Identifying the Optimum Strategy for Identifying Adults and Children With Celiac Disease: A Cost-Effectiveness and Value of Information Analysis.

OBJECTIVES: Celiac disease (CD) is thought to affect around 1% of people in the United Kingdom, but only approximately 30% are diagnosed. The aim of this work was to assess the cost-effectiveness of strategies for identifying adults and children with CD in terms of who to test and which tests to use. METHODS: A decision tree and Markov model were used to describe testing strategies and model long-term consequences of CD. The analysis compared a selection of pre-test probabilities of CD above which patients should be screened, as well as the use of different serological tests, with or without genetic testing. Value of information analysis was used to prioritize parameters for future research. RESULTS: Using serological testing alone in adults, immunoglobulin A (IgA) tissue transglutaminase (tTG) at a 1% pre-test probability (equivalent to population screening) was most cost-effective. If combining serological testing with genetic testing, human leukocyte antigen combined with IgA tTG at a 5% pre-test probability was most cost-effective. In children, the most cost-effective strategy was a 10% pre-test probability with human leukocyte antigen plus IgA tTG. Value of information analysis highlighted the probability of late diagnosis of CD and the accuracy of serological tests as important parameters. The analysis also suggested prioritizing research in adult women over adult men or children. CONCLUSIONS: For adults, these cost-effectiveness results suggest UK National Screening Committee Criteria for population-based screening for CD should be explored. Substantial uncertainty in the results indicate a high value in conducting further research.

Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement.

Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning.

ESPGHAN Position Paper on Management and Follow-up of Children and Adolescents With Celiac Disease.

OBJECTIVES: To gather the current evidence and to offer recommendations for follow-up and management. METHODS: The Special Interest Group on Celiac Diseases of the European Society of Paediatric Gastroenterology Hepatology and Nutrition formulated ten questions considered to be essential for follow-up care. A literature search (January 2010-March 2020) was performed in PubMed or Medline. Relevant publications were identified and potentially eligible studies were assessed. Statements and recommendations were developed and discussed by all coauthors. Recommendations were voted upon: joint agreement was set as at least 85%. RESULTS: Publications (n = 2775) were identified and 164 were included. Using evidence or expert opinion, 37 recommendations were formulated on: The need to perform follow-up, its frequency and what should be assessed, how to assess adherence to the gluten-free diet, when to expect catch-up growth, how to treat anemia, how to approach persistent high serum levels of antibodies against tissue-transglutaminase, the indication to perform biopsies, assessment of quality of life, management of children with unclear diagnosis for which a gluten-challenge is indicated, children with associated type 1 diabetes or IgA deficiency, cases of potential celiac disease, which professionals should perform follow-up, how to improve the communication to patients and their parents/caregivers and transition from pediatric to adult health care. CONCLUSIONS: We offer recommendations to improve follow-up of children and adolescents with celiac disease and highlight gaps that should be investigated to further improve management.

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.

Review on pediatric coeliac disease from a clinical perspective.

Coeliac disease is an immune-mediated condition characterized by chronic inflammation of the small bowel with villous atrophy driven by gluten ingestion in genetically predisposed individuals. It occurs frequently in both children and adults, affecting 1-4% of the population. The disease is associated with both gastrointestinal and extra-intestinal symptoms related to malabsorption and/or immune activation, and autoantibodies to tissue transglutaminase. Removal of gluten from the diet results in resolution of symptoms and enteropathy in the majority of patients. A good diagnostic work-up is important to avoid unnecessary restrictive diets in children. In this review on pediatric coeliac disease, we address epidemiology including predisposing environmental factors and possible preventive strategies, as well as the clinical presentation, diagnosis and follow-up. What is Known: •Primary prevention of coeliac disease is not possible; however, secondary prevention by targeting high-risk groups is recommended. •The diagnosis is safe without duodenal biopsies if specific conditions are met, also in asymptomatic children. What is New: •HLA-DQ typing is not routinely required for the diagnosis, whereas it can rule out coeliac disease if HLA-DQ2 and HLA-DQ8 are absent. •Follow-up could be improved by a more rational use of (laboratory) tests, increased intention to dietary compliance and quality of life.

