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Objectives: The objective of this study was to assess the association between serological markers and changes of the intestinal mucosa in children with celiac disease (CD)., Methods: Clinical data from CD patients under 15 years old were collected from the participating centers in an on-line multicenter nationwide observational Spanish registry called REPAC-2 (2011-2017). Correlation between anti-tissue transglutaminase antibodies (t-TGA) levels and other variables, including mucosal damage and clinical findings (symptoms, age, and gender), was assessed., Results: A total of 2955 of 4838 patients had t-TGA and a small bowel biopsy (SBB) performed for CD diagnosis. A total of 1931 (66.2%) patients with normal IgA values had a Marsh 3b-c lesion and 1892 (64.9%) had t-TGA Immunoglobulin A (IgA) ≥ 10 times upper limit of normal (ULN). There is a statistically significant association between t-TGA IgA levels and the degree of mucosal damage ( P < 0.001), the higher the t-TGA IgA levels the more severe the mucosal damage. Those patients who reported symptoms had more severe mucosal damage ( P = 0.001). On the contrary, there was a negative association between age and changes of the intestinal mucosa ( P < 0.001). No association was found with gender. Regarding the IgA-deficient patients, 47.4% (18 cases) had t-TGA Immunoglobulin A (IgA) ≥ 10 times ULN and a Marsh 3b-c lesion was observed in 68.4% (26 patients). No statistical relation was found between t-TGA IgG levels and the changes of the intestinal mucosa, neither a relation with age, gender, or symptoms., Conclusions: There is a positive correlation between t-TGA IgA levels and the severity of changes of the intestinal mucosa. Such correlation was not found in IgA-deficient patients who had positive t-TGA IgG serology. The results in this group of patients support the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition recommendations about the need of performing a SBB in IgA-deficient individuals despite high t-TGA IgG levels., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

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., Competing Interests: Mearin received receipt of grants/research supports from Research Grant Eurospital, ThermoFisher and BioHit and served as member of advisory board and consultancy and speaker from ThermoFisher. Agardh received receipt of grants/research supports from Novo Nordisk Foundation and served as member of advisory board from Takeda and ThermoFischer. Antunes received receipt of payment/honorarium for lectures from Danone, Catassi received receipt of payment/honorarium for consultation from Dr Schar Food. Dolinsek received receipt of payment/honorarium for lectures from Medis, Abbot, Merit. Guandalini served as member of advisory board from ExeGIPharma, Imaware. Koletzko received receipt of grants/research supports from Mead-Johnson, Biogaia; served as member of advisory board from Abbvie, Danone, Jannsen, Sanofi, Takeda; receipt of payment/honorarium for lectures from Danone, Mead-Johnson, Nestlé Nutrition, Pfizer, Takeda; receipt of payment/honorarium for consultation from Danone. Korponay-Szabó other support from patent on celiac disease rapid test licensed to Labsystems Oy, Vantaa, Finland. Kurppa received receipt of grants/research supports from Finnish Pediatric Foundation, Päivikki, and Sakari Sohlberg Foundation; served as member of advisory board from Finnish Coeliac Society; receipt of payment/honorarium for lectures from Thermo Fisher; and receipt of payment/honorarium for consultation from Takeda. Rodriguez-Herrera received other support from Patent and detecting gluten peptides in human fluids, March 29, 2019—Universidad de Sevilla. Shamir received receipt of grants/research supports from Helmsley Foundation; served as member of advisory board: Nestle Nutrition Institute, Teva; receipt of payment/honorarium for lectures from Abbott, Nutricia, Nestle Nutrition Institute; receipt of payment/honorarium for consultation from Abbott, Else, Nutricia, Nestle Nutrition Institute and Stock shareholder from NGS. Ciacci received receipt of honoraria or consultation fees from Takeda, GSK, Mediserve, Biogen Celltrion. The remaining authors report no conflicts of interest., (Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

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.

Objectives: Several cases of eating disorders (EDs) have been reported in patients with celiac disease (CD), suggesting that ED could be a comorbidity associated with CD. Few epidemiological studies have, however, assessed this potential association. We aimed to evaluate the risk of EDs in individuals diagnosed with CD in comparison to healthy controls., Methods: A total of 98 cases and 98 controls matched for sex, age, and body mass index between 10 and 23 years old were studied. A questionnaire was completed on medical history and sociodemographic as well as anthropometric characteristics. Various ED screening self-reported tests were administered., Results: A total of 61.2% of the study population were girls with a mean age of 15.3 ± 3.7 years old. Patients with CD scored nonsignificantly higher on all the ED screening tests than control participants. No differences were observed between study groups in terms of the frequency of individuals who exceeded the clinical cutoff identifying those at risk of ED. Patients with CD above 13 years old were associated with a 2.15-point increase in the Eating Attitude Test score compared with controls [β-coefficient = 2.15 SE 1.04; P = 0.04] after adjusting for various confounders., Conclusions: Although being a patient with CD was associated with a significantly higher Eating Attitude Test score in individuals older than 13 years old, no clear differences were observed between individuals with CD and controls in terms of risk of ED when other screening tests were used. More studies with larger samples and prospective designs are warranted to confirm these findings.

