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The worldwide prevalence of asymptomatic coeliac disease (CD) is increasing, which is in part due to the routine screening of children with risk factors. Both symptomatic and asymptomatic patients with CD are at risk of long-term complications. The objective of this study was to compare the clinical characteristics of asymptomatic and symptomatic children at the time of CD diagnosis. A case–control study was conducted using data from a cohort of 4838 CD patients recruited from 73 centers across Spain between 2011 and 2017. A total of 468 asymptomatic patients (cases) were selected and matched by age and sex with 468 symptomatic patients (controls). Clinical data, including any reported symptoms, as well as serologic, genetic, and histopathologic data were collected. No significant differences were found between the two groups in most clinical variables, nor in the degree of intestinal lesion. However, the asymptomatic patients were taller (height z-score −0.12 (1.06) vs. −0.45 (1.19), p < 0.001) and were less likely to have anti transglutaminase IgA antibodies ≥ 10 times the upper normal limit (66.2% vs. 758.4%, p = 0.002). Among the 37.1% of asymptomatic patients who were not screened for CD due to the absence of risk factors, only 34% were truly asymptomatic, while the remaining 66% reported non-specific CD-related symptoms. Therefore, expanding CD screening to any child who undergoes a blood test could reduce the burden of care for some children, as many of those considered asymptomatic reported non-specific CD-related symptoms.

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).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.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 ( P0.001), 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 ( P0.001). 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.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.

Over the last several decades, there has been a tendency towards a predominance of less symptomatic forms of coeliac disease (CD) and an increase in the patient age at diagnosis. This study aimed to assess the clinical presentation and diagnostic process of paediatric CD in Spain.A nationwide prospective, observational, multicentre registry of new paediatric CD cases was conducted from January 2011 to June 2017. The data regarding demographic variables, type of birth, breast-feeding history, family history of CD, symptoms, height and weight, associated conditions, serological markers, human leukocyte antigen (HLA) phenotype, and histopathological findings were collected.In total, 4838 cases (61% girls) from 73 centres were registered. The median age at diagnosis was 4 years. Gastrointestinal symptoms were detected in 71.4% of the patients, and diarrhoea was the most frequent symptom (45.9%). The most common clinical presentation was the classical form (65.1%) whereas 9.8% ofthe patients were asymptomatic. There was a trend towards an increase in the age at diagnosis, proportion of asymptomatic CD cases, and usage of anti-deamidated gliadin peptide antibodies and HLA typing for CD diagnosis. There was, however, a decreasing trend in the proportion of patients undergoing biopsies. Some of these significant trend changes may reflect the effects of the 2012 ESPGHAN diagnosis guidelines.Paediatric CD in Spain is evolving in the same direction as in the rest of Europe, although classical CD remains the most common presentation form, and the age at diagnosis remains relatively low.

Coeliac disease is a systemic immune-mediated disorder triggered by the ingestion of gluten, which is given in genetically predisposed subjects. It manifests with a wide variety of clinical symptoms, specific serological markers, HLA-DQ2/DQ8 haplotype, and enteropathy. The criteria followed for this have usually been those established by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) since 1969. These criteria have advanced from the need of several intestinal biopsies to, thanks to the development of serological tests of high sensitivity and specificity, considering the enteropathy as one more element in this diagnosis and makes it possible to perform a diagnosis without the need of an intestinal biopsy in certain circumstances. The updated review of the 2012 criteria in 2019 provides new evidence on some aspects, such as the role of HLA, the diagnosis of asymptomatic patients, and the effectiveness of the serological markers. These aspects are reviewed in detail, with the aim of facilitating the rational application of the new 2020 criteria at all care levels. In this sense, Paediatric Primary Care is fundamental in the search for active cases and to perform a first serological study, being recommended that the diagnosis is always establishedby a Paediatric Gastroenterologist, La enfermedad celíaca es un proceso sistémico de carácter inmunológico, desen-cadenado por el consumo de gluten, que se da en sujetos genéticamente predispuestos. Se expresa con una gran variedad de síntomas clínicos, marcadores serológicos específicos, hap-lotipo HLA-DQ2/DQ8 y enteropatía. El tratamiento consiste en eliminar de por vida el gluten de la dieta, por lo que es fundamental un diagnóstico adecuado. Los criterios seguidos para ello han sido habitualmente los establecidos por la European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) desde 1969. Estos criterios han ido evolucionando desde la necesidad de varias biopsias intestinales para el diagnóstico a, gracias al desarrollo de pruebas serológicas de alta sensibilidad y especificidad, considerar la enteropatía como un elemento más en este diagnóstico y posibilitar en determinadas circunstancias realizarlo sin necesidad de biopsia intestinal. La revisión actualizada en 2019 de los criterios 2012 aporta nueva evidencia sobre algunos aspectos, como el papel del HLA, el diagnóstico de los pacientes asintomáticos y la eficacia de los marcadores serológicos. Estos aspectos se revisan en detalle,con el objetivo de facilitar la aplicación de los nuevos criterios 2020 de una forma racional en todos los niveles asistenciales. En este sentido el pediatra de Atención Primaria es fundamental para la búsqueda activa de casos y realizar un primer estudio serológico, recomendándose que el diagnóstico sea siempre establecido por un pediatra gastroenterólogo

