A comprehensive Israeli study on early acid-suppressive medication use in infants has uncovered conflicting results that highlight how research methodology can significantly impact our understanding of celiac disease risk factors.
At a Glance
- Research examining 79,820 children found seemingly contradictory results depending on study design
- In cohort analysis, acid-suppressive therapy in the first 6 months of life appeared to increase celiac disease autoimmunity risk by 52%
- When using a test-negative case-control design, no significant association was found
- Researchers suggest healthcare utilization behavior—not the medications themselves—may explain the cohort study’s findings
- The study emphasizes the importance of controlling for confounding variables in medical research
Understanding the Research Approach
Researchers from Tel Aviv University have conducted an extensive study investigating whether acid-suppressive medications given to infants might influence their risk of developing celiac disease autoimmunity. The investigation, led by Tomer Achler and published in JAMA Network Open, examined data from Maccabi Healthcare Services in Israel, analyzing records from nearly 80,000 children. What makes this study particularly valuable is its dual methodological approach, which revealed how research design can dramatically affect outcomes.
The research team defined acid-suppressive therapy as the use of proton-pump inhibitors or histamine-2 receptor antagonists within the first six months of life. They measured celiac disease autoimmunity through positive anti-transglutaminase 2 enzyme-linked immunosorbent assay tests, a standard diagnostic indicator for the condition. By following ethical approval guidelines and adhering to STROBE reporting standards, the researchers ensured methodological rigor throughout the investigation.
Conflicting Results Based on Study Design
When analyzed using a traditional cohort study approach, the data showed a concerning association: children who received acid-suppressive medications in early infancy had a celiac disease autoimmunity rate of 1.6%, compared to just 1.0% among non-users. The adjusted hazard ratio of 1.52 suggested these medications might increase the risk by more than 50%. This finding would naturally concern parents and healthcare providers about prescribing such medications to infants.
However, when the same data was examined using a test-negative case-control design—a method specifically chosen to control for healthcare utilization behaviors—the results told a different story. This alternative analysis yielded an adjusted odds ratio of 1.07, showing no statistically significant association between the medications and celiac disease autoimmunity. This striking discrepancy between the two approaches raised important questions about what was really being measured.
The Hidden Influence of Healthcare Behavior
The researchers concluded that the association found in the cohort study likely reflected confounding factors rather than a direct pharmacological effect. Specifically, children who receive acid-suppressive medications may have parents who seek medical care more frequently and are more vigilant about health concerns. This increased interaction with the healthcare system naturally leads to more testing and a higher likelihood of receiving various diagnoses, including celiac disease autoimmunity.
The research team acknowledged several limitations to their work. The study focused on celiac disease autoimmunity rather than biopsy-confirmed celiac disease, employed a retrospective design, and couldn’t account for all potential behavior-related covariates. Despite these limitations, the findings demonstrate the critical importance of considering how research design can influence medical conclusions and highlight the value of using multiple methodological approaches to verify findings.
Implications for Patients and Healthcare Providers
For adults with health concerns, particularly those over 40 who may be caring for both children and aging parents, this study offers a valuable lesson in interpreting medical research. When reading about health risks, it’s important to consider whether associations might be explained by factors beyond direct biological effects. In the case of acid-suppressive medications and celiac disease, the evidence does not support restricting these medications when medically necessary for infants.
The study also demonstrates why researchers are increasingly using multiple analytical approaches to ensure their findings are robust. The authors specifically recommend including test-negative analysis in future studies exploring celiac disease associations to better control for healthcare utilization patterns. This methodological insight may lead to more accurate understanding of true risk factors for celiac disease and other autoimmune conditions.
