Insufficient glucuronide formation in the newborn and its relationship to the pathogenesis of icterus neonatorum.

In the last few years the pathogenesis of icterus neonatorum and kernikterus has aroused renewed interest (Napp and Plotz, 1949; Obrinsky, Allen and Anderson, 1954; Billing, Cole and Lathe, 1954; Meyer, 1956). The discovery by Schmid (1956) and Billing, Cole and Lathe (1957) that bilirubin is excreted in the bile as a glucuronide now makes it possible to reinvestigate this problem more specifically. The accumulation of bilirubin in the blood after birth suggests that the excretory capacity of the liver is inadequate. Such an inadequacy has been demonstrated only indirectly, either by the diminished ability of newborn and premature infants to excrete bromsulphalein dye (Mollison and Cutbush, 1949; Yudkin and Gellis, 1949; Obrinsky, Denley and Brauer, 1952; Perl, 1957) or by the fact that an inverse relationship exists between the amount of bile pigment in the meconium and the subsequent rise of the bilirubin in the serum (Ross, Waugh and Malloy, 1937; Fashena, 1948; Napp and Plotz, 1949; Vest, 1958). It therefore seemed promising to investigate the glucuronic acid conjugating ability of the liver in newborn and premature infants. Storey and Dutton (1955) have demonstrated that the conjugation of substances like p-aminophenol, menthol and others with glucuronic acid is catalyzed by an enzyme system in the microsomes of the liver and requires uridine diphosphate glucuronic acid (UDPGA) as the glucuronide donor. The enzymatic formation of bilirubin glucuronyl seems to involve the same system (Schmid, Hammaker and Axelrod, 1957). A diminished glucuronide synthesis in young animals as compared with adult animals was demonstrated in vitro with liver tissue from mice (Karunairatnam, Kerr and Levvy, 1949), rabbits (Hartiala and Pulkkinen, 1955) and rats (Vest, 1958). The purpose of this paper is to report the results of an investigation into the capacity of the liver of full term and premature infants to form glucuronides. Method