Early Gluten Intake Tied to Celiac Risk in Predisposed Children

By Will Boggs MD

August 15, 2019

NEW YORK (Reuters Health) - Higher gluten intake during the first five years of life appears to be associated with an increased risk of celiac disease autoimmunity and celiac disease in genetically predisposed children, according to findings from the TEDDY study group.

Gluten consumption and certain HLA antigen genotypes contribute to celiac disease development, but it remains unclear whether the amount of gluten consumed triggers celiac disease.

For their analysis, published August 13 in JAMA, Dr. Daniel Agardh from Lund University, in Malmoe, Sweden, and colleagues from six centers in Finland, Germany, Sweden and the U.S. used data from 6,605 genetically at-risk children in The Environmental Determinants of Diabetes in the Young (TEDDY) prospective birth cohort study.

They assessed the link between gluten intake in the first five years of life and celiac disease autoimmunity, as determined by positive tissue transglutaminase (tTG) autoantibodies in two consecutive serum samples, or celiac disease diagnosed by a positive intestinal biopsy or, in the absence of a biopsy, an average tTG autoantibody level of 100 units or more.

Overall, 21% tested positive for tTG autoantibodies at least once, 18% developed celiac disease autoimmunity (at a median age of 3.3 years) and 7% developed celiac disease (seroconverted at a median age of 3.0 years).

The risk of celiac disease autoimmunity and celiac disease was highest among children homozygous for HLA DR3-DQ2 and those with Swedish residence, female sex and a family history of celiac disease.

Each 1-g/day increase in gluten consumption was associated with a 30% increased risk of celiac disease autoimmunity and a 50% increased risk of celiac disease by age 3, both significant findings.

In post hoc analysis, gluten consumption greater than 2 g/day at 2 years of age was associated with a 49% higher risk of celiac disease autoimmunity (P=0.002) and a 75% higher risk of celiac disease (P=0.02) compared with gluten consumption of 2 g/day or less.

"The finding of a cutpoint at which gluten intake was associated with an increased risk is relevant for gluten feeding recommendations in at-risk children," the researchers note. "However, this conclusion was based on a post hoc analysis and should be confirmed."

Dr. Maureen M. Leonard from MassGeneral Hospital for Children in Boston, who co-authored a linked editorial, told Reuters Health by email, said it was surprising how much a small amount of gluten - "just 2 grams of gluten, or approximately 1 slice of bread (or less)" - can affect risk.

"While future studies are needed to confirm the findings, this study shows that 7% of children with HLA-compatible genetics developed celiac disease during the study, and the peak incidence for celiac disease diagnosis was between 2 and 3 years of age," she said. "Thus, the incidence of celiac disease is very high in this cohort and develops quite early."

If prospective studies support the findings, she said, "it would suggest that genetic screening for HLA genotype is warranted in children in order to guide early child feeding practices."

Dr. Leonard added, "Future studies are needed to confirm these findings before a recommendation is made to change the current practice of gluten introduction into a child's diet. A diet rich in whole grains, fiber, and fruits and vegetables is suggested."

Dr. Paula Crespo-Escobar of European University Miguel de Cervantes, in Valladolid, Spain, who has also examined the role of gluten intake at an early age in the development of celiac disease, told Reuters Health by email, "I think that we have to be very cautious interpreting these results from a clinical point of view."

"We can recommend to introduce the gluten progressively, not in huge quantities," said Dr. Crespo-Escobar, who was not involved in the new work. "But I don't consider it practical to establish exact amounts of gluten for introduction, when we have other studies with different results."

Dr. Ron Shaoul of Technion Faculty of Medicine and Ruth Children's Hospital, in Haifa, Israel, who recently reviewed gluten intake limits in the treatment of celiac disease, said the findings bolster previous research from Sweden showing a link between gluten intake at a young age and the risk of celiac disease.

"The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) committee of nutrition already suggested limiting the amount of gluten during infancy based on these studies, and this should now be universally implemented," Dr. Shaoul, who was not involved in the study, told Reuters Health by email.

"Although HLA testing is not universal, pediatricians and family practitioners definitely need to track high-risk populations and to instruct the parents to limit their gluten intake during complementary food introduction and later through infancy," he said.

Dr. Karl Marild from Sahlgrenska Academy and Queen Silvia Children's Hospital, Gothenburg, Sweden, who studies celiac disease, told Reuters Health by email, "While this is a very well-conducted and large study, it has an observational study design, and hence I would not recommend to change the advice on childhood feeding practices before these results are confirmed in a randomized clinical trial. Even in well-conducted observational studies, one can never rule out the risk of non-causal explanations, related to, for example, unmeasured or residual confounding."

"Although the presented results are very convincing in themselves, previous studies in this field have shown inconsistent results, and they seem to vary across countries (also in this study, the results varied somewhat across study sites)," said Dr. Marild, who also was not involved in the research. "It is possible that the amount of gluten acts together with other environmental risk factors to increase the risk of celiac disease, and that the difference in exposure to these environmental triggers explains some of the differences found in celiac risk across countries/study sites."

He added, "It is very difficult to accurately derive the amount of gluten intake from food; there is no gold-standard, which makes it difficult to study this exposure."

Dr. Agardh did not respond to a request for comments.

SOURCE: http://bit.ly/33vFZYb and http://bit.ly/33wqhvT

JAMA 2019.