Gluten-free diet for pediatric patients with coeliac disease: A position paper from the ESPGHAN gastroenterology committee, special interest group in coeliac disease.

BACKGROUND AND OBJECTIVE: Coeliac disease is a chronic, immune-mediated disorder for which the only treatment consists of lifelong strict adherence to gluten-free diet (GFD). However, there is a lack of evidence-based guidelines on the GFD dietary management of coeliac disease. This position paper, led by the Special Interest Group in coeliac disease of the European Society of Pediatric, Gastroenterology Hepatology, and Nutrition, supported by the Nutrition Committee and the Allied Health Professionals Committee, aims to present evidence-based recommendations on the GFD as well as how to support dietary adherence. METHODS: A wide literature search was performed using the MeSH Terms: "diet, gluten free," "gluten-free diet," "diets, gluten-free," "gluten free diet," and "coeliac disease" in Pubmed until November 8th, 2022. RESULTS: The manuscript provides an overview of the definition of the GFD, regulations as basis to define the term "gluten-free," which foods are naturally gluten-free and gluten-containing. Moreover, it provides recommendations and educational tips and infographics on suitable food substitutes, the importance of reading food labels, risk of gluten cross-contact at home and in public settings, nutritional considerations as well as factors associated to dietary adherence based on available evidence, or otherwise clinical expertise. CONCLUSIONS: This position paper provides guidance and recommendations to support children with coeliac disease to safely adhere to a GFD.

The Gluten-Free Diet for Celiac Disease: Critical Insights to Better Understand Clinical Outcomes.

The gluten-free diet (GFD) remains a complex paradigm in managing celiac disease (CeD) in children and adults, and there are many reasons why GFD adherence should be strict to improve outcomes. However, this is a challenging task for patients, since they need to have access to quality healthcare resources that facilitate optimal GFD adherence. Understanding the strengths and weaknesses of the GFD, tackling coexisting nutritional deficiencies, and dealing with complex situations, such as seronegative CeD or non-responsive CeD, all require the involvement of a multidisciplinary team. The short- and long-term follow-up of CeD patients should preferably be performed by a combined Gastroenterology and Nutrition service with well-defined quality standards and the multidisciplinary involvement of physicians, nurses, dietitians, and psychologists. Nutritional advice and counseling by an experienced dietitian can reduce the costs associated with long-term follow-up of CeD patients. Likewise, psychological interventions may be essential in specific scenarios where implementing and sustaining a lifelong GFD can cause a significant psychological burden for patients. This manuscript aims to provide guidelines to improve clinical practice in the follow-up and monitoring of CeD patients and provide information on the nutritional risks of an ill-advised GFD. Clinicians, biochemists, food technologists, dietitians, and psychologists with a global view of the disease have been involved in its writing.

Ethical Considerations Within the ESPGHAN Community.

There are limited data on ethical issues related to the daily practice of members of the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN). The role of the ESPGHAN Ethics Committee (EC) is to provide advice on such matters to its members. The present survey aimed to evaluate the current function, and reasons that ESPGHAN members consulted the ECs. One hundred and five participants from 24 different countries answered the questionnaire. Thirty-five point seven percent of the participants used the ESGHAN EC to ask about clinical practice problems and patient-related issues whereas 21.4% ask about human research questions. An important additional finding was that 66.3% of respondents consulted their hospital's EC when they had ethical concerns and 17.4% consulted with other colleagues with expertise. This is the first survey in the ESPGHAN and Europe that analyses ethical issues that are important to members of the National Societies for Pediatric Gastroenterology Hepatology and Nutrition.

Analysis of gluten immunogenic peptides in feces to assess adherence to the gluten-free diet in pediatric celiac patients.

