Celiac Disease Not Tied to Gluten Timing in Infants

Diana Phillips

January 19, 2015

The timing of gluten introduction into an infant's diet does not appear to influence a child's subsequent risk of developing celiac disease (CD), investigators report in an article published online January 19 in Pediatrics. The new finding, from a multinational prospective birth cohort study, challenges some current ideas on how best to prevent the onset of the autoimmune disorder.

Previous studies have suggested that the age at first exposure to gluten, as well as breast-feeding and its interaction with gluten during weaning, might influence disease onset, note Carin Andren Aronsson, MSc, from the Department of Clinical Sciences at Lund University, Molmo, Sweden, and colleagues in The Environmental Determinants of Diabetes in the Young (TEDDY) study.

Although the general recommendation is to introduce small amounts of gluten while the infant is still breast-fed, preferably between 4 and 6 months of age, "the trials on which the recommendations are based are few and have not yet been evaluated in longitudinal studies to confirm whether these infant feeding practices are valid in different populations," the authors write.

Therefore, to determine whether timing of gluten introduction is an independent risk factor for CD, the authors examined data from the TEDDY birth cohort. Infants were eligible for the TEDDY cohort if they were born at one of six research centers in Finland, Germany, Sweden, and the United States between September 2004 and February 2010 and if they screened positive for type 1 diabetes mellitus–associated, high-risk HLA-genotypes.

In the current study, the investigators focused on members of a subset of the TEDDY cohort who had been tested for CD autoimmunity (CDA) with tissue transglutaminase autoantibodies (tTGA). A total of 6436 patients met the study criteria. During a median follow-up of 5 years, 773 patients (12%) tested positive for CDA and 307 (5%) were diagnosed with CD, including 20 children whose diagnosis was based on high tTGA levels.

"Of the 773 children who tested positive for tTGA, 283 [37%] were positive at 24 months, 536 [68%] at 36 months, 658 [85%] at 48 months, and 185 [24%] children were tested positive in samples collected before the age of 24 months," they state.

With respect to feeding practices, gluten was introduced at a median 21.7 weeks in Sweden, at 26.1 weeks in Finland, and at 30.4 weeks in Germany and the United States.

In unadjusted analyses, risk factors significantly associated with the development of CDA and CD were the HLA-DR3-DQ2 genotype, Sweden as country of residence, female sex, and family history of the disease.

The timing of gluten introduction was not associated with risk for CDA and CD by 5 years of age, after adjusting for those factors. The lack of association between timing of gluten introduction and CDA or CD held true both in overall analyses and subset analyses by country of origin.

There was an increased risk for CDA in infants who breast-fed for more than 1 month after gluten introduction (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.05 - 1.44) compared with those who stopped breast-feeding at or before gluten introduction. However, the association was not significant for CD (HR, 1.13; 95% CI, 0.88 - 1.46). Both analyses were adjusted for HLA genotype, country of origin, sex, and family history.

"Despite differences in timing of gluten introduction between participating countries, the time to first introduction to gluten-containing cereals was not found to be a risk factor for CDA or CD," the authors report. "Instead, we found a significantly increased risk for CDA, but not for CD, among children being breastfed for >1 month after gluten introduction, in the overall analysis."

The authors speculate that the increased risk for CD among Swedish children "could be caused by a higher intake of gluten-containing cereals at time of weaning, although this assumption needs to be explored in future studies."

The authors have disclosed no relevant financial relationships.

Pediatrics. Published online January 19, 2015.

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