Use of Acid-Suppressive Medications in Infants May Lead to Allergic Diseases

While there was no association between prenatal exposure to acid-suppressive medications and allergic diseases in kids, infant exposure was linked to a higher risk of developing asthma, a South Korean nationwide cohort study showed.

Among over 84,000 pairs of infants exposed and unexposed to proton pump inhibitors (PPIs) and histamine 2 receptor antagonists (H2RAs), the propensity score-matched hazard ratio for risk of asthma was moderately increased (HR 1.16, 95% CI 1.14-1.18), as was the risk for food allergy (HR 1.28, 95% CI 1.10-1.49), reported Ju-Young Shin, PhD, of Sungkyunkwan University in South Korea, and co-authors.

However, risks were not substantially increased for allergic diseases overall (HR 1.06, 95% CI 1.04-1.07), allergic rhinitis (HR 1.02, 95% CI 1.01-1.03), or atopic dermatitis (HR 1.05, 95% CI 1.02-1.08), they noted in JAMA Pediatrics.

Furthermore, Shin and team found no meaningful associations between prenatal exposure to acid-suppressive medications and risk of allergic diseases, with propensity score-matched hazard ratios for prenatally exposed children versus unexposed children ranging from 1.01 to 1.02 (95% CI 1.01-1.03) for allergic diseases overall, asthma, allergic rhinitis, and atopic dermatitis.

“There is a plausible biological mechanism for the association of ASMs [acid-suppressive medications] with allergic diseases,” the authors wrote. “Acid-suppressive medications may interfere with the digestion of food antigens, resulting in the sensitization of the immune system to predispose children to allergic diseases. Moreover, ASMs may alter the composition and function of the gut microbiome, a known predictor of allergic diseases.”

“However, existing studies did not account for potential confounding by indication and within-family shared factors, which are important factors associated with allergic diseases,” they continued. “In the current study, which controlled for numerous potential confounders, including indications (e.g., GERD [gastroesophageal reflux disease]), we found no meaningful associations between prenatal ASM use and allergic diseases in offspring.”

Moreover, while they did find a higher risk of allergic diseases associated with infant use, “the risk was substantially lower than in existing literature,” they added.

This cohort study included data from the National Health Insurance Service database in South Korea on mother-child pairs from January 2007 through December 2020.

Prenatal exposure analyses included 808,067 propensity score-matched pairs of mothers; 763,755 received H2RAs and 36,529 received PPIs. Mean age was 31.8 years.

The infant exposure analyses included 84,263 pairs of infants exposed (mean follow-up 3.5 years) and unexposed (mean follow-up 3.6 years) to acid-suppressive medications. Infants who were diagnosed with respiratory conditions, severe liver failure, heart failure, or primary immunodeficiency disease in the first 6 months of life, and those who had been followed for less than 1 year after birth, were excluded.

Exposure to acid-suppressive medications was defined as one or more prescriptions for a PPI or H2RA.

Sibling-matched cohorts were also created to address unmeasured, within-family genetic, lifestyle, and social confounders and their effect on the development of allergic diseases. Siblings who had different levels of medication exposure were identified. The increased risk for asthma development remained high within the sibling-matched cohort (HR 1.13, 95% CI 1.09-1.17), whereas the risk for development of other allergic diseases remained the same (HR 1.01, 95% CI 0.997-1.01).

Shin and colleagues noted that exposure misclassification was possible, since they could not determine whether patients actually took the prescribed medication. Furthermore, outcome misclassification was also possible since outcomes were based on relevant ICD-10 diagnosis codes.