Objectives: The aim of the study was to compare the dietary pattern between subjects with celiac disease (CD) (cases) and subjects without (healthy controls) CD., Methods: A case-control design study was conducted. A total of 98 subjects with CD (age 10-23 years) were matched by age, sex, and body mass index with 98 nonceliac participants. A nonconsecutive 3-day food record was completed to assess energy, nutrient, and food intake and evaluate the participant's adherence to recommendations. Differences in energy, nutrients, food consumption, and compliance with general recommendations between cases and control groups were assessed by Student t test. Pearson chi-squared test was used to compare categorical variables. Sociodemographic, personal, and family history data were collected., Results: Compared with the control group, the cases with CD reported a significantly higher consumption of added sugar (P < 0.001) and total fat (P < 0.017). Mean fiber consumption was below the nutritional recommendations in both groups. Participants with CD consumed significantly lower amounts of foods rich in starch (P < 0.001) and higher amounts of foods rich in protein such as meat, fish, and eggs (P = 0.007). Subjects with CD showed a significantly lower percentage of adherence to recommendations for folic acid (53.2 vs 70.5; P < 0.001), calcium (49.0 vs 56.3; P = 0.025), iron (57.4 vs 78.0; P < 0.001), and magnesium (50.0 vs 63.9; P < 0.001)., Conclusions: The subjects with CD showed a more unbalanced diet than controls in terms of added sugars, total fat, and micronutrient consumption.

Background: The European Society for Paediatric Gastroenterology, Hepatology and Nutrition recommended in 2008, based on observational data, to avoid both early (<4 months) and late (≥7 months) introduction of gluten and to introduce gluten while the infant is still being breast-fed. New evidence prompted ESPGHAN to revise these recommendations., Objective: To provide updated recommendations regarding gluten introduction in infants and the risk of developing coeliac disease (CD) during childhood., Summary: The risk of inducing CD through a gluten-containing diet exclusively applies to persons carrying at least one of the CD risk alleles. Because genetic risk alleles are generally not known in an infant at the time of solid food introduction, the following recommendations apply to all infants, although they are derived from studying families with first-degree relatives with CD. Although breast-feeding should be promoted for its other well-established health benefits, neither any breast-feeding nor breast-feeding during gluten introduction has been shown to reduce the risk of CD. Gluten may be introduced into the infant's diet anytime between 4 and 12 completed months of age. In children at high risk for CD, earlier introduction of gluten (4 vs 6 months or 6 vs 12 months) is associated with earlier development of CD autoimmunity (defined as positive serology) and CD, but the cumulative incidence of each in later childhood is similar. Based on observational data pointing to the association between the amount of gluten intake and risk of CD, consumption of large quantities of gluten should be avoided during the first weeks after gluten introduction and during infancy. The optimal amounts of gluten to be introduced at weaning, however, have not been established.

Objectives: A large retrospective multicentre study was conducted in Spain to evaluate the efficiency of the new European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) criteria for the diagnosis of coeliac disease (CD)., Methods: The study protocol was approved by the ethics committee of Hospital Universitari i Politècnic La Fe (Valencia, Spain). The present study included 2177 children (ages 0.6-15.9 years) with small bowel biopsy (SBB) performed for diagnostic purposes (from 2000 to 2009) and with a minimum 2-year follow-up after biopsy., Results: CD was diagnosed in 2126 patients (97.5%) and excluded in 51 (2.5%). Tissue transglutaminase antibodies (TG2A), anti-endomysial antibodies (EMA), and human leukocyte antigen (HLA) were reported in 751 patients, 640 symptomatic and 111 asymptomatic. TG2A levels >10 times the upper limit of normal, plus positive EMA and HLA DQ2 and/or DQ8 haplotypes, were found in 336 symptomatic patients, all of them with final diagnosis of CD. In 65 of 69 asymptomatic patients, 65 had confirmed CD and 4 did not have CD. According to the 2012 ESPGHAN guidelines, SBB may have been omitted in 52% of the symptomatic patients with CD with serologic and HLA available data. Gluten challenge was performed in 158 children, 75 of them <2 years at first biopsy. Only 1 patient in whom according to the new proposed diagnostic criteria gluten challenge would not have been mandatory did not relapse., Conclusions: Our results support the new ESPGHAN 2012 guidelines for diagnosis of CD can be safely used without the risk of overdiagnosis. A prospective multicentre study is needed to confirm our results.

Objectives: The aim of this study was to assess the incidence and clinical pattern of celiac disease (CD) presently diagnosed in Spanish children., Methods: A prospective, multicenter, nationwide registry of new cases of CD in children <15 years was conducted from June 1, 2006 to May 31, 2007. The parameters studied were age at diagnosis, sex, clinical symptoms, associated diseases, nutritional status, CD serology, histological lesions, and HLA-DQ2/-DQ8. The crude incidence rate of CD was calculated as new cases per 1000 live births and as new cases per 100,000 person-years <15 years of age., Results: A total of 974 new cases of CD were included. The median age at diagnosis was 2.3 years; 39.5% of CD diagnoses occurred in the first 2 years, 42% between 2 and 6, and 18.4% from 6 to 15. Total number of cases in each age group was 385, 409, and 180, respectively. Regarding clinical presentation 70.9% showed classical symptoms, 21.9% were nonclassical, and 7% were asymptomatic. A total of 95.7% of 931, 94.7% of 611, and 86.7% of 651 children tested positive, respectively, for immunoglobulin A (IgA) anti-transglutaminase type 2 antibodies, IgA endomysial antibodies, and IgA anti-gliadin antibodies. Villous atrophy was observed in 92.4% and increased intraepithelial lymphocytes with crypt hyperplasia in 3.3%. Of the children, 55% had normal growth, and 3.4% were overweight. The HLA phenotype was DQ2: 88.3%, DQ2/DQ8: 8.4%, and DQ8: 2.3%. The incidence rate was 7.9 cases of CD per 1000 live births and 54 cases per 100,000 person-years., Conclusions: In Spain, the most frequent clinical presentation of CD is the classical form, mainly diagnosed during the first 2 years of life. The observed incidence of CD in Spanish children is much higher than the present CD incidence rates observed in other European countries.