Association between 4%-tetrasodium EDTA and sepsis in neonatal piglets: A retrospective cohort study.

BACKGROUND: Central line-associated bloodstream infections are a major concern for children with intestinal failure and in animal research using parenteral nutrition (PN). In neonatal piglets receiving PN, we compared sepsis, line occlusions, line replacements, mortality, and costs with and without the use of a 4%-tetrasodium ethylenediaminetetraacetic acid (T-EDTA) locking solution. METHODS: We performed a retrospective review of piglets with a central venous jugular catheter enrolled in 14-day exclusive PN (TPN) trials or in 7-day short bowel syndrome (SBS) trials, before and after initiation of T-EDTA. Lines were locked with a 1-ml solution for 2 h daily (T-EDTATPN, n = 17; T-EDTASBS, n = 48) and compared with our prior standard of care using 1.5-ml heparin flushes twice daily (CONTPN, n = 34; CONSBS, n = 48). Line patency and signs of sepsis were checked twice daily. Jugular catheters were replaced for occlusions whenever possible. Humane end points were used for sepsis not responding to antibiotic treatment or unresolved catheter occlusions. RESULTS: Compared with CON, sepsis was reduced using T-EDTA, significantly for TPN (P = 0.006) and with a trend for SBS piglets (P = 0.059). Line occlusions necessitating line changes were reduced 15% in TPN studies (P = 0.16), and no line occlusions occurred for T-EDTA SBS piglets. CONCLUSION: In our neonatal piglet research, use of T-EDTA locking solution decreased sepsis and, although not statistically significant, reduced occlusions requiring line replacements. Given the expense of animal research, adding a locking solution must be cost-effective, and we were able to show that T-EDTA significantly reduced total research costs and improved animal welfare.

In parenteral nutrition-fed piglets, fatty acids vary by lipid emulsion and tissue sampled.

BACKGROUND: Children with intestinal failure without liver disease may be given soy-based lipid emulsion (SLE) or mixed lipid emulsion (MLE; containing soy, medium-chain triglyceride, olive, and/or fish oils). Both differ in essential fatty acid content: MLE has added arachidonic acid (AA) and docosahexaenoic acid (DHA). The aim of this study, in neonatal piglets, was to compare serum and tissue fatty acid composition when the emulsions were given at unrestricted doses. METHODS: We compared SLE (n = 15) and MLE (n = 15) at doses of 10-15 g/kg/day in parenteral nutrition (PN). On day 14 we collected serum and tissues. Using gas-liquid chromatography, percentage fatty acids were measured in serum, brain, and liver phospholipid. Comparisons were made to reference values from litter-matched controls (n = 8). RESULTS: Comparing median values, linoleic acid (LA) was lower for MLE vs SLE in serum (-27%), liver (-45%), and brain (-33%) (P < 0.001). AA was lower for MLE in serum (-25%), liver (-40%), and brain (-10%). DHA was higher for MLE in serum (+50%), liver (+200%), and brain (+10%). AA levels were lower for MLE vs control piglets in serum (-81%), liver (-63%), and brain (-9%). DHA levels were higher in serum (+41%), liver (+38%), and brain (+19%). CONCLUSION: This study in piglets has shown that, at unrestricted doses, MLE treatment is associated with low serum and tissue AA compared with SLE and healthy litter-matched controls. Although not yet proven, low tissue AA levels may have functional consequences, and these data support current practice avoiding MLE dose restriction.

Review and Critical Appraisal of Clinical Practice Guidelines of Modalities Used in the Diagnosis of Celiac Disease.

