Bilirubinemia of the Newborn

A common problem in neonates.

Some types pathologic and some physiologic.

Bilirubin may be unconjugated or conjugated; differentiating important for diagnosis.

If pathologic, varying effect on management (e.g., sepsis, Rh incompatibility, GI obstruction, Gilbert, AVM, sickle cell, biliary atresia).

Clinical, epidemiologic, and genetic risk factors associated with significant hyperbilirubinemia include preterm gestational age, exclusive breastfeeding, glucose-6-phosphate dehydrogenase deficiency, Rh/ABO incompatibility, East Asian or Native American ethnicity, any jaundice observed in the first 24 h of life (hemolysis until proven otherwise), cephalohematoma or significant bruising after delivery, and Hx of a previous sibling treated with phototherapy.

Risks specific to a primary pathologic cause of bilirubinemia

Acute bilirubin encephalopathy (unconjugated bilirubin may penetrate brain cells and cause dysfunction in either pathologic or physiologic states)

Kernicterus (chronic and permanent sequelae of bilirubin neurotoxicity)

Factors that increase blood-brain barrier permeability to unconjugated bilirubin (hypoxia, hypercarbia, acidosis, hyperosmolality, hypertension, seizure activity, and sepsis)

Drugs (e.g., sulfonamides, ceftriaxone, ampicillin, salicylates, furosemide, contrast dye) that displace bilirubin from albumin, which can increase free fraction of unconjugated bilirubin in the blood

Conversely, binding of some drugs to albumin may be altered in the presence of hyperbilirubinemia in the neonatal period

Physiologic states (dehydration, hypercarbia, and acidosis) may displace bilirubin

Surgery may increase load of heme to be degraded (e.g., hematoma absorption)

Primary pathology

Bilirubin is derived from the catabolism of proteins that contain heme, usually, from the breakdown of hemoglobin from RBCs.

Heme is oxidized to biliverdin and then reduced to bilirubin, which is unconjugated, nonpolar, and lipid soluble.

Unconjugated bilirubin circulates bound to albumin in equilibrium with its unbound fraction that readily crosses the blood-brain barrier and can cause neurotoxicity.

Bilirubin is conjugated in the liver cell microsomes by the enzyme (UDP)-glucuronyl transferase, to form the polar, water-soluble glucuronide of bilirubin.

Most of the conjugated bilirubin is excreted as bile, which is metabolized by intestinal flora and excreted in the feces.

The danger of unconjugated hyperbilirubinemia is bilirubin-induced neurologic dysfunction.

Bilirubinemia peaks in term infants between 3–5 d; preterm infants 5–6 d

Clinical features of bilirubin encephalopathy are lethargy, anorexia, nausea, vomiting, and opisthotonic posturing.

The ability of anesthetic agents to displace bilirubin from albumin has not been well studied.

Nonpathologic, physiologic jaundice due to immature hepatic glucuronyl transferase

Pathologic hyperbilirubinemia due to many causes (isoimmunization, erythrocyte biochemical defects, erythrocyte structural defects, infection)

Excess bilirubin production from RBC breakdown (intravascular hemolysis or polycythemia, extravascular bruising or cephalohematoma)

Decreased removal of bilirubin through gut (decreased meconium evacuation and increased enterohepatic recirculation; decreased bile flow due to liver disease or cholestasis)

Breastfeeding jaundice (occurs in first wk after birth and implies inadequate hydration or caloric intake)

Breast-milk jaundice (unidentified factors in normal mature human milk that cause increased reabsorption of UB from gut) can last for 3–4 wk up to 3 mo