Infant exposure to acid-suppressive medications linked to modest asthma risk

Researchers found no association between prenatal exposure to acid-suppressive medications and risk for allergic diseases in children, according to a study published in JAMA Pediatrics.

Infants exposed to these medications had a higher risk for developing asthma, although this risk was not as large as previously reported, Yunha Noh, PharmD, PhD, postdoctoral fellow in the School of Pharmacy at Sungkyunkwan University in Suwon, South Korea, and colleagues wrote.

The study involved 4,149,257 mother-child pairs from South Korea’s National Health Insurance Service database, including children born between April 1, 2008, and Dec. 31, 2019.

Researchers used propensity scores to match and compare individuals who were and were not exposed to acid-suppressive medications (ASMs) for prenatal exposure and infant exposure analyses. They also compared matched children who were and were not exposed with siblings to explore genetic, lifestyle and social confounders shared by families.

Researchers defined ASM exposure as one or more prescriptions for a proton pump inhibitor (PPI) or histamine 2 receptor antagonist (H2RA) at any time during pregnancy for prenatal analyses and during the first 6 months of life for infant exposures.

Prenatal exposure

Propensity score matching resulted in 808,067 pairs of exposed and unexposed women (mean age, 31.8 years; standard deviation, 4.2), including 763,755 women who received H2RAs and 36,529 who received PPIs.

After mean follow-up of 2.6 years, incidence rates of allergic diseases per 1,000 person-years included 306.1 for children with prenatal exposure and 300.7 for those without prenatal exposure, for a difference of 5.4 per 1,000 person-years.

Researchers calculated propensity score-matched hazard ratios of 1.01 (95% CI, 1.01-1.02) for allergic diseases overall, 1.02 (95% CI, 1.01-1.03) for asthma, 1.02 (95% CI, 1.01-1.02) for allergic rhinitis, 1.02 (95% CI, 1.01-1.02) for atopic dermatitis and 1.03 (95% CI, 0.98-1.07) for food allergy.

Results of the sibling-matched analysis of prenatal exposure, which included 630,940 mother-child pairs, resembled those of the propensity score-matched analysis but did not reach statistical significance (HR for allergic diseases overall = 1.01; 95% CI, 0.997-1.01).

Infant exposure

Infant exposure analyses included 84,263 propensity score-matched pairs, including 74,188 infants who received H2RAs and 7,496 who received PPIs.

After mean follow-up of 3.5 years for exposed infants and 3.6 years for unexposed infants,

incidence rates of allergic diseases per 1,000 person-years included 218.1 for exposed infants and 205.2 for unexposed infants, for a difference of 12.8 per 1,000 person-years.

HRs in this cohort included 1.16 (95% CI, 1.14-1.18) for asthma and 1.28 (95% CI, 1.1-1.03) for food allergy, which researchers called moderate increases, as well as 1.02 (95% CI, 1.01-1.03) for allergic rhinitis, 1.05 (95% CI, 1.02-1.08) for atopic dermatitis, and 1.06 (95% CI, 1.05-1.07) for allergic diseases overall.

In the sibling-matched analysis, asthma risk (adjusted HR = 1.13; 95% CI, 1.09-1.17) remained significantly higher among exposed children, but there was no significant difference in risk for food allergy.

Additionally, the researchers found that separate comparisons of participants who used H2RAs or PPIs appeared similar and robust across all sensitivity analyses.

Implications

Based on these findings, the researchers concluded that there is no association between prenatal exposure to ASMs and risk for allergic diseases. Exposure during infancy appeared associated with a greater risk for asthma, the researchers continued, but this risk was more modest than indicated by previous studies.

The researchers advised clinicians to carefully weigh the benefits of prescribing ASMs to children against this small but potential risk for asthma and then closely monitor their patients for clinically relevant safety signals.