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

To investigate if the amount of gluten intake during the first 5 years of life in genetically predisposed children is associated with increased risk of celiac disease autoimmunity and celiac disease.This prospective observational birth cohort study, The Environmental Determinants of Diabetes in the Young (TEDDY), followed children from birth up to 15 years of age at 6 clinical research centers in Finland, Sweden, Germany, and the United States. Between 2004 and 2010, 8676 newborns carrying HLA antigen genotypes associated with type 1 diabetes and celiac disease were enrolled. Data on gluten intake were available in 6605 children (49% female) and this was the group included in the analysis. Median follow-up was 9.0 years (range, 1.0–13.0 years).Serum tissue transglutaminase (tTG) autoantibodies were measured annually in 6757 children from the age of 2 years. Gluten intake was estimated from 3-day food records collected at ages 6, 9, and 12 months and then biannually until 5 years old. Composite foods and recipes were broken down to ingredients. Absolute gluten intake (grams/day) was calculated.The primary outcome was celiac disease autoimmunity, defined as positive tTG autoantibodies found in 2 consecutive serum samples. Radiobinding assays were used to measure autoantibodies. In the US centers, IgA–tTG autoantibodies were measured. In the European centers, both IgA and IgG–tTG autoantibodies were measured. Diagnosis of celiac disease was confirmed by intestinal biopsy (Marsh score ≥2) or if a biopsy was not done, by persistently elevated tTG autoantibody levels (average of 2 yearly samples ≥ 100 U). Decision to perform endoscopy and biopsy was not determined by study protocol.1216 (18%) children developed celiac disease autoimmunity, and 447 (7%) developed celiac disease. The incidence for both outcomes peaked at 2 to 3 years of age. Children homozygous for HLA DR3-DQ2 were at the highest risk of celiac disease autoimmunity and celiac disease. Swedish residence, female sex, and family history of celiac disease were also associated with increased risk for both outcomes. The authors found that higher gluten intake during the first 5 years after birth was associated with an increased risk of celiac disease autoimmunity (hazard ratio, 1.30 [95% CI, 1.22–1.38]; absolute risk of 28.1% by the age of 3 years if a reference amount of gluten was consumed; absolute risk was 34.2% if the gluten amount consumed was 1-g/d higher than the reference amount. Similarly, the authors found that higher gluten intake during the first 5 years after birth was associated with an increased risk of celiac disease (hazard ratio, 1.50 [95% CI, 1.35–1.66]; absolute risk by the age of 3 years if the reference amount of gluten was consumed, 20.7%; absolute risk if the gluten amount consumed was 1-g/d higher than the reference amount, 27.9%. A post hoc analysis that focused on dietary gluten intake at the age of 2 years (just prior to the peak of celiac disease autoimmunity or celiac disease) found that daily gluten consumption of as little as 2 g (equivalent to 1 slice of bread) was associated with an increased risk of developing celiac disease autoimmunity or celiac disease; that risk was further increased for each gram of gluten ingested beyond this threshold.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.In an accompanying editorial, it was pointed out that the amount of gluten ingested during the first 5 years after birth cannot completely explain the increased prevalence of celiac disease. Previous work examining the relationship between HLA genetics, gluten consumption, and celiac disease prevalence found no significant relationship between the amount of gluten ingested and the prevalence of celiac disease. As well, the prevalence of celiac disease in Finland is higher (1%–2.5%) than in Italy (0.7%–1.1%), yet infant wheat consumption in Italy is much higher than in Finland. Further investigation is needed, but pediatricians could consider counseling families of known genetic predisposition for celiac disease or type 1 diabetes to delay or diminish gluten ingestion in infants.