Do functional gut parameters predict enteral autonomy and chronic cholestasis in pediatric intestinal failure?

Parenteral nutrition (PN) dependency in patients with intestinal failure (IF) can lead to complications including liver disease. Therefore, IF management strives to wean patients off PN. In adult IF, chronic cholestasis is predicted by the functional gut parameters citrulline (CIT) and enteroendocrine fibroblast growth factor 19 (FGF19), which inhibits hepatic bile salt synthesis. We investigated 1) whether CIT, FGF19 and a marker for enterocyte damage (urinary intestinal fatty acid-binding protein (I-FABP)) are associated with enteral autonomy within 60 days after intestinal surgery in neonates, and 2) the longitudinal patterns of CIT, FGF19, total bile salts and C4 (marker for bile salt synthesis) in subgroups of children on long-term PN (short bowel syndrome (SBS) and functional IF).

A prospective two-center cohort study, including 1) neonates with PN-need after intestinal surgery and 2) children (aged <18y) with >6 months PN-dependency. CIT, FGF19, and I-FABP were measured post-surgery in neonates. CIT, FGF19, total bile salts and C4 were assessed on inclusion in children with long-term PN-dependency. Associations were analyzed using Cox regression models. Longitudinal patterns were analyzed using linear mixed-effects models.

Of 50 neonates, 52 % reached enteral autonomy. Residual small bowel length <75 cm (hazard ratio 0.23, p = 0.046), but not CIT, FGF19 or I-FABP concentrations, was negatively associated with 60-day enteral autonomy. Children with SBS (n = 20) had dysregulated bile salt synthesis with lower FGF19 (24.4 vs 108.8 pg/mL, p = 0.004) and higher C4 concentrations (110.3 vs 30.9 pg/mL, p = 0.024) than children with functional IF (n = 20). In children with long-term PN, CIT concentration significantly increased with decreasing PN-dependency and total bile salt concentration significantly increased with increasing PN-duration.

Functional gut biomarkers provided no additional value in predicting enteral autonomy in neonates post-intestinal surgery over residual small bowel length. In children on long-term PN, enhanced bile salt synthesis was observed in those with SBS.

Overview of Medical research in the Netherlands (OMON) NL-OMON27840 (previously NTR6080), https://trialsearch.who.int/Trial2.aspx?TrialID=NL-OMON27840.