Celiac Disease Management in the United Kingdom Specialist Pediatric Gastroenterology Centers-A Service Survey.

OBJECTIVES: The 2012 European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines on celiac disease (CD) recommended a no-biopsy pathway (NBP) for symptomatic children with high immunoglobin A (IgA)-based anti-tissue transglutaminase (TGA-IgA) titers, positive anti-endomysial antibody and human leukocyte antigen (HLA)-DQ2/DQ8 status. We aimed to understand variations in practice amongst specialist pediatric gastroenterology centers (SPGIC) in the United Kingdom (UK). METHODS: A survey questionnaire was sent to all UK SPGIC (n = 29) providing endoscopy services for CD diagnosis. It was divided into four main subgroups: analyzing diagnosis of CD through adherence to the ESPGHAN (2012) guidelines, post-diagnosis care and long-term follow-up and discharge from pediatric services. RESULTS: All 29 responded. NBP was implemented in 28 of 29 centers. Five of 29 centers had already stopped HLA-DQ2/DQ8 testing for NBP diagnosis. Twenty six of 29 centers were performing endoscopy on screening-identified children (mostly asymptomatic, "at-risk" patients). Diagnosis was communicated by a doctor in 65% SPGIC (n = 19). Most centers (n = 23) waited 6-12 months post-diagnosis to start gluten-free oats. Routine vitamin D supplementation was commenced by 4 of 29 centers. All centers repeated TGA-IgA to assess normalization but at varying times post-GFD. Follow-up was with a combination of doctors/dieticians (n = 26). Eleven of 29 centers discharged their patient to primary care. CONCLUSIONS: There was excellent uptake of ESPGHAN guidelines (2012) in the UK and adherence to guidelines is generally good. Despite published evidence and pragmatic advice from the British Society of Paediatric Gastroenterology Hepatology and Nutrition and National Institute for Health and Care Excellence, significant differences remain in diagnostic and ongoing management practice and are opportunities for research and directive evidence-based follow-up guidance.

Diagnosis and management of coeliac disease in children.

Coeliac disease (CD) is an autoimmune gluten-dependent condition with a prevalence of 1% in the population, if screened. However, approximately only a third of children with CD are diagnosed. When CD is suspected, serological screening with anti-tissue transglutaminase titres should be performed. Children with a positive result should be referred to a specialist in CD for confirmation of the diagnosis. The European Society for Paediatric Gastroenterology Hepatology and Nutrition revised their diagnostic guidance for CD in 2020 and this article discusses the current diagnostic pathways. Lifelong strict adherence to a gluten-free diet is necessary to prevent complications. Nurses and specialist paediatric dietitians have an important role in recognising and diagnosing CD early, as well as offering ongoing dietary and clinical support.

European Society Paediatric Gastroenterology, Hepatology and Nutrition Guidelines for Diagnosing Coeliac Disease 2020.

OBJECTIVES: The ESPGHAN 2012 coeliac disease (CD) diagnostic guidelines aimed to guide physicians in accurately diagnosing CD and permit omission of duodenal biopsies in selected cases. Here, an updated and expanded evidence-based guideline is presented. METHODS: Literature databases and other sources of information were searched for studies that could inform on 10 formulated questions on symptoms, serology, HLA genetics, and histopathology. Eligible articles were assessed using QUADAS2. GRADE provided a basis for statements and recommendations. RESULTS: Various symptoms are suggested for case finding, with limited contribution to diagnostic accuracy. If CD is suspected, measurement of total serum IgA and IgA-antibodies against transglutaminase 2 (TGA-IgA) is superior to other combinations. We recommend against deamidated gliadin peptide antibodies (DGP-IgG/IgA) for initial testing. Only if total IgA is low/undetectable, an IgG-based test is indicated. Patients with positive results should be referred to a paediatric gastroenterologist/specialist. If TGA-IgA is ≥10 times the upper limit of normal (10× ULN) and the family agrees, the no-biopsy diagnosis may be applied, provided endomysial antibodies (EMA-IgA) will test positive in a second blood sample. HLA DQ2-/DQ8 determination and symptoms are not obligatory criteria. In children with positive TGA-IgA <10× ULN at least 4 biopsies from the distal duodenum and at least 1 from the bulb should be taken. Discordant results between TGA-IgA and histopathology may require re-evaluation of biopsies. Patients with no/mild histological changes (Marsh 0/I) but confirmed autoimmunity (TGA-IgA/EMA-IgA+) should be followed closely. CONCLUSIONS: CD diagnosis can be accurately established with or without duodenal biopsies if given recommendations are followed.

