Early use of acid-suppressive therapy in infants may be associated with a higher rate of celiac disease autoimmunity in a cohort study of 79,820 children in Israel, although a second study design showed no clear link.
Investigators included children born between 2005 and 2020. They found that those who received acid-suppressive therapy (AST) during the first 6 months of life had a 52% higher risk of developing celiac disease autoimmunity (CDA) compared with those who didn't. The adjusted hazard ratio (HR) was 1.52 (95% confidence interval [CI] = 1.33–1.74).
“This study suggests that the association between early-life use of acid-suppressive therapy and development of [CDA] is suspected to be confounded by health care utilization behavior,” wrote lead study author Tomer Achler, BMedSc, MPH, of the Tel Aviv University, and colleagues.
AST included proton-pump inhibitors (PPI) such as omeprazole and histamine-2 receptor antagonists (H2RA) like ranitidine, defined as at least one prescription purchase.
Among 19,955 AST users, 1.6% of them tested positive for CDA compared with 1.0% among 59,865 nonusers (P < .001). The median age at CDA diagnosis was 4.7 years.
A separate test-negative case-control study involving 24,684 children found no statistically significant difference in AST use between those who tested positive for CDA (5.0%) and those who tested negative (4.6%). The adjusted odds ratio was 1.07 (95% CI = 0.94–1.23, P = .25).
The test-negative design helped control for health care–seeking behavior and suggested that the link seen in the cohort study might not be causal.
Longer AST use was associated with higher risk. Children with more than 1 month of AST use had an adjusted HR of 1.65 (95% CI = 1.34–2.03). Separate adjusted HRs were 1.57 for PPIs and 1.51 for H2RAs.
Children who used AST were also more likely to be tested for CDA, with testing rates of 44.9% among AST users compared with 32.1% among nonusers (P < .001). The adjusted HR for being tested was 1.57 (95% CI = 1.53–1.61).
Diagnosis of CDA was based on positive anti–transglutaminase 2 (TG2) immunoglobulin A antibody tests. Biopsy confirmation wasn't required, consistent with updated European and American guidelines.
The investigators noted that CDA rates and AST use have both risen in Israel in recent years. Higher socioeconomic status was associated with both higher AST use and more CDA testing.
The study had limitations, including reliance on serologic tests rather than biopsy and incomplete information on why CDA testing was performed.
The investigators recommended that future research on diseases diagnosed through testing should use a test-negative design. No competing interests were reported.
Source: JAMA Network Open