PURPOSE: In celiac disease (CD) there is a need for precise and non-invasive tools to assess dietary compliance to the gluten-free diet (GFD). Our aim is to evaluate the efficacy of the detection of gluten immunogenic peptides (GIP) in feces, to monitor in real life, the adherence to GFD in pediatric patients with CD. METHODS: A cross-sectional, prospective study was conducted. Fecal samples from CD children were analyzed by a rapid immunochromatographic (IC) test and by an ELISA method, both based on the antigliadin 33-mer monoclonal antibody. RESULTS: Group 1 comprises 43 children on a GFD. According to the food records (FR), 39/43 patients were compliant with the GFD and gluten consumption was recorded in 4. GIP were detected in 15/43 individuals by the ELISA method and also in 7 by IC strips. Group 2: comprise 18 children at CD diagnosis; GIP levels decreased over time (p < 0.001) in a non-linear way (p = 0.028) after starting a GFD and were below the detection limit on the third day in most individuals. CONCLUSION: GIP were detected, both by ELISA and by IC strips, in CD patients on a GFD, in which no consumption of gluten had been registered on the FR, confirming GIP detection to be superior to FR discovering involuntary transgressions. Despite a positive correlation between the amount of gluten intake and the concentration of GIP in feces, the interindividual variations observed suggest gastrointestinal factors influencing GIP recovery need to be further investigated.

Growth rate of coeliac children is compromised before the onset of the disease.

INTRODUCTION: Growth impairment has often been described in children who develop coeliac disease (CD). Based on data from the multicentre, longitudinal PreventCD study, we analysed the growth patterns of infants at genetic risk of CD, comparing those who developed CD by 6 years of age (CD 'cases', 113 infants) versus those who did not develop CD by 6 years (no CD 'controls', 831 infants). METHODS: Weight and length/height were measured using a longitudinal protocol. Raw measurements were standardised, computing z-scores for length/height and weight; a linear mixed model was fitted to the data in order to compare the rate of growth in the two cohorts. RESULTS: Neither cases nor controls had significant growth failure. However, when the mean z-scores for weight and height were analysed, there was a difference between the two groups starting at fourth month of life. When the growth pattern in the first year was analysed longitudinally using mixed models, it emerged that children who develop CD had a significantly lower growth rate in weight z-score (-0.028/month; 95% CI -0.038 to -0.017; p<0.001) and in length/height z-score (-0.018/month; 95% CI -0.031 to -0.005; p=0.008) than those who do not develop CD. When the whole follow-up period was analysed (0-6 years), differences between groups in both weight and length/height z-scores were confirmed. CONCLUSION: The growth of children at risk of CD rarely fell below 'clinical standards'. However, growth rate was significantly lower in cases than in controls. Our data suggest that peculiar pathways of growth are present in children who develop CD, long before any clinical or serological signs of the disease appear.

Clinical validation of an evidence-based method to adjust Pancreatic Enzyme Replacement Therapy through a prospective interventional study in paediatric patients with Cystic Fibrosis.

BACKGROUND: A method to adjust Pancreatic Enzyme Replacement Therapy in Cystic Fibrosis is not currently available. OBJECTIVES: To assess the in vivo efficacy of a method to adjust the dose of enzymatic supplement in CF extrapolated from previous in vitro digestion studies (theoretical optimal dose, TOD). Secondly, to assess how individual patient characteristics influence the expected coefficient of fat absorption (CFA) and thus to identify an individual correction factor to improve TOD. METHODS: A prospective interventional study in 43 paediatric patients with CF from 5 European centres. They followed a 24h fixed diet with the theoretical optimal dose for each meal. Faecal collection was carried out between colorimetric markers in order to include all the faeces corresponding to the fixed diet. Beta regression models were applied to assess the associations of individual patient characteristics with the CFA. RESULTS: Median CFA was 90% (84, 94% 1st, 3rd Q.) with no significant differences among centres. Intestinal transit time was positively associated with CFA (p = 0.007), but no statistical associations were found with and age, gender, phenotype or BMI. Regression model showed no improvement of the in vitro predicted theoretical optimal dose when taking individual patient characteristics into account. CONCLUSION: Strict adherence to the theoretical optimal dose of enzymatic supplement for a prescribed meal, led to median CFA levels at the clinical target of 90% with a low variability between patients. The proposed method can be considered as a first approach for an evidence-based method in PERT dosing based on food characteristics. Results have to be confirmed in free dietary settings.

