The liver is responsible for the conjugation of bilirubin, which results from the breakdown of RBCs. When RBCs reach the end of their life span, their membranes rupture, and hemoglobin is released. The hemoglobin is phagocytosed by macrophages; it then splits into heme and globin. Heme is broken down by the reticuloendothelial cells, converted to bilirubin, and released in an unconjugated form. Unconjugated (indirect) bilirubin is relatively insoluble and almost entirely bound to circulating albumin, a plasma protein. Bilirubin that is not bound to albumin, or free bilirubin, can easily cross the blood–brain barrier and cause neurotoxicity (see below - acute bilirubin encephalopathy or kernicterus).

Unconjugated bilirubin must be conjugated so it becomes soluble and excretable. In the liver, the unbound bilirubin is conjugated with glucuronic acid in the presence of the enzyme glucuronyl transferase. The conjugated form of bilirubin (direct bilirubin) is soluble and excreted from liver cells as a constituent of bile. Along with other components of bile, direct bilirubin is excreted into the biliary tract system that carries the bile into the duodenum. The effectiveness of bilirubin excretion through the feces depends on the stooling pattern of the newborn and the substances in the intestine that break down conjugated bilirubin.

Feeding is important in reducing serum bilirubin levels because it stimulates peristalsis and produces a more rapid passage of meconium, thus diminishing the amount of reabsorption of unconjugated bilirubin. Feeding also introduces bacteria to aid in the reduction of bilirubin to urobilinogen. Colostrum, a natural laxative, facilitates the passage of meconium in breastfed infants. When levels of unconjugated bilirubin exceed the ability of the liver to conjugate it, plasma levels of bilirubin increase, and jaundice appears. Hyperbilirubinemia is the term for excessive bilirubin in the bloodstream.  Jaundice, when the skin and sclera has a visible yellowish color, is caused by hyperbilirubinemia. It is likely to appear when the total serum bilirubin (TSB) level exceeds 6 to 7 mg/dl.

A newborn is at risk for hyperbilirubinemia because of distinctive aspects of normal neonatal physiology, such as:

• Higher RBC mass at birth

• Shorter lifespan of neonatal RBCs create the need for greater bilirubin synthesis

• Ability of the liver to conjugate bilirubin is reduced during the first few days after birth

• Fewer bilirubin binding sites because newborns have lower serum albumin levels

• In the intestines, conjugated bilirubin becomes unconjugated and recirculated through the enterohepatic circulation, which increases serum bilirubin levels

Every newborn should be assessed for jaundice at least every 8 to 12 hours. To differentiate cutaneous jaundice from normal skin color, the nurse applies pressure with a finger over a bony area (e.g., the nose, forehead, sternum) for several seconds to empty all the capillaries in that spot, then releases the pressure by lifting the finger. If jaundice is present, the blanched area will appear yellowish before the capillaries refill. The conjunctival sacs and buccal mucosa also are assessed, especially in darker-skinned infants. Assessing for jaundice in natural light is recommended because artificial lighting and reflection from walls can distort the actual skin color.  Jaundice begins at the head and moves down the body as the amount increases in the body.  

Visual assessment of jaundice alone does not provide an accurate assessment of hyperbilirubinemia, especially in dark-skinned newborns. The total serum bilirubin (TSB) level or the transcutaneous bilirubin (TcB) level is an alternative method of assessing bilirubin levels. If the TcB level is greater than 12 to 15 mg/dl, a serum bilirubin check is performed as a confirmatory test. Another way to assess for hyperbilirubinemia is to draw a serum bilirubin value. Levels, TcB or TSB, are interpreted by plotting them on an hour-specific nomogram to determine the infant’s risk for hyperbilirubinemia. Repeat testing is based on the risk level (low, intermediate, or high), the age of the neonate, and the progression of jaundice.