Earlier studies have found no effect of early introduction of gluten on the risk of developing CD, but those studies used a gluten dose of only 0.7 g/week, note Dr. Gideon Lack of King's College London and colleagues in JAMA Pediatrics.
In the Enquiring About Tolerance (EAT) study, the researchers compared exclusive breastfeeding with introduction of six allergenic foods, including gluten at 3.2 g/week, alongside breastfeeding to infants' diets from age 4 months. The current analysis includes 1,004 children who were tested for anti-transglutaminase type 2 (TG2) antibodies at age 3 years.
The median age at gluten introduction was 4 months in the early-introduction group versus 7 months in the control group. Between ages 4 and 6 months, the mean gluten consumption was 2.66 g/week in the early-introduction group and 0.49 g/week in the control group.
Gluten consumption in both groups increased after age 6 months and reached similar amounts by age 9 months.
Seven of 516 children (1.4%) in the control group had a diagnosis of CD confirmed by a pediatric gastroenterologist, compared with none of the 488 children tested in the early-intervention group (P=0.02).
All seven children diagnosed with CD had anti-TG2-antibody levels greater than or equal to 10 times above the reference range and were positive for endomysial antibodies. All five children who underwent HLA typing were positive for HLA-DQ2 or -DL8.
Six of the seven children developed gastrointestinal symptoms directly before the diagnosis, and all six experienced an improvement in symptoms after introduction of a gluten-free diet.
"The results of this analysis suggest that it may have been premature to discount the effect of age of introduction of gluten on the development of CD," the authors conclude. "The European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) also currently recommends the introduction of low doses of gluten initially despite limited evidence to support this recommendation, and the results from the EAT Study suggest that a higher dose may be an important prevention strategy."
Dr. Joseph A. Murray of Mayo Clinic, in Rochester, Minnesota, who has studied strategies of gluten introduction and their relationship to celiac disease, told Reuters Health by email, "This study is intriguing, but I would want to see them followed to age 10 years. I suspect that, over time, enough gluten is eaten that there may be catch-up."
"An important thing about this study is that it is a general-population sample, not a group with very high genetic risk like the other studies," he said. "That means that it is relevant to general advice, not just those with a family history."
Dr. Murray added, "The other thing that could be relevant is, they got several foods, not just gluten. It might have improved the microbiome to help tolerance in a nonspecific way."
Dr. Benjamin Lebwohl of The Celiac Disease Center at Columbia University, in New York City, told Reuters Health by email, "The results of this trial offer a glimmer of hope, after several negative trials, that we may one day develop an effective feeding-recommendation strategy to reduce the risk of developing celiac disease."
"The timing of gluten introduction may turn out to matter after all," he said. "It is possible that early exposure to gluten, if done at the right time and quantity, could be an effective prevention strategy. But it is premature to conclude that we have identified the precise strategy that will work."
"Though the results of this study are promising, there are some important caveats," Dr. Lebwohl said. "The follow-up time was short, and it is not clear that these results will endure in the long term. There were zero cases of celiac disease identified in the intervention arm, which is so unexpected that this needs to be replicated."
Neither Dr. Murray nor Dr. Lebwohl was involved in the trial.
By Will Boggs
SOURCE: https://bit.ly/3mXWBl5 JAMA Pediatrics, online September 28, 2020.
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