Pediatric Intestinal Failure Associated Eating Disorder: An Overview of the Importance of Oral Feeding in a Population at Risk for Feeding Difficulties.

Achieving feeding skills and food acceptance is a multi-layered process. In pediatric intestinal failure (PIF), oral feeding is important for feeding skills development, physiologic adaptation, quality of life and the prevention of eating disorders. In PIF, risk factors for feeding difficulties are common and early data suggests that feeding difficulties are prevalent. There is a unique paradigm for the feeding challenges in PIF. Conventional definitions of eating disorders have limited application in this context. A pediatric intestinal failure associated eating disorder (IFAED) definition that includes feeding/eating skills dysfunction, psychosocial dysfunction, and the influence on weaning nutrition support is proposed.

Mechanical Complications in Central Lines Using Taurolidine Versus Ethanol Lock Therapy in Children With Intestinal Failure.

OBJECTIVES: Ethanol lock therapy (ELT) is effective in reducing rates of catheter-related-bloodstream infections (CRBSI) in the pediatric intestinal failure (IF) population; however, ELT may increase the risk of line occlusion and breakage, significantly impacting preservation of vascular access. During a period of ethanol shortage, Health Canada temporarily approved the use of taurolidine lock therapy (TLT) in pediatric iF patients previously utilizing ELT. This provided a unique opportunity to directly compare rates of central venous catheter (CVC) complications, including CRBSi, breaks, occlusions, repairs and replacements in patients who utilized both ELT and TLT. METHODS: A retrospective study of pediatric IF patients managed by three Western Canadian intestinal rehabilitation programs was performed. Event rates in patients who used both ELT and TLT during the study period were compared using Poisson regression analysis. RESULTS: In 13 patients with 10,187 catheter days (CDs), TLT (vs ELT) had lower rates of CVC breaks (1.11 vs 5.19/1000 CDs, P < 0.001), occlusions (0.83 vs 4.06/1000 CDs, P  = 0.01) and repairs (1.94 vs 5.64/1000 CDs, P  = 0.01). There was no difference in CRBSI rates (0.83 vs 2.03/1000 CDs, P  = 0.25) or rates of CVC replacements due to mechanical events (0.28 vs 1.81/1000 CDs, P  = 0.08). CONCLUSIONS: Although there was no difference in CRBSI rates, TLT was associated with lower rates of mechanical complications compared to ELT in this study. Taurolidine may be a suitable alternative to ethanol in preventing CRBSI and may be associated with improved preservation of central lines in children with IF.

The prevalence of feeding difficulties and potential risk factors in pediatric intestinal failure: Time to consider promoting oral feeds?

BACKGROUND & AIMS: Although nutritional care is a cornerstone in the management of pediatric intestinal failure (IF), little is known about feeding difficulty (FD) prevalence. The aim of this study was to determine the frequency of FD and associated factors and to characterize eating behaviours in two pediatric IF rehabilitation centres (Hôpital-Necker Enfants Malades (NEM), France and Alberta Children's Hospital (ACH), Canada). METHODS: Parents of children (aged 1-18 years) on home parenteral nutrition (PN) for >3 months followed at NEM and ACH completed two validated tools: Montreal Children's Feeding scale for severity of FD, Child Eating Behaviour Questionnaire and a pediatric IF-specific questionnaire for FD associated risk factors. RESULTS: In the entire cohort (n = 59, median 5.2 years), 15% had mild, 19% had moderate and 25% had severe FD. No FD was seen in 53% vs 11% and severe FD was seen in 20% vs. 39% of the NEM and ACH cohorts respectively (p = 0.003). Current ETF was less common at NEM vs. ACH (3% vs. 50%, p < 0.001). The FD score was associated with current enteral tube feed (ETF) use (p = 0.04). Compared to healthy reference children, the NEM cohort did not differ for the enjoyment of food, whereas the ACH cohort's enjoyment was lower (p < 0.0001). The ACH cohort scored higher for food avoidance behaviours: food fussiness (p < 0.02), satiety responsiveness (p < 0.0001), and slowness in eating (p < 0.0001) while the NEM cohort was not different from healthy reference children. In the entire cohort, according to parental recall, 60% were reported to be NPO for >12 weeks in the first 6 months of life, and late introduction of purees (>9 months) and lumpy textures (>1 year) were found in 40% and 58%, respectively. Parent-recalled ETF differed between NEM and ACH in the first 6 months of life (45% vs 76%, p = 0.03). CONCLUSIONS: Feeding difficulty and associated risk factors, including early ETF, prolonged NPO and delays in achieving feeding milestones were frequently reported in pediatric IF. Feeding medicalization with the use of ETF may inadvertently contribute to FD and eating disorder behavioural characteristics. This study highlights the need for FD prevention and an increased focus on establishing healthy eating. Future prospective study of FD, associated risk factors and clinical outcomes are merited.

