Which factors contribute to the development of physiologic jaundice in unconjugated hyperbilirubinemia?

Updated: May 21, 2019
  • Author: Hisham Nazer, MBBCh, FRCP, DTM&H; Chief Editor: BS Anand, MD  more...
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Physiologic jaundice is a mild unconjugated hyperbilirubinemia that affects nearly all newborns and resolves within the first several weeks after birth. It has been shown that bilirubin production in a term newborn is 2-3 times higher than in adults. It is caused by increased bilirubin production, decreased bilirubin clearance, and increased enterohepatic circulation. The following factors contribute to the development of physiologic jaundice:

  • Inefficient hepatic excretion of unconjugated bilirubin

  • Portal venous shunting through a patent ductus venosus

  • Shortened red blood cell survival

  • Immaturity of hepatic bilirubin clearance - Bilirubin-UGT activity is only 1% of normal adult levels at birth, regardless of gestational age; enzyme activity increases to adult levels by the 14th week of life; the main precipitant factors are decreased energy intake and delayed closure of the ductus venosus

  • Hydrolysis of conjugated bilirubin - The activity of beta-glucuronidase is increased in newborns, which leads to greater hydrolysis of conjugated bilirubin to the unconjugated form; the unconjugated bilirubin is reabsorbed from the intestine through the process of enterohepatic circulation

  • Low bacterial degradation of bilirubin - In neonates, the bacterial degradation of bilirubin is reduced because the intestinal flora is not fully developed; this may lead to increased absorption of unconjugated bilirubin [16]

Bilirubin and drug metabolism in neonates can also be affected by the influences of ethnicity on UGT1A1 haplotype mutations. [17] A cohort study of 241 consecutive term Asian infants reported that not only was there a variance in the prevalence of hypomorphic haplotypes, but also that the frequency varied between the different races. [18] For example, Indian neonates were more likely to have at least 1 hydromorphic haplotype (64%) than were Chinese (48%) and Malay (31%) neonates. There was also a trend between the number of G71R mutations and the need for phototherapy.

The peak total serum bilirubin level in physiologic jaundice typically is 5-6 mg/dL (86-103 µmol/L), occurs 48-120 hours after birth, and does not exceed 17-18 mg/dL (291-308 µmol/L). Higher levels of unconjugated hyperbilirubinemia are pathologic and occur in various conditions.

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