A Clinician's Guide to Gluten Challenge.

Gluten challenge is an essential clinical tool that involves reintroducing or increasing the amount of gluten in the diet to facilitate diagnostic testing in celiac disease (CD). Nevertheless, there is no consensus regarding the applications of gluten timing, dosing, and duration in children. This review aims to summarize the current evidence, discuss practical considerations, and proposes a clinical algorithm to help guide testing in pediatric patients. Childhood development, social circumstances, and long-term health concerns must be considered when identifying a candidate for gluten challenge. Based on previous studies, the authors suggest baseline serology followed by a minimum of 3-6 grams of gluten per day for over 12 weeks to optimize diagnostic accuracy for evaluation of CD. A formal provider check-in at 4-6 weeks is essential so the provider and family can adjust dosing or duration as needed. Increasing the dose of gluten further may improve diagnostic yield if tolerated, although in select cases a lower dose and shorter course (6-12 weeks) may be sufficient. There is consensus that mild elevations in celiac serology (<10 times the upper limit of normal) or symptoms, while supportive are not diagnostic for CD. Current North American Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines recommend histologic findings of intraepithelial lymphocytosis, crypt hyperplasia, and villous atrophy as the accurate and most appropriate endpoint for gluten challenge.

Inflammatory Bowel Disease Among Canadian Children: Comparison Between Children of Non-European Descent and Children of European Descent.

BACKGROUND: Inflammatory bowel disease (IBD) phenotypes may differ between countries and ancestral groups. The study aim was to examine ancestry and subtype variations of children newly diagnosed with IBD. METHODS: Children newly diagnosed with IBD enrolled into the Canadian Children Inflammatory Bowel Disease Network inception cohort study were categorized into 8 ancestral groups. Prospectively collected data at diagnosis and follow-up were compared between ancestral groups. RESULTS: Among 1447 children (63.2% Crohn's disease, 30.7% ulcerative colitis), 67.8% were European, 9.4% were South Asian, 3.8% were West Central Asian and Middle Eastern, 2.3% were African, 2.2% were East/South East Asian, 2.0% were Caribbean/Latin/Central/South American, 9.9% were mixed, and 2.6% were other. Children of African descent with ulcerative colitis had an older age of diagnosis compared with children of European descent (median 15.6 years vs 13.3 years; P = .02). Children of European descent had a higher proportion of positive family history with IBD (19.3% vs 12.1%; P = .001) compared with children of non-European descent. Children of European descent also had a lower proportion of immigrants and children of immigrants compared with children of non-European descent (9.8% vs 35.9%; P < .0001; and 3.6% vs 27.2%; P < .0001, respectively) . CONCLUSIONS: Important differences exist between different ancestral groups in pediatric patients with IBD with regard to age of diagnosis, family history, and immigrant status. Our study adds to the knowledge of the impact of ancestry on IBD pathogenesis.

This study explores the ancestral and phenotypic variation of Canadian children newly diagnosed with inflammatory bowel disease. It identifies differences between children of European and non-European descent in phenotypes of inflammatory bowel disease, disease location and behavior, family history, and immigrant status.

Characteristics of Pediatric Patients With Celiac Disease Identified Due to an Affected First-Degree Family Member.

The incidence of celiac disease in first-degree relatives of affected individuals is higher than in the general population, yet the clinical characteristics of this unique subset of patients has not been well described. Through a retrospective review of patients seen in a tertiary care pediatric celiac disease clinic, we identified 49 patients diagnosed with celiac disease following screening due to an affected first-degree relative. Although 51% of patients screened due to an affected first-degree relative were asymptomatic, their disease histology was as severe as those screened for symptoms suggestive of celiac disease. These findings support current recommendations to screen all first-degree relatives of patients with celiac disease regardless of clinical symptoms.

Evaluation of Hepatitis in Pediatric Patients With Presumed Nonalcoholic Fatty Liver Disease.

