Delays in gluten introduction, onset of celiac disease in at-risk infants linked

Among infants at-risk for celiac disease, delayed introduction of dietary gluten was associated with delayed onset of disease, according to new research data.

To explicate the correlation between age of introduction to dietary gluten and risk for celiac disease (CD), Elena Lionetti, MD, PhD, department of pediatrics at the University of Catania, Italy, and colleagues conducted a multicenter, prospective intervention trial (CELIPREV) between 2003 and 2008. They compared outcomes of infants with familial risk for CD who either had early or delayed introduction of gluten to their diet.

Elena Lionetti

Participants were randomly assigned to introduce gluten at age 6 months (group A) or 12 months (group B), and daily intake was assessed by a questionnaire. HLA genotype was determined at 15 months, CD serology was performed at 15, 24 and 36 months and at 5, 8 and 10 years. Patients who were seropositive for CD also had biopsy performed.

Among children (n=707) still participating at 36 months (group A, n=379; 49.6% girls; median age at study completion, 7.9 years), 553 had standard-risk or high-risk HLA genotypes and completed the study. At 2 years 16% of group A had CD autoimmunity and 12% had overt CD, compared with 7% and 5%, respectively, of group B (P=.002; P=.01). CD autoimmunity differences were no longer significant at 5 years (21% vs. 20%), nor was overt disease (16% vs. 16%). At 10 years risk for CD autoimmunity was 37.9% in high-risk HLA genotypes compared with 19.2% for standard-risk genotypes (HR=0.5; 95% CI, 0.3-0.7). Risk for overt disease was 25.8% among high-risk HLA genotypes vs. 15.8% for standard-risk genotypes (HR=0.6; 95% CI, 0.3-1).

“Postponing the introduction of gluten had two potentially positive consequences,” the researchers concluded. “First, it delayed the development of celiac disease, which might reduce the negative effect of the disease on vulnerable organs such as the brain. Second, it reduced the prevalence, albeit nonsignificantly, of celiac disease autoimmunity at any age among children carrying the high-risk HLA genotype.”

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, wrote that this and related studies “will change the conceptual landscape” of celiac disease. The CELIPREV researchers, they said, found “first, the timing of introduction of gluten in high-risk children does not appear to influence the development of CD in childhood. Second, there is no evidence that the duration of breast-feeding or the maintenance of breast-feeding when gluten is introduced influences the risk of CD later in life. Finally, the only identified risk factor for CD later in life is the HLA genotype.”

For more information:

Lionetti E. N Engl J Med. 2014;371:1295-1303.

Ludvigsson JF. N Engl J Med. 2014;371:1341-1343.

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