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 Politecnic 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

[ES]: La enfermedad celíaca (EC) es una enteropatía crónica de carácter autoinmune causada por el gluten y prolaminas relacionadas que tiene lugar en individuos genéticamente susceptibles. Aunque es una enfermedad poligénica, destaca la fuerte asociación con genes localizados en la región HLA (human leukocyte antigen). La gran mayoría de los pacientes celíacos presentan el heterodímero HLA-DQ2, en concreto, la variante o isoforma conocida como DQ2.5, que en afectados de ascendencia europea se estima presente en el 90-96%. [EN]: Coeliac disease (CD) is a chronic autoimmune enteropathy triggered by gluten and related prolamines in genetically predisposed individuals. Although CD is a polygenic disease, there is a strong association with genes of the human leukocyte antigen (HLA) region. Most patients present the HLA-DQ2 heterodimer, specifically the DQ2.5 isoform, which is present in around 90-96% of patients of European ancestry.

Introduction: the recent economic and financial crisis has affected most Western countries, especially families of low socioeconomic classes. We speculate that worsening of socioeconomic condition associated with the crisis would increase obesity, mainly in disadvantaged families. Material and methods: cross-sectional study of the 290,111 children aged three to 12 years old attending public school during the term 2014-2015 in Madrid City, by means of a stratified weighted sample randomly chosen, taking into account age (grade), city district and schools. The questionnaire included weight and height (auto-reported), dietary report (weekly frequency of intake), as well as socioeconomic variables. Results: 1,208 questionnaires were evaluated from 64 classes. Half of participants were boys; 42% were younger than five years old, 35% were between six and eight years old, and 23% older than eight. Undernutrition was present in 5.0%, and excess of weight (overweight + obesity) in 36.7%. Undernutrition was higher in children under the age of six (9.1%). No relationship was found between undernutrition and the characteristics of the families but was slightly higher in families where both parents were unemployed. Excess of weight was higher in children of non-Spaniard parents (44% vs 32%, p < 0.0001), as well as in those families with economic problems (41% vs 31%, p = 0.0005). Only for meat, grains and dairy, the weekly intake was close to the recommendations. Conclusions: children from lower income households were at a higher risk of being overweight compared with their peers. Participation in a school-based food aid program may reduce food insecurity for children and their families.

