Coeliac Disease Case-Control Study: Has the Time Come to Explore beyond Patients at Risk?

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.

Correlation of Anti-Tissue Transglutaminase Antibodies With the Mucosal Changes and IgA Status of Children With Celiac Disease.

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.

Spanish National Registry of Paediatric Coeliac Disease: Changes in the Clinical Presentation in the 21st Century.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Infections in early life as risk factor for coeliac disease]. / Infecciones en la primera infancia como factor de riesgo de enfermedad celiaca.

INTRODUCTION: Among the environmental factors that can affect the pathological response to gluten in coeliac disease (CD), the factors that influence the immune response, such as infections and use of antibiotics, are proposed. Our objective is to determine the relationship between infections in early life and the risk of CD. PATIENTS AND METHODS: A retrospective case-control study, including patients aged 0-16 years with a diagnosis of CD was performed between the years 2014-2018. An analysis was made of documented infections in the first 6 months of life, types of infection (respiratory, gastrointestinal, urinary, others), microorganisms involved, and antibiotic therapy used. RESULTS: A total of 93 coeliac patients, 93 controls, and 237 infectious episodes were registered. Documented infections affected 67.7% of coeliac patients and 50.5% of controls (P = .017), with a mean of 1.49 ± 1.53 episodes in the coeliac group and 1.05 ± 1.5 in the controls (P = .016). Documented infections in the first 6 months of life doubles the risk of developing CD (OR 2.05; 95% CI; 1.13-3.73), with this risk being higher for respiratory infections, which multiply the risk by 2.3 (OR 2.30, 95% CI; 1.28-4.14). Also, having 3 or more respiratory infections in the first 6 months of life multiplied the risk by 2.8 (OR 2.79, 95% CI; 1.03-7.54). No differences were found related to the types of involved microorganism or regarding the use of antibiotics. CONCLUSIONS: Infections in the first 6 months of life increase the risk of developing CD, especially for respiratory infections and, to a greater extent, if 3 or more episodes occur. The use of antibiotics in this period of life has not been related to an increased risk of CD.

Brain docosahexaenoic acid status and learning in young rats submitted to dietary long-chain polyunsaturated fatty acid deficiency and supplementation limited to lactation.

N-3 fatty acid deficiency has been related to decreased docosahexaenoic acid (DHA) and increased docosapentaenoic acid (DPA) levels in brain and to learning disadvantages. The influence of n-3 deficiency and supplementation on brain fatty acids and learning were investigated in young rats. Newborn Wistar rats were assigned to three groups of cross-foster mothers. The control group (C) was nursed by mothers that received essential fatty acids during pregnancy and lactation, and the deficient group (D) was nursed by mothers that did not receive those fatty acids. The supplemental group (S) had the same conditions as D, receiving an additional DHA and arachidonic acid supplement during lactation. Cerebral cortex and hippocampus fatty acid composition was examined using thin-layer and capillary column gas chromatography, and learning was measured by passive-avoidance procedure. D brains showed low DHA and high DPA levels, but S brain composition was similar to C. Learning in the S group was unaffected, but in the D group, it was poorer than C. Learning was directly correlated with DHA levels and inversely with DPA levels in brain. Low DHA and high DPA brain levels both were correlated with poor learning. DPA seems not to be a suitable brain functional analogue of DHA, and DHA supplementation reversed both biochemical and learning adverse effects observed in n-3 deficiency.

[Warning signs of eating, depressive, learning disorders and violent behavior among teenagers in Cantabria, Spain]. / Signos de alerta de trastornos alimentarios, depresivos, del aprendizaje y conductas violentas entre adolescentes de Cantabria.

BACKGROUND: Teenagers relatively frequently suffer from eating, depressive learning and violent behavior disorders which are often detected late. This study was aimed at investigating the presence of warning signs among teenagers in view of these disorders and to relate them to the social and family environment and living habits. METHODS: A descriptive, cross-sectional study by means of a survey of 2,178 teenagers in the 12-16 age range, representative of the teenagers of Cantabria. The warning signs were defined based on the American Medical Association and American Psychiatric Association criteria. RESULTS: Warning signs of learning disorders related to the male gender, attending public schools and repeating a year were found among 4.2% of the teenagers. Warning signs of eating disorders and depressive disorders, both related to the female gender, were found respectively among 4.3% and 10.2% of the teenagers. A total of 8.4% showed warning signs of violent behavior, more often among males. The signs investigated are spread homogeneously, increasing with age, and are significantly related to a higher degree of smoking, drinking and illegal drugs, episodes of drunkenness and a certain use of free time on the part of the teenagers, with a higher degree of consumption of addictive substances among friends and family members. CONCLUSIONS: The routine assessment during the teen years of warning signs of having the disorders studied would make their early detection possible.

