 ...

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