Incidence of Paediatric Stricturing Duodenal Crohn Disease: A 19-Year Population-based Cohort Study.

OBJECTIVES: Stricturing duodenal Crohn disease (CD) is a rare but serious presentation of CD causing significant morbidity. We aim to provide the first robust incidence data and case studies on this severe presentation in children. METHODS: A regional cohort of prospectively acquired incident cases of paediatric CD diagnosed <16 years of age in South-East Scotland was captured over a 19-year period (1999-2018). A retrospective review was conducted on the medical records of all patients together with a review of the available literature and consensus guidelines. Incidence rates for all CD and for duodenal stricturing CD were calculated. RESULTS: A total of 247 new cases of paediatric CD were diagnosed within the study period. Median age at diagnosis was 12.5 years with 62% male predominance. Overall paediatric CD incidence rate was 5.70/100,000/year with a specific duodenal B2 phenotype disease incidence rate of 0.05/100,000/year; representing 0.8% of incident cases at diagnosis. Two incident cases of stricturing duodenal CD presented with systemic symptoms of weight loss, abdominal pain, anorexia, and lethargy, together with persistent vomiting suggestive of obstruction. Both cases partially responded to intensive medical therapy but eventually required laparoscopic gastroduodenostomy. A detailed literature search confirmed there are no paediatric incidence data, guidelines, or case reports relating to duodenal stricture as either a presentation or complication of CD. CONCLUSIONS: Duodenal structuring disease is a rare but serious presentation of CD causing significant morbidity and not currently covered in the paediatric literature or consensus guidelines. Best practice medical and surgical management remain uncertain and require further research.

Paediatric Endoscopy Global Rating Scale: Development of a Quality Improvement Tool and Results of a National Pilot.

INTRODUCTION AND OBJECTIVES: The endoscopy Global Rating Scale (GRS) is a web-based self-assessment quality improvement (QI) tool that provides a framework for service improvement. Widespread use of the GRS in adult endoscopy services in the United Kingdom (UK) has led to a demonstrable improvement in quality. The adult GRS is not directly applicable to paediatric endoscopy services. The objective of this study is to develop and pilot a paediatric endoscopy Global Rating Scale (P-GRS) as a QI tool. METHODS: Members of the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) Endoscopy Working Group collaborated with the Joint Advisory Group on Gastrointestinal Endoscopy (JAG) to develop the P-GRS. After a period of consultation, this was piloted nationally at 9 centres and data were collected prospectively at 2 census points, May and December 2016. RESULTS: The P-GRS mirrors the adult GRS by dividing care into 4 domains and includes 19 standards with several measures that underpin the standards. Eight services completed the online P-GRS return in May 2016 and 6 in December 2016. All pilot sites identified areas that needed improvement and post-pilot reflected on the key challenges and developments. Several positive developments were reported by the pilot sites. CONCLUSIONS: The national pilot helped ensure that the P-GRS developed was relevant to the paediatric endoscopy services. The pilot demonstrated that even in the first year of engaging with this QI tool, services were starting to identify areas that needed improvement, share best practice documents, put in place QI plans, and support greater patient involvement in services.

Characterisation of osteoprotegerin autoantibodies in coeliac disease.

