Carbon monoxide and bilirubin production in neonates.

Abstract

Jaundice is a common neonatal syndrome. Neonatal hyperbilirubinemia is a complex biologic phenomenon resulting from increased production and limited elimination of bilirubin during the transitional time after birth. Bilirubin production is 2 to 3 times higher in normal term newborns compared with adults, and is greatly exacerbated by hemolysis from any cause, the breakdown of extravascular blood, the shorter red cell life span associated with prematurity, maternal diabetes, cholestasis, unknown factors associated with ethnicity, and many other conditions. Thus, increased bilirubin production is an important contributing cause of all kinds of neonatal jaundice. The ability to predict the degree of jaundice based on the rate of bilirubin production is limited because bilirubin elimination varies greatly from individual to individual in the transitional time after birth. Nonetheless, identifying high producers of bilirubin is important for the diagnosis of hemolysis or the recognition of other risk factors associated with increased bilirubin production. Such risk factors have been identified in the new AAP practice parameter on the management of hyperbilirubinemia in the healthy term neonate1 as important exclusions for a neonate enrolled into the recommended management algorithm. Moreover, information about bilirubin production provides an accurate means of targeting individuals or populations for treatment with heme oxygenase (HO) inhibitors or for assessing the treatment efficacy of a particular HO inhibitor in an individual patient, monitoring directly the mechanism of action of the drug and evaluating dose response. Because carbon monoxide (CO) and biliverdin are produced in equimolar amounts and biliverdin is quantitatively reduced to bilirubin, the measurement of CO in breath or blood can be used as an index of heme degradation and bilirubin production in vivo. The validity of this approach has been well-established.2 The association of increased CO production with kernicterus and death related to hyperbilirubinemia in jaundiced Nigerian infants …