Bile acid metabolism is altered in neonates on parenteral nutrition (PN), predisposing them to parenteral nutrition-associated liver disease. Cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme in the bile acid synthesis pathway, is repressed by fibroblast growth factor 19 (FGF19) and phytosterols (PS). We describe a case of a preterm infant who developed necrotizing enterocolitis (NEC) and received exclusive PN for over 2 months. Our objective was to serially assess CYP7A1 activity and plasma FGF19 and PS concentrations in this infant case compared to five healthy preterm infants. We found that CYP7A1 activity increased during the first 2 weeks of life in control infants but was undetectable in the infant case. FGF19 concentrations were high at birth in all infants and subsequently declined and did not differ between the case and control infants. As expected, PS concentrations were elevated in the infant case and continued to increase despite lipid minimization. In conclusion, CYP7A1 activity was gradually upregulated in healthy preterm infants but remained suppressed in the infant requiring prolonged PN. Preterm infants also had elevated FGF19 concentrations at birth, which decreased with advancing postnatal age.
Keywords: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BA, bile acid; C4, 7α-hydroxy-4-cholestene-3-one; CYP7A1, cholesterol 7α-hydroxylase; DMG, N, N-dimethylglycine; DOL, day of life; ELISA, enzyme-linked immunosorbent assay; FGF19, fibroblast growth factor 19; FXR, Farnesoid X receptor; IRB, institutional review board; LC-MS/MS, liquid chromatography/tandem mass spectrometry; NEC, necrotizing enterocolitis; NPO, nil per os; PN, parenteral nutrition; PNALD, parenteral nutrition-associated liver disease; PS, phytosterols; bile acid metabolism; cholesterol 7-alpha hydroxylase; farnesoid x receptor; fibroblast growth factor 19; intravenous lipid emulsion.