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

IF 7.4 2区医学 Q1 NUTRITION & DIETETICS

Clinical nutrition Pub Date : 2025-08-28 DOI:10.1016/j.clnu.2025.08.030

Lotte E. Vlug , Frank G. Schaap , Kaatje Lenaerts , Esther G. Neelis , Hans M. van Eijk , Sander M.J. van Kuijk , Merit M. Tabbers , Sjoerd C.J. Nagelkerke , René M.H. Wijnen , Edmond H.H.M. Rings , Jessie M. Hulst , Steven W.M. Olde Damink , Barbara A.E. de Koning

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引用次数: 0

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.

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肠道功能参数能否预测小儿肠衰竭患者的肠自主性和慢性胆汁淤积？

背景和目的肠衰竭（IF）患者的肠外营养（PN）依赖可导致包括肝脏疾病在内的并发症。因此，IF管理努力使患者戒除PN。在成人IF中，慢性胆汁淤积是由功能肠道参数瓜氨酸（CIT）和肠内分泌成纤维细胞生长因子19 （FGF19）预测的，它们抑制肝胆盐的合成。我们研究了1)CIT、FGF19和肠细胞损伤标志物（尿肠脂肪酸结合蛋白（I-FABP））是否与新生儿肠道手术后60天内的肠自主相关，以及2)长期PN（短肠综合征（SBS）和功能性IF）患儿亚组中CIT、FGF19、总胆汁盐和C4（胆汁盐合成标志物）的纵向模式。方法采用前瞻性双中心队列研究，纳入1)肠道手术后需要pn的新生儿和2)6个月pn依赖的儿童（18岁）。术后测量新生儿CIT、FGF19和I-FABP。评估CIT、FGF19、总胆盐和C4在长期pn依赖患儿中的纳入情况。使用Cox回归模型分析相关性。纵向模式分析使用线性混合效应模型。结果50例新生儿中，52%达到肠内自主。残余小肠长度75 cm（风险比0.23,p = 0.046）与60天肠内自主性呈负相关，但CIT、FGF19或I-FABP浓度与此无关。SBS患儿（n = 20）胆盐合成失调，FGF19较低（24.4 vs 108.8 pg/mL, p = 0.004）， C4浓度较高（110.3 vs 30.9 pg/mL, p = 0.024），高于功能性IF患儿（n = 20）。在长期PN患儿中，CIT浓度随PN依赖性的降低而显著升高，总胆汁盐浓度随PN持续时间的增加而显著升高。结论功能性肠道生物标志物在预测新生儿肠道术后肠自主性方面没有额外的价值。在长期服用PN的儿童中，观察到SBS患者胆盐合成增强。临床试验注册：荷兰医学研究概述（OMON） NL-OMON27840（以前的NTR6080）， https://trialsearch.who.int/Trial2.aspx?TrialID=NL-OMON27840。

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来源期刊

Clinical nutrition 医学-营养学

CiteScore

14.10

自引率

6.30%

发文量

356

审稿时长

28 days

期刊介绍： Clinical Nutrition, the official journal of ESPEN, The European Society for Clinical Nutrition and Metabolism, is an international journal providing essential scientific information on nutritional and metabolic care and the relationship between nutrition and disease both in the setting of basic science and clinical practice. Published bi-monthly, each issue combines original articles and reviews providing an invaluable reference for any specialist concerned with these fields.