Neonatal Hyperbilirubinemia (Jaundice)
Jaundice is seen in approximately half of all newborns. Although neonatal hyperbilirubinemia is usually a benign and physiologic condition, very high bilirubin levels occur in certain pathologic conditions and are potentially injurious to the central nervous system.
Bilirubin is a product of heme catabolism. Red cell hemoglobin accounts for approximately 85% of all bilirubin. In newborns, the normal hemoglobin level is 15-18 mg/dl. The rate of neonatal RBC destruction is higher than in adults resulting in greater quantity of hemoglobin release. Excessive bruising from birth trauma or abnormal blood collections such as in a cephalohematoma may further add to the rate of RBC destruction and bilirubin formation.
Heme is catabolized to unconjugated bilirubin in the reticuloendothelial system. Unconjugated bilirubin is bound to albumin in the plasma and transported bound to albumin to the liver and is conjugated with glucuronic acid in the hepatocytes; the conjugation is catalyzed by glucuronyl transferase. Conjugated bilirubin is secreted into the bile and enters the duodenum. In the small bowel, some of the bilirubin is hydrolyzed to yield unconjugated bilirubin and glucuronic acid. Most unconjugated bilirubin is excreted in the stool, but some is reabsorbed and returned to the liver for re-conjugation (enterohepatic circulation).
The level of glucuronyl transferase is initially low in the newborn and any increase in the rate of bilirubin formation can overwhelm the capacity to conjugate, thus resulting in elevated bilirubin levels.
When the serum level of unconjugated bilirubin exceeds the albumin binding capacity, bilirubin diffuses into the central nervous system and may result in permanent neurological damage or death (bilirubin encephalopathy with kernicterus).
Conjugated bilirubin is water soluble and does not diffuse into the central nervous system so it is not capable of causing kernicterus.
Factors such as acidosis and hypoalbuminemia may reduce the ability of albumin to bind to conjugated bilirubin. The specific serum level of unconjugated bilirubin that results in kernicterus is unknown, but for the term infant it has traditionally been defined as a concentration of 20 mg/dl. In the low birthweight infant, the level is proportionately lower.
More information on Jaundice
Physiologic (Nonpathologic) Hyperbilirubinemia
The most common cause of neonatal jaundice is physiologic hyperbilirubinemia.
In the term infant, physiologic hyperbilirubinemia appears at about two days of age, peaks at 10 to 12 mg/dl at three to four days and disappears by four to seven days. Low birthweight infants have exaggerated and prolonged physiologic hyperbilirubinemia, which may persist for 10 to 14 days.
The following scenarios suggest pathologic hyperbilirubinemia:
- Clinical jaundice within the first 24 hours of life.
- Total serum bilirubin more than 12 mg/dl in a term infant.
- Clinical jaundice persisting for more than 10 days in a term infant.
Pathologic hyperbilirubinemia may result from overproduction or under-secretion of bilirubin, or sometimes from a combination of the two.