Background: There is controversy over the recommendations for specific serological strategies implemented and the need for a biopsy to confirm celiac disease (CeD). We reviewed and appraised the current clinical practice guidelines (CPGs) to assess the quality and reliability of recommendations for CeD diagnosis in pediatric and adult populations. Methods: We searched databases, including MEDLINE, EMBASE, Web of Science, and CINAHL, between December 2010 and January 2021 for CPGs. Four independent reviewers extracted data. Appraisal of Guidelines Research and Evaluation (AGREE II) criteria were applied by two reviewers, and a standardized score was calculated for each of the six domains. A cut-off of 60% was used to identify high-quality guidelines. Results: A total of 654 records were identified, 10 of which were eligible for data extraction. Both adult and pediatric CPGs averaged above 70% for the domains of 'scope and purpose' and 'clarity and presentation'. For 'stakeholder involvement', the mean adult and pediatric CPG scores were below the cut-off. Only one adult-focused guideline exceeded the cut-off for the 'rigour of development' domain. 'Applicability' scores were most alarming, with adult CPGs averaging 21% and pediatric CPGs averaging 23%. Conclusion: Our review and appraisal of the CPGs for the diagnosis of CeD highlight significant discrepancies in clinical recommendations and some concerns regarding methodological rigour, particularly in stakeholder engagement, rigour, and applicability. Creating a Canadian guideline of high methodological quality that overcomes these weaknesses is critical to optimize patient care and ensuring accurate diagnoses in CeD.

Intestinal Failure-Associated Liver Disease and Growth Pre- and Post-Transition to a Composite Lipid Emulsion.

OBJECTIVES: Infants with intestinal failure have an increased risk of intestinal failure-associated liver disease (IFALD). Composite intravenous lipid emulsion (ILE) may reduce the risk of cholestasis. The primary outcome was to compare IFALD rates in infants with intestinal failure, between those receiving a composite ILE versus soybean oil ILE. The secondary outcome compared growth between these 2 groups. METHODS: At our 2 tertiary neonatal/pediatric hospitals, we identified all patients (≤1 year old) who received ≥6 weeks parenteral nutrition (PN) from 2010 to 2018. Data included liver and growth parameters. IFALD was defined as serum conjugated bilirubin (CB) >33 µmol/L (≥2 mg/dL). Nonparametric tests were used for all comparisons. RESULTS: Fifty infants (35 composite ILE, 15 soybean oil ILE) were included. Those on composite ILE received PN for longer (10.1 vs 7.6 weeks; P = 0.001) and had higher baseline CB (29 vs 6.5 µmol/L; P = 0.001). No differences were found by 6 weeks (14.5 vs 5 µmol/L; P = 0.54) and by PN cessation (4 vs 4 µmol/L; P = 0.33). The proportion of patients with IFALD decreased from 54% to 20% for composite ILE, while stable given soybean oil ILE (7%). There were no differences in weight, length, or head circumference z scores ( P > 0.05). CONCLUSIONS: In our institutions, over 8 years, chronic intestinal failure was rare. Composite ILE was the predominant lipid choice for infants who needed longer courses of PN or had developed cholestasis. Despite longer PN duration, and higher baseline CB, overall rates of IFALD decreased with composite ILE. Regardless of parenteral lipid used, there were no differences in growth.

Variation in Testing for and Incidence of Celiac Autoimmunity in Canada: A Population-Based Study.