In 2017, the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition published clinical practice guidelines for the assessment and diagnosis of nonalcoholic fatty liver disease (NAFLD). We determined how frequently these investigations suggest an alternate etiology for chronic hepatitis in 8- to 17-year-old patients with body mass index >85%, elevated alanine aminotransferase and radiographic steatosis, and rates of adherence to 2017 guidelines. Methods: We conducted a retrospective chart review of patients presenting to McMaster Children's Hospital from 2017-2020 for evaluation of suspected NAFLD. Bloodwork was reviewed. Results: Ninety-five patients met inclusion criteria. Abnormal bloodwork that required further testing was found in 28.4%; a different chronic liver disease was ultimately diagnosed in 11.6%. Only 9.5% received comprehensive, additional bloodwork for other causes of liver disease. Conclusion: A high proportion of patients evaluated for suspected NAFLD had bloodwork possibly suggesting an alternate diagnosis. Comprehensive testing was infrequently performed. These results reinforce the importance of maintaining a differential diagnosis among children presumed to have NAFLD.

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.

Overview of the Pediatric Endoscopy Quality Improvement Network Quality Standards and Indicators for Pediatric Endoscopy: A Joint NASPGHAN/ESPGHAN Guideline.

INTRODUCTION: Pediatric-specific quality standards for endoscopy are needed to define best practices, while measurement of associated indicators is critical to guide quality improvement. The international Pediatric Endoscopy Quality Improvement Network (PEnQuIN) working group was assembled to develop and define quality standards and indicators for pediatric gastrointestinal endoscopic procedures through a rigorous guideline consensus process. METHODS: The Appraisal of Guidelines for REsearch and Evaluation (AGREE) II instrument guided PEnQuIN members, recruited from 31 centers of various practice types representing 11 countries, in generating and refining proposed quality standards and indicators. Consensus was sought via an iterative online Delphi process, and finalized at an in-person conference. Quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. RESULTS: Forty-nine quality standards and 47 indicators reached consensus, encompassing pediatric endoscopy facilities, procedures, endoscopists, and the patient experience. The evidence base for PEnQuIN standards and indicators was largely adult-based and observational, and downgraded for indirectness, imprecision, and study limitations to "very low" quality, resulting in "conditional" recommendations for most standards (45/49). CONCLUSIONS: The PEnQuIN guideline development process establishes international agreement on clinically meaningful metrics that can be used to promote safety and quality in endoscopic care for children. Through PEnQuIN, pediatric endoscopists and endoscopy services now have a framework for auditing, providing feedback, and ultimately, benchmarking performance. Expansion of evidence and prospective validation of PEnQuIN standards and indicators as predictors of clinically relevant outcomes and high-quality pediatric endoscopic care is now a research priority.

Pediatric Endoscopy Quality Improvement Network Quality Standards and Indicators for Pediatric Endoscopy Facilities: A Joint NASPGHAN/ESPGHAN Guideline.

INTRODUCTION: There is increasing international recognition of the impact of variability in endoscopy facilities on procedural quality and outcomes. There is also growing precedent for assessing the quality of endoscopy facilities at regional and national levels by using standardized rating scales to identify opportunities for improvement. METHODS: With support from the North American and European Societies of Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN and ESPGHAN), an international working group of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) used the methodological strategy of the Appraisal of Guidelines for REsearch and Evaluation (AGREE) II instrument to develop standards and indicators relevant for assessing the quality of facilities where endoscopic care is provided to children. Consensus was reached via an iterative online Delphi process and subsequent in-person meeting. The quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development and Evaluation) approach. RESULTS: The PEnQuIN working group achieved consensus on 27 standards for facilities supporting pediatric endoscopy, as well 10 indicators that can be used to identify high-quality endoscopic care in children. These standards were subcategorized into three subdomains: Quality of Clinical Operations (15 standards, 5 indicators); Patient and Caregiver Experience (9 standards, 5 indicators); and Workforce (3 standards). DISCUSSION: The rigorous PEnQuIN process successfully yielded standards and indicators that can be used to universally guide and measure high-quality facilities for procedures around the world where endoscopy is performed in children. It also underscores the current paucity of evidence for pediatric endoscopic care processes, and the need for research into this clinical area.

