Cleavage of the alpha-methene bridge of heme by membrane-bound heme oxygenase yields equimolar amounts of biliverdin, carbon monoxide, and reduced iron. Biliverdin is catalyzed by biliverdin reductase to bilirubin. The process occurs in all nucleated cells except mature anucleated red blood cells. Neonates in whom bilirubin production is increased tend to have higher bilirubin concentrations, and excessive bilirubin production or impairment of elimination causes dramatic deviations from the hour-specific nomogram that can be seen as “jumping” percentile tracks early in the postnatal period or later in the first week after birth. After formation, bilirubin diffuses into the circulation. In the absence of conjugates, the total bilirubin concentration in plasma is the sum of bilirubin bound to albumin plus a minimal amount of free bilirubin. Bilirubin is excreted more slowly in newborns than in adults. Although no clinical tests can measure bilirubin uptake and conjugation by the liver, an elevated hour-specific total bilirubin value when bilirubin production is normal or decreasing is a sign of impaired or abnormally delayed bilirubin excretion. The accuracy and precision of clinical laboratory total bilirubin measurements are a concern, and studies are underway to assess whether measurements of free bilirubin, the bilirubin-binding constant, the bilirubin:albumin ratio, or albumin binding capacity might improve the ability to identify infants at greater risk for bilirubin-induced neuroinjury rather than simply those at greater risk for having a higher bilirubin concentration.

Competitive inhibitors of heme oxygenase (HO) have been studied as interventional agents for neonatal hyperbilirubinemia. Several naturally occurring and synthetic metalloporphyrins have been shown to be potent inhibitors of HO activity and effective in reducing bilirubin concentrations in vitro and in vivo. Targeting HO may aid in preventing hyperbilirubinemia in newborns. Tin mesoporphyrin (SnMP) has emerged as a potential agent for reducing total bilirubin concentrations in preterm newborns. Adverse effects associated with SnMP use include photosensitization (which complicates its use in conjunction with phototherapy), and potential inhibition of several other enzymes that have essential roles in metabolism. Clinical studies of SnMP have shown that it prevents excessive neonatal hyperbilirubinemia and reduces the need for neonatal phototherapy in term and near-term infants. Because further research, specifically safety investigations, are complicated, use of SnMP should be reserved for neonates who are at especially high risk for developing bilirubin-induced neurologic dysfunction or participating in clinical trials.

A previous retrospective study showed an increased frequency of neonatal hyperbilirubinemia at high altitude in Colorado. In a prospective study we found that 39% of newborns at 3100 m altitude vs 16% at 1600 m exhibited hyperbilirubinemia, defined as a day 3 serum bilirubin level of 205 mumol/L or higher. Increased bilirubin production at 3100 m vs 1600 m was shown by increased levels of corrected carboxyhemoglobin. This finding was supported by increased erythropoietin and bilirubin values in cord blood and increased hematocrit values at day 3 among infants at 3100 m vs 1600 m. The sustained elevation in bilirubin for breast-fed vs formula-fed infants at 1600 m was observed for both feeding types at 3100 m. The findings suggested that there is a hematologic response to decreased oxygen availability at high altitude, resulting in increased bilirubin production accompanied by delayed bilirubin clearance.

The nucleotide sequence of spinach chloroplast methionine elongator tRNA (sp. chl. tRNAm Met) has been determined. This tRNA is considerably more homologous to E. coli tRNAm Met (67% homology) than to the three known eukaryotic tRNAm Met (50-55% homology). Sp. chl. tRNAm Met, like the eight other chloroplast tRNAs sequenced, contains a methylated GG sequence in the dihydrouridine loop and lacks unusual structural features which have been found in several mitochondrial tRNAs.