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, 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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)514-523
Number of pages10
JournalJAMA - Journal of the American Medical Association
Volume322
Issue number6
DOIs
StatePublished - Aug 13 2019

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Glutens
Celiac Disease
Autoimmunity
Incidence
Autoantibodies
Type 1 Diabetes Mellitus
Finland
HLA Antigens
Sweden
Germany

ASJC Scopus subject areas

  • Medicine(all)

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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. / Andrén Aronsson, Carin; Lee, Hye Seung; Hård Af Segerstad, Elin M.; Uusitalo, Ulla; Yang, Jimin; Koletzko, Sibylle; Liu, Edwin; Kurppa, Kalle; Bingley, Polly J.; Toppari, Jorma; Ziegler, Anette G.; She, Jin Xiong; Hagopian, William A.; Rewers, Marian; Akolkar, Beena; Krischer, Jeffrey P.; Virtanen, Suvi M.; Norris, Jill M.; Agardh, Daniel.

In: JAMA - Journal of the American Medical Association, Vol. 322, No. 6, 13.08.2019, p. 514-523.

Research output: Contribution to journalArticle

Andrén Aronsson, C, Lee, HS, Hård Af Segerstad, EM, Uusitalo, U, Yang, J, Koletzko, S, Liu, E, Kurppa, K, Bingley, PJ, Toppari, J, Ziegler, AG, She, JX, Hagopian, WA, Rewers, M, Akolkar, B, Krischer, JP, Virtanen, SM, Norris, JM & Agardh, D 2019, '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', JAMA - Journal of the American Medical Association, vol. 322, no. 6, pp. 514-523. https://doi.org/10.1001/jama.2019.10329
Andrén Aronsson, Carin ; Lee, Hye Seung ; Hård Af Segerstad, Elin M. ; Uusitalo, Ulla ; Yang, Jimin ; Koletzko, Sibylle ; Liu, Edwin ; Kurppa, Kalle ; Bingley, Polly J. ; Toppari, Jorma ; Ziegler, Anette G. ; She, Jin Xiong ; Hagopian, William A. ; Rewers, Marian ; Akolkar, Beena ; Krischer, Jeffrey P. ; Virtanen, Suvi M. ; Norris, Jill M. ; Agardh, Daniel. / 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. In: JAMA - Journal of the American Medical Association. 2019 ; Vol. 322, No. 6. pp. 514-523.
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title = "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",
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.",
author = "{Andr{\'e}n Aronsson}, Carin and Lee, {Hye Seung} and {H{\aa}rd Af Segerstad}, {Elin M.} and Ulla Uusitalo and Jimin Yang and Sibylle Koletzko and Edwin Liu and Kalle Kurppa and Bingley, {Polly J.} and Jorma Toppari and Ziegler, {Anette G.} and She, {Jin Xiong} and Hagopian, {William A.} and Marian Rewers and Beena Akolkar and Krischer, {Jeffrey P.} and Virtanen, {Suvi M.} and Norris, {Jill M.} and Daniel Agardh",
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TY - JOUR

T1 - 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

AU - Andrén Aronsson, Carin

AU - Lee, Hye Seung

AU - Hård Af Segerstad, Elin M.

AU - Uusitalo, Ulla

AU - Yang, Jimin

AU - Koletzko, Sibylle

AU - Liu, Edwin

AU - Kurppa, Kalle

AU - Bingley, Polly J.

AU - Toppari, Jorma

AU - Ziegler, Anette G.

AU - She, Jin Xiong

AU - Hagopian, William A.

AU - Rewers, Marian

AU - Akolkar, Beena

AU - Krischer, Jeffrey P.

AU - Virtanen, Suvi M.

AU - Norris, Jill M.

AU - Agardh, Daniel

PY - 2019/8/13

Y1 - 2019/8/13

N2 - 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.

AB - 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.

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