Hemolysis of red blood cells → release of heme and globin (protein)→ heme is broken down into iron (conserved) and carbon monoxide (exhaled), and biliverdin → biliverdin is metabolized to bilirubin (yellow pigment) → free bilirubin (unconjugated, fat soluble, and indirect) and then binds to albumin and is carried to the liver → in the liver it is conjugated (made water soluble, direct) → conjugated bilirubin is excreted as part of bile into the intestine → bacteria in the intestine further metabolizes bilirubin into urobilinogen and this end product is excreted in stool, giving it a characteristic brown color, and urine, giving it a characteristic yellow color.

Blood tests can measure the amount of conjugated (direct) and unconjugated (indirect) bilirubin. When certain dyes are added to a blood sample, conjugated (water soluble) bilirubin acts directly with the dyes so it is called “direct bilirubin.” Unconjugated (fat-soluble) bilirubin does not react to the dyes until alcohol is added to the solution, so it is called “indirect bilirubin.”

Jaundice, a yellow discoloration of the skin, sclera, body fluids, and mucous membranes, normally develops in approximately 65% of full-term newborns and 80% of preterm newborns beginning after the infant is 24 hours old. This is a mild self-limiting condition and is not associated with disease pathology. Clinical jaundice appears at a bilirubin level of 5 mg/dl and begins on the head and then travels down the chest and abdomen to the distal extremities. Pathology is suspected if jaundice is present within the first 24 hours after birth, if the total serum bilirubin level rises by more than 5 mg/dl per day, or if signs and symptoms of disease pathology are present. A normal bilirubin level is between 0.2 and 1.4 mg/dl. Table 41-1 presents the differences between physiological and pathological jaundice.

Excess bilirubin in the blood is called hyperbilirubinemia. By the time a full-term infant is 72 hours old his or her bilirubin level may reach 6 mg/dl. This level decreases to 2-3 mg/dl by the time the infant is 5 days old and remains at this level for up to 14 days.

Hyperbilirubinemia develops because of more rapid red blood cell destruction in the newborn, lower levels of glucuronyl transferase (the enzyme used to conjugate bilirubin), and low albumin levels. Slow intestinal motility and low gut bacteria also play a role because conjugated bilirubin stays in the intestine longer, where it then becomes unconjugated and is reabsorbed. Feeding the infant encourages the passage of meconium, which is rich in bilirubin, increases intestinal bacteria, and stimulates peristalsis, thereby decreasing the amount of unconjugated bilirubin that is reabsorbed.

Unconjugated hyperbilirubinemia may also develop because of rapid red blood cell destruction due to maternal antibodies, as occurs in Rh incompatibility, abnormal red blood cell shape, sepsis, prematurity, bile duct obstruction, or abnormal red blood cell enzymes. The rate of conjugation may be dramatically slowed due to low levels or complete absence of the enzyme that adds sugar to fat-soluble bilirubin so that it becomes water soluble (UDP-glucuronosyltransferase). Premature infants, infants
of Asian race, and infants born at high altitudes are at higher risk of hyperbilirubinemia than are full-term white or black infants or infants born at sea level.

Free bilirubin, which is neurologically toxic, is deposited in brain cells if serum unconjugated bilirubin levels exceed the binding capacity of albumin. Bilirubin bound to albumin can also cross the blood-brain barrier if the infant has acidosis, hypoxia, hypoperfusion, hyperosmolality, or sepsis. The administration of sodium bicarbonate to correct acidosis has been implicated in brain damage caused by high bilirubin levels. Signs of bilirubin encephalopathy (kernicterus) include lethargy, hypotonia, poor sucking, and a high pitched cry. Left untreated, the infant may develop cerebral palsy, deafness, severe muscle spasms, mental retardation, and seizures. Serum bilirubin levels do not indicate how much of a risk the infant with hyperbilirubinemia faces.

Colostrum, a form of breast milk produced during the first 48-72 hours of breastfeeding, is a natural laxative that encourages the passage of meconium, which is high in bilirubin. Breast-fed infants may develop early-onset or late-onset jaundice. Early-onset jaundice (breast-feeding jaundice) develops in 13-25% of breast-fed infants between 2 and 7 days of age and may be triggered by a low fluid intake secondary to low breast milk production or poor feeding by the infant. Signs that inadequate breast milk is being produced or consumed
include a weight loss of approximately 10% since birth, less than six wet diapers per day, fewer than four bowel movements per day, and nursing fewer than eight times per day for at least 10 minutes each time. Treatment is aimed at increasing the infant’s intake of breast milk or formula. Sugar water supplements do not reduce bilirubin levels.