Detection and quantification of gluten immunogenic peptides in feces of infants and their relationship with diet

Background: there are no effective methods to easily control the correct adherence to a gluten-free diet (GFD) in celiac disease (CD) patients. Aim: to assess the sensitivity and specificity of a rapid immunochromatographic (IC) test that detects gluten immunogenic peptides (GIP) in feces, compared to an enzyme-linked immunosorbent assay (ELISA) method. Methods: fecal samples from healthy infants were analyzed by a rapid IC test and ELISA, both methods are based on the anti-gliadin 33-mer monoclonal antibody. Group 1 included infants aged from 6 to 24 months, with an unrestricted consumption of gluten containing cereals. Group 2 (negative controls) was comprised of infants aged from 0 to 6 months, either breastfed or formula fed who had never ingested gluten. Results: in group 1 (n = 34), all infants had positive values by ELISA, the mean was 13.13 μgGIP/g (range 0.56-46.79). The IC test was negative in 5/20 cases and there was a significant correlation (p=0.006) between the mean daily gluten intake and GIP in feces. In group 2 (n = 20), all the samples were negative by both methods. Moreover, the Kappa Fleiss concordance index (Kappa = 0.79 CI95% [0.616, 0.965]) indicated a moderate concordance between both methods. Conclusions: according to our results, both methods are highly specific. However, the ELISA test had a higher sensitivity. Although we found a significant correlation between the amount of gluten consumed and GIP recovery in feces, further studies are needed to clarify the impact of individual confounding factors in GIP recovery

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Differences in the macronutrient and dietary fibre profile of gluten-free products as compared to their gluten-containing counterparts.

BACKGROUND/OBJECTIVES: Gluten-free diet is the lifelong therapy for patients with coeliac disease. A wide range of gluten-free products (GFP) is available, which mimics the characteristics of their gluten-containing counterparts (GCC). The aim of this study was to compare the macronutrient and dietary fibre composition of GFP and GCC currently available in Spain. SUBJECTS/METHODS: A cross-sectional study analysing the nutritional differences between 621 GFP and 600 GCC based on labelling information was conducted. Food items were categorized in one of 14 food groups. The first six ingredients were noted for each food item. A linear regression model was used to explain differences in nutritional composition between GFP and GCC and three independent models were created for bread, pasta and biscuits. RESULTS: Results showed that GCC had higher protein content than GFP, especially in flour, bread, pasta and pizza. Bread had higher total and saturated fat contents in the GFP in which palm oil was the main fat used. Flours and starchy ingredients used in GFP formulation were mainly rice and corn flours and corn starch, and palm oil was the most commonly used fat. CONCLUSIONS: In conclusion, GFP cannot currently be considered as equivalent substitutes for their GCC. The reformulation of the GFP with more healthy ingredients and ingredients is encouraged, using a healthy oil, pseudocereals and whole flour.

Detection and quantification of gluten immunogenic peptides in feces of infants and their relationship with diet.

BACKGROUND: there are no effective methods to easily control the correct adherence to a gluten-free diet (GFD) in celiac disease (CD) patients. AIM: to assess the sensitivity and specificity of a rapid immunochromatographic (IC) test that detects gluten immunogenic peptides (GIP) in feces, compared to an enzyme-linked immunosorbent assay (ELISA) method. METHODS: fecal samples from healthy infants were analyzed by a rapid IC test and ELISA, both methods are based on the anti-gliadin 33-mer monoclonal antibody. Group 1 included infants aged from 6 to 24 months, with an unrestricted consumption of gluten containing cereals. Group 2 (negative controls) was comprised of infants aged from 0 to 6 months, either breastfed or formula fed who had never ingested gluten. RESULTS: in group 1 (n = 34), all infants had positive values by ELISA, the mean was 13.13 µgGIP/g (range 0.56-46.79). The IC test was negative in 5/20 cases and there was a significant correlation (p=0.006) between the mean daily gluten intake and GIP in feces. In group 2 (n = 20), all the samples were negative by both methods. Moreover, the Kappa Fleiss concordance index (Kappa = 0.79 CI95% [0.616, 0.965]) indicated a moderate concordance between both methods. CONCLUSIONS: according to our results, both methods are highly specific. However, the ELISA test had a higher sensitivity. Although we found a significant correlation between the amount of gluten consumed and GIP recovery in feces, further studies are needed to clarify the impact of individual confounding factors in GIP recovery.