Autoantibodies neutralising the effect of the bone regulatory cytokine osteoprotegerin (OPG) have been described in a patient with severe osteoporosis and coeliac disease. This study aimed to determine the prevalence and epitope specificity of autoantibodies to OPG in patients with coeliac disease, and correlate their presence with bone mineral density. A direct enzyme-linked immunosorbent assay was developed and used to screen patients with coeliac disease for autoantibodies to OPG. Recombinant fragments of OPG were made to evaluate the epitope specificity and affinity of these antibodies. Phenotype information of the patients was obtained by case note review. Raised titres of antibodies to OPG were found in 7/71 (9.8 %) patients with coeliac disease, compared with 1/72 (1.4 %) non-coeliac osteoporosis clinic control patients (p < 0.05). Our results suggest that a polyclonal antibody response to OPG is raised in these patients capable of recognising different epitopes of OPG with varying affinity. The titre of OPG antibodies was associated with lower bone mineral density Z-score of the hip in coeliac patients on univariate (p < 0.05) and multivariate analysis including age, sex height and weight as covariates (p < 0.01). Polyclonal antibodies to OPG are more common in patients with coeliac disease and are independently associated with lower bone mineral density Z-scores of the hip. Further work is required to establish the clinical utility of testing for OPG antibodies.

Updated European guidelines for coeliac disease in children.

In January 2020, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) updated its guidelines for the diagnosis of paediatric coeliac disease. The revised ESPGHAN guidelines offer a more streamlined approach to diagnostic pathways for the detection of this disease in children. This article provides an update for clinicians on how to diagnose and manage coeliac disease in children based on the revised guidelines and other available literature.

No-biopsy strategy for coeliac disease is applicable in adult patients: a 'real-world' Scottish experience.

Objective: Emergency interim guidance from the British Society for Gastroenterology (BSG) states that a no-biopsy strategy is possible to diagnose coeliac disease (CD) in adults with elevated transglutaminase IgA antibody (TGA-IgA) levels. We aimed to determine if the suggested TGA-IgA ≥10× ULN is safe and robust in making the diagnosis in adult patients in Scotland. We also aimed to establish if any important co-diagnoses would be missed if no biopsy was performed. Method: All positive coeliac serology results for patients aged >15 years in Scotland in 2016 (Grampian 2019) were accessed. Data were collected on demographics, TGA-IgA titres, D1 sampling, histology and macroscopic findings at upper and lower gastrointestinal (GI) endoscopy. Results: 1037/1429 patients with positive serology proceeded to biopsy, of which 796/1037 (76.8%) were diagnosed as CD. A total of 320/322 (99.37%) patients with TGA-IgA ≥10× ULN were diagnosed as CD giving the cut-off a positive predictive value of 99.38%. No significant co-pathology was found at endoscopy in these patients. Conclusion: Our results show that a no-biopsy strategy using a cut-off of TGA-IgA ≥10× ULN is safe to diagnose CD and that no important pathology would be missed. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition 2020 and BSG COVID-19 interim guidelines are applicable to adult patients in Scotland.

The diagnostic accuracy of fecal calprotectin during the investigation of suspected pediatric inflammatory bowel disease.

OBJECTIVES: Fecal calprotectin (FC) is elevated in patients with inflammatory bowel disease (IBD). Studies evaluating FC during the initial investigation of children with suspected IBD have been limited, especially with regard to their small patient groups. We aimed to evaluate the diagnostic accuracy of FC in a large regional cohort of children undergoing full upper and lower endoscopy for suspected IBD, comparing FC with six common blood parameters. METHODS: Using a retrospective case-control design all FC measurements carried out between 2005 and 2010 in children <18 years old were obtained. All IBD and non-IBD patients who had a FC measurement available before full endoscopic evaluation for suspected bowel inflammation were examined. FC was measured using the PhiCal Test. Multivariate analyzes and receiver operating characteristic curve generation were used to derive significance. RESULTS: A total of 190 patients (91 IBD and 99 non-IBD controls) met the inclusion criteria. Median FC at diagnosis for the IBD group was 1,265 µg/g (interquartile range (IQR) 734-2,024 µg/g), compared with 65 µg/g (IQR 20-235 µg/g) in controls (P<0.001). FC levels did not vary significantly between patients with Crohn's disease, ulcerative colitis, and IBD unclassified and were not influenced by age or disease location. FC was found to be far superior to commonly utilized blood parameters such as C-reactive protein and white cell count (both P<0.01), with an area under the curve of 0.93 (95% confidence interval 0.89-0.97). CONCLUSIONS: This study demonstrates that FC is an invaluable tool in determining those children who may require endoscopy for suspected IBD, and elevated values should prompt further investigation.