The goal of this study was to determine whether age at introduction to gluten was associated with risk for celiac disease (CD) in genetically predisposed children.
TEDDY (The Environmental Determinants of Diabetes in the Young) is a prospective birth cohort study. Newborn infants (N = 6436) screened for high-risk HLA-genotypes for CD were followed up in Finland, Germany, Sweden, and the United States. Information about infant feeding was collected at clinical visits every third month. The first outcome was persistent positive for tissue transglutaminase autoantibodies (tTGA), the marker for CD. The second outcome was CD, defined as either a diagnosis based on intestinal biopsy results or on persistently high levels of tTGA.
Swedish children were introduced to gluten earlier (median: 21.7 weeks) compared with children from Finland (median: 26.1 weeks), Germany, and the United States (both median: 30.4 weeks) (P < .0001). During a median follow-up of 5.0 years (range: 1.7–8.8 years), 773 (12%) children developed tTGA and 307 (5%) developed CD. Swedish children were at increased risk for tTGA (hazard ratio: 1.74 [95% CI: 1.47–2.06]) and CD (hazard ratio: 1.76 [95% CI: 1.34–2.24]) compared with US children, respectively (P < .0001).Gluten introduction before 17 weeks or later than 26 weeks was not associated with increased risk for tTGA or CD, adjusted for country, HLA, gender, and family history of CD, neither in the overall analysis nor on a country-level comparison.
In TEDDY, the time to first introduction to gluten introduction was not an independent risk factor for developing CD.
Comments
RISK OF CELIAC DISEASE IN CHILDREN: TIMING OF GLUTEN INTRODUCTION OR WHAT ELSE?
Dear Editor, we read with interest the recent paper by Aronsson CA et al. (1) The goal of this study was to determine whether age at introduction to gluten was associated with risk for celiac disease (CD) in genetically predisposed children. In this prospective birth cohort study, time to first introduction of gluten is not an independent risk factor for developing CD by 5 years of age, neither on an overall level nor on a country level comparison. The authors speculate that the increased risk of CD among Swedish children compared with children from other countries could be caused by a higher intake of gluten-containing cereals at time of weaning. We want to underline that also Lionetti E. et al.(2) conclude that neither the delayed introduction of gluten nor breast-feeding modified the risk of CD among at-risk infants. Today a metabolic fingerprint for CD has been defined with a good predictive capacity. It was found to be made up by three components: one related to malabsorption, one to energy metabolism, and the third related to alterations in gut microflora or intestinal permeability(3). Furthermore, recent studies suggest that the genotype of infants at family risk for CD, influences the early gut microbiota composition which results with an overall lack of bacteria of the phylum Bacteriodetes along with a high abundance of Firmicutes(4,5). The interaction between HLA, Microbiota and Metabolome is the method through which the individual responds to stimulation with gluten. In this context, we retain it could be interesting to understand the mechanisms of development of CD in the presence of the same familial HLA rather than identify the best range for the introduction of the well-known stimulus.
REFERENCES
1) Aronsson CA, Lee HS, Liu E et al. Age at Gluten Introduction and Risk of Celiac Disease. Pediatrics. 2015 Jan 19. pii: peds.2014-1787. [Epub ahead of print] 2) Lionetti E, Castellaneta S, Francavilla R, et al. Introduction of gluten, HLA status, and the risk of celiac disease in children. N Engl J Med. 2014 Oct 2;371:1295-303. 3) Bertini I, Calabr? A, De Carli Vet al. The metabonomic signature of celiac disease. J Proteome Res. 2009 Jan;8:170-7. 4) Sellitto M, Bai G, Serena G, et al. Proof of concept of microbiome- metabolome analysis and delayed gluten exposure on celiac disease autoimmunity in genetically at-risk infants. PLoS One. 2012;7 5) Olivares M, Neef A, Castillejo G et al. The HLA-DQ2 genotype selects for early intestinal microbiota composition in infants at high risk of developing coeliac disease. Gut. 2014, Epub ahead of print
Conflict of Interest:
None declared