Alimentos libres de gluten y nutrición: situación actual de los pacientes celíacos, necesidades destacadas, retos futuros / No disponible

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Diez años de seguimiento de la cohorte española del estudio Europeo PreventCD: lecciones aprendidas / Ten years of follow-up of the Spanish cohort of the European PreventCD study: the lessons learned

Objetivo: evaluar la influencia del consumo de gluten en el desarrollo de enfermedad celiaca y describir la historia natural de la misma, en una cohorte española de riesgo genético participante en el estudio Europeo PreventCD. Métodos: estudio prospectivo multicéntrico doble ciego, incluyendo 225 niños, controlados desde el nacimiento, en tres centros de Madrid, Reus y Valencia, todos HLA-DQ2/HLA-DQ8 positivos y con un familiar de primer grado con enfermedad celiaca. Entre cuatro y diez meses, la ingesta de gluten estaba pautada por protocolo. Entre los 11-36 meses, la ingesta fue libre, siendo cuantificada prospectivamente mediante registros dietéticos. Se realizaron visitas clínicas y análisis de anticuerpos específicos de enfermedad celiaca periódicamente. Conclusiones: ni la cantidad de gluten consumida entre los 11 y los 36 meses ni la duración de la lactancia son factores de riesgo de desarrollo de EC en la población española, siendo el genotipo HLA y el sexo los factores más relevantes asociados a la misma. En este grupo de riesgo, la mayoría de casos debutaron antes de los dos años, encontrándose a esta temprana edad pacientes con escasa expresividad clínica

Aim: to evaluate the influence of gluten consumption on celiac disease development and to describe its natural history in the Spanish cohort of the European PreventCD study. Methods: prospective multi-center double blind study of 225 children that were followed up from birth. All cases were HLA-DQ2/HLA-DQ8 positive with a 1st degree relative with celiac disease and were followed up in three centers from Madrid, Reus and Valencia. Gluten intake was determined between four and ten months according to the protocol. Gluten intake was ad libitum between eleven and 36 months and was prospectively quantified by means of dietary records. Clinical visits and specific antibody analysis for celiac disease were performed periodically. Results: twenty-six cases were diagnosed, all had a positive biopsy and serology; 21 had gastrointestinal symptoms and five were asymptomatic. In addition, 2,565 food records were analyzed and statistically significant differences (p < 0.001) were found with regard to gluten consumption among the three centers, although not between celiac and non-celiac children (p = 0.025). The HLA-DQ2.5/DQ2.5 and DQ2.5/DQ2.2 genotypes had a relative risk of 4.7 (95% CI: 0.80-27.55; p = 0.08), which was higher than for the rest of genotypes. Female gender also had a relative risk that was five times higher than that for males. Conclusions: the amount of gluten intake between 11 and 36 months or the duration of breast feeding were not risk factors for the development of CD in the Spanish population. The HLA genotype and gender were the most relevant associated factors. In this at-risk group, the disease presented before two years of age in the majority of the cases with a weak clinical expression

Ten years of follow-up of the Spanish cohort of the European PreventCD study: the lessons learned.

AIM: to evaluate the influence of gluten consumption on celiac disease development and to describe its natural history in the Spanish cohort of the European PreventCD study. METHODS: prospective multi-center double blind study of 225 children that were followed up from birth. All cases were HLA-DQ2/HLA-DQ8 positive with a 1st degree relative with celiac disease and were followed up in three centers from Madrid, Reus and Valencia. Gluten intake was determined between four and ten months according to the protocol. Gluten intake was ad libitum between eleven and 36 months and was prospectively quantified by means of dietary records. Clinical visits and specific antibody analysis for celiac disease were performed periodically. RESULTS: twenty-six cases were diagnosed, all had a positive biopsy and serology; 21 had gastrointestinal symptoms and five were asymptomatic. In addition, 2,565 food records were analyzed and statistically significant differences (p < 0.001) were found with regard to gluten consumption among the three centers, although not between celiac and non-celiac children (p = 0.025). The HLA-DQ2.5/DQ2.5 and DQ2.5/DQ2.2 genotypes had a relative risk of 4.7 (95% CI: 0.80-27.55; p = 0.08), which was higher than for the rest of genotypes. Female gender also had a relative risk that was five times higher than that for males. CONCLUSIONS: the amount of gluten intake between 11 and 36 months or the duration of breast feeding were not risk factors for the development of CD in the Spanish population. The HLA genotype and gender were the most relevant associated factors. In this at-risk group, the disease presented before two years of age in the majority of the cases with a weak clinical expression.

