Early environmental risk factors and coeliac disease in adolescents: a population-based cohort study in Denmark.

OBJECTIVES: Our aim was to investigate the association between early environmental factors and the development of coeliac disease (CeD) in adolescents, recruited from a cohort nested in the Danish National Birth Cohort (DNBC). DESIGN: The study was designed as a prospective cohort study, nested in DNBC PARTICIPANTS: The Glutenfunen cohort comprises 1266 participants, nested in DNBC. All participants were screened for CeD, and in total, 28 cases of biopsy proven CeD were identified. Data about breastfeeding, timing of introduction to solid food in infancy, use of antibiotics, infections and symptoms were parentally reported prospectively at 6 months and 18 months, respectively. We estimated ORs and 95% CIs of CeD in adolescents using logistic regression analysis. RESULTS: Viral croup reported at 18 months of age was associated with CeD in adolescents with an OR of 3.2 (95% CI: 1.2 to 8.7). Furthermore, otitis media also reported at 18 months of age was linked with CeD with an OR of 3.2 (95% CI: 1.5 to 7.3). We were not able to find any statistical associations between CeD and breastfeeding, frequency of infections, parentally reported use of antibiotic and timing of solid foods. CONCLUSION: In this study, we present an overview of the relationship between early environmental factors and occurrence of CeD in adolescents. Our findings, despite limitations due to a limited number of cases of CeD, suggest a role of viral infections in the pathogenesis of CeD.

Pediatric Celiac Disease and Selective IgA Deficiency: Unexpected Sequence of Events.

PURPOSE: Selective IgA deficiency (IgAD) is the most common primary immunodeficiency, frequently leading to only minor clinical complaints. IgAD may be associated with autoimmune diseases such as celiac disease (CeD). Although IgAD is thought to precede CeD and autoimmunity, the association between the two conditions has not been clarified. METHODS: Routine techniques were used to measure serum IgA and celiac diagnostic markers as transglutaminase 2 IgA (TG2-IgA) and deamidated gliadin IgG and for immunohistochemistry for IgG, IgM, and IgA. RESULTS: We report two childhood cases of complete IgA deficiency that evolved after the diagnosis of CeD and the start of a gluten-free diet. Histology showed persistence of IgA in the intestinal mucosa. CONCLUSION: Both children with CeD showed IgA deficiency that unexpectedly developed after the initiation of a gluten-free diet. This supports IgA deficiency as a process that develops gradually and occurs due to specific defects in immunoregulation.

The effect of gluten in adolescents and young adults with gastrointestinal symptoms: a blinded randomised cross-over trial.

BACKGROUND: The popularity of the gluten-free diet and sales of gluten-free products have increased immensely. AIMS: To investigate whether gluten induces gastrointestinal symptoms, measured by self-reported questionnaires, as well as mental health symptoms in adolescents from a population-based cohort. METHODS: The eligible participants (n = 273) were recruited from a population-based cohort of 1266 adolescents and had at least four different gastrointestinal symptoms. Phase one (n = 54) was a run-in phase where the participants lived gluten-free for 2 weeks. If they improved they continued to phase 2 (n = 33), a blinded randomised cross-over trial. Participants were blindly randomised either to start with 7 days of gluten, eating two granola bars containing 10 g of gluten or to 7 days on placebo, eating two granola bars without gluten, followed by the reverse and separated by a 7-day washout period. The effects of the intervention on gastrointestinal symptoms and mental health symptoms were assessed. RESULTS: In total, 54/273 participants entered the run-in phase and 35 were eligible for randomization. A total of 33 were randomised and 32 completed the trial. The median age was 20.3 (IQR 19.2-20.9) and 32/33 participants were females. Compared with a placebo, gluten did not induce gastrointestinal symptoms. The difference in the average VAS was -0.01 (95% confidence interval -2.07 to 2.05). Nor did we find a difference in the outcomes measuring mental health. CONCLUSION: Compared with placebo, adding gluten to the diet did not induce gastrointestinal symptoms or worsened mental health in adolescents recruited from a population-based cohort. The trial registration number is NCT04639921.

High Prevalence of Celiac Disease Among Danish Adolescents: A Population-based Study.

OBJECTIVES: The objective of this study was to establish an unselected cohort of Danish adolescents and estimate the prevalence of undiagnosed celiac disease (CeD). METHODS: The Glutenfunen cohort participants were recruited from an unselected subsample of the Danish National Birth Cohort, defined as participants living in the Island of Funen, Denmark. We invited all 7431 eligible participants in the age range of 15 to 21 years to a clinical visit. CeD diagnosis was based on screening with IgA transglutaminase antibodies (TG2-IgA) and if positive, was followed by duodenal biopsies compatible with CeD (Marsh 2-3). We calculated the prevalence of CeD in the Glutenfunen cohort as the number of CeD cases diagnosed before and during the study divided by the number of participants in the Glutenfunen cohort. RESULTS: We included 1266 participants in the Glutenfunen cohort (17%, 1266/7431). 1.1% (14 of 1266 participants) had CeD diagnosed before entering the cohort and based on the Danish National Patient Register, 0.2% of the nonparticipants (14 of 6165) had a diagnosis of CeD. In total, 2.6% (33 participants) had TG2 IgA above the upper limit of normal. Nineteen participants had duodenal biopsies compatible with CeD. The prevalence of CeD in the Glutenfunen cohort was 2.6% [(14 + 19)/1266]. CONCLUSIONS: Our study suggests that CeD is much more common than expected among Danish adolescents, comparable to other European countries, and that the majority were asymptomatic or oligosymptomatic and were only found because of the screening procedure.