BACKGROUND & AIMS: The incidence of biopsy-confirmed celiac disease has increased. However, few studies have explored the incidence of celiac autoimmunity based on positive serology results. METHODS: A population-based cohort study assessed testing of tissue transglutaminase antibodies (tTG-IgA) in Alberta from 2012 to 2020. After excluding prevalent cases, incident celiac autoimmunity was defined as the first positive tTG-IgA result between 2015 and 2020. Testing and incidence rates for celiac autoimmunity were calculated per 1000 and 100,000 person-years, respectively. Incidence rate ratios (IRRs) were calculated to identify differences by demographic and regional factors. Average annual percent changes (AAPCs) assessed trends over time. RESULTS: The testing rate of tTG-IgA was 20.2 per 1000 person-years and remained stable from 2012 to 2020 (AAPC, 1.2%; 95% confidence interval [CI], -0.5 to 2.9). Testing was higher in female patients (IRR, 1.66; 95% CI, 1.65-1.66), those living in metropolitan areas (IRR, 1.39; 95% CI, 1.38-1.40), and in areas of lower socioeconomic deprivation (lowest compared to highest IRR, 1.24; 95% CI, 1.23-1.25). Incidence of celiac autoimmunity was 33.8 per 100,000 person-years and increased from 2015 to 2020 (AAPC, 6.2%; 95% CI, 3.1-9.5). Among those with tTG-IgA results ≥10 times the upper limit of normal, the incidence was 12.9 per 100,000 person-years. The incidence of celiac autoimmunity was higher in metropolitan settings (IRR, 1.28; 95% CI, 1.21-1.35) and in the least socioeconomically deprived areas compared to the highest (IRR, 1.22; 95% CI, 1.14-1.32). CONCLUSIONS: Incidence of celiac autoimmunity is high and increasing, despite stable testing rates. Variation in testing patterns may lead to underreporting the incidence of celiac autoimmunity in nonmetropolitan areas and more socioeconomically deprived neighborhoods.

Food Environment and Youth Intake May Influence Uptake of Gluten-Free Food Guide Recommendations in Celiac Disease.

A gluten-free (GF) food guide for children and youth (4-18 years) living with celiac disease (CD) has been developed and extensively evaluated by stakeholders, including registered dietitians. A case study analysis was conducted on data from 16 households of youth with CD to examine how factors related to parental food literacy, the home food environment, and food purchasing patterns may influence food guide uptake by Canadian youth with CD and their families. Households were of higher socioeconomic status, parents had good food literacy, and the home food availability of fruits, vegetables and GF grains was diverse. However, households also had a diverse supply of convenience foods and snack options. Youth reported consuming a larger proportion of these foods (>35% dietary intake) and had suboptimal diet quality. Dietary intake of fruits and vegetables were below GF plate model recommendations by over 30%. Despite limited economical barriers, good parental food literacy, and diverse food availability, meeting fruit and vegetable recommendations based on the pediatric GF food guide remains a major challenge. Findings inform that effective strategies and healthy public policies to support the uptake of GF food guide recommendations are needed to improve the health outcomes of youth with CD.

The effect of fecal microbial transplant on intestinal microbial composition in short-bowel neonatal piglets.

BACKGROUND: Short-bowel syndrome (SBS) in neonates is associated with microbial dysbiosis due to intestinal surgery, prolonged hospitalization, enteral nutrition, and repeated antibiotic exposure. Sepsis and liver disease, leading causes of morbidity and mortality in SBS, may relate to such intestinal dysbiosis. We investigated the safety and feasibility of fecal microbial transplant (FMT) to alter intestinal microbial composition in SBS piglets. METHODS: Following a 75% distal small-intestinal resection, piglets were fed parenteral nutrition with an elemental diet and randomized to saline (SAL; n = 12) or FMT (n = 12) treatments delivered by gastric tube on day 2 (d2). The FMT donor was a healthy adult pig. Comparisons were also made to healthy sow-fed littermate controls (SOW; n = 6). Stool samples were collected daily, and tissue samples were collected at baseline and termination. Microbial DNA was extracted from stool and analyzed using 16S ribosomal RNA sequencing. RESULTS: All piglets survived to the end point. On d2-d4, FMT piglets had some differences in microbiota composition compared with SAL, SOW, and donor counterparts. Between base and term, there were transitory changes to alpha and beta diversity in FMT and SAL. CONCLUSION: FMT treatment in postsurgical neonatal piglets with SBS appears safe, with no increase in sepsis and no mortality. In SBS piglets, FMT induced transient changes to the intestinal microbiota. However, these changes did not persist long-term.

Nutritional considerations of a paediatric gluten-free food guide for coeliac disease.