Anti-gliadin antibodies in breast milk from celiac mothers on a gluten-free diet.

PURPOSE: To analyze the presence of total IgA and anti-gliadin antibodies (AGA) in BM from CD mothers who follow a gluten-free diet (GFD) and from mothers on a normal gluten-containing diet (ND). METHODS: 218 samples of mature milk were obtained at different months of lactation (1-6) from 83 mothers (2 or more samples per mother) from Italy (Naples), The Netherlands (Leiden) and Spain (Madrid, Valencia and Reus): 42 CD mothers on GFD for more than 2 years and 41 non-CD mothers on a ND. Whey samples were analyzed for AGA-IgA by an indirect homemade ELISA and for total IgA (g/L) by a commercial ELISA kit. RESULTS: AGA-IgA was detected in BM, both in mothers on a GFD and mothers on a ND. AGA-IgA levels in both groups of mothers, CD and non-CD, show the same trend towards decreasing slightly along the months of lactation (p = 0.91). A different trend is observed for total IgA levels, decreasing markedly in CD mothers from the first month of lactation onwards but remaining stable in non-CD mothers (p = 0.048). A statistically significant association was found between the means of total IgA and AGA-IgA (p < 0.001). CONCLUSION: AGA-IgA is present in BM from mothers on a ND as well as in BM from mothers who had been on a GFD for years. This reflects the existence of a long-lasting immunological memory independent of the mother's diet. If the presence of these antibodies has any role in promoting the acquisition of gluten tolerance in the infant, our study shows that children of CD mothers would be on equal conditions as children of non-CD mothers.

Innovative approach for self-management and social welfare of children with cystic fibrosis in Europe: development, validation and implementation of an mHealth tool (MyCyFAPP).

INTRODUCTION: For the optimal management of children with cystic fibrosis, there are currently no efficient tools for the precise adjustment of pancreatic enzyme replacement therapy, either for advice on appropriate dietary intake or for achieving an optimal nutrition status. Therefore, we aim to develop a mobile application that ensures a successful nutritional therapy in children with cystic fibrosis. METHODS AND ANALYSIS: A multidisciplinary team of 12 partners coordinate their efforts in 9 work packages that cover the entire so-called 'from laboratory to market' approach by means of an original and innovative co-design process. A cohort of 200 patients with cystic fibrosis aged 1-17 years are enrolled. We will develop an innovative, clinically tested mobile health application for patients and health professionals involved in cystic fibrosis management. The mobile application integrates the research knowledge and innovative tools for maximising self-management with the aim of leading to a better nutritional status, quality of life and disease prognosis. Bringing together different and complementary areas of knowledge is fundamental for tackling complex challenges in disease treatment, such as optimal nutrition and pancreatic enzyme replacement therapy in cystic fibrosis. Patients are expected to benefit the most from the outcomes of this innovative project. ETHICS AND DISSEMINATION: The project is approved by the Ethics Committee of the coordinating organisation, Hospital Universitari La Fe (Ref: 2014/0484). Scientific findings will be disseminated via journals and conferences addressed to clinicians, food scientists, information and communications technology experts and patients. The specific dissemination working group within the project will address the wide audience communication through the website (http://www.mycyfapp.eu), the social networks and the newsletter.

The role of gluten consumption at an early age in celiac disease development: a further analysis of the prospective PreventCD cohort study.

