IT SEEMS well established that there is a relationship between breast feeding and neonatal hyperbilirubinemia.1-5 Transient unconjugated hyperbilirubinemia observed for several days in the neonatal period, and clinically referred to as physiologic jaundice, is believed to be the result of a maturational delay in the development of the hepatic enzymes associated with bilirubin conjugation in the liver.6-8 Both pregnane-3\g=a\, 20\g=a\-and pregnane-3\g=a\,20\g=b\-diol show in vitro inhibition of conjugation in a system using o-aminophenol and bilirubin as substrates with microsomal fractions prepared from rat and guinea pig liver.9-11 An in vitro inhibition is also demonstrable with breast milk of some nursing infants with so-called physiologic hyperbilirubinemia in the same system.12Arias et al have reported the isolation of the 3\g=a\,20\g=b\ isomer from breast milk.2 They have estimated that approximately 1 mg of the substance is excreted per day in the mother's milk. Two full-term infants orally fed the 3\g=a\,20\g=b\ isomer from the sixth and eighth day of life, respectively, showed a secondary increase in serum unconjugated bilirubin,13 after the bilirubin values had fallen from an initially elevated level. Ordi¬ narily, one would not have anticipated this result after the apparent maturation of the conjugation mechanism. It was therefore decided to repeat this study on a larger series of infants. Since the in vitro effect of the two isomers is similar, we have undertaken to assess the effect of oral administration of both fractions * on bilirubin metabolism in newborn infants and, in addition, to com¬ pare this effect with the naturally occurring events in a series of control babies.
Methods and MaterialsTwenty full-term infants receiving a cows' milk formulât were divided into three groups for pur¬ poses of the study. The first two groups were fed a pregnanediol, and the third group served as a control.All the infants were healthy and did not re¬ ceive any medications except vitamin K, 2 mg intramuscularly, at birth. There were no blood group incompatibilities. No other feedings were given during the period of the study. Serum bilirubin was determined by tin· method of Malloy and Evelyn" on the third day of life and every second day thereafter. Beginning on tin-fifth day for a five-day period, groups 1 and 11 received a pregnanediol orally (see below). Group 111 infants served as controls ; no pregnanediol was fed but serum bilirubins were determined in the same manner as groups I and II. There were no differences in clinical management between the three groups.Graut' I (Infants Fed Pregnane-3a,20/3-diol).-A. There were 13 infants in this group. One milli¬ gram of the substance dissolved in triple distilled ethyl alcohol was mixed with 3 cc distilled water and 0.6 cc of an ACD vitamin mixture (Tri-Vi-Sol). The mixture was shaken well and 0.6 cc was administered by dropper 15 minutes before each feeding. The infants were fed at four hour inter¬ vals. A fresh mixture was prepared daily for the five consecutiv...
