Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2019 Aug 13;322(6):514-523.
doi: 10.1001/jama.2019.10329.

Association of Gluten Intake During the First 5 Years of Life With Incidence of Celiac Disease Autoimmunity and Celiac Disease Among Children at Increased Risk

Carin Andrén Aronsson  1 , Hye-Seung Lee  2 , Elin M Hård Af Segerstad  1 , Ulla Uusitalo  2 , Jimin Yang  2 , Sibylle Koletzko  3   4 , Edwin Liu  5 , Kalle Kurppa  6 , Polly J Bingley  7 , Jorma Toppari  8   9 , Anette G Ziegler  10 , Jin-Xiong She  11 , William A Hagopian  12 , Marian Rewers  13 , Beena Akolkar  14 , Jeffrey P Krischer  2 , Suvi M Virtanen  15   16   17 , Jill M Norris  18 , Daniel Agardh  1 ; TEDDY Study Group
Affiliations
Observational Study

Association of Gluten Intake During the First 5 Years of Life With Incidence of Celiac Disease Autoimmunity and Celiac Disease Among Children at Increased Risk

Carin Andrén Aronsson et al. JAMA. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Koletzko reported being a member of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition guideline group for celiac disease and a member of the PreventCD consortium. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flowchart of The Environmental Determinants of Diabetes in the Young Population Cohort
Figure 2.
Figure 2.. Mean Daily Gluten Intake up to the Age of 5 Years by Country and Overall
Error bars indicate 95% CIs.
See this image and copyright information in PMC

Comment in

References

    1. Biesiekierski JR. What is gluten? J Gastroenterol Hepatol. 2017;32(suppl 1):78-81. doi:10.1111/jgh.13703 - DOI - PubMed
    1. Lebwohl B, Sanders DS, Green PHR. Coeliac disease. Lancet. 2018;391(10115):70-81. doi:10.1016/S0140-6736(17)31796-8 - DOI - PubMed
    1. Tjon JM, van Bergen J, Koning F. Celiac disease: how complicated can it get? Immunogenetics. 2010;62(10):641-651. doi:10.1007/s00251-010-0465-9 - DOI - PMC - PubMed
    1. Bouziat R, Hinterleitner R, Brown JJ, et al. . Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease. Science. 2017;356(6333):44-50. doi:10.1126/science.aah5298 - DOI - PMC - PubMed
    1. Kemppainen KM, Lynch KF, Liu E, et al. ; TEDDY Study Group . Factors that increase risk of celiac disease autoimmunity after a gastrointestinal infection in early life. Clin Gastroenterol Hepatol. 2017;15(5):694-702.e5, e5. doi:10.1016/j.cgh.2016.10.033 - DOI - PMC - PubMed

Publication types

MeSH terms