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Timing of gluten introduction in infancy doesn’t matter

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Results change the celiac landscape

The findings of these two multicenter clinical trials will change the conceptual landscape of celiac disease.

From now on, it will be difficult for anyone to continue to recommend the introduction of gluten specifically at the age of 4-6 months, because this will not reduce the risk of developing celiac disease. And although breastfeeding is important to overall health, it doesn’t appear to protect against celiac disease.

Jonas F. Ludvigsson, M.D., Ph.D., is in the department of medical epidemiology and biostatistics at the Karolinska Institute, Stockholm, and the department of pediatrics at Orebro (Sweden) University Hospital. Peter H. R. Green, M.D., is at the Celiac Disease Center at Columbia University, New York. These remarks were taken from their editorial accompanying Dr. Lionetti’s and Dr. Vriezinga’s reports (N. Engl. J. Med. 2014 October 2 [doi:10.1056/NEJMe1408011]).


 

FROM THE NEW ENGLAND JOURNAL OF MEDICINE

References


The timing of introducing gluten into babies’ diets doesn’t alter their risk for developing celiac disease later, according to two separate reports published online Oct. 1 in the New England Journal of Medicine.

Currently, many clinicians recommend introducing small amounts of gluten during a proposed “window of opportunity” at 4-6 months of age – preferably while maintaining breast-feeding, which is considered protective – as a way of preventing the later development of celiac disease, especially in at-risk children. But this advice is based on the findings of a few small observational studies and remains controversial. To better examine whether the timing of gluten introduction influences the risk for celiac disease, separate groups of investigators performed prospective, randomized clinical trials assessing different dietary interventions in at-risk children.

New clinical trials suggest that introducing gluten into a 4-6 month old child's diet will not reduce their risk of developing celiac disease. © Renata Osinska/Thinkstock

New clinical trials suggest that introducing gluten into a 4-6 month old child's diet will not reduce their risk of developing celiac disease.

They found that neither introducing small amounts of gluten at 4-6 months of age nor delaying that introduction until 12 months of age reduced the risk of later celiac disease, and that breastfeeding status also did not significantly affect that risk.

In the Risk of Celiac Disease and Age at Gluten Introduction (CELIPREV) trial, 707 newborns who had at least one affected first-degree relative were enrolled at 20 medical centers across Italy during a 5-year period. They were randomly assigned to gluten introduction (in the form of pasta, semolina, or biscuits) at age 6 months (379 babies) or delayed introduction at age 12 months (328 babies) and were followed for 5-11 years.

Overall, at age 10 years the prevalence of celiac disease autoimmunity was 16.5%, and the prevalence of overt celiac disease was 13.2%, said Dr. Elena Lionetti of the department of pediatrics at the University of Catania, Italy, and her associates.

At 2 years of age, the proportion of children with overt celiac disease was significantly higher in the group in which gluten was introduced at 6 months (12%) than in the delayed-introduction group (5%). However, that difference quickly resolved, so that by age 5 and persisting through age 10, the proportions of children with overt celiac disease were the same (16%) in both study groups. This pattern was the same for the proportions of children with celiac disease autoimmunity.

In addition, “We did not detect an effect of breastfeeding on the development of celiac disease: the mean duration of breastfeeding was very similar for at-risk children among whom celiac disease developed and at-risk children in whom the disorder did not develop (5.6 and 5.8 months, respectively),” the investigators said.

The only factor that was significantly associated with the development of both celiac autoimmunity and overt celiac disease was carrying a high-risk HLA genotype. The type of relative with celiac disease, the number of affected relatives, the child’s dietary pattern, and the presence or absence of early intestinal infection all showed no association.

“Our findings do not support the ‘window of tolerance’ hypothesis” and instead indicate that early dietary factors seem to play a minor role in celiac disease risk, Dr. Lionetti and her associates noted (N. Engl. J. Med. 2014 Oct. 2 [doi:10.1056/NEJMoa1400697]).

In the European multicenter project Prevent Coeliac Disease (PreventCD), 963 high-risk infants aged 0-3 months were enrolled through celiac disease organizations in Croatia, Germany, Hungary, Israel, Italy, the Netherlands, Poland, and Spain. They were randomly assigned to receive either a small amount of wheat gluten (483 babies) or a matching placebo (480 babies) every day from 4 months through 6 months of age. The amount of gluten was equivalent to 2%-3% of that contained in a slice of bread.

At the conclusion of this intervention, parents were advised to introduce gluten gradually, in accordance with standardized recommendations. Parents also were allowed to breastfeed according to their own preferences, which permitted the researchers to assess several subgroups according to the duration and exclusivity of breastfeeding, said Dr. Sabine L. Vriezinga of the department of pediatrics at Leiden (the Netherlands) University Medical Center, and her associates.

The primary outcome of the trial – the frequency of celiac disease at age 3 years – was not significantly different between babies who received gluten (5.9%) and those who did not (4.5%). It also was no different among babies who were not breastfed, were breastfed for 3 or fewer months, were breastfed for 4-5 months, or were breastfed for 6 or more months. And it was not influenced by the country of origin; the number and type of affected relatives; the presence or absence of rotavirus vaccination; the presence or absence of early gastrointestinal or respiratory infections; or the mean dietary intake of gluten, the investigators said (N. Engl. J. Med. 2014 October 2 [doi:10.1056/NEJMoa1404172]).

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