Long-term teduglutide associated with improved response in pediatric short bowel syndrome-associated intestinal failure.

OBJECTIVES: Patients with short bowel syndrome-associated intestinal failure (SBS-IF) require long-term parenteral nutrition and/or intravenous fluids (PN/IV) to maintain fluid or nutritional balance. We report the long-term safety, efficacy, and predictors of response in pediatric patients with SBS-IF receiving teduglutide over 96 weeks. METHODS: This was a pooled, post hoc analysis of two open-label, long-term extension (LTE) studies (NCT02949362 and NCT02954458) in children with SBS-IF. Endpoints included treatment-emergent adverse events (TEAEs) and clinical response (≥20% reduction in PN/IV volume from baseline). A multivariable linear regression identified predictors of teduglutide response; the dependent variable was mean change in PN/IV volume at each visit over 96 weeks. RESULTS: Overall, 85 patients were analyzed; 78 patients received teduglutide in the parent and/or LTE studies (any teduglutide [TED] group), while seven patients did not receive teduglutide in either the parent or LTE studies. Most TEAEs were moderate or severe in intensity in both groups. By week 96, 82.1% of patients from the any TED group achieved a clinical response, with a mean fluid decrease of 30.1 mL/kg/day and an energy decrease of 21.6 kcal/kg/day. Colon-in-continuity, non-White race, older age at baseline, longer duration of teduglutide exposure, and increasing length of remaining small intestine were significantly associated with a reduction in mean PN/IV volume requirements. CONCLUSIONS: In pediatric patients with SBS-IF, teduglutide treatment resulted in long-term reductions in PN/IV requirements. The degree of PN/IV volume reduction depended on the duration of teduglutide exposure, underlying bowel anatomy, and demographics.

Infant formulas for the treatment of functional gastrointestinal disorders: A position paper of the ESPGHAN Nutrition Committee.

Functional gastrointestinal disorders (FGID), such as infant regurgitation, infant colic, and functional constipation, are common and typically physiological phenomena during the early months of an infant's life and account for frequent consultations with pediatricians. Various infant formulas are marketed for their management and are frequently given by parents to infants before a medical consultation. However, the evidence supporting their effectiveness is limited and some have altered nutritional compositions when compared to standard formulas. Thus, these products should only be used under medical supervision and upon medical advice. Marketing and over-the-counter sales do not ensure proper medical guidance and supervision. The aim of this position paper is to review the current evidence regarding the safety and efficacy of formulas specifically formulated for addressing regurgitation, colic, and constipation, recognized as FGID. The objective is to provide guidance for clinical management based on the highest quality of available evidence. A wide search using Pubmed, MEDLINE, EMBASE and Cochrane Database of Systematic Reviews was performed including the MESH terms infant formula, colic, constipation, regurgitation, reflux, palmitate, lactase, lactose, magnesium, hydrolyzed protein, prebiotics or probiotics. 752 papers were identified and screened. Finally, 72 papers were included in the paper. In the absence of evidence, recommendations reflect the authors' combined expert opinion. Final consensus was obtained by multiple e-mail exchange and meetings of the Nutrition Committee. (1) For breastfed infants experiencing FGID such as regurgitation, colic, or constipation, transitioning from breastfeeding to commercial formulas is not recommended. (2) In general, whether an infant is breastfed or formula-fed, it's crucial to reassure parents that FGIDs are normal and typically do not necessitate treatment or change to a special formula. (3) Thickened formulas, often termed anti-reflux formulas, may be considered in specific cases of regurgitation. (4) The usage of specialized formulas for infants with colic is not advised due to a lack of clinical evidence. (5) In the case of constipation in infants, the use of formulas enriched with high ß-palmitate and increased magnesium content may be considered to soften the stool. Generally, there is limited evidence supporting the use of specialized formulas for FGID. Breastfeeding should never be discontinued in favor of formula feeding.

Measuring body composition in pediatric patients with complex diagnoses: Acceptability, practicality, and validation of different techniques.

BACKGROUND: Body composition could help identify malnutrition in pediatric patients, but there is uncertainty over which techniques are most suitable and prevailing opinion that measurements are difficult to obtain in practice. This study examined the acceptability, practicality, reliability, and validity of different anthropometric and body composition measurements in patients with complex diagnoses in a tertiary pediatric hospital. METHODS: A total of 152 children aged 5-18 years had weight, height, body mass index (BMI), mid-upper arm circumference (MUAC), 4-site skinfold thicknesses (SFT), bioelectrical impedance analysis (BIA), and dual-energy x-ray absorptiometry (DXA) assessed on admission and discharge. Acceptability was assessed in a continuous scale, practicality with number/percentage of successful measurements, reliability with intraclass correlation coefficients and coefficients of repeatability, and validity between "simpler" techniques and DXA with Bland-Altman analysis of agreement and Cohen kappa. RESULTS: Techniques were overall acceptable. Measurements were successful in >50%, with patient refusal uncommon. Coefficients of repeatability were good (0.3 cm MUAC and height, 0.2 kg weight, and 1.0 mm SFTs). All techniques significantly overestimated DXA fat mass, but BMI and triceps SFT better identified abnormal fat mass (κ = 0.46 and 0.49). BIA fat-free mass was not significantly different from DXA, with substantial agreement between techniques (κ = 0.65). CONCLUSION: Body composition by a range of techniques is acceptable, practical, and reliable in a diverse group of children with complex diagnoses. BIA seems a good alternative to DXA for assessing fat-free mass, triceps SFT, and BMI for fat mass but should be used with care as it could overestimate total fat mass in individuals.

Malnutrition enteropathy in Zambian and Zimbabwean children with severe acute malnutrition: A multi-arm randomized phase II trial.

Malnutrition underlies almost half of all child deaths globally. Severe Acute Malnutrition (SAM) carries unacceptable mortality, particularly if accompanied by infection or medical complications, including enteropathy. We evaluated four interventions for malnutrition enteropathy in a multi-centre phase II multi-arm trial in Zambia and Zimbabwe and completed in 2021. The purpose of this trial was to identify therapies which could be taken forward into phase III trials. Children of either sex were eligible for inclusion if aged 6-59 months and hospitalised with SAM (using WHO definitions: WLZ <-3, and/or MUAC <11.5 cm, and/or bilateral pedal oedema), with written, informed consent from the primary caregiver. We randomised 125 children hospitalised with complicated SAM to 14 days treatment with (i) bovine colostrum (n = 25), (ii) N-acetyl glucosamine (n = 24), (iii) subcutaneous teduglutide (n = 26), (iv) budesonide (n = 25) or (v) standard care only (n = 25). The primary endpoint was a composite of faecal biomarkers (myeloperoxidase, neopterin, α1-antitrypsin). Laboratory assessments, but not treatments, were blinded. Per-protocol analysis used ANCOVA, adjusted for baseline biomarker value, sex, oedema, HIV status, diarrhoea, weight-for-length Z-score, and study site, with pre-specified significance of P < 0.10. Of 143 children screened, 125 were randomised. Teduglutide reduced the primary endpoint of biomarkers of mucosal damage (effect size -0.89 (90% CI: -1.69,-0.10) P = 0.07), while colostrum (-0.58 (-1.4, 0.23) P = 0.24), N-acetyl glucosamine (-0.20 (-1.01, 0.60) P = 0.67), and budesonide (-0.50 (-1.33, 0.33) P = 0.32) had no significant effect. All interventions proved safe. This work suggests that treatment of enteropathy may be beneficial in children with complicated malnutrition. The trial was registered at ClinicalTrials.gov with the identifier NCT03716115.