Background: We previously found that the introduction of small quantities of gluten at 4-6 mo of age did not reduce the risk of celiac disease (CD) in a group of high-risk children. However, the consumption of high amounts of gluten early in life has been suggested to increase CD risk.Objective: The aim of this study was to evaluate this hypothesis by using data from the previous study of the PreventCD trial (www.preventcd.com).Design: Gluten intake was prospectively quantified by using specific food records between 11 and 36 mo of age in 715 children positive for the human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8 from 5 European countries. According to the PreventCD protocol, infants received 100 mg immunologically active gluten/d or placebo from 4 to 6 mo of age, with a stepwise and fixed gluten increase until age 10 mo and unrestricted intake thereafter. The primary outcome of the present study was the impact of the amount of gluten consumed from age 10 mo onward on CD development.Results: Mean daily gluten intakes from 10 mo onward were significantly different between countries for children at all ages (P < 0.001) but not between children who developed CD and those who did not within the same country (P > 0.05). The variables country, sex, intervention group, and gluten consumption pattern did not show significant associations with CD development risk (HRs not significant). In addition, the interaction between HLA risk group and gluten consumption pattern showed no significant risk on CD development, except for the DQ2.2/DQ7 haplotype (HR: 5.81; 95% CI: 1.18, 28.74; P = 0.031).Conclusions: Gluten consumption patterns as well as the amount of gluten consumed at 11-36 mo of age do not influence CD development for most related HLA genotypes in children with a genetic risk. This study reports the gluten consumption pattern in children at risk of CD from different European countries. This trial was registered at www.controlled-trials.com as ISRCTN74582487.

Nutrition of infants and young children (one to three years) and its effect on later health: A systematic review of current recommendations (EarlyNutrition project).

BACKGROUND: EarlyNutrition ( www.project-earlynutrition.eu ) is an international research project investigating the effects of early nutrition on metabolic programming. OBJECTIVE: To summarize, by performing a systematic review, current standards, recommendations, guidelines, and regulations (hereafter, referred to as documents) on the nutrition of children up to three years of age. Special emphasis was placed on long-term effects of early nutrition, such as the risk of cardiovascular disease, hypertension, overweight, obesity, metabolic syndrome, diabetes, or glucose intolerance. METHODS: MEDLINE, selected databases, and websites were searched for documents published between 2008 and January 2013. RESULTS: Forty two documents met the inclusion criteria. The strongest and most consistent evidence for a protective, long-term effect was documented for breastfeeding. Also, limiting the intake of sodium and rapidly absorbed carbohydrates, use of a specific meal pattern, reducing the consumption of saturated fatty acids by replacing them with polyunsaturated fatty acids, and lowering the intake of trans fatty acids, seems beneficial. Many documents did not evaluate long-term outcomes of interest to us, or reported insufficient or imprecise data. Inconsistency in recommendations for some outcomes and research gaps were identified. CONCLUSIONS: Our findings may serve as a helpful tool in planning further research, preventive actions against important diet-related diseases, and guidelines improvement.

Optimal nutrition in lactating women and its effect on later health of offspring: A systematic review of current evidence and recommendations (EarlyNutrition project).

BACKGROUND: EarlyNutrition ( www.project-earlynutrition.eu ) is an international research consortium investigating the effects of early nutrition on metabolic programming. OBJECTIVE: To summarize current evidence and standards, recommendations, guidelines, and regulations on nutrition or supplements in lactating women with emphasis placed on long-term health effects in offspring, including cardiovascular disease, hypertension, overweight/obesity, metabolic syndrome, diabetes, or glucose intolerance. METHODS: Medline, Embase, selected databases and websites were searched for documents published between 2010 and 2015. RESULTS: Thirteen documents met the inclusion criteria. Effects of maternal long-chain polyunsaturated fatty acid (LC-PUFA) supplementation on overweight/obesity or hypertension in offspring were assessed in 10 studies. One study described the effect of maternal vitamin D supplementation on overweight/obesity, and the remaining 2 studies assessed the effects of maternal probiotic/synbiotic supplementation during lactation on overweight/obesity or metabolic syndrome in their infants. Forty-one documents contained dietary recommendations on various macro- and micronutrients for lactating women, but without consideration of our long-term health outcomes in infants. CONCLUSION: Literature on nutrition of lactating women and its effect on their infants' later health with respect to metabolic programming outcomes appeared to be scarce, and focused mostly on supplementation of LC-PUFA's. No recent guidelines or recommendations were available, highlighting the significant research gaps regarding this topic.