The gluten-free (GF) diet is the only treatment for coeliac disease (CD). While the GF diet can be nutritious, increased reliance on processed and packaged GF foods can result in higher fat/sugar and lower micronutrient intake in children with CD. Currently, there are no evidence-based nutrition guidelines that address the GF diet. The objective of this cross-sectional study was to describe the methodological considerations in forming a GF food guide for Canadian children and youth (4-18 years) with CD. Food guide development occurred in three phases: (1) evaluation of nutrient intake and dietary patterns of children on the GF diet, (2) pre-guide stakeholder consultations with 151 health care professionals and 383 community end users and (3) development of 1260 GF diet simulations that addressed cultural preferences and food traditions, diet patterns and diet quality. Stakeholder feedback identified nutrient intake and food literacy as important topics for guide content. Except for vitamin D, the diet simulations met 100 % macronutrient and micronutrient requirements for age-sex. The paediatric GF plate model recommends intake of >50 % fruits and vegetables (FV), <25 % grains and 25 % protein foods with a stronger emphasis on plant-based sources. Vitamin D-fortified fluid milk/unsweetened plant-based alternatives and other rich sources are important to optimise vitamin D intake. The GF food guide can help children consume a nutritiously adequate GF diet and inform policy makers regarding the need for nutrition guidelines in paediatric CD.

Evaluation of a paediatric gluten-free food guide by children and youth with coeliac disease, their parents and health care professionals.

There are currently no universal evidence-based nutrition guidelines that address the gluten-free (GF) diet for children/youth (4-18 years). A GF food guide was created to help children/youth with coeliac disease (CD) and their families navigate the complexities of following a GF diet. Guide formation was based on pre-guide stakeholder consultations and an evaluation of nutrient intake and dietary patterns. The study objective was to conduct an evaluation on guide content, layout, feasibility and dissemination strategies from end-stakeholder users (children/youth with CD, parents/caregivers and health care professionals). This is a cross-sectional study using a multi-method approach of virtual focus groups and an online survey to conduct stakeholder evaluations. Stakeholders included children/youth (4-18 years), their parents/caregivers in the coeliac community (n 273) and health care professionals (n 80) with both paediatric and CD experience from across Canada. Thematic analysis was performed on focus group responses and open-ended survey questions until thematic saturation was achieved. χ2 and Fisher's exact statistical analyses were performed on demographic and close-ended survey questions. Stakeholders positively perceived the guide for content, layout, feasibility, ethnicity and usability. Stakeholders found the material visually appealing and engaging with belief that it could effectively be used in multi-ethnic community and clinical-based settings. Guide revisions were made in response to stakeholder consultations to improve food selection (e.g. child-friendly foods), language (e.g. clarity) and layout (e.g. organisation). The evaluation by end-stakeholders provided practical and patient-focused feedback on the guide to enable successful uptake in community and clinical-based settings.

Association Between Celiac Disease and Autism Spectrum Disorder: A Systematic Review.

OBJECTIVE: The aim of the study was to perform a systematic review assessing the research investigating the association between celiac disease (CD) and autism spectrum disorder (ASD). METHODS: A literature search of MEDLINE and EMBASE was performed without limits placed on year or language. Observational studies reporting on the occurrence of CD among patients with ASD and/or the occurrence of ASD among patients with CD were included. Study design, characteristics, diagnostic criteria for ASD and CD, and the frequency of positive cases in the studied sample were recorded. Study quality was assessed using an adapted Newcastle-Ottawa Quality Assessment Scale. Due to substantial heterogeneity between studies, a meta-analysis was not performed. RESULTS: Of the 298 unique citations identified within our search strategy, 17 articles evaluating the association between CD and ASD were included. Of those articles, 13 observed samples of patients with ASD, and 6 observed samples of patients with CD. Overall, most studies had small sample sizes and reported no evidence for an association between the 2 conditions. However, a limited number of population-based studies of higher quality suggested a potential association between CD and ASD. CONCLUSIONS: Most studies assessing an association between CD and ASD are at risk for systematic and/or random error. A potential link has, however, been shown in a handful of high-quality studies, and, therefore, this comorbidity cannot be ruled out. Future studies should recruit larger sample sizes, include precise definitions of CD and ASD, and exclude patients with ASD on a gluten-free diet.

