The discovery that bilirubin must be conjugated with glucuronic acid in the liver to form a water-soluble compound, before the conjugate can be excreted by the kidney, stimulated these investigators to evaluate the conjugating ability of the liver in newborn and premature infants. For this purpose, acetanilid was selected to assess glucuronide formation. In the adult, after oral administration of this compound, about 80% is excreted in the urine in the form of a glucuronide conjugate when administered in a dose of 10 mg/kg of body weight.
The amount of the acetanilid glucuronide excreted in the urine in 24 hours, was determined in a group of 94 subjects comprising premature and full-term infants and older children. It was found that newborn, and especially premature infants, excrete only a few per cent of the administered acetanilid as glucuronide conjugate in 24 hours. In 48 hours, the total excretion in newborn infants is only about 10% or less.
The ability to conjugate acetanilid increases steadily until, at the age of 3 months, normal capacity (80% excretion) is generally reached. Improvement in the capacity to carry out this conjugation is rapid following birth, and by about 10 days of age is about one third of normal although the capacity of the mature adult is not achieved until about the age of 3 months.
The authors discuss the reasons for believing the failure of excretion of conjugated acetanilid is a reflection of inability of the conjugating mechanism in the liver rather than a reduced excretory capacity in the kidney in the early weeks of life. These clinical investigations are in agreement with the findings from direct estimation of conjugating activity of specimens of liver obtained from experimental animals.