Skip to Main Content


  • In the immediate neonatal period, unconjugated hyperbilirubinemia is associated with kernicterus, an irreversible neurologic disorder that occurs when unbound bilirubin is deposited in the brain.
  • Visual assessment of jaundice is inaccurate, especially in darkly pigmented infants.
  • Increased enterohepatic circulation is an important cause of neonatal jaundice.
  • It is imperative to interpret bilirubin levels in terms of the infant's age in hours.
  • Knowledge of risk factors for severe hyperbilirubinemia is necessary to initiate early treatment.
  • Jaundice that persists longer than 2 weeks or appears beyond the immediate neonatal period is almost always a manifestation of pathology.
  • Conjugated hyperbilirubinemia is virtually always pathologic.


Jaundice is a yellowish-green discoloration of the skin and sclera caused by hyperbilirubinemia. It is apparent when the serum bilirubin reaches 5 mg/dL.1 In newborns, some degree of hyperbilirubinemia is virtually universal. Recent reviews demonstrate that hyperbilirubinemia remains one of the common reasons for readmission to the hospital in the neonatal period, especially with the advent of early newborn discharge.1,2 Consequently, emergency department (ED) physicians must be familiar with the management of the jaundiced newborn.


Although sequelae from hyperbilirubinemia are relatively rare, unconjugated bilirubin is potentially toxic to the developing CNS. Cases of kernicterus continue to occur worldwide and provide a stark reminder of the importance of maintaining a healthy respect for the complications of hyperbilirubinemia. Conjugated hyperbilirubinemia, although not directly neurotoxic, is often a marker for serious underlying disease.13


Bilirubin is largely formed by the destruction of red blood cells and the catabolism of heme proteins. Heme is converted to biliverdin, which is converted to bilirubin by biliverdin reductase. Bilirubin is transported to the liver, where it undergoes enzymatic-mediated conversion from an insoluble unconjugated form to a water-soluble conjugate. The conjugating enzyme is uridine diphosphate glucuronosyltransferase (UGT), which is markedly diminished in the newborn infant. The insoluble form of bilirubin is indirect reacting, the water-soluble form direct reacting. After conjugation, bilirubin is excreted in the bile and from there into the intestinal tract. In the intestinal tract, some of the conjugated bilirubin is reconverted to the unconjugated variety by beta glucuronidase. This allows its reabsorption into the enterohepatic circulation. Bilirubin metabolism is summarized in Figure 12–1.15

Figure 12-1.
Graphic Jump Location

Neonatal bile pigment metabolism. RBC, erythrocytes; RE, reticuloendothelial.


At elevated levels, the unconjugated form is potentially neurotoxic in the newborn. Bilirubin enters the brain if it is unbound to albumin, unconjugated, or if the blood–brain barrier has been disrupted from a number of causes, including sepsis, acidosis, and prematurity. The concentration of bilirubin in the brain and the duration of exposure are important determinants of neurotoxicity.


The newborn is especially vulnerable to hyperbilirubinemia for several reasons. Increased hemolysis secondary to shortened red blood cell survival time or fetal–maternal blood group incompatibility can result in increased ...

Want remote access to your institution's subscription?

Sign in to your MyAccess profile while you are actively authenticated on this site via your institution (you will be able to verify this by looking at the top right corner of the screen - if you see your institution's name, you are authenticated). Once logged in to your MyAccess profile, you will be able to access your institution's subscription for 90 days from any location. You must be logged in while authenticated at least once every 90 days to maintain this remote access.


About MyAccess

If your institution subscribes to this resource, and you don't have a MyAccess profile, please contact your library's reference desk for information on how to gain access to this resource from off-campus.

Subscription Options

AccessPediatrics Full Site: One-Year Subscription

Connect to the full suite of AccessPediatrics content and resources including 20+ textbooks such as Rudolph’s Pediatrics and The Pediatric Practice series, high-quality procedural videos, images, and animations, interactive board review, an integrated pediatric drug database, and more.

$595 USD
Buy Now

Pay Per View: Timed Access to all of AccessPediatrics

24 Hour Subscription $34.95

Buy Now

48 Hour Subscription $54.95

Buy Now

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.