Resumen Introduccion Tal como se reflejo en el Estudio Cooperativo Europeo del periodo 1991-1993, tienden a reducirse las diferencias norte/sur en las tasas de incidencia de colitis ulcerosa (CU) y enfermedad de Crohn (EC). No hay estudios que hayan actualizado el estado de la cuestion en Navarra. Objetivos Nos planteamos conocer la incidencia actual de la enfermedad inflamatoria intestinal (EII) en Navarra. Pacientes y metodos Estudio prospectivo y poblacional de la incidencia de EII en Navarra en el periodo 2001-2003, en una poblacion de 569.628 habitantes (284.620 varones). Se recogen la totalidad de los casos diagnosticados en todos los centros publicos y privados de Navarra con capacidad de diagnosticar una EII. Se calculan las tasas crudas y las tasas especificas ajustadas a la poblacion estandar europea. Resultados Se diagnosticaron 288 casos (176 CU, 102 EC y 10 colitis indeterminadas [CI]). Las tasas crudas para CU,EC y CI fueron de 10,29, 5,96 y 0,58 casos/100.000 habitantes/ano, respectivamente (incluida la poblacion de 0-14 anos de edad). Las tasas especificas (intervalo de confianza del 95%) fueron de 9,57 (7,27-12,57) y 5,85 (3,99-8,14) casos/100.000 habitantes/ano para CU y EC, respectivamente. Conclusiones La incidencia de CU y EC en Navarra ha aumentado en la ultima decada, con tasas cercanas a las referidas en los paises del norte de Europa y algo superiores a las de los ultimos estudios prospectivos espanoles.

To determine nitrate concentrations in drinking water in a sample of Spanish cities.We used ion chromatography to analyze the nitrate concentrations of public drinking water in 108 Spanish municipalities with more than 50,000 inhabitants (supplying 21,290,707 potential individuals). The samples were collected between January and April 2012. The total number of samples tested was 324.The median nitrate concentration was 3.47 mg/L (range: 0.38-66.76; interquartile range: 4.51). The water from 94% of the municipalities contained less than 15 mg/L. The concentration was higher than 25mg/L in only 3 municipalities and was greater than 50mg/L in one.Nitrate levels in most public drinking water supplies in municipalities inhabited by almost half of the Spanish population are below 15 mg/L.

Heat shock proteins (HSP) are thought to play a role in the immune response making probable their contribution to celiac disease (CD). We studied the polymorphisms in the 5′ regulatory region of the HSP70-1 gene and performed genomic HLA-DQ and -DR typing in 128 CD patients and 94 healthy controls from Navarra (Spain). The frequency of the C allele of the HSP70-1, characterized by the intermediate electrophoretic mobility of DNA, was significantly increased among CD patients (64.5% vs 37.2%. p −7 ). When subjects were stratified by the HLA II genotype, differences were statistically significant between DR3-negative or DR3-DQB1∗02-negative CD patients and matched controls. Homozygosity for the DQB1∗02 allele was present in 48.4% of CD patients and 12.8% of controls (OR = 6.4; CI:3.1 to 13.8; p −7 ). Similar increased risk was observed for DQB1∗02/∗02, DRB1∗03/-, or DRB1∗03/07 patients. Furthermore, those individuals expressing the classical HLA alleles in CD (DQB1∗02/∗02, DRB1∗03/∗07) who also carried the HSP70-1 CC genotype were twelve times more likely to develop the disease than the matched controls. We therefore conclude that although HSP70-1 gene does not seem to be primarily associated with CD, it might be a component of the high risk haplotype, playing a role as an additional predisposing gene for the disease.

Malabsorption-maldigestion syndromes are commonly found in several gastrointestinal diseases. Quantitative measures of fecal nutrients are important tools for the detection and diagnosis of these syndromes. Adequate food intake is important in the nutrition of children, especially during the first year of life. We have analyzed 180 stools of healthy children, divided into four age groups, to obtain the reference intervals of the major nutrients such as water, fat, nitrogen, sugar, and starch. Quantification of the nutrients was done by means of a near-infrared analyzer (Fenir 8820). Results show that this instrument exhibits a low coefficient of variation for all the nutrients except for starch. Fecal water, fat, nitrogen, and sugar concentrations ranged from 68.7 to 96.1 g/100 g, 0 to 14.5 g/100 g, 1.3 to 2.3 g/100 g, and 0.7 to 3.8 g/100 g, respectively. The results for the starch analyses were not acceptable because of instrument limitations. Near-infrared reflectance spectroscopy appears to be an alternative to standard chemical methods.

