Determination of fetal bile acids and related steroidal compounds and their profile in neonatal biological fluids

Abstract

The unusual bile acids hydroxylated at 1 beta-, 2 beta-, 4 beta-, 6 alpha- and 19-positions of cholic and chenodeoxycholic acids have been found from the meconium, neonatal bile, blood and urine, and amniotic fluid and pregnant urine by GC-MS analysis. These hydroxylated bile acids and their conjugates were synthesized as their references from the corresponding usual bile acids as starting materials, and the simultaneous and high performance analytical methods were developed by GC-MS, HPLC and enzyme immunoassay. The above mentioned unusual bile acids were identified and determined in significant amounts of the total bile acids in the biological fluids from neonates and pregnant women, but not from normal adults. We, therefore, proposed that they should be called as "fetal bile acids". Application of the developed methods was performed for the studies on the dynamic profile of fetal bile acids in developing fetus and neonates, and the clinical diagnosis of the hepatobiliary diseases of infants and congenital bile acid biosynthetic disorders, Zellweger syndrome, celebrotendinus xanthomatosis, 3-oxo-delta 4-steroid 5 beta-reductase deficiency and congenital biliary atresia. Analyses of steroidal hormones, equine estrogens and 18-hydroxycortisol were also described.