FODMAP intake in children with coeliac disease influences diet quality and health-related quality of life and has no impact on gastrointestinal symptoms.

Children with coeliac disease (CD) following the gluten-free diet may experience ongoing gastrointestinal symptoms despite strict adherence. The study objective was to evaluate the association between foods high in fermentable oligo/di/monosaccharides, and polyols (FODMAP) and gastrointestinal symptoms, and the potential implications to diet quality and health-related quality of life in CD children. Dietary intake was studied in age-sex matched children 5-18 years (CD, n = 46; non-coeliac mild chronic gastrointestinal complaints [GIC], n = 46; healthy controls [HC], n = 46). CD children consumed fewer foods high in FODMAPs compared to GIC and HC (p < .0001). FODMAP intake was not related to gastrointestinal symptoms in CD children (p > 0.05) but was positively associated with child health-related quality of life (p < 0.05). FODMAP intake from fruits and vegetables was positively associated with diet adequacy and total diet quality in CD children (p < 0.05). FODMAP intake may influence diet quality and health-related quality of life but has no impact on gastrointestinal symptoms in CD children.

Comparing the Intestinotrophic Effects of 2 Glucagon-Like Peptide-2 Analogues in the Treatment of Short-Bowel Syndrome in Neonatal Piglets.

BACKGROUND: In treating short-bowel syndrome (SBS), autonomy from parenteral nutrition (PN) relies upon intestinal adaptation, which can be augmented by glucagon-like peptide-2 (GLP-2) analogues. In neonatal piglets with SBS, we compared intestinal adaptation following treatment with 2 GLP-2 analogues: teduglutide (TED) and apraglutide (APRA) METHODS: Following 75% distal small-intestinal resection, piglets were allocated to 4 treatment groups: saline (CON: n = 8), twice weekly APRA (5 mg/kg/dose; n = 8), and TED once daily (TED, 0.05 mg/kg/dose; n = 8) or twice daily (TEDBID, 0.05 mg/kg/dose; n = 7). Pharmacokinetic (PK) studies were undertaken, and on day 7, small-intestinal length and weight were measured and jejunal tissue collected for histology. RESULTS: PK profiles were different between the 2 analogues. To achieve a comparable exposure to APRA, TED requires twice daily injection (TEDBID). Compared with CON, APRA and TEDBID increased small-bowel length (cm) (CON: 141, APRA: 166, TED: 153, TEDBID: 165; P = .004), whereas APRA increased small-bowel weight (g) (CON: 26, APRA: 33, TED: 28, TEDBID: 31; P = .007) and villus height (mm) (CON: 0.59, APRA: 0.90, TED: 0.58, TEDBID: 0.74; P < .001). CONCLUSION: APRA injected only twice during the 7 consecutive days demonstrated a superior intestinotrophic effect compared with TED injected once daily. Even at more comparable drug exposure, when TED was injected twice a day, APRA showed superior trophic activity at the mucosal level. This is highly relevant for the treatment of pediatric SBS, given the markedly lower dose frequency by subcutaneous injection of APRA.

Transitioning From Nasogastric Feeding Tube to Gastrostomy Tube in Pediatric Patients: A Survey on Decision-Making and Practice.