Pediatric Endoscopy Quality Improvement Network Quality Standards and Indicators for Pediatric Endoscopic Procedures: A Joint NASPGHAN/ESPGHAN Guideline.

INTRODUCTION: High-quality pediatric gastrointestinal procedures are performed when clinically indicated and defined by their successful performance by skilled providers in a safe, comfortable, child-oriented, and expeditious manner. The process of pediatric endoscopy begins when a plan to perform the procedure is first made and ends when all appropriate patient follow-up has occurred. Procedure-related standards and indicators developed to date for endoscopy in adults emphasize cancer screening and are thus unsuitable for pediatric medicine. METHODS: With support from the North American and European Societies of Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN and ESPGHAN), an international working group of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) used the methodological strategy of the Appraisal of Guidelines for REsearch and Evaluation (AGREE) II instrument to develop standards and indicators relevant for assessing the quality of endoscopic procedures. Consensus was sought via an iterative online Delphi process and finalized at an in-person conference. The quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. RESULTS: The PEnQuIN working group achieved consensus on 14 standards for pediatric endoscopic procedures, as well as 30 indicators that can be used to identify high-quality procedures. These were subcategorized into three subdomains: Preprocedural (3 standards, 7 indicators), Intraprocedural (8 standards, 18 indicators), and Postprocedural (3 standards, 5 indicators). A minimum target for the key indicator, "rate of adequate bowel preparation," was set at ≥80%. DISCUSSION: It is recommended that all facilities and individual providers performing pediatric endoscopy worldwide initiate and engage with the procedure-related standards and indicators developed by PEnQuIN to identify gaps in quality and drive improvement.

Pediatric Endoscopy Quality Improvement Network Quality Standards and Indicators for Pediatric Endoscopists and Endoscopists in Training: A Joint NASPGHAN/ESPGHAN Guideline.

INTRODUCTION: High-quality pediatric endoscopy requires reliable performance of procedures by competent individual providers who consistently uphold all standards determined to assure optimal patient outcomes. Establishing consensus expectations for ongoing monitoring and assessment of individual pediatric endoscopists is a method for confirming the highest possible quality of care for such procedures worldwide. We aim to provide guidance to define and measure quality of endoscopic care for children. METHODS: With support from the North American and European Societies of Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN and ESPGHAN), an international working group of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) used the methodological strategy of the Appraisal of Guidelines for REsearch and Evaluation (AGREE) II instrument to develop standards and indicators relevant for assessing the quality of endoscopists. Consensus was sought via an iterative online Delphi process and finalized at an in-person conference. The quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. RESULTS: The PEnQuIN working group achieved consensus on 6 standards that all providers who perform pediatric endoscopy should uphold and 2 standards for pediatric endoscopists in training, with 7 corresponding indicators that can be used to identify high-quality endoscopists. Additionally, these can inform continuous quality improvement at the provider level. Minimum targets for defining high-quality pediatric ileocolonoscopy were set for 2 key indicators: cecal intubation rate (≥90%) and terminal ileal intubation rate (≥85%). DISCUSSION: It is recommended that all individual providers performing or training to perform pediatric endoscopy initiate and engage with these international endoscopist-related standards and indicators developed by PEnQuIN.

Pediatric Endoscopy Quality Improvement Network Pediatric Endoscopy Reporting Elements: A Joint NASPGHAN/ESPGHAN Guideline.