Exploring Informational Needs of Parents of Children with Intestinal Failure: A Thematic Analysis.

PURPOSE: Information seeking has been observed to be important for the coping and empowerment of parents of children with rare diseases. This study was conducted to understand the education needs of families of children with pediatric intestinal failure (IF) and how technology might be effectively leveraged to address these needs. DESIGN AND METHODS: A qualitative methodology using thematic analysis was utilized. Purposeful sampling was adopted to recruit 10 parents/caregivers of children with IF. Participants participated in a 1:1 semi-structured interview. Interviews were recorded, transcribed and themes identified through open and focused coding. RESULTS: Four themes emerged: (1) reliable electronic or printed information resources relevant to their child's unique needs were lacking; (2) an educational program with in-person and hands-on learning was preferred for transition to home; (3) practical and relatable information was valued over medical knowledge as children's needs evolved; and (4) creation of electronic resources would be useful for information seeking and sharing. CONCLUSION: To cope with the responsibilities of caring for a child with IF, participants sought information beyond what they received. Participants preferred a blended approach of care team discussions and electronic tools for receiving knowledge and skills. Parents' connections with other caregivers was important for practical day-to-day management information, as well as supporting their well-being. PRACTICE IMPLICATIONS: Development and implementation of accessible digital resources with emphasis on practical information is required. Beyond medical and practical informational needs, building resilience and supporting psychologic needs for parents/caregivers of children with IF emerged as important needs to address.

The role of dietary fibre and prebiotics in the paediatric diet.

Dietary fibres are resistant to digestion and absorption. Prebiotics are fermentable dietary fibres that confer health benefits through their effects on microbiome composition and activity. The range of physiological benefits from consuming dietary fibres is broad. Encouraging children to eat fibre-rich foods promotes a nutrient-dense diet. Introducing a variety of dietary fibre sources to young children helps establish future dietary choices and a more diverse intestinal microbiota. Low-fibre intake is associated with a higher prevalence of constipation and obesity.

Prevalence of Malnutrition in Pediatric Hospitals in Developed and In-Transition Countries: The Impact of Hospital Practices.

Presently, undernutrition still goes undetected in pediatric hospitals despite its association with poor clinical outcomes and increased annual hospital costs, thus affecting both the patient and the health care system. The reported prevalence of undernutrition in pediatric patients seeking care or hospitalized varies considerably, ranging from 2.5 to 51%. This disparity is mostly due to the diversity of the origin of populations studied, methods used to detect and assess nutritional status, as well as the lack of consensus for defining pediatric undernutrition. The prevalence among inpatients is likely to be higher than that observed for the community at large, since malnourished children are likely to have a pre-existent disease or to develop medical complications. Meanwhile, growing evidence indicates that the nutritional status of sick children deteriorates during the course of hospitalization. Moreover, the absence of systematic nutritional screening in this environment may lead to an underestimation of this condition. The present review aims to critically discuss studies documenting the prevalence of malnutrition in pediatric hospitals in developed and in-transition countries and identifying hospital practices that may jeopardize the nutritional status of hospitalized children.

Assessment of Malnutrition Risk in Canadian Pediatric Hospitals: A Multicenter Prospective Cohort Study.

