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  1. I. Definition. When the rate of bilirubin production exceeds the rate of elimination, the end result is an increase in the total serum bilirubin (TSB), a clinical condition called hyperbilirubinemia. The accumulation of bilirubin (the yellow-orange pigment) in the skin, the sclera, and the mucosa is called jaundice. See Chapter 91 for a basic overview of bilirubin metabolism and hyperbilirubinemia. Chapter 51 provides information on rapid "on-call" assessment and management.

  2. II. Incidence. Neonatal hyperbilirubinemia is a common problem. Approximately 60–70% of term infants and ~80% of preterm infants develop jaundice in the first week of life. Incidence is higher in populations living at higher altitudes. Incidence also varies with ethnicity. It is lower in African Americans and higher in East Asians, Greeks living in Greece, and American Indians.

  3. III. Pathophysiology

      1. A. Physiologic jaundice. In full-term newborns, a physiologic progressive elevation of serum unconjugated bilirubin develops to a mean peak of 5–6 mg/dL between 60 and 72 h of age. Premature neonates may experience higher mean peak concentrations as much as 10–12 mg/dL by the fifth day of life. Physiologic ranges of TSB remain controversial because levels are affected by several factors, such as gestational age, birthweight, disease state, degree of hydration, nutritional status, and ethnic background. Data from recent studies suggest that the upper limits of TSB levels (95th percentile) found in diverse populations of normal newborn maybe as high as 17–18 mg/dL. Studies published on predominantly breast-fed infants suggest that a typical peak for TSB is approximately 8–9 mg/dL.

          1. 1. Exclusion criteria for diagnosis of physiologic jaundice:

              1. a. Jaundice appearing within the first 24 h of life.

              1. b. TSB level >95th percentile for age in hours based on a nomogram for hour-specific serum bilirubin concentration. (See Figure 92–1.)

              1. c. Bilirubin level increasing at a rate >0.2 mg/dL/h or >5 mg/dL/day.

              1. d. Direct serum bilirubin level >1.5–2.0 mg/dL or >10–20% of the TSB.

              1. e. Jaundice persisting for >2 weeks in full-term infants.

          1. 2. Physiology. Benign neonatal bilirubinemia, better known as physiologic jaundice, is a nonpathologic condition that develops in virtually all newborns due to distinctive aspects of normal newborn physiology that predisposes them to increased bilirubin production and limited elimination. Because recent data suggest that the upper limit of "physiologic jaundice" in diverse populations is a TSB level of 17–18 mg/dL, a stable 4- to 5-day-old breast-fed infant with bilirubin levels of 15–16 mg/dL may not need an elaborate workup for hyperbilirubinemia but will require close follow-up to ensure that bilirubin levels do not continue to rise to critical levels.

          1. 3. Mechanisms that predispose newborn infants to hyperbilirubinemia:

              1. a. Increased bilirubin synthesis due to larger red blood cell (RBC) mass, increased hemoglobin breakdown up to two to three times the adult rate (due to shorter life span of neonatal RBCs), and increased rate of RBC degradation in the bone marrow before release to the circulation.

              1. b. Decreased binding and transport. Decreased hepatic uptake of bilirubin from plasma due to decreased plasma albumin and liver transfer protein, ...

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