A modest risk of developing asthma is associated with infant exposure to acid-suppressive medication (ASM); however, no association exists between prenatal exposure to ASMs and allergic diseases in offspring, according to study findings published in the Journal of the American Medical Association Pediatrics.

Gastroesophageal reflux disease is frequently treated during pregnancy with histamine 2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs). Given the prevalence and increase in allergic diseases, investigators in South Korea sought to assess the association of prenatal or infant exposure to ASMs with allergic disease risk in children.

The researchers assessed 2 types of exposure to H2RAs and PPIs: infant exposure (ie, 1 or more ASM prescriptions during the first 6 months of life) and prenatal exposure (ie, 1 or more ASM prescriptions at any time during pregnancy). Women who had no ASM prescription from 30 days before pregnancy to the delivery date represented the prenatal comparative group, and infants having no ASM prescription during the first 6 months of life represented the infant comparative group.

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The investigators conducted a nationwide cohort study using data from South Korea’s National Health Insurance Service mother-child-linked database, which included 4,149,257 mother-child pairs of neonates (live births) born from April 2008 through December 2019. Children were followed up to 13 years of age and assessed for asthma, atopic dermatitis, food allergy, and allergic rhinitis. The researchers used propensity score (PS)-matched and sibling-matched analyses, hazard ratios, and Cox proportional hazards regression models.

After finding that 881,639 infants in the database were prenatally exposed to ASM, researchers created 808,067 PS-matched (1:1) pairs (with 763,755 receiving H2RAs and 36,529 receiving PPIs) that were included in prenatal exposure analyses (mean [SD] age of mothers, 31.8 [4.2]). Mean follow-up was 2.6 [2.7] years for exposed and comparative groups. The PS-matched hazard ratios (HRs) for prenatal ASM exposure were as follows: overall allergic diseases HR, 1.01 (95% CI, 1.01-1.02); asthma HR, 1.02 (95% CI, 1.01-1.03); atopic dermatitis HR, 1.02 (95% CI, 1.01-1.02); food allergy HR, 1.03 (95% CI, 0.98-1.07); and allergic rhinitis HR, 1.02 (95% CI, 1.01-1.02). In sibling-matched analyses, similar to the PS-matched analyses, investigators found nonsignificant HRs (allergic diseases HR, 1.01; 95% CI, 0.997-1.010).

After finding that 84,380 infants in the database were exposed to ASMs during early infancy, investigators included 84,263 matched pairs in infant exposure analyses (with 74,188 receiving H2RAs and 7496 receiving PPIs). Mean follow-up was 3.5 (2.8) years (exposed group) and 3.6 (2.8) years (comparative group). The PS-matched HRs for infant ASM exposure were as follows: overall allergic diseases HR, 1.06 (95% CI, 1.05-1.07); asthma HR, 1.16 (95% CI, 1.14-1.18); atopic dermatitis HR, 1.05 (95% CI, 1.02-1.08); food allergy HR was 1.28 (95% CI, 1.10-1.49); and allergic rhinitis HR, 1.02 (95% CI, 1.01-1.03). In sibling-matched analyses, asthma risk remained significantly higher among children exposed to ASMs during infancy (HR, 1.13; 95% CI, 1.09-1.17). When analyzed separately, results were similar for H2RAs and PPIs, robust across all sensitivity analyses. Inconsistent findings between overall and sibling cohorts suggests familial confounding in the overall cohort.

Study limitations include exposure misclassification given the uncertainty of prescribed ASMs actually taken; possible exposure misclassification due to the potential use of over-the-counter low-dose H2RAs; possible outcome misclassification from use of ICD-10 codes; unaccounted-for factors that may have affected the risk of study outcomes; protopathic bias; and residual confounding from socioeconomic status, disease severity, and microbiome or environmental data.

“We found no meaningful associations between prenatal exposure to ASMs and risk of allergic diseases in offspring in both PS-matched and sibling-matched analyses,” investigators concluded. They wrote “Infant exposure to ASMs was associated with a higher risk of developing asthma, although the magnitude was more modest than previously reported.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Noh Y, Jeong HE, Choi A, et al. Prenatal and infant exposure to acid-suppressive medications and risk of allergic diseases in childrenJAMA Pediatr. Published online January 9, 2023. doi:10.1001/jamapediatrics.2022.5193

This article originally appeared on Pulmonology Advisor