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

Clinical Nutrition, vol. 53, pp. 168–176

Abstract

BACKGROUND & AIMS: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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. CLINICAL TRIAL REGISTRATION: Overview of Medical research in the Netherlands (OMON) NL-OMON27840 (previously NTR6080), https://trialsearch.who.int/Trial2.aspx?TrialID=NL-OMON27840.

Authors 13

1. Lotte E. Vlug

   Erasmus MC · Erasmus MC - Sophia Children’s Hospital

   Affiliation as printed

   Department of Pediatrics, Division of Gastroenterology, Erasmus MC University Medical Center Sophia Children's Hospital, Rotterdam, the Netherlands

2. Frank G. Schaap

   Maastricht University Medical Centre · Maastricht University

   Affiliation as printed

   Department of Surgery, NUTRIM Institute of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht University Medical Center, Maastricht, the Netherlands

3. Kaatje Lenaerts

   Maastricht University Medical Centre · Maastricht University

   Affiliation as printed

   Department of Surgery, NUTRIM Institute of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht University Medical Center, Maastricht, the Netherlands

4. Esther G. Neelis

   Erasmus MC · Erasmus MC - Sophia Children’s Hospital

   Affiliation as printed

   Department of Pediatrics, Division of Gastroenterology, Erasmus MC University Medical Center Sophia Children's Hospital, Rotterdam, the Netherlands

5. Hans M. van Eijk

   Maastricht University Medical Centre · Maastricht University

   Affiliation as printed

   Department of Surgery, NUTRIM Institute of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht University Medical Center, Maastricht, the Netherlands

6. Sander M. J. van Kuijk

   Maastricht University Medical Centre · Maastricht University

   Affiliation as printed

   Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Center, Maastricht, the Netherlands

7. Merit Monique Tabbers

   Emma Kinderziekenhuis · Amsterdam University Medical Centers · University of Amsterdam

   Affiliation as printed

   Department of Pediatric Gastroenterology, Hepatology and Nutrition, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands

8. Sjoerd C. J. Nagelkerke

   Emma Kinderziekenhuis · Amsterdam University Medical Centers · University of Amsterdam

   Affiliation as printed

   Department of Pediatric Gastroenterology, Hepatology and Nutrition, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands

9. Rene M. H. Wijnen

   Erasmus MC · Erasmus MC - Sophia Children’s Hospital

   Affiliation as printed

   Department of Pediatric Surgery, Erasmus MC University Medical Center Sophia Children's Hospital, Rotterdam, the Netherlands

10. Edmond H.H.M. Rings Aachen

    Leiden University Medical Center · Erasmus MC · Erasmus MC - Sophia Children’s Hospital

    Affiliation as printed

    Department of Pediatrics, Division of Gastroenterology, Erasmus MC University Medical Center Sophia Children's Hospital, Rotterdam, the Netherlands; Department of Pediatrics, Leiden University Medical Center Willem Alexander Children's Hospital, Leiden, the Netherlands

11. Jessie M. Hulst

    University of Toronto · Hospital for Sick Children

    Affiliation as printed

    Division of Pediatric Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pediatrics & Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada

12. Steven W.M. Olde Damink

    Maastricht University Medical Centre · Maastricht University · Essen University Hospital

    Affiliation as printed

    Department of Surgery, NUTRIM Institute of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht University Medical Center, Maastricht, the Netherlands; Department of General, Visceral, Vascular and Transplantation Surgery, University Hospital Essen, Essen, Germany

13. Barbara A. E. de Koning

    Erasmus MC · Erasmus MC - Sophia Children’s Hospital

    Affiliation as printed

    Department of Pediatrics, Division of Gastroenterology, Erasmus MC University Medical Center Sophia Children's Hospital, Rotterdam, the Netherlands. Electronic address: b.dekoning@erasmusmc.nl