Search

Background: High gluten intake is associated with increased risk of celiac disease (CD) in children at genetic risk., Objectives: We aimed to investigate if different dietary gluten sources up to age 2 y confer different risks of celiac disease autoimmunity (CDA) and CD in children at genetic risk., Methods: Three-day food records were collected at ages 6, 9, 12, 18, and 24 mo from 2088 Swedish genetically at-risk children participating in a 15-y follow-up cohort study on type 1 diabetes and CD. Screening for CD was performed with tissue transglutaminase autoantibodies (tTGA). The primary outcome was CDA, defined as persistent tTGA positivity. The secondary outcome was CD, defined as having a biopsy specimen showing Marsh score ≥ 2 or an averaged tTGA level ≥ 100 Units. Cox regression adjusted for total gluten intake estimated HRs with 95% CIs for daily intake of gluten sources., Results: During follow-up, 487 (23.3%) children developed CDA and 242 (11.6%) developed CD. Daily intake of ≤158 g porridge at age 9 mo was associated with increased risk of CDA (HR: 1.53; 95% CI: 1.05, 2.23; P = 0.026) compared with no intake. A high daily bread intake (>18.3 g) at age 12 mo was associated with increased risk of both CDA (HR: 1.47; 95% CI: 1.05, 2.05; P = 0.023) and CD (HR: 1.79; 95% CI: 1.10, 2.91; P = 0.019) compared with no intake. At age 18 mo, milk cereal drink was associated with an increased risk of CD (HR: 1.16; 95% CI: 1.00, 1.33; P = 0.047) per 200-g/d increased intake. No association was found for other gluten sources up to age 24 mo and risk of CDA or CD., Conclusions: High daily intakes of bread at age 12 mo and of milk cereal drink during the second year of life are associated with increased risk of both CDA and CD in genetically at-risk children., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Objective: Higher gluten intake, frequent gastrointestinal infections and adenovirus, enterovirus, rotavirus and reovirus have been proposed as environmental triggers for coeliac disease. However, it is not known whether an interaction exists between the ingested gluten amount and viral exposures in the development of coeliac disease. This study investigated whether distinct viral exposures alone or together with gluten increase the risk of coeliac disease autoimmunity (CDA) in genetically predisposed children., Design: The Environmental Determinants of Diabetes in the Young study prospectively followed children carrying the HLA risk haplotypes DQ2 and/or DQ8 and constructed a nested case-control design. From this design, 83 CDA case-control pairs were identified. Median age of CDA was 31 months. Stool samples collected monthly up to the age of 2 years were analysed for virome composition by Illumina next-generation sequencing followed by comprehensive computational virus profiling., Results: The cumulative number of stool enteroviral exposures between 1 and 2 years of age was associated with an increased risk for CDA. In addition, there was a significant interaction between cumulative stool enteroviral exposures and gluten consumption. The risk conferred by stool enteroviruses was increased in cases reporting higher gluten intake., Conclusions: Frequent exposure to enterovirus between 1 and 2 years of age was associated with increased risk of CDA. The increased risk conferred by the interaction between enteroviruses and higher gluten intake indicate a cumulative effect of these factors in the development of CDA., Competing Interests: Competing interests: HH is a shareholder and chairman of the board of Vactech Ltd, which develops vaccines against picornaviruses., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: High gluten intake during childhood may confer risk of celiac disease., Objectives: To investigate if the amount of gluten intake is associated with celiac disease autoimmunity and celiac disease in genetically at-risk children., Design, Setting, and Participants: The participants in The Environmental Determinants of Diabetes in the Young (TEDDY), a prospective observational birth cohort study designed to identify environmental triggers of type 1 diabetes and celiac disease, were followed up at 6 clinical centers in Finland, Germany, Sweden, and the United States. Between 2004 and 2010, 8676 newborns carrying HLA antigen genotypes associated with type 1 diabetes and celiac disease were enrolled. Screening for celiac disease with tissue transglutaminase autoantibodies was performed annually in 6757 children from the age of 2 years. Data on gluten intake were available in 6605 children (98%) by September 30, 2017., Exposures: Gluten intake was estimated from 3-day food records collected at ages 6, 9, and 12 months and biannually thereafter until the age of 5 years., Main Outcomes and Measures: The primary outcome was celiac disease autoimmunity, defined as positive tissue transglutaminase autoantibodies found in 2 consecutive serum samples. The secondary outcome was celiac disease confirmed by intestinal biopsy or persistently high tissue transglutaminase autoantibody levels., Results: Of the 6605 children (49% females; median follow-up: 9.0 years [interquartile range, 8.0-10.0 years]), 1216 (18%) developed celiac disease autoimmunity and 447 (7%) developed celiac disease. The incidence for both outcomes peaked at the age of 2 to 3 years. Daily gluten intake was associated with higher risk of celiac disease autoimmunity for every 1-g/d increase in gluten consumption (hazard ratio [HR], 1.30 [95% CI, 1.22-1.38]; absolute risk by the age of 3 years if the reference amount of gluten was consumed, 28.1%; absolute risk if gluten intake was 1-g/d higher than the reference amount, 34.2%; absolute risk difference, 6.1% [95% CI, 4.5%-7.7%]). Daily gluten intake was associated with higher risk of celiac disease for every 1-g/d increase in gluten consumption (HR, 1.50 [95% CI, 1.35-1.66]; absolute risk by age of 3 years if the reference amount of gluten was consumed, 20.7%; absolute risk if gluten intake was 1-g/d higher than the reference amount, 27.9%; absolute risk difference, 7.2% [95% CI, 6.1%-8.3%])., Conclusions and Relevance: Higher gluten intake during the first 5 years of life was associated with increased risk of celiac disease autoimmunity and celiac disease among genetically predisposed children.

Background & Aims: Early nutrition may affect the risk of celiac disease. We investigated whether amount of gluten in diet until 2 years of age increases risk for celiac disease., Methods: We performed a 1-to-3 nested case-control study of 146 cases, resulting in 436 case-control pairs matched for sex, birth year, and HLA genotype generated from Swedish children at genetic risk for celiac disease. Newborns were annually screened for tissue transglutaminase autoantibodies (tTGA). If tested tTGA positive, time point of seroconversion was determined from frozen serum samples taken every 3 months. Celiac disease was confirmed by intestinal biopsies. Gluten intake was calculated from 3-day food records collected at ages 9, 12, 18 and 24 months. Odds ratios (OR) were calculated through conditional logistic regression., Results: Breastfeeding duration (median, 32 wk) and age at first introduction to gluten (median, 22 wk) did not differ between cases and tTGA-negative controls. At the visit before tTGA seroconversion, cases reported a larger intake of gluten than controls (OR, 1.28; 95% confidence interval [CI], 1.13-1.46; P = .0002). More cases than controls were found in the upper third tertile (ie, >5.0 g/d) before they tested positive for tTGA seroconversion than controls (OR, 2.65; 95% CI, 1.70-4.13; P < .0001). This finding was similar in children homozygous for DR3-DQ2 (OR, 3.19; 95% CI, 1.61-6.30; P = .001), heterozygous for DR3-DQ2 (OR, 2.24; 95% CI, 1.08-4.62; P = .030), and for children not carrying DR3-DQ2 (OR, 2.43; 95% CI, 0.90-6.54; P = .079)., Conclusions: The amount of gluten consumed until 2 years of age increases the risk of celiac disease at least 2-fold in genetically susceptible children. These findings may be taken into account for future infant feeding recommendations., (Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Maternal diet during pregnancy has been proposed to increase the risk of autoimmune diseases., Objective: The objective was to investigate the association between maternal consumption of gluten-containing foods during late pregnancy and subsequent risk of celiac disease in the offspring., Design: Genetically susceptible children prospectively followed from birth were screened annually for tissue transglutaminase autoantibodies (tTGAs). Children testing persistently positive for tTGAs were further evaluated for celiac disease. Diagnosis of celiac disease was confirmed by intestinal biopsy or was considered likely if the mean tTGA concentration was >100 units in 2 consecutive samples. A questionnaire on the mother's diet in late pregnancy was completed by 3-4.5 mo postpartum. Mothers were divided into 3 groups based on the tertiles of their consumption of gluten-containing foods (servings/d). The association between maternal gluten-containing food consumption and the risk of celiac disease was studied by using a time-to-event analysis., Results: At the time of analysis, 359 (5%) of the 6546 children developed celiac disease. Compared with the middle category of maternal gluten-containing food consumption (servings/d), low (HR: 0.87; 95% CI: 0.67, 1.13; P = 0.296) and high (HR: 0.84; 95% CI: 0.65, 1.09; P = 0.202) consumption was not associated with risk of celiac disease in the child after adjustment for country, human leukocyte antigen genotype, family history of celiac disease, maternal education, and sex of the child. Median maternal daily consumption frequency of gluten-containing foods was higher (P < 0.0001) in Finland (5.3; IQR: 3.9-6.9), Germany (4.3; IQR: 3.1-5.5), and Sweden (3.7; IQR: 2.8-4.9) than in the United States (3.4; IQR: 2.3-4.9). No significant interaction was found between country of residence and the mothers' consumption of gluten-containing foods in relation to risk of celiac disease., Conclusion: The frequency of gluten-containing food consumption during late pregnancy is not associated with risk of celiac disease in the offspring., (© 2015 American Society for Nutrition.)

