The long-term objective of this research is increased understanding of the pathophysiology of neonatal hyperbilirubinemia so that this common health problem may be alleviated.
The specific aim of this proposal is to test three current hypotheses which relate breast-milk composition to neonatal jaundice. These hypotheses suggest: (1) Elevated breast-milk lipase activity is present in certain milks. The lipase-catalyzed hydrolysis of milk triglycerides to free fatty acids is, therefore, increased and high concentrations of fatty acids are absorbed by the neonate that inhibit hepatic bilirubin glucuronyltransferase (BGT). Decreased BGT activity impairs bilirubin conjugation and excretion resulting in hyperbilirubinemia. (2) An unknown inhibitor(s) present in certain human milk samples similarly inhibits either BGT or another step in the hepatic clearance of bilirubin. (3) Alternatively, human milk may not interfere with hepatic bilirubin excretion but, rather, promote increased intestinal absorption of bilirubin, thus decreasing clearance. This could occur due to Beta-glucuronidase, an enzyme in human milk and neonatal intestinal tissue and bacteria which cleaves glucuronic acid from bilirubin glucuronides producing unconjugated bilirubin which is more easily absorbed from the gut. A prospective protocol involving 100 breast- and 50 formula-fed infants and their mothers will address these hypotheses by examining breast-milk, formula, serum and stool samples. Analyses will include lipase (lipoprotein lipase and bile salt stimulated lipase), free fatty acids, BGT inhibition, Beta-glucuronidase, total and direct bilirubin, total lipid, protein, albumin, bile salts and stool bile pigments. A new assay will be developed to test for inhibition of all steps of bilirubin metabolism using the intact hepatocyte in order to complement more limited microsomal assays. In 15 neonates from each feeding group quantitative stool cultures will be obtained along with milk analyses of immunologic components (IgG, A, M, SIgA, E.coli antibodies, lymphocyte subpopulations, lactoferrin and lysozyme). This will allow testing of the related hypotheses that immunologic factors in milk foster the development of the characteristic gut flora with high Beta-glucuronidase activity seen in breast-fed infants. Statistical analysis will compare the above data as a function of feeding composition and bilirubin level.

Project Start
1986-06-01
Project End
1989-05-31
Budget Start
1987-06-01
Budget End
1988-05-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Gourley, G R; Kreamer, B; Arend, R (1992) The effect of diet on feces and jaundice during the first 3 weeks of life. Gastroenterology 103:660-7
Rosensweig, J N; Gourley, G R (1991) Verotoxic Escherichia coli in human disease. J Pediatr Gastroenterol Nutr 12:295-304
Jakaite, D; Gourley, G R; Pellett, J R (1991) Erosions of the angelchik prosthesis in pediatric-sized developmentally disabled patients. J Pediatr Gastroenterol Nutr 13:186-91
Gourley, G R; Kreamer, B; Arend, R (1990) Excremental studies in human neonates. Identification of zinc coproporphyrin as a marker for meconium. Gastroenterology 99:1705-9
Odell, G B; Mogilevsky, W S; Gourley, G R (1990) High-performance liquid chromatographic analysis of bile pigments as their native tetrapyrroles and as their dipyrrolic azosulfanilate derivatives. J Chromatogr 529:287-98
Gourley, G R; Gourley, M F; Arend, R et al. (1989) The effect of saccharolactone on rat intestinal absorption of bilirubin in the presence of human breast milk. Pediatr Res 25:234-8
Treem, W R; Malet, P F; Gourley, G R et al. (1989) Bile and stone analysis in two infants with brown pigment gallstones and infected bile. Gastroenterology 96:519-23
Goodman, G M; Gourley, G R (1988) Ascites complicating ventriculoperitoneal shunts. J Pediatr Gastroenterol Nutr 7:780-2
Gourley, G R; Arend, R; Mogilevsky, W S et al. (1986) Bilirubin conjugate excretion and bilirubin uridine diphosphoglucuronyltransferase activity in nonjaundiced homozygous and heterozygous Gunn rats. J Lab Clin Med 108:436-41