Early gluten exposure failed to reduce celiac disease risk in high-risk children

Exposing infants with high risk for celiac disease to gluten at age 4 to 6 months did not reduce risk for developing the disease by age 3 years, according to recent study data.

To test the hypothesis that celiac disease may be prevented by exposing genetically predisposed, preferably breast-fed, infants aged 16 to 24 weeks to small quantities of gluten, M. Luisa Mearin, MD, PhD, pediatric gastroenterologist and associate professor of pediatrics at the University of Leiden, and colleagues collaborated in a prospective, multinational dietary-intervention study (PreventCD) from May 2007 to September 2013. HLA-DQ2- or HLA-DQ8-positive children with one or more first-degree relatives with celiac disease were randomly assigned to 100 mg gluten daily (n=475) or placebo (n=469) at age 16 to 24 weeks. Participants were then followed until age 3 years, and serum antibodies associated with celiac disease were measured periodically throughout follow-up.

M. Luisa Mearin

Celiac disease was diagnosed by small-bowel biopsy in 77 children. To avoid underestimation, researchers included three additional children diagnosed with celiac disease based on ESPGHAN criteria, totaling 80 diagnoses (median age, 2.8 years; 58% girls). By age 3 years, cumulative incidence was 5.2% (95% CI, 3.6-6.8), with 5.9% (95% CI, 3.7-8.1) in the gluten group and 4.5% (95% CI, 2.5-6.5) in the placebo group (gluten group HR=1.23; 95% CI, 0.79-1.91). Elevated celiac antibody levels also were similar between groups, with 7% (95% CI, 4.7-9.4) in the gluten group compared with 5.7% (95% CI, 3.5-7.9) in the placebo group (HR=1.14; 95% CI, 0.76-1.73). Breast-feeding did not significantly influence outcomes (P=.28).

“Our results indicate that the early introduction (at 16 weeks of age) of small quantities of gluten did not reduce the risk of celiac disease at 3 years of age in genetically predisposed children from high-risk families,” the researchers wrote. “Therefore, our results do not support the protective effect that we had hypothesized.”

“Since a second increase in diagnoses before puberty is expected, it is essential to continue the follow-up up of this unique cohort of children,” Mearin told Healio.com/Gastroenterology “The PreventCD group is motivated to continue the project and is looking for research funding bodies to make this possible. We will also study material obtained during the study, including serum, peripheral blood cells and small bowel biopsies, trying to understand how celiac disease develops in these very young children. Although the results of our study increase our knowledge of celiac disease, we find ourselves at the beginning of research concerning prevention of the disease.”

Jonas F. Ludvigsson

In an accompanying editorial, Jonas F. Ludvigsson, MD, PhD, from Karolinska Institutet and Örebro University Hospital, Sweden, and Peter H.R. Green, MD, from the Celiac Disease Center at Columbia University, College of Physicians and Surgeons, commented on the PreventCD study and the related CELIPREV trial. They said although both studies “differ on important points and yield slightly different information … their main findings do agree,” and will likely “alter the treatment of children who are at increased risk” for celiac disease. “From now on, it will be hard for anyone to continue to recommend the introduction of gluten specifically at the age of 4 to 6 months, since Vriezinga et al did not find that exposure to gluten at this age decreased the risk of celiac disease.” – by Adam Leitenberger

For more information:

Ludvigsson JF. N Engl J Med. 2014;371:1341-43.

Vriezinga SL. N Engl J Med. 2014;371:1304-15.

Disclosure: See the study for a full list of relevant financial disclosures.