INTRODUCTION: High-quality procedure reports are a cornerstone of high-quality pediatric endoscopy as they ensure the clear communication of procedural events and outcomes, guide patient care and facilitate continuous quality improvement. The aim of this document is to outline standardized reporting elements that achieved international consensus as requirements for high-quality pediatric endoscopy procedure reports. METHODS: With support from the North American and European Societies of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN and ESPGHAN), an international working group of the Pediatric Endoscopy Quality Improvement Network (PEnQuIN) used Delphi methodology to identify key elements that should be found in all pediatric endoscopy reports. Item reduction was attained through iterative rounds of anonymized online voting using a 6-point scale. Responses were analyzed after each round and items were excluded from subsequent rounds if ≤50% of panelists rated them as 5 ("agree moderately") or 6 ("agree strongly"). Reporting elements that ≥70% of panelists rated as "agree moderately" or "agree strongly" were considered to have achieved consensus. RESULTS: Twenty-six PEnQuIN group members from 25 centers internationally rated 63 potential reporting elements that were generated from a systematic literature review and the Delphi panelists. The response rates were 100% for all three survey rounds. Thirty reporting elements reached consensus as essential for inclusion within a pediatric endoscopy report. DISCUSSION: It is recommended that the PEnQuIN Reporting Elements for pediatric endoscopy be universally employed across all endoscopists, procedures and facilities as a foundational means of ensuring high-quality endoscopy services, while facilitating quality improvement activities in pediatric endoscopy.

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.

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.

SCYL1 disease and liver transplantation diagnosed by reanalysis of exome sequencing and deletion/duplication analysis of SCYL1.

SCYL1 disease results from biallelic pathogenic variants in SCYL1. We report two new patients with severe hepatic phenotype requiring liver transplantation. Patient charts reviewed. DNA samples and skin fibroblasts were utilized. Literature was reviewed. 13-year-old boy and 9-year-old girl siblings had acute liver insufficiency and underwent living related donor liver transplantation in infancy with no genetic diagnosis. Both had tremor, global developmental delay, and cognitive dysfunction during their follow-up in the medical genetic clinic for diagnostic investigations after their liver transplantation. Exome sequencing identified a likely pathogenic variant (c.399delC; p.Asn133Lysfs*136) in SCYL1. Deletion/duplication analysis of SCYL1 identified deletions of exons 7-8 in Patient 1. Both variants were confirmed in Patient 2 and the diagnosis of SCYL1 disease was confirmed in both patients at the age of 13 and 9 years, respectively. SCYL1 protein was not expressed in both patients' fibroblast using western blot analysis. Sixteen patients with SCYL1 disease reported in the literature. Liver phenotype (n = 16), neurological phenotype (n = 13) and skeletal phenotype (n = 11) were present. Both siblings required liver transplantation in infancy and had variable phenotypes. Exome sequencing may miss the diagnosis and phenotyping of patients can help to diagnose patients.

The Gluten Free Diet: Assessing Adherence in a Pediatric Celiac Disease Population.

BACKGROUND: A strict, lifelong, gluten-free diet (GFD) remains the sole treatment for celiac disease (CD). The assessment of adherence to the GFD in pediatric studies is often based on self-report and visual analogue scales which lack proven validity. We sought to compare parental-report of GFD adherence to expert registered dietitian (RD) assessments, the best available standard. METHODS: Parents of children with biopsy-proven CD scored their adherence to the GFD on a five-point Likert scale similar to that used in previous pediatric CD studies. Each family was then evaluated by an RD expert in CD management who conducted a comprehensive and standardized assessment and scored the family's adherence. The agreement between parents and the RD was assessed using paired t test and intraclass correlation coefficient (ICC) based on their scores. RESULTS: One hundred twenty-two children and their families participated in the study, with a median of 32 months on a GFD. Excellent adherence (score 5 out of 5) was attributed to 60.5% of the sample by the RD. The parents scored adherence higher than the RD by an average difference of 0.41 scale points (95% CI, 0.28-0.54; P < 0.001). The agreement between parents and the registered dietitian was poor (ICC = 0.21). CONCLUSION: Reliance on self-report through Likert scales for GFD adherence overestimates adherence and misses opportunities for patient and family education. Approximately 40% of children with CD have ongoing gluten exposure, highlighting the need for regular assessment by an RD expert in the GFD to identify education and counselling needs for children with CD.