OBJECTIVE: To assess the prevalence, causes, and consequences of malnutrition, as well as the evolution of nutritional status, in Canadian pediatric health care institutions. STUDY DESIGN: In this multicenter prospective cohort study, a total of 371 patients were recruited from pediatric hospitals in 5 Canadian provinces. Subjects were aged 1 month to 18 years; admitted to a medical, surgical, or oncology ward; and had a planned hospital stay of >48 hours. Data on demographics, medical condition, anthropometric measures, and dietary intake were collected. The Screening Tool Risk on Nutritional Status and Growth (STRONGkids) and Subjective Global Nutritional Assessment (SGNA) were applied at admission. Malnutrition was defined as a weight-for-age, height-for-age, body mass index-for-age, or weight-for-length/height z score <-2 SD. RESULTS: Among 307 subjects (median age, 5.3 years; median length of stay, 5 days), 19.5% were malnourished on admission. Both STRONGkids and SGNA classifications were associated with baseline nutritional status. Mean weight-for-age z score was lower at discharge compared with admission (-0.14 vs -0.09; P < .01), and nearly one-half of all patients lost weight during their hospital stay. Only one-half of the children who were malnourished or screened as high risk of malnutrition were visited by a dietitian during their stay. The percentage of patients who lost weight during hospitalization was significantly greater in the group not visited by a dietitian (76.5 vs 23.5%; P < .01). CONCLUSION: Nutritional status deterioration and malnutrition are common in hospitalized Canadian children. Screening tools, anthropometric measurements, and dietitian consultation should be used to establish adequate nutritional support.

The glucagon like peptide-2 'axis': Capacity for production and response following intestinal resection or repair of gastroschisis in infants.

PURPOSE: This study investigates the relationship between the enteric hormone glucagon-like peptide 2 (GLP-2) production, sensitivity, and intestinal adaptation in infants following resection or repair of gastroschisis. METHODS: With IRB approval (UCalgary #10656), consent was obtained from families of infants undergoing surgery for prospective monitoring of nutritional status, GLP-2 levels, and where possible, tissue sampling. RESULTS: Infants who adapted and weaned from parenteral nutrition (PN) had increased GLP-2 (86±32) n=24 vs. controls: 45±20 n=10 and vs. patients on prolonged PN: 42±6 pM, n=10). This was maintained to one year: weaned patients: 72±49 vs. non-weaned: 35±15 pM (p<0.05). Infants with gastroschisis (n=33) had decreased GLP-2 levels until enteral function was achieved and then became elevated: (21±15 with first feeding vs. 102±60 at full feeds and 60±19 pM at one year). There were no changes in the density or distribution of GLP-2 producing L-cells related to gestational age, nor in the expression of the GLP-2 receptor. CONCLUSION: GLP-2 levels correlate with intestinal adaptation in infants, and with recovery of intestinal function in gastroschisis. GLP-2 productive capacity (L-cell expression) and GLP-2 receptor expression do not vary with maturity. The findings support a role for GLP-2 in regulating intestinal function. Further study is suggested.

A safety and pharmacokinetic dosing study of glucagon-like peptide 2 in infants with intestinal failure.

BACKGROUND & AIMS: Glucagon-like peptide 2 (GLP-2) analogues are approved for adults with intestinal failure (IF), but no studies have included infants. This study examined the pharmacokinetics (PK), safety, and nutritional effects of GLP-2 in infants with IF. METHODS: With parental consent (Health Canada Protocol:150,979), parenteral nutrition (PN)-dependent infants were treated with 5-20-µg/kg/day GLP-2 for 3days (phase 1), and if tolerated continued for 42days (phase 2). Nutritional therapy was by primary caregivers, and follow-up was to one year. RESULTS: Six patients were enrolled, age 5.4±3.2months, bowel length: 27±12% of predicted, PN dependent (67±18% of calories). GLP-2 did not affect vital signs, nor were there significant adverse events during the trial. Dosing 5µg/kg/day gave GLP-2 levels of 52-57pmol/L, with no change in half-life or endogenous GLP-2 levels. Enteral feeds, weight, Z scores, stooling frequency, and citrulline levels improved numerically. The trial was discontinued early because of a drop in potency. CONCLUSIONS: GLP-2 was well tolerated in infants, and pK was similar to children with no changes in endogenous GLP-2 release. The findings suggest that GLP-2 ligands may be safely used in infants and may have beneficial effects on nutritional status. Further study is required. LEVEL OF EVIDENCE: 2b Prospective Interventional Study.

