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Longitudinal Micronutrient Exposure Reveals Country-Specific Associations with Risk of Celiac Disease in Genetically Susceptible Children: The Prospective TEDDY Cohort: Nutrient Intake and Risk of Celiac Disease

Yang, Jimin ; Mramba, Lazarus K ; Hård af Segerstad, Elin M LU orcid ; Kurppa, Kalle ; Uusitalo, Ulla M ; Andrén Aronsson, Carin LU orcid ; Rewers, Marian J. ; McIndoe, Richard ; Toppari, Jorma and Ziegler, Anette-Gabriele , et al. (2026) In American Journal of Clinical Nutrition
Abstract
Abstract
Background
The role of nutrient intake in celiac disease pathogenesis is poorly understood.
Objective
To examine whether longitudinal childhood intake of selected vitamins and minerals is associated with celiac disease autoimmunity (CDA, primary outcome) and celiac disease (secondary outcome) in genetically at-risk children.
Methods
A total of 6,520 HLA-conferred at-risk children in the observational TEDDY study were prospectively screened for tissue transglutaminase autoantibodies (tTGA) annually from ages 2 to 13 years. CDA was defined as persistent tTGA positivity in two samples ≥3 months apart. Celiac disease was defined by biopsy-confirmed Marsh score ≥2 or mean tTGA ≥100 U/mL in two consecutive... (More)
Abstract
Background
The role of nutrient intake in celiac disease pathogenesis is poorly understood.
Objective
To examine whether longitudinal childhood intake of selected vitamins and minerals is associated with celiac disease autoimmunity (CDA, primary outcome) and celiac disease (secondary outcome) in genetically at-risk children.
Methods
A total of 6,520 HLA-conferred at-risk children in the observational TEDDY study were prospectively screened for tissue transglutaminase autoantibodies (tTGA) annually from ages 2 to 13 years. CDA was defined as persistent tTGA positivity in two samples ≥3 months apart. Celiac disease was defined by biopsy-confirmed Marsh score ≥2 or mean tTGA ≥100 U/mL in two consecutive samples. Micronutrient intake was assessed via repeated 3-day food records, and adjusted hazard ratios (HRs) were estimated using time-dependent Cox proportional hazards and Bayesian joint models.
Results
Out of 6,520 children, 1,268 (19%) developed CDA and 479 (7.8%) were diagnosed with celiac disease. Results from both models suggested heterogeneity in associations by country as nutrients such as folate showing sporadic associations in the same or opposite direction across ages. Higher vitamin D intake (every 5 μg/1000 kcal) at multiple ages was associated with increased risk of CDA and celiac disease in Sweden, with the strongest at age 5 years for CDA (HR: 1.23, 95%CI: 1.11, 1.37; p<0.001) and at age 4 years for celiac disease (HR: 1.20, 95%CI: 1.03, 1.40; p=0.021). Higher iron intake (every 5 mg/1000 kcal) was also associated with increased risks of CDA and celiac disease in Sweden, with the highest observed up to age 5 years (HR: 1.70, 95%CI: 1.39, 2.08; p<0.001 for CDA and HR:1.80, 95%CI: 1.37, 2.36; p<0.001 for celiac disease).
Conclusions
Modest country-specific associations were found between childhood micronutrient intake with the risk of CDA and celiac disease, potentially reflecting influence from regional dietary practices, fortification policies, and host factors in disease pathogenesis. (Less)
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type
Contribution to journal
publication status
published
subject
in
American Journal of Clinical Nutrition
article number
101276
publisher
Elsevier
ISSN
1938-3207
DOI
10.1016/j.ajcnut.2026.101276
language
English
LU publication?
yes
id
c285b492-4573-4e66-8ea3-30fe8e557283
date added to LUP
2026-03-27 08:43:12
date last changed
2026-03-27 09:26:52
@article{c285b492-4573-4e66-8ea3-30fe8e557283,
  abstract     = {{Abstract<br/>Background<br/>The role of nutrient intake in celiac disease pathogenesis is poorly understood.<br/>Objective<br/>To examine whether longitudinal childhood intake of selected vitamins and minerals is associated with celiac disease autoimmunity (CDA, primary outcome) and celiac disease (secondary outcome) in genetically at-risk children.<br/>Methods<br/>A total of 6,520 HLA-conferred at-risk children in the observational TEDDY study were prospectively screened for tissue transglutaminase autoantibodies (tTGA) annually from ages 2 to 13 years. CDA was defined as persistent tTGA positivity in two samples ≥3 months apart. Celiac disease was defined by biopsy-confirmed Marsh score ≥2 or mean tTGA ≥100 U/mL in two consecutive samples. Micronutrient intake was assessed via repeated 3-day food records, and adjusted hazard ratios (HRs) were estimated using time-dependent Cox proportional hazards and Bayesian joint models.<br/>Results<br/>Out of 6,520 children, 1,268 (19%) developed CDA and 479 (7.8%) were diagnosed with celiac disease. Results from both models suggested heterogeneity in associations by country as nutrients such as folate showing sporadic associations in the same or opposite direction across ages. Higher vitamin D intake (every 5 μg/1000 kcal) at multiple ages was associated with increased risk of CDA and celiac disease in Sweden, with the strongest at age 5 years for CDA (HR: 1.23, 95%CI: 1.11, 1.37; p&lt;0.001) and at age 4 years for celiac disease (HR: 1.20, 95%CI: 1.03, 1.40; p=0.021). Higher iron intake (every 5 mg/1000 kcal) was also associated with increased risks of CDA and celiac disease in Sweden, with the highest observed up to age 5 years (HR: 1.70, 95%CI: 1.39, 2.08; p&lt;0.001 for CDA and HR:1.80, 95%CI: 1.37, 2.36; p&lt;0.001 for celiac disease).<br/>Conclusions<br/>Modest country-specific associations were found between childhood micronutrient intake with the risk of CDA and celiac disease, potentially reflecting influence from regional dietary practices, fortification policies, and host factors in disease pathogenesis.}},
  author       = {{Yang, Jimin and Mramba, Lazarus K and Hård af Segerstad, Elin M and Kurppa, Kalle and Uusitalo, Ulla M and Andrén Aronsson, Carin and Rewers, Marian J. and McIndoe, Richard and Toppari, Jorma and Ziegler, Anette-Gabriele and Hagopian, William A. and Akolkar, Beena and Krischer, Jeffrey P. and Norris, Jill M. and Virtanen, Suvi M and Agardh, Daniel and TEDDY study group, The}},
  issn         = {{1938-3207}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{American Journal of Clinical Nutrition}},
  title        = {{Longitudinal Micronutrient Exposure Reveals Country-Specific Associations with Risk of Celiac Disease in Genetically Susceptible Children: The Prospective TEDDY Cohort: Nutrient Intake and Risk of Celiac Disease}},
  url          = {{http://dx.doi.org/10.1016/j.ajcnut.2026.101276}},
  doi          = {{10.1016/j.ajcnut.2026.101276}},
  year         = {{2026}},
}