DEVELOPMENT AND VALIDATION OF TWO FOOD FREQUENCY QUESTIONNAIRES TO ASSESS GLUTEN INTAKE IN CHILDREN UP TO 36 MONTHS OF AGE.

BACKGROUND AND OBJECTIVE: precise information on gluten consumption is crucial for specifically studying the impact of gluten introduction and gluten intake in celiac disease development. Our aim was to develop and validate tools (food frequency questionnaires, FFQs) for the assessment of gluten consumption in Spanish children aged 7-36 months. METHODS: a total of 342 children, who attended primary healthcare centers for routine health surveys or La Fe Hospital for minor health problems as well as healthy children (recruited in nurseries and primary schools) participated in this survey. We have developed two different FFQs (one for 7-12 months and other for 13-36 months). For validation, results from two FFQs were compared with results of 2-day food records and also with the gold standard 7-day records. The mean gluten intake obtained by the 2DR vs. FFQ and the 7DR vs. FFQ, were compared using the Bland Altman plot method and also Lin's concordance correlation coefficient. RESULTS: we found a good agreement between our FFQs and the 2DR and 7DR according to the results of both the Bland-Altman plots and Lin's concordance correlation coefficient. CONCLUSIONS: our two new FFQs are therefore the only validated questionnaires available to determine gluten consumption in Spanish children. They are user-friendly and offer excellent instruments to assess gluten intake in children up to 36 months of age.

Antecedentes y objetivos: una información precisa sobre el consumo de gluten es muy importante para estudiar el verdadero impacto de la introducción y la ingesta de gluten en el desarrollo de la enfermedad celiaca. El objetivo del estudio fue desarrollar y validar herramientas (cuestionarios de frecuencia de consumo, CFC) para evaluar el consumo de gluten en niños con edades comprendidas entre los 7 y 36 meses. Métodos: se incluyeron un total de 342 niños reclutados en el Hospital Universitario y Politécnico de La Fe, así como en guarderías y escuelas de primaria con problemas menores de salud. Se desarrollaron dos CFC diferentes (uno para niños de 7 a 12 meses y otro para niños de 13 a 36 meses). Para su validación, los resultados obtenidos con los CFC se compararon con un registro alimentario de dos días (2RA) y también con un registro alimentario de soete días (7RA), considerado el "estándar de oro". La ingesta media de gluten obtenida de la comparación del 2RA vs. CFC y de 7RA vs. CFC fueron comparadas usando el método de Bland Altman plot y también el coeficiente de correlación de concordancia de Lin's. Resultados: de acuerdo a los resultados de los dos métodos estadísticos usados para la validación, se encontró una buena correlación entre los CFC y los registros alimentarios de dos y siete días, lo que indica que los CFC son fiables para la evaluación de la ingesta de gluten. Conclusiones: estos dos nuevos CFC son los únicos validados y disponibles en España para la evaluación de la ingesta de gluten. Además, son herramientas útiles y fáciles de usar para el cálculo del consumo de gluten en niños de hasta tres años de edad.

Development and validation of two food frequency questionnaires to assess gluten intake in children up to 36 months of age / Desarrollo y validación de dos cuestionarios de frecuencia de consumo para evaluar la ingesta de gluten en niños hasta los 3 años

Background and objective: precise information on gluten consumption is crucial for specifically studying the impact of gluten introduction and gluten intake in celiac disease development. Our aim was to develop and validate tools (food frequency questionnaires, FFQs) for the assessment of gluten consumption in Spanish children aged 7-36 months. Methods: a total of 342 children, who attended primary healthcare centers for routine health surveys or La Fe Hospital for minor health problems as well as healthy children (recruited in nurseries and primary schools) participated in this survey. We have developed two different FFQs (one for 7-12 months and other for 13-36 months). For validation, results from two FFQs were compared with results of 2-day food records and also with the gold standard 7-day records. The mean gluten intake obtained by the 2DR vs. FFQ and the 7DR vs. FFQ, were compared using the Bland Altman plot method and also Lin’s concordance correlation coefficient. Results: we found a good agreement between our FFQs and the 2DR and 7DR according to the results of both the Bland-Altman plots and Lin’s concordance correlation coefficient. Conclusions: our two new FFQs are therefore the only validated questionnaires available to determine gluten consumption in Spanish children. They are user-friendly and offer excellent instruments to assess gluten intake in children up to 36 months of age (AU)