Objectives: The goal of this study was to determine whether age at introduction to gluten was associated with risk for celiac disease (CD) in genetically predisposed children., Methods: TEDDY (The Environmental Determinants of Diabetes in the Young) is a prospective birth cohort study. Newborn infants (N = 6436) screened for high-risk HLA-genotypes for CD were followed up in Finland, Germany, Sweden, and the United States. Information about infant feeding was collected at clinical visits every third month. The first outcome was persistent positive for tissue transglutaminase autoantibodies (tTGA), the marker for CD. The second outcome was CD, defined as either a diagnosis based on intestinal biopsy results or on persistently high levels of tTGA., Results: Swedish children were introduced to gluten earlier (median: 21.7 weeks) compared with children from Finland (median: 26.1 weeks), Germany, and the United States (both median: 30.4 weeks) (P < .0001). During a median follow-up of 5.0 years (range: 1.7-8.8 years), 773 (12%) children developed tTGA and 307 (5%) developed CD. Swedish children were at increased risk for tTGA (hazard ratio: 1.74 [95% CI: 1.47-2.06]) and CD (hazard ratio: 1.76 [95% CI: 1.34-2.24]) compared with US children, respectively (P < .0001).Gluten introduction before 17 weeks or later than 26 weeks was not associated with increased risk for tTGA or CD, adjusted for country, HLA, gender, and family history of CD, neither in the overall analysis nor on a country-level comparison., Conclusions: In TEDDY, the time to first introduction to gluten introduction was not an independent risk factor for developing CD., (Copyright © 2015 by the American Academy of Pediatrics.)

Tissue transglutaminase (tTG) autoantibodies decline after gluten-free diet in patients with coeliac disease. We tested the hypothesis that gluten-free diet-induced change in tTG autoantibody levels affects subsets of peripheral blood lymphocytes. Peripheral blood was obtained from 20 children with biopsy-proven active coeliac disease. Gluten-free diet was initiated and the children examined again after three and six months. tTG autoantibodies were measured in radioligand binding assays and lymphocyte subsets by flow cytometry. IgA-tTG levels at diagnosis, 2204 U/ml (median, range 113-24990), were reduced over six months to 76 U/ml (median, range 1-1261) (P < 0.001). At six months, 12/20 (60%) children had reduced their IgA-tTG levels to < 100 U/ml and these children showed a decrease in B cells (mean change -3.8%, P = 0.014), CD4+ T cells (mean -4.32%, P = 0.011) and CD4+ T cells expressing CD25high (mean change -0.62%, P = 0.036). In contrast, the CD4+CD25(high)CCR4+ T cell population increased during the same period (mean change 11.5%, P = 0.0036). The decline in IgA-tTG levels correlated to the decrease in B cells (r = 0.56, P = 0.01), CD4+ T cells (r = 0.66, P = 0.004) as well as CD4+CD25high T cells (r = 0.59, P = 0.01). A negative correlation was found between the decline in IgA-tTG and CD4+CD25high T cells expressing CD45RO (r = -0.49, P = 0.03) and CCR4 (r = -0.54, P = 0.01). This is the first observational study on the effect of gluten-free diet on concurrent changes of tTG autoantibodies and specific peripheral blood lymphocyte subsets. Our data suggest that flow cytometry may be a useful complement to tTG autoantibodies when studying the effects of gluten-free diet in children with coeliac disease.