Infectious Disease

Use of acid suppressant medications in infancy raises childhood risk for wheeze, asthma

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Infants exposed to acid suppressant medications did not experience an increased risk for allergen sensitization in early childhood, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice.

But they did show an increased risk for recurrent wheeze and asthma, Lacey B. Robinson, MD, MPH, an allergist/immunologist with the division of rheumatology, allergy and immunology at Massachusetts General Hospital, and colleagues wