Breast Milk Jaundice: In Vitro Inhibition of Rat Liver Bilirubin-Uridine Diphosphate Glucuronyltransferase Activity and Z Protein-Bromosulfophthalein Binding by Human Breast Milk

Abstract

Extract: Twenty-four samples of breast milk from nine mothers of infants suffering from breast milk jaundice were studied. Eight samples of milk from mothers of nonjaundiced infants, along with five formula milks enriched with polyunsaturated fatty acids, served as controls. Milks from mothers with jaundiced infants had no inhibitory effect when assayed immediately after thawing. However, after these milk samples were stored at 4°, they strongly inhibited bilirubin conjugation (80.3% inhibition of uridine diphosphate glucuronyltransferase (UDPGT) activity) and bromosulfophthalein (BSP) binding to cytoplasmic Z protein (dye binding inhibited 82.1%). There was no effect on BSP binding to Y protein (see Table 1). Heating the milk to 56° modified the results in the following manner; when the milk was heated immediately after thawing, no inhibitory effect was seen, even after storage for 96 hr. On the other hand, when the milk was first stored at 96 hr and then heated, it had the same inhibitory effects as the milks which were stored without heating. The present study shows that pathologic breast milk will inhibit BSP-Z protein binding only when stored under conditions that also cause the appearance of the capacity to inhibit bilirubin conjugation in vitro, as well as causing the liberation of nonesterifled fatty acids. Thus, the appearance of this inhibitory capacity in vitro seems linked to the lipolytic activity particular to pathologic milks. Speculation: By demonstrating that the in vitro inhibition of bilirubin conjugation by pathologic milks is due to the tying up of hepatic transport proteins, we have furnished the missing link in the sequence of events following ingestion of potentially inhibitory milk resulting in neonatal jaundice. We call the pediatrician's attention to the key role of ingested free fatty acids in the etiology of this condition.