BACKGROUND: Tube feeding via nasogastric tubes (NGTs) and gastrostomy tubes (GTs) is a common practice for children unable to meet their nutrition needs by oral feeding alone. There is currently a lack of evidence-based guidance specific for the process of transitioning from an NGT to GT as a longer-term enteral access device. Uncertainty in the literature about feeding tube choices, practices, and transitions requires clinicians to draw on incomplete and sometimes conflicting evidence, personal experience, economic realities, and compassion to deliver supportive child-centered care. METHODS: The ASPEN Enteral Nutrition Task Force Pediatric Work Group designed a survey to explore current practice of enteral access device safety and use among pediatric clinicians practicing in the US and Canada. The survey aimed to define time frames, parameters, and decision points to guide clinicians and families in the transition from NG to GT feeding. RESULTS: 258 clinicians, 55% practicing in an inpatient setting, 17% in-home patient setting, and 28% practicing in both inpatient and outpatient setting. 22% were physicians, 42% were dietitians, 32% were nurses or advanced practice nurses, 2% were pharmacists. The most common feeding tubes used were NGTs followed by GTs. Majority of respondents indicated that they did not have a specific timeline for when an NGT should be changed to a GT. Highest ranked patient factors or clinical considerations prior to recommending changing from an NGT to a GT were exceeding the duration for temporary feeding or the need for an extended duration of tube feeding. Highest physician barriers to GT placement were the reluctance for referral from primary care doctors for GT placement. Majority of respondents reported the use of NGTs for enteral access at home and that parents were taught how to place the NGTs for home use but without consistently being taught the use of pH paper to verify NGT tip location or being provided with the pH paper to perform this task at home. CONCLUSIONS: This survey is the first step to address the knowledge gap surrounding feeding tube choices by ascertaining the current standard of practice regarding enteral access devices and appropriate timing of transitioning from NGT to GT feeding. The results highlight current practice variability and concerns. Information from the survey was used to formulate a decision tree to guide the transition of NGT to GT feeding that nutrition support professionals can use to advocate for best practices in their hospital and community settings.

Intestinal resection affects whole-body arginine synthesis in neonatal piglets.

BACKGROUND: Previous studies in piglets show a direct relationship between intestinal mass and arginine (Arg) synthesis. We aimed to study the effects of 75% intestinal resection on whole-body Arg synthesis. METHODS: Piglets were allocated to sham or jejunocolic (JC) surgery and to enteral nutrition (EN) at 20% [sham (n = 8), JC (n = 10)], or 40% [sham (n = 4), JC (n = 5)]. A gastric tube was placed for EN and a venous catheter for parenteral nutrition and blood sampling. On day 6, a primed bolus and constant infusion of Arg m + 2 label and proline m + 1 label was delivered. In addition, 40% EN piglets received a citrulline (Cit) m + 3 tracer. Blood sampling was undertaken and whole-body Arg synthesis was calculated. On day 7, intestinal length was measured, and samples were collected for gene expression (PCR quantification) and histopathology. RESULTS: On Day 7, sham piglets showed intestinal lengthening compared to JC (p = 0.02). Whole-body Arg synthesis was similar between groups (p = 0.50). Adjusting for absolute small intestinal length, JC piglets had greater Arg synthesis (p = 0.01). Expression of arginosuccinase was upregulated in the jejunum of JC compared to sham on 20% EN (p = 0.03). CONCLUSION: This demonstrates for the first-time adaptive changes in intestinal Arg synthesis following intestinal resection. IMPACT: The intestine makes a critical contribution to whole-body arginine synthesis, particularly in neonates, a human population at risk for short bowel syndrome. Therefore, we studied intestinal arginine synthesis in a neonatal piglet model of short bowel syndrome and demonstrated adaptive changes in the intestine that may preserve whole-body arginine synthesis, despite loss of intestinal mass. This research adds new information to our understanding of the effects a massive intestinal resection has on amino acid metabolism during neonatal development.

Durability of Linear Small-Intestinal Growth Following Treatment Discontinuation of Long-Acting Glucagon-Like Peptide 2 (GLP-2) Analogues.

