When the rate of bilirubin production exceeds the rate of elimination, the end result is a rise in the total serum bilirubin (TSB), a clinical condition called hyperbilirubinemia. The accumulation of bilirubin manifests as yellow discoloration of the skin, sclera, and mucosa called jaundice. Neonates with severe hyperbilirubinemia (defined as a TSB >25 mg/dL in late preterm and term infants) are at risk for bilirubin-induced neurologic dysfunction (BIND), which occurs when bilirubin crosses the blood–brain barrier and binds to targeted brain tissues. Hyperbilirubinemia presents as either unconjugated hyperbilirubinemia or conjugated hyperbilirubinemia. The 2 forms involve different causes and complications. In contrast to unconjugated hyperbilirubinemia, which can be transient and physiologic in the newborn period, conjugated hyperbilirubinemia is always pathologic and requires thorough investigation. See Chapter 98 for a discussion of conjugated hyperbilirubinemia (direct) and Chapters 62 and 63 for rapid “on-call” assessment and management of the 2 conditions.
Neonatal hyperbilirubinemia is a common problem to address in the newborn period. It occurs in approximately 60% to 70% of term and approximately 80% of preterm infants in the first week of life. The incidence of severe hyperbilirubinemia is approximately 0.14%. Incidence is higher in populations living at higher altitudes and varying ethnicities such as East Asians, Greeks, and Native Americans; it is generally lower in African Americans.
Bilirubin is a product of heme degradation (80%–90% derived from hemoglobin found in red blood cells [RBCs]). The enzyme heme oxygenase catalyzes the breakdown of heme in reticuloendothelial system, resulting in the formation of equimolar quantities of carbon monoxide (CO) and biliverdin. Biliverdin then is converted to bilirubin by the enzyme biliverdin reductase. Bilirubin is carried bound to albumin for uptake in the liver, followed by conjugation and then excretion in the bile. Gut bacteria convert conjugated bilirubin into urobilin and stercobilin. There are 3 main basic pathophysiologic mechanisms responsible for development of unconjugated hyperbilirubinemia: overproduction, decreased uptake, and impaired conjugation.
“Physiologic” unconjugated hyperbilirubinemia. The pathophysiologic mechanisms of neonatal jaundice involve 2 major contributing factors. First is the greater production of bilirubin secondary to increased heme turnover. The other is decreased ability of the newborn liver to conjugate bilirubin. Both factors are interrelated and important. Because all newborns have transient immaturity of the conjugating enzyme uridine diphosphate glucoronyl transferase (UDPGT), overproduction becomes the determining factor of exaggerated physiologic or pathologic jaundice. Bilirubin can function as an antioxidant, and some degree of hyperbilirubinemia may be physiologic and beneficial. Accepted “normal” or physiologic ranges of TSB levels vary widely because levels are influenced by many diverse factors such as gestational age, birthweight, disease state, degree of hydration, nutritional status, racial background, breast feeding, and other genetic and epidemiologic factors. Although most of these infants are healthy and will not need therapy, they need to be monitored closely as severe unconjugated hyperbilirubinemia can become potentially toxic ...