Editors:Cloherty, John P.; Eichenwald, Eric C.; Stark, Ann R.Title:
Manual of Neonatal Care, 6th Edition
Copyright ©2008 Lippincott Williams & Wilkins
> Table of Contents > 18 - Neonatal Hyperbilirubinemia
Camilia R. MartinJohn P. Cloherty
The normal adult serum bilirubin level is <1 mg/dL. Adults appear jaundiced when the serum bilirubin level is >2 mg/dL, andnewborns appear jaundiced when it is >7 mg/dL. Between 25% and 50% of all term newborns and a higher percentage of premature infants develop clinical jaundice. Also, 6.1% of well term newborns have a maximal serum bilirubin level >12.9 mg/dL.A serum bilirubin level >15 mg/dL is found in 3% of normal term babies.
Physical examination is not a reliable measure of serum bilirubin.
A. Source of bilirubin.
Bilirubin is derived from the breakdown of heme-containing proteins in the reticuloendothelial system. The normal newbornproduces 6 to 10 mg of bilirubin/kg/day, as opposed to the production of 3 to 4 mg/kg/day in the adult.
The major heme-containing protein is
red blood cell (RBC) hemoglobin.
Hemoglobin released from senescent RBCs in thereticuloendothelial system is the source of 75% of all bilirubin production. One gram of hemoglobin produces 34 mg of bilirubin.Accelerated release of hemoglobin from RBCs is the cause of hyperbilirubinemia in isoimmunization (e.g., Rh and ABOincompatibility), erythrocyte biochemical abnormalities (e.g., glucose-6-phosphate dehydrogenase [G6PD] and pyruvate kinasedeficiencies), abnormal erythrocyte morphology (e.g., hereditary spherocytosis [HS]), sequestered blood (e.g., bruising andcephalohematoma), and polycythemia.
The other 25% of bilirubin is called
It is derived from hemoglobin released by ineffectiveerythropoiesis in the bone marrow, from other heme-containing proteins in tissues (e.g., myoglobin, cytochromes, catalase, andperoxidase), and from free heme.
B. Bilirubin metabolism.
The heme ring from heme-containing proteins is oxidized in reticuloendothelial cells to
by the microsomal enzymeheme oxygenase. This reaction releases
carbon monoxide (CO)
(excreted from the lung) and
(reutilized). Biliverdin is thenreduced to bilirubin by the enzyme
Catabolism of 1 mol of hemoglobin produces 1 mol each of CO andbilirubin. Increased bilirubin production, as measured by CO excretion rates, accounts for the higher bilirubin levels seen inAsian, Native American, and Greek infants.
Bilirubin is nonpolar, insoluble in water, and is transported to liver cells bound to serum
Bilirubin boundto albumin does not usually enter the central nervous system (CNS) and is thought to be nontoxic. Displacement of bilirubin fromalbumin by drugs, such as the sulfonamides, or by free fatty acids (FFAs) at high molar ratios of FFA: albumin, may increasebilirubin toxicity (see Table 18.1).
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