Children who were genetically susceptible to celiac disease and consumed high amounts of gluten at 12 months of age were at least twice as likely to develop the autoimmune disorder as genetically predisposed children who consumed less gluten, researchers reported in the March issue of Clinical Gastroenterology and Hepatology.

The association was similar among children who carried any of the major human leukocyte antigen (HLA) risk genotypes for celiac disease, said Dr. Carin Aronsson at Lund University in Sweden and her associates. “Because these HLA risk genotypes are widely distributed in the general population, these findings may have consequence for future infant feeding recommendations,” they said. They recommended repeating the study in other countries to confirm the link.

In order to develop celiac disease, patients must consume gluten and carry at least one of the relevant DR3-DQ2 and DR4-DQ8 HLA risk haplotypes. But because gluten is widely consumed in products containing wheat, rye, and barley, and because about half of whites have at least one of the two haplotypes, gluten intolerance probably depends on other environmental factors, the researchers said. To further study these factors, they compared 3-day food diaries collected at ages 9, 12, 18, and 24 months for 146 children with positive tissue transglutaminase autoantibody (tTGA) assays and biopsy-confirmed celiac disease (cases) and 436 tTGA-negative children (controls). Cases and controls were matched by age, sex, and HLA genotype (Clin Gastroenterol Hepatol. 2015 Oct 7. doi: 10.1016/j.cgh.2015.09.030 ).

The food diaries revealed higher gluten intake among cases, compared with controls, beginning at the age of 12 months, said the researchers. Notably, cases consumed a median of 4.9 g of gluten a day before tTGA seroconversion, 1 g more than the median amount for controls of the same age (odds ratio, 1.3; 95% confidence interval, 1.1-1.5; P = .0002). Furthermore, significantly more cases than controls consumed the highest tertile of gluten, more than 5 g per day, before seroconversion (OR, 2.7; 95% CI, 1.7-4.1; P less than .0001). These associations were similar among children of all haplotype profiles and trended in the same direction among children with and without first-degree relatives with celiac disease.

Cases and controls resembled each other in terms of breastfeeding duration, age at first introduction to gluten, and total daily caloric intake, the investigators noted. “The prospective design of this birth cohort study enabled us to obtain the diet information before seroconversion of tTGA as a marker of celiac disease,” they said. “This eliminated the risk of reporting biases or a change in feeding habits because of the knowledge of serology results or disease status.” But they did not analyze the number of daily servings of foods that contained gluten. “We cannot exclude the possibility that the number of portions given frequently during the course of the day may have different effects on disease risk,” they said.

The National Institutes of Health, Juvenile Diabetes Research Foundation, and the Centers for Disease Control and Prevention funded the study. The investigators had no disclosures.


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