BACKGROUND: Short-bowel syndrome is the leading cause of pediatric intestinal failure, resulting in dependency on long-term parenteral nutrition (PN). To promote enteral autonomy in neonates, a key outcome may be intestinal growth in length. The purpose of this study was to determine if intestinal lengthening persists following discontinuation of treatment with 1 of 2 GLP-2 analogues with different pharmacokinetic profiles. METHODS: Neonatal short-bowel piglets were assigned to saline control (S), 7-day treatment with teduglutide (T) (0.05 mg/kg twice daily), or 7-day treatment with apraglutide (A) (5 mg/kg twice weekly). Comparisons were made between day 7 and day 14 endpoints using analysis of variance. Data included small-intestine length, weight, histology, and quantitative polymerase chain reaction analysis of mucosal transcripts for peptide growth factors and their receptors, nutrient transporters, and tight-junction proteins. RESULTS: Compared with control, 7 days of GLP-2 analogue treatment induced mucosal adaptation based on villus hyperplasia (P = .003), which was not durable 7 days after treatment cessation (day 14; P = .081). Treatment increased intestinal growth in length by day 7 (P = .005), which was maintained (by T) or further increased (by A) at day 14 (P < .001). No significant differences in mucosal transcripts were detected. CONCLUSION: Unlike mucosal adaptation, intestinal growth appears to be a lasting outcome of treatment with long-acting GLP-2 analogues in a neonatal piglet short-bowel model. This has significant clinical implications for neonates, given their potential for intestinal growth. Intestinal lengthening varies between analogues with different half-lives; however, molecular mechanisms require further elucidation.

In the Short-term, Milk Fat Globule Epidermal Growth Factor-8 Causes Site-specific Intestinal Growth in Resected Piglets.

OBJECTIVES: Short bowel syndrome (SBS) remains the leading cause of neonatal intestinal failure. Milk fat globule epidermal growth factor-8 (MFG-E8), present in human milk, has homology with epidermal growth factor (EGF), known to enhance adaptation in SBS. In this pilot study, the role of oral MFG-E8 treatment in SBS was explored in neonatal piglets. METHODS: Neonatal piglets underwent 75% intestinal resection, either distal (jejunal-colonic [JC] anastomosis) or mid-intestinal (jejunal-ileal [JI] anastomosis). Piglets were randomized to intragastric treatment with MFG-E8  (5 mg/kg per day) or saline and were maintained on parenteral nutrition and enteral nutrition for 7 days. Adaptation was assessed by intestinal length and weight, histopathology, fecal fat analysis and RT-qPCR analysis of mucosal transcripts, including growth factors. RESULTS: JI piglets demonstrated intestinal lengthening (P < 0.001), 2-fold greater in ileum than jejunum (P = 0.02), where lengthening was increased by MFG-E8 treatment (P = 0.02). JC piglets did not exhibit jejunal lengthening, regardless of treatment. Fat absorption was greater for JI piglets (P = 0.02), unaffected by treatment. In JI piglets, expression of Egf was increased in the ileum (P < 0.01) and MFG-E8 treatment increased Egfr (receptor) expression (P = 0.02). CONCLUSIONS: MF-EG8 demonstrated site-specific trophic effects, only with JI anatomy. This may limit the utility of this treatment for SBS, except for rare patients with retained ileum. The mechanisms of these site-specific effects, however, and the role of MFG-E8 in neonatal gut growth and in diseases, such as necrotizing enterocolitis that commonly target ileum, warrant further exploration.

NASPGHAN Nutrition University (N2U): A Survey of its Efficacy as Continuing Nutrition Education for North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition.

The North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) developed NASPGHAN Nutrition University (N2U) in 2012 to improve nutrition education for pediatric gastroenterology providers. A total of 543 providers (physicians, registered dietitians, and advanced practice nurses) have applied to N2U and 285 have attended this 2-day course. We used survey methodology to compare attendees to applicants who did not attend. Course attendees reported more confidence than nonattendees in the nutritional management of patients with short bowel syndrome, feeding disorders, and gastrointestinal allergies, even though they were seen at similar frequency in both groups. Eighty-eight percent of attendees disseminated the information they learned at N2U through venues such as grand rounds or guideline/policy development. These results demonstrate the benefit of N2U in enhancing nutrition education for pediatric gastroenterology practitioners.