Safety and Dosing Study of Glucagon-Like Peptide 2 in Children With Intestinal Failure.

BACKGROUND AND AIMS: A glucagon-like peptide 2 (GLP-2) analogue is approved for adults with intestinal failure, but no studies of GLP-2 have included children. This study examined the pharmacokinetics, safety, and nutritional effects of GLP-2 in children with intestinal failure. METHODS: Native human GLP-2(1-33) was synthesized following good manufacturing practices. In an open-label trial, with parental consent, 7 parenteral nutrition-dependent pediatric patients were treated with subcutaneous GLP-2 (20 µg/kg/d) for 3 days (phase 1) and, if tolerated, continued for 42 days (phase 2). Nutritional treatment was directed by the primary caregivers. Patients were followed to 1 year. RESULTS: Seven patients were enrolled (age: 4.0 ± 0.8 years; bowel length, mean ± SEM: 24% ± 4% of predicted). All were parenteral nutrition dependent since birth, receiving 44% ± 5% of calories by parenteral nutrition. GLP-2 treatment had no effect on vital signs (blood pressure, heart rate, and temperature) and caused no significant adverse events. Peak GLP-2 levels were 380 pM (day 3) and 295 pM (day 42), with no change in half-life or endogenous GLP-2 levels. Nutritional indices showed a numeric improvement in z scores and citrulline levels; the z score was maintained while citrulline levels returned to baseline once GLP-2 was discontinued. CONCLUSIONS: GLP-2 was well tolerated in children, with a pharmacokinetic profile similar to that of adults. There were no changes in endogenous GLP-2 release or metabolism. These results suggest that GLP-2 ligands may be safely used in pediatric patients; larger trials are suggested to investigate nutritional effects.

Nutritional support of infants with intestinal failure: something more than fishy is going on here!

BACKGROUND: This review will highlight recent advances in the care of infants with Intestinal Failure, focusing on the benefits of a multi-disciplinary team and the types of nutrition used. METHODS: Recent best "practices" from the literature are described, including strategies for promoting intestinal adaptation, the use of lipid sparing Parenteral Nutrition (PN) and the effects of the associated high glucose infusion rates. Special emphasis will be placed on lipid minimization and specialized lipid emulsions including fish oil, and blended lipid sources such as SMOF. Enteral nutritional therapy will be reviewed, including the rationale for the use of expressed breast milk or elemental formula in preference to partial milk hydrolysates. The utility and indications for the use of formula additives and the use of nutritional supplements and the timing and rate of advancement of feeds, and the optimal strategy for preserving oral feeding skills will be reviewed. Treatments to optimize intestinal adaptation such as the use of dietary supplements including vegetable oils, fat emulsions and medium-chain triglycerides will be discussed. Feeding strategies will be described. The rationale and effects of using rotating antibiotics to treat small intestinal bacterial overgrowth will be reviewed. RESULTS: The long-term consequences and complications of the different types of nutritional therapy will be examined, with a focus on growth and development. The potential and described effects of established and novel lipid therapies on neurological development will be reviewed in detail. CONCLUSION: Areas of interest for potential future research will be explored for all aspects of nutritional therapy with a discussion of future strategies which may enhance the intestinal adaptive process, and thus aid our goal of making the adaptation process occur more quickly and shortening the time of PN.

Elements of successful intestinal rehabilitation.