Signos de alerta de trastornos alimentarios, de depresión, del aprendizaje y conductas violentas entre adolescentes de Cantabria / Warning signs of eating, depressive, learning disorders and violent behavior among teenagers in Cantabria, Spain

Fundamento: Los adolescentes presentan con relativa frecuencia trastornos de la conducta alimentaria, depresivos, del aprendizaje y conductas violentas, detectados tardíamente en muchas ocasiones. El objetivo de este trabajo fue investigar la presencia de signos de alerta ante estos trastornos entre los adolescentes y relacionarlos con el entorno social y familiar y los hábitos de vida. Métodos: Estudio transversal descriptivo, mediante encuesta a 2.178 adolescentes de 12 a 16 años, representativos de los adolescentes de Cantabria. Los signos de alerta se definieron a partir de los criterios de la Asociación Médica Americana y Asociación Americana de Psiquiatría. Resultados: El 4,2 por ciento de los adolescentes presenta signos de alerta de trastornos del aprendizaje, asociados al sexo masculino, a la asistencia a colegios públicos y a repetir curso. El 4,3 por ciento y el 10,2 por ciento presentan signos de alerta de trastornos de la conducta alimentaria y trastornos depresivos, respectivamente, estando ambos asociados al sexo femenino. El 8,4 por ciento tiene signos de alerta de conductas violentas, más frecuente en varones. Los signos investigados están distribuidos homogéneamente y aumentan con la edad. Están asociados de forma estadísticamente significativa con mayor consumo de tabaco, alcohol y drogas ilegales, episodios de embriaguez y determinado uso del tiempo libre por parte de los propios adolescentes, y con mayor consumo de sustancias adictivas por amigos y familiares. Conclusiones: La prevalencia de signos de alerta en la adolescencia y sus consecuencias individuales y familiares, a corto y a largo plazo, justifican la detección en atención primaria, mediante cuestionarios sencillos que orienten al diagnóstico precoz (AU)

Background: Teenagers relatively frequently suffer from eating, depressive learning and violent behavior disorders which are often detected late. This study was aimed at investigating the presence of warning signs among teenagers in view of these disorders and to relate them to the social and family environment and living habits. Methods: A descriptive, cross-sectional study by means of a survey of 2,178 teenagers in the 12-16 age range, representative of the teenagers of Cantabria. The warning signs were defined based on the American Medical Association and American Psychiatric Association criteria. Results: Warning signs of learning disorders related to the male gender, attending public schools and repeating a year were found among 4.2% of the teenagers. Warning signs of eating disorders and depressive disorders, both related to the female gender, were found respectively among 4.3% and 10.2% of the teenagers. A total of 8.4% showed warning signs of violent behavior, more often among males. The signs investigated are spread homogeneously, increasing with age, and are significantly related to a higher degree of smoking, drinking and illegal drugs, episodes of drunkenness and a certain use of free time on the part of the teenagers, with a higher degree of consumption of addictive substances among friends and family members. Conclusions: The routine assessment during the teen years of warning signs of having the disorders studied would make their early detection possible (AU)

Long-chain polyunsaturated fatty acids in rat maternal milk, offspring brain and peripheral tissues in essential fatty acid deficiency.

Fatty acid status in humans is usually related to plasma or red blood cell fatty acid profiles. The aim of the study was to explore whether a maternal deficiency in dietary essential fatty acids would differentially affect lipid fractions in several tissues of the offspring, including brain. Female Wistar rats were fed an essential fatty acid-deficient diet during 3 months before mating. The fatty acid composition of different lipid fractions was examined in maternal milk, and in plasma, red blood cells, liver, adipose tissue, cerebral cortex and hippocampus of the offspring using thin layer and capillary column gas chromatography. Lipid fractions from most tissues of deprived offspring showed a common fatty acid profile characterized by elevated 20:3 omega9/20:4 omega6 ratio, and decreased docosahexaenoic acid and arachidonic acid. However, arachidonic acid was not affected in brain, even though 22:5 omega6 was increased in phospholipids of cerebral cortex and hippocampus. The present results demonstrate different degrees of resistance to essential fatty acid deficiency in lipid fractions and tissues. This suggests a priority distribution of arachidonic acid to preferential areas and shows that blood phospholipid fatty acids do not exactly reflect brain phospholipid status.