A single nucleotide polymorphism genetic risk score to aid diagnosis of coeliac disease: a pilot study in clinical care.

BACKGROUND: Single nucleotide polymorphism-based genetic risk scores (GRS) model genetic risk as a continuum and can discriminate coeliac disease but have not been validated in clinic. Human leukocyte antigen (HLA) DQ gene testing is available in clinic but does not include non-HLA attributed risk and is limited by discrete risk stratification. AIMS: To accurately characterise both HLA and non-HLA coeliac disease genetic risk as a single nucleotide polymorphism-based GRS and evaluate diagnostic utility. METHODS: We developed a 42 single nucleotide polymorphism coeliac disease GRS from a European case-control study (12 041 cases vs 12 228 controls) using HLA-DQ imputation and published genome-wide association studies. We validated the GRS in UK Biobank (1237 cases) and developed direct genotyping assays. We tested the coeliac disease GRS in a pilot clinical cohort of 128 children presenting with suspected coeliac disease. RESULTS: The GRS was more discriminative of coeliac disease than HLA-DQ stratification in UK Biobank (receiver operating characteristic area under the curve [ROC-AUC] = 0.88 [95% CIs: 0.87-0.89] vs 0.82 [95% CIs: 0.80-0.83]). We demonstrated similar discrimination in the pilot clinical cohort (114 cases vs 40 controls, ROC-AUC = 0.84 [95% CIs: 0.76-0.91]). As a rule-out test, no children with coeliac disease in the clinical cohort had a GRS below 38th population centile. CONCLUSIONS: A single nucleotide polymorphism-based GRS may offer more effective and cost-efficient testing of coeliac disease genetic risk in comparison to HLA-DQ stratification. As a comparatively inexpensive test it could facilitate non-invasive coeliac disease diagnosis but needs detailed assessment in the context of other diagnostic tests and against current diagnostic algorithms.

Composite Lipid Emulsion for the Infant at Risk of Intestinal Failure-associated Liver Disease: The Canadian Perspective.

Currently, in North America we are fortunate to have a number of available options for lipid emulsions to be used in the parenteral nutrition regimens for infants and children, including for long-term parenteral nutrition given intestinal failure. Neonates and infants in particular are at risk for intestinal failure-associated liver disease (IFALD). The choice of parenteral lipid emulsion will influence the risk and severity of IFALD. The purpose of this review is to discuss the rationale for the composite lipid emulsion SMOFlipid that includes soybean, medium-chain triglycerides, olive and fish oils for IFALD, with focus on the Canadian practice and experience.

Folate content of gluten-free food purchases and dietary intake are low in children with coeliac disease.

The lack of mandated folate enrichment of gluten-free (GF) grains in Canada has been suspected to contribute to suboptimal folate intake among children suffering from Celiac disease (CD). Children with CD on the gluten-free diet (GFD) face nutrient imbalances (higher fat/sugar, lower folate) from processed GF foods. The study objective examined folate intake in children with CD and folate content of household food purchases. Households collected food receipts for 30 days to assess folate content. Folate-rich foods were defined as ≥60 µg dietary folate equivalent (DFE)/100g. Two 24-hour recalls assessed children's intake. Households (n = 73) purchased >17,000 food items. Median child age was 10.5 y (IQR: 8.4-14.1). GF folate-rich foods represented <15% of all household food purchases and 69% of children had low folate intakes. Folate-rich foods consumed included legumes/GF-breakfast cereals. These represented 5% of GF-food purchases/intake. Few were fortified with folate. Findings highlight the need for mandated GF folate food fortification policy.