ABSTRACT. Objective. The objective of this study was to evaluate the roles of production and conjugation of bilirubin, individually and in combination, in the mechanism of neonatal jaundice.Methods. A cohort of healthy, term male newborns was sampled on the third day of life, coincident with routine metabolic screening, for blood carboxyhemoglobin determination, a reflection of heme catabolism, and for serum unconjugated and conjugated bilirubin fractions, reflecting bilirubin conjugation. The former was determined by gas chromatography, corrected for inspired CO (COHbc), and expressed as percentage of total hemoglobin. Serum bilirubin fractions were quantified by alkaline methanolysis and reverse phase high performance liquid chromatography. The sum of all bilirubin fractions comprised serum total bilirubin (STB). Conclusions. Within the range of STB concentrations encountered, both increasing bilirubin production and diminishing bilirubin conjugation contributed to STB. The production/conjugation index confirmed that imbalance between production and conjugation of bilirubin plays an important role in the mechanism of neonatal bilirubinemia. Pediatrics 2002;110(4). URL: http://www. pediatrics.org/cgi/content/full/110/4/e47; alkaline methanolysis, bilirubin, bilirubin conjugation, carbon monoxide, carboxyhemoglobin, gas chromatography, hemolysis, high performance liquid chromatography, physiologic jaundice.
Total conjugated bilirubin (TCB) was comprised of the sum of the conjugated fractions and was expressed as percentage of STB (TCB[%]). A "bilirubin production/conjugation index" (COHbc/[TCB(%)]ABBREVIATIONS. STB, serum total bilirubin; CO, carbon monoxide; COHb, carboxyhemoglobin; COHbc, COHb corrected for inspired CO; UGT, uridine diphosphoglucuronate glucuronosyltransferase 1A1; G-6-PD, glucose-6-phosphate dehydrogenase; TCB, serum total conjugated bilirubin. J aundice is common during the first days of postnatal life and affects almost two thirds of human newborns. The mechanism of this bilirubinemia is multifactorial, as recently summarized, and comprises primarily processes contributing to increased bilirubin load, or diminished bilirubin clearance. 1,2 The former may be the result of factors that augment bilirubin production and the enterohepatic circulation, whereas the latter is primarily the result of immature conjugative capacity, although impaired hepatic uptake or excretion may also play a part. It has been suggested that serum total bilirubin (STB) concentrations that remain within the physiologic range result from equilibrium between bilirubin production and elimination. In contrast, in some neonates, imbalance between these processes may occur, with bilirubin production being relatively higher than conjugation. This imbalance is thought to result in hyperbilirubinemia. 3 Assessment of the role of hemolysis may be accomplished through assessment of endogenous carbon monoxide (CO) production by accurately measuring blood carboxyhemoglobin (COHb), or end tidal CO, both with correction for ambient ...