Antecedentes y objetivos: una información precisa sobre el consumo de gluten es muy importante para estudiar el verdadero impacto de la introducción y la ingesta de gluten en el desarrollo de la enfermedad celiaca. El objetivo del estudio fue desarrollar y validar herramientas (cuestionarios de frecuencia de consumo, CFC) para evaluar el consumo de gluten en niños con edades comprendidas entre los 7 y 36 meses. Métodos: se incluyeron un total de 342 niños reclutados en el Hospital Universitario y Politécnico de La Fe, así como en guarderías y escuelas de primaria con problemas menores de salud. Se desarrollaron dos CFC diferentes (uno para niños de 7 a 12 meses y otro para niños de 13 a 36 meses). Para su validación, los resultados obtenidos con los CFC se compararon con un registro alimentario de dos días (2RA) y también con un registro alimentario de siete días (7RA), considerado el “estándar de oro”. La ingesta media de gluten obtenida de la comparación del 2RA vs. CFC y de 7RA vs. CFC fueron comparadas usando el método de Bland Altman plot y también el coeficiente de correlación de concordancia de Lin’s. Resultados: de acuerdo a los resultados de los dos métodos estadísticos usados para la validación, se encontró una buena correlación entre los CFC y los registros alimentarios de dos y siete días, lo que indica que los CFC son fiables para la evaluación de la ingesta de gluten. Conclusiones: estos dos nuevos CFC son los únicos validados y disponibles en España para la evaluación de la ingesta de gluten. Además, son herramientas útiles y fáciles de usar para el cálculo del consumo de gluten en niños de hasta tres años de edad (AU)

Randomized feeding intervention in infants at high risk for celiac disease.

BACKGROUND: A window of opportunity has been suggested for reducing the risk of celiac disease by introducing gluten to infants at 4 to 6 months of age. METHODS: We performed a multicenter, randomized, double-blind, placebo-controlled dietary-intervention study involving 944 children who were positive for HLA-DQ2 or HLA-DQ8 and had at least one first-degree relative with celiac disease. From 16 to 24 weeks of age, 475 participants received 100 mg of immunologically active gluten daily, and 469 received placebo. Anti-transglutaminase type 2 and antigliadin antibodies were periodically measured. The primary outcome was the frequency of biopsy-confirmed celiac disease at 3 years of age. RESULTS: Celiac disease was confirmed by means of biopsies in 77 children. To avoid underestimation of the frequency of celiac disease, 3 additional children who received a diagnosis of celiac disease according to the 2012 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition diagnostic criteria (without having undergone biopsies) were included in the analyses (80 children; median age, 2.8 years; 59% were girls). The cumulative incidence of celiac disease among patients 3 years of age was 5.2% (95% confidence interval [CI], 3.6 to 6.8), with similar rates in the gluten group and the placebo group (5.9% [95% CI, 3.7 to 8.1] and 4.5% [95% CI, 2.5 to 6.5], respectively; hazard ratio in the gluten group, 1.23; 95% CI, 0.79 to 1.91). Rates of elevated levels of anti-transglutaminase type 2 and antigliadin antibodies were also similar in the two study groups (7.0% [95% CI, 4.7 to 9.4] in the gluten group and 5.7% [95% CI, 3.5 to 7.9] in the placebo group; hazard ratio, 1.14; 95% CI, 0.76 to 1.73). Breast-feeding, regardless of whether it was exclusive or whether it was ongoing during gluten introduction, did not significantly influence the development of celiac disease or the effect of the intervention. CONCLUSIONS: As compared with placebo, the introduction of small quantities of gluten at 16 to 24 weeks of age did not reduce the risk of celiac disease by 3 years of age in this group of high-risk children. (Funded by the European Commission and others; PreventCD Current Controlled Trials number, ISRCTN74582487.).