PURPOSE: The optimal therapy for intestinal failure (IF) is unknown. The results of a systematic, protocol-driven management strategy by a multidisciplinary team are described. METHODS: Intestinal failure was defined as bowel length of less than 40 cm or parenteral nutrition (PN) for more than 42 days. A multidisciplinary team and protocol to prevent PN-associated liver disease (PNALD) were instituted in 2006. Data were gathered prospectively with consent and ethics board approval. RESULTS: From 1998 to 2006, 33 patients were treated (historical cohort) with an overall survival of 72%. Rotating prophylactic antibiotics for bacterial overgrowth were given to 27% of patients; 6% had lipid-sparing PN, and none received fish oil-based lipids. Median time to intestinal rehabilitation was 7 ± 3.1 months, and 27% of patients who developed PNALD died. From 2006 to 2009, 31 patients were treated. Seventy-seven percent received PAB; 60%, lipid-sparing PN; and 47%, parenteral fish oil emulsion. Eighty-seven percent weaned from PN at 3.9 ± 3.8 months, and no patients developed PNALD with 100% survival. Novel lipid therapies were associated with changes in essential fatty acid profile and one case of clinical essential fatty acid deficiency. CONCLUSION: The institution of a multidisciplinary team and a protocol-driven strategy to prevent PNALD improves survival in IF. Further studies are recommended.

The assessment, and glucagon-like peptide-2 modulation, of intestinal absorption and function.

The treatment of patients with short bowel syndrome is hampered by a lack of treatment and measurement methods. This article reviews our evolving understanding of the role of glucagon-like peptide 2 (GLP-2) in controlling the adaptive process. The ability of the remnant intestine to produce GLP-2 appears to be predictive of the adaptive process; exogenous GLP-2 may be a therapy to augment adaptation. Strategies for monitoring patients, including conventional means, such as anthropomorphic measurements, plasma levels of specific nutrients, and vitamins and radiological contrast studies are reviewed. Investigational methods, such as nutrient balance studies, plasma citrulline levels, and the absorption of inert sugars (3-0 methyl glucose, mannitol, and lactulose) are discussed with the evidence to support their use.

Relationship between biopsy-proven parenteralnutrition-associated liver fibrosis and biochemical cholestasis in children with short bowel syndrome.

PURPOSE: The aim of the study was to determine the frequency of biochemical cholestasis (direct bilirubin [DB] > or =2 mg/dL) in children with short bowel syndrome and biopsy-proven parenteral nutrition (PN)-associated liver disease and to define predictive factors for the occurrence and degree of hepatic fibrosis. METHODS: After institutional review board approval, a retrospective review was conducted of patients followed by 2 multidisciplinary intestinal rehabilitation programs between January 1, 2000, and September 30, 2008. Inclusion criteria were exposure to PN (>30 days) and having undergone a liver biopsy. Liver biopsy specimens were graded from 0 to 3 based upon degree of fibrosis in the pathology report. The most recent DB within 10 days before biopsy was recorded. RESULTS: A total of 66 children underwent 83 liver biopsy procedures. The most common diagnoses included necrotizing enterocolitis (NEC) (36.4%), gastroschisis (22.7%), and intestinal atresia (15.1%). Median age at biopsy was 6.1 months with a median duration of PN of 4.7 months. Of the patients, 70.3% had a history of exposure to parenteral omega-3 lipid emulsion. Of the liver biopsy specimens, 89% (74/83) demonstrated some degree of fibrosis (fibrosis scale 1-3), including 9.6% (8/83) with evidence of cirrhosis. 83% of biopsies without fibrosis and 55% of biopsies with fibrosis were obtained in patients without evidence of biochemical cholestasis (P = .20). Three (37%) of the 8 patients with cirrhosis on liver biopsy had no evidence of biochemical cholestasis. Univariate analysis identified only gestational age (GA) at birth as significantly associated with the degree of liver fibrosis (P = .03). A multivariate logistic regression model accounting for multiple biopsy procedures in patients revealed that GA was a predictor of fibrosis only in patients with a diagnosis other than NEC (P < .01). CONCLUSIONS: In children with short bowel syndrome, biochemical cholestasis does not reflect the presence or degree of histologically confirmed PN-associated liver fibrosis. Careful follow-up, combined with further refinement of diagnostic and hepatoprotective strategies, may be warranted in this patient population.