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.

Diet patterns in an ethnically diverse pediatric population with celiac disease and chronic gastrointestinal complaints.

INTRODUCTION: Celiac disease (CD) is an autoimmune disease requiring lifelong adherence to the gluten-free diet (GFD). The GFD has significant nutritional limitations which may result in poor diet quality (DQ). We hypothesized that biopsy-proven children with CD (CCD) would have dietary patterns characterized by high saturated fat/simple sugar intake with a low micronutrient density contributing to lower DQ when compared to children with mild-gastrointestinal complaints (GI-CON). In addition, we hypothesized that ethnicity may further impact DQ. METHODS: Socio-demographic (age, CD duration, parent/child ethnicity, education), household characteristics, anthropometric, dietary intake (24-h recalls), gastrointestinal pain and adherence was collected in CCD (n = 243) and GI-CON (n = 148). Dietary patterns were determined using k-mean Cluster Analysis. RESULTS: GI-CON had significantly lower DQ than CCD (p < 0.001). Most CCD and GI-CON (>80%) had dietary patterns characterized by1) Western Diet (Cluster 1: %BMR: 110-150, low DQ, high fat, moderate CHO, high sodium) and 2) High Fat-Western Diet (Cluster 2: %BMR:130-150, low DQ, high Fat, high processed meats, high fat dairy products, CHO. Fewer children (<20%) had Prudent, Lower Fat/High Carbohydrate dietary patterns (% BMR:100-150, higher DQ, lower fat/sodium, higher CHO) with a greater proportion of non-Caucasian CCD consuming a Prudent dietary pattern. Seventy-seven percent and 37.5% of CCD and GI-CON, respectively, did not meet estimated average requirements for folate (p < 0.001). CONCLUSIONS: CCD and GI-CON have predominantly Western dietary patterns with low DQ, particularly GI-CON. Non-caucasian CCD consume more prudent dietary patterns with higher DQ. Nutrition education is warranted to ensure optimal DQ in children with chronic gastrointestinal diseases.

In Screening for Celiac Disease, Deamidated Gliadin Rarely Predicts Disease When Tissue Transglutaminase Is Normal.

OBJECTIVE: While tissue transglutaminase (tTG) antibodies are the most established serological test for celiac disease, newer deamidated gliadin peptide (DGP) screening tests are increasingly being completed. No pediatric study has systematically assessed the incidence of celiac disease in patients with an isolated positive DGP result. We sought to determine the positive predictive value of DGP serology for biopsy-confirmed celiac disease in pediatric patients with elevated DGP and normal tTG, to help guide clinicians' decision making when screening for this common condition and avoid unnecessary invasive follow-up diagnostic testing. METHODS: A multicenter retrospective review of children, from birth to age 18, with isolated DGP immunoglobulin G (IgG) positive serology referred to 3 Canadian centers was completed. The positive predictive value of an isolated elevated DGP result was calculated. RESULTS: Forty patients with DGP positive, tTG negative serology underwent endoscopy with duodenal biopsy. Of these, only 1 patient had biopsy-confirmed celiac disease. This patient was IgA deficient. This yields a positive predictive value of 2.5% (95% confidence interval 0.1%-14.7%) for isolated DGP IgG positive serology. CONCLUSIONS: In isolation, DGP positive serology has a poor positive predictive value for celiac disease in children, especially in IgA sufficient individuals. Our findings suggest that DGP IgG testing should not be completed as part of the initial screening for celiac disease in the pediatric population as it does not effectively differentiate between individuals with and without the disease. Further research is needed to clarify to role of DGP IgG in children under the age of 2 and those with IgA deficiency.