Effects of Gluten Intake on Risk of Celiac Disease: A Case-Control Study on a Swedish Birth Cohort

Clin Gastroenterol Hepatol. 2016 Mar;14(3):403-409.e3. doi: 10.1016/j.cgh.2015.09.030. Epub 2015 Nov 25.


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.

Keywords: Diet; Pediatric; TEDDY Study; Wheat.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Autoantibodies / blood
  • Biopsy
  • Case-Control Studies
  • Celiac Disease / chemically induced*
  • Celiac Disease / epidemiology*
  • Child
  • Child, Preschool
  • Diet / adverse effects*
  • Female
  • GTP-Binding Proteins / immunology
  • Glutens / administration & dosage*
  • Glutens / adverse effects*
  • Humans
  • Infant
  • Intestines / pathology
  • Male
  • Protein Glutamine gamma Glutamyltransferase 2
  • Risk Assessment
  • Sweden / epidemiology
  • Transglutaminases / immunology


  • Autoantibodies
  • Glutens
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins

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