PROLONGED NEONATAL UNCONJUGATED HYPERBILIRUBINEMIA ASSOCIATED WITH BREAST FEEDING AND A STEROID, PREGNANE-3(ALPHA), 20(BETA)-DIOL, IN MATERNAL MILK THAT INHIBITS GLUCURONIDE FORMATION IN VITRO.

Abstract

The effect of mothers milk from the mothers of 7 jaundiced children was compared with milk from control mothers and from pregnant and postpartum cows on glucuronyl transferase activity in vitro. This infant jaundice a syndrome of severe and prolonged unconjugated hyperbilirubinemia occurred in association with breast feeding in 7 unrelated full-term infants. In vitro the breast milk obtained from the mothers of the 7 infants consistently inhibited glucuronyl transferase activity when compared with 99 milk specimens from 71 women whose infants did not have this syndrome. In vitro isolation of steroid products in the 2 milk pools (i.e. jaundiced infant vs. nonjaundiced) located a steroid pregnane-3(alpha)20(beta)-diol that was consistently present in the mothers milk from the jaundiced infant group but never present in control mothers milk. In vitro this steroid inhibited competitively glucuronyl transferase activity. The precursor of the isolated steroid pregnane-3(alpha)20(beta)-diol is unknown as are its mechanisms of action. The steroid metabolite is unknown in human tissues but is a major progesterone metabolite in guinea pigs and cattle. The same mothers whose breast milk inhibited glucuronyl transferase in vitro had serum samples tested similarly and the sera was no more inhibitory than that of normal mothers.