Use of Acid-Suppressing Meds During Pregnancy Not Linked to Offspring Allergy Risk, Study Finds

Use of histamine 2 receptor antagonists and other acid-suppressing medications (ASMs) during pregnancy was not associated with greater prevalence of allergic disease in offspring in a newly reported nationwide cohort study from South Korea.

Exposure to acid-suppressing medications during infancy was linked to greater asthma risk in the study, but the association was not as strong as those reported in several previously published, widely reported studies.

The findings, published online Jan. 9 in JAMA Pediatrics, have clinical implications for pediatricians and other clinicians caring for infants, wrote researcher Ju-Yung Shin, PhD, of Sungkyunkwan University in South Korea, and colleagues.

The researchers noted that ASMs are widely prescribed during pregnancy to treat gastroesophageal reflux disease (GERD), and they are also increasingly prescribed to pediatric populations.

They added that a "plausible biologic mechanism" may link the use of histamine 2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) to allergic disease.

"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," they wrote. "Moreover, ASMs may alter the composition and function of the gut microbiome, a known predictor of allergic diseases."

Multiple epidemiological studies have suggested a positive association between allergic diseases in offspring and ASM use during pregnancy and infancy, but the researchers noted that these studies "did not fully address confounding by indication and within-family shared factors."

"Given that asthma and GERD are often concomitant (up to 80% of patients with asthma have GERD) and asthma may induce GERD or vice versa, prior findings could have been confounded by GERD rather than showing a true association between allergic diseases and ASM use. Likewise, allergic diseases are highly heritable and affected by familial factors (e.g., genetic and environmental factors); thus, lack of adjustment for familial factors is another potential source of bias," they wrote.

In an effort to address confounding and other limitations in past studies examining prenatal and early-life ASM exposure and allergic disease, the researchers conducted a nationwide, cohort study using data from South Korea’s National Health Insurance Service mother-child–linked database from Jan. 1, 2007, to Dec. 31, 2020.

Propensity scoring (PS) was used to adjust for potential confounding, including clinical indications for ASM use (e.g., GERD), and sibling-matched analyses were conducted to explore the influence of factors shared within families.

Participants included mother-child pairs of neonates born from April 1, 2008, to Dec. 31, 2019.

Approximately 4.1 million mother-child pairs were included in the analysis, with 808,067 propensity-score matched pairs included in the prenatal exposure analysis.

In the prenatal-use analysis, "the PS-matched HR was 1.01 (95% CI, 1.01-1.02) for allergic diseases overall (asthma: HR, 1.02 [95% CI, 1.01-1.03]; allergic rhinitis: HR, 1.02 [95% CI, 1.01-1.02]; atopic dermatitis: HR, 1.02 [95% CI, 1.01-1.02]; food allergy: HR, 1.03 [95% CI, 0.98-1.07])."

Analyses matching sibling pairs showed similar hazard ratios (HRs) to the PS-matches analyses (allergic diseases: HR, 1.01; 95% CI, 0.997-1.01).

"Infant exposure analyses included 84 263 PS-matched pairs (74 188 received H2RAs, 7496 received PPIs)," the study authors wrote. "The PS-matched HR was 1.06 (95% CI, 1.05-1.07) for allergic diseases overall (asthma: HR, 1.16 [95% CI, 1.14-1.18]; allergic rhinitis: HR, 1.02 [95% CI, 1.01-1.03]; atopic dermatitis: HR, 1.05 [95% CI, 1.02-1.08]; food allergy: HR, 1.28 [95% CI, 1.10-1.49]); asthma risk (HR, 1.13; 95% CI, 1.09-1.17) remained significantly higher among children exposed to ASMs during infancy in sibling-matched analyses. The findings were similar for H2RAs and PPIs analyzed separately and were robust across all sensitivity analyses."

The large sample size was cited by the researchers as a study strength, while limitations included the potential for exposure and outcome misclassification, incomplete data on maternal smoking status and other risk factors for pediatric allergy, and the inclusion of only South Korean parent-child pairs in the cohort.

The researchers noted that the latter limitation may at least partially explain the smaller association between infant ASM exposure and allergic disease than associations reported in other studies.

Funding for this study was provided by the National Research Foundation of Korea and the Ministry of Food and Drug Safety of South Korea. Shin reported receiving grants from the National Research Foundation of Korea, the Ministry of Food and Drug Safety, the Ministry of Health and Welfare, the government-wide R&D fund for infectious disease research, Daiichi Sankyo, GSK, and Pfizer outside the submitted work.

Noh Y, et al "Prenatal and infant exposure to acid-suppressive medications and risk of allergic diseases in children" JAMA Pediatr 2023: DOI: 10.1001/jamapediatrics.2022.5193.