Childhood obesity has increased considerably in most countries in recent years. Obese children already have many co-morbidities since infancy, which can have serious consequences in adulthood. From a health standpoint, the most appropriate to address this problem is primary prevention. This article aims to summarize the relevant aspects from the point of view of prevention of childhood obesity, and in particular to those related to physical activity. To this end, health and education professionals have a role. In all cases, it is necessary to perform the evaluation of programs to see if they are really effective. Developing new programs should be based on previous experiences that had positive results. As most interventions to date have not been very effective, much more research is needed in this area in the future.

Both calcium and vitamin D are essential nutrients with a crucial role in bone health, although in recent years there has been much controversy about the contributions required from both molecules to ensure adequate health. For vitamin D, in a short time, we have seen how it has gone from a recommendation of 400 IU daily, to 200 IU and again to 400 IU, with some statements that not only its influence on skeletal tissue has been taken into account, but also on the development of chronic diseases, which has led to new expectations. Our goal is to provide an update to paediatricians on this issue and propose recommendations for intake in the light of the latest information. For vitamin D the Committee proposes an intake of 400 IU/day in children under 1 year and 600 IU/day after that age.

Infants and toddlers represent a risk population for iron deficiency (ID), due to their relatively high requirements, which are frequently associated with a poor intake of iron-rich foods. A possible association between ID and impaired cognitive and psychomotor development has been described, and it has been suggested that some of these effects can be irreversible. For this reason, prevention of ID has become a subject of much concern. To promote an adequate dietetic iron intake is the most important approach for the prevention of ID. Exclusive breast-feeding provides adequate amounts of iron during the first 4-6 months of life, and iron-fortified formula should be used when an alternative is necessary. Fortified cereals and foods containing haem iron, such as meat, should be introduced early in complementary feeding. In toddlers, iron requirements can be satisfied with a daily consumption of at least one serving of iron-containing foods, along with enhancers of iron absorption. When daily requirements are not properly met by food intake, and in some high-risk populations, screening for ID and iron supplementation should be considered.

An aberrant immune response triggered by dietary gluten is the main driving force underlying celiac disease (CD), but other biologic pathways that are dysregulated also participate in disease development. Genetic variation within these pathways might influence expression, contributing to susceptibility to CD. We have investigated the implication of ubiquitin D (UBD), a member of the ubiquitin–proteasome system that is strongly upregulated in the intestinal mucosa of active CD. Reverse transcriptase-polymerase chain reaction analysis of intestinal biopsy sample pairs (at diagnosis vs treated) from 30 CD patients confirmed overexpression of UBD in active disease tissue (fold change = 8.3; p = 0.0022). In silico prediction tools identified rs11724 as a putative regulatory single nucleotide polymorphism and association analysis of 468 CD patients and 459 controls revealed that the minor rs11724*C allele was more frequent among patients (minor allele frequency = 0.44 vs 0.39; odds ratio [OR] = 1.23; p = 0.028) and suggested a dominant allele effect (OR = 1.49; p = 0.0045). Correlation of the rs11724 genotype and UBD mRNA levels (OR = 0.76; p = 0.0021) further supports its implication in disease development.

As reflected in the European Collaborative Study on Inflammatory Bowel Disease (1991-1993), differences between northern and southern European countries in the incidence of ulcerative colitis (UC) and Crohn's disease (CD) show a tendency to decrease. No data are available on the current incidence of these diseases in Navarre (northern Spain).To determine the present incidence of inflammatory bowel disease (IBD) in Navarra.A prospective, population-based study was performed to determine the incidence of IBD in Navarra between 2001 and 2003. Total population: 569,628 inhabitants (284,620 males). All cases of IBD diagnosed in any public or private hospital in Navarre were included in the study. Crude rates and age- and sex-specific rates adjusted to the European standard population were calculated.A total of 288 cases were diagnosed (UC 176, CD 102, indeterminate colitis 10). Crude rates of UC, CD and indeterminate colitis were 10.29, 5.96 and 0.58 cases/100,000 inhabitants/year respectively (the population aged 0-14 years of age was included). Specific rates were 9.57 (95% CI, 7.27-12.57) and 5.85 (95% CI, 3.99-8.14) cases/100,000 inhabitants/year for UC and CD, respectively.The incidence of UC and CD in Navarra has increased in the last decade, with rates close to those of northern European countries and higher than those recently published in Spanish prospective studies.