Celiac Disease Linked to Infant Infections

Emma Hitt, PhD

December 20, 2012

Infections among children younger than 2 years may be linked to an increased risk for celiac disease, according to a new study conducted in Sweden.

Anna Myléus, MD, PhD, from the University of Umeå, Sweden, and colleagues report their findings in an article published online December 19 and in the December 2012 issue of Biomedcentral Pediatrics.

"This study suggests that having repeated infectious episodes early in life increases the risk for later celiac disease," Dr. Myléus and colleagues conclude. "In addition, we found a synergistic effect between early infections and daily amount of gluten intake, more pronounced among infants when breastfeeding had been discontinued prior to gluten introduction," they add.

According to the researchers, between 1984 and 1996, in Sweden, the incidence of celiac disease increased 4-fold in children younger than 2 years and then declined again after that.

"The reasons behind the epidemic are still not fully understood," the authors note, although they suggest that infections may play a role.

"Gastroenteritis increases gut permeability and subsequent gluten penetration, which could convey an increased risk for celiac disease," they write.

The current study sought to investigate the association between celiac disease and infections by comparing cases of celiac disease diagnosed in children younger than 2 years with referents selected at random from a national population register after fulfilling matching criteria. All new reported cases were invited between 1992 and 1995, when the register encompassed 40% of the Swedish child population.

Parents of children with celiac disease and referent participants provided information via a questionnaire regarding family characteristics, infant feeding, and overall health of the child. The final analyses included 954 children with complete information, including 373 (79%) children with celiac disease and 581 (61%) referent participants.

The occurrence of at least 3 infectious episodes, regardless of type of infection, during the first 6 months of life was associated with a significantly increased risk for later celiac disease, a finding that held true after adjusting for both infant feeding and socioeconomic status (odds ratio [OR] 1.5; 95% confidence interval [CI], 1.1 - 2.0; P = .009).

Furthermore, a synergistic association was observed if large quantities of dietary gluten were introduced to infants' diet after stopping breast-feeding (OR, 5.6; 95% CI, 3.1 - 10; P < .001 for larger vs lesser quantities of gluten).

They authors note that they did not observe a significantly increased celiac disease risk resulting from parental-reported gastroenteritis, possibly because of the small number of children with this specific infection. However, the finding with nongastrointestinal infections "suggests that infections, irrespective of localization, affect celiac disease risk, although the molecular mechanisms behind this finding remain to be clarified."

The authors speculate that changes in microbiota as a result of infections may trigger immune system and mucosal barrier changes that could contribute to celiac disease risk. In addition, antibiotic use may play a role.

The authors have disclosed no relevant financial relationships.

BMC Pediatrics. Published online December 19, 2012. Abstract