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TOPLINE:

The early-life use of acid-suppressive therapy was significantly associated with an increased risk for celiac disease autoimmunity in a cohort analysis but not in a test-negative case-control analysis, with the association possibly confounded by healthcare utilization patterns.

METHODOLOGY:

• The early-life use of acid-suppressive therapy has increased globally over the past two decades, raising concerns about a related increased risk for celiac disease.
• Researchers conducted a retrospective study and included both a matched cohort and a test-negative case-control design to assess the association between the early-life use of acid-suppressive therapy and the risk for celiac disease autoimmunity.
• The early-life use of acid-suppressive therapy was defined as a purchase of either proton-pump inhibitors or histamine-2 receptor antagonists for at least 1 month during the first 6 months of life.
• The primary outcome was a diagnosis of celiac disease autoimmunity, determined via anti-transglutaminase 2 enzyme-linked immunosorbent assay. In the cohort study, the outcome was time to first positive test; in the test-negative design, the outcome was acid-suppressive therapy use.

TAKEAWAY:

• The cohort included 79,820 children (46.4% girls), with 19,955 having used acid-suppressive therapy. The test-negative case-control design included 24,684 children (62.2% girls), of whom 6176 tested positive and 18,508 tested negative for celiac disease autoimmunity.
• In the cohort analysis, the early-life use of acid-suppressive therapy was significantly associated with a higher risk for celiac disease autoimmunity (adjusted hazard ratio [AHR], 1.52), with a greater risk when used for more than 1 month (AHR, 1.65).
• The association between acid-suppressive therapy and celiac disease autoimmunity was also significant (AHR, 1.57), and even higher (AHR, 1.74) in those who used the therapy more than once.
• However, in the test-negative case-control design, no significant association was found between acid-suppressive therapy and testing positive for celiac disease autoimmunity (adjusted odds ratio, 1.07).
• These conflicting results suggest healthcare utilization behavior as a potential confounder in the observed association.

IN PRACTICE:

“We recommend that studies exploring associations using test results for outcomes in celiac disease should report a test-negative analysis as part of their results,” the authors wrote.

SOURCE:

This study was led by Tomer Achler, BMedSc, MPH, School of Medicine, Tel Aviv University Faculty of Medical and Health Sciences, Tel Aviv, Israel. It was published online in JAMA Network Open.

LIMITATIONS:

This study assessed celiac disease autoimmunity rather than biopsy-confirmed celiac disease. Additional limitations included its retrospective design, missing information about testing indications, and lack of behavior-related covariates that may have illuminated the observed associations.

DISCLOSURES:

This study did not report any source of funding. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.