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TEL AVIV, Israel – April 20, 2025 – Research led by Tel Aviv University has produced conflicting findings regarding a potential link between the use of acid-suppressing medications in early infancy and the later development of celiac disease autoimmunity. While one part of the study suggested an increased risk, another analysis failed to confirm a significant association, highlighting the complexity of establishing a definitive connection.
The study, published in JAMA Network Open, investigated the increasingly common practice of prescribing acid-suppressive therapies, such as proton-pump inhibitors (PPIs) like omeprazole (Prilosec) and histamine-2 receptor antagonists (H2RAs) like ranitidine (Zantac), to infants within their first six months of life. Previous observational studies had hinted at potential long-term adverse effects, including fractures and celiac disease.
Celiac disease is an immune disorder where consuming gluten leads to damage in the small intestine. Its prevalence has been rising in many parts of the world. Researchers hypothesized that acid suppressants might contribute to its development by interfering with protein digestion and altering the gut microbiome.
To explore this, the researchers employed two different retrospective observational methods using population-level data from Maccabi Healthcare Services, which covers a significant portion of the Israeli population. Data included children born between 2005 and 2020.
In the first approach, a matched cohort study involving 79,820 children, researchers compared those who received acid suppressants in the first six months (19,955 infants) with those who did not. This analysis found that 1.6% of infants exposed to the medication developed celiac disease autoimmunity, compared to 1.0% of unexposed infants. After adjusting for other factors, this represented a 52% higher risk (adjusted hazard ratio of 1.52) for those who took the medication. The association was even stronger for infants who used the therapy for more than one month (adjusted hazard ratio of 1.65).
However, a second analysis using a test-negative case-control design yielded different results. This part involved 24,684 children who had undergone testing for celiac disease autoimmunity. Among those who tested positive, 5.0% had used acid suppressants in early infancy, while 4.6% of those who tested negative had used them. The calculated adjusted odds ratio was 1.07, which was not statistically significant, meaning this analysis did not find a clear link between medication use and a positive test result.
The authors of the study, titled “Early-Life Exposure to Acid-Suppressive Therapy and the Development of Celiac Disease Autoimmunity,” acknowledge the discrepancy. They suggest the positive association found in the cohort study might be influenced by residual confounding – factors not fully accounted for, such as the underlying reasons why some infants received the medication or were later tested for celiac disease.
Ultimately, the research underscores the challenges of drawing firm conclusions from observational data alone. While the cohort study suggests a possible association worthy of further investigation, the lack of confirmation in the test-negative analysis means the question of whether early-life acid suppressant use truly increases celiac disease risk remains unanswered.
Disclaimer: This news article is based on findings reported in a study published in JAMA Network Open (“Early-Life Exposure to Acid-Suppressive Therapy and the Development of Celiac Disease Autoimmunity,” Tomer Achler et al.). Observational studies like this can identify associations but cannot definitively prove cause and effect due to potential limitations and confounding factors. The results presented are mixed and inconclusive. This information should not replace professional medical advice. Always consult with a healthcare provider regarding medical conditions or treatment decisions.
