A1 Refereed original research article in a scientific journal
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
Authors: Carin Andrén Aronsson, Hye-Seung Lee, Elin M. Hård af Segerstad, Ulla Uusitalo, Jimin Yang, Sibylle Koletzko, Edwin Liu, Kalle Kurppa, Polly J. Bingley, Jorma Toppari, Anette G. Ziegler, Jin-Xiong She, William A. Hagopian, Marian Rewers, Beena Akolkar, Jeffrey P. Krischer, Suvi M. Virtanen, Jill M. Norris, Daniel Agardh; for the TEDDY Study Group
Publisher: American Medical Association
Publication year: 2019
Journal: JAMA: Journal of the American Medical Association
Journal name in source: JAMA - Journal of the American Medical Association
Volume: 322
Issue: 6
First page : 514
Last page: 523
Number of pages: 10
ISSN: 0098-7484
eISSN: 2168-6211
DOI: https://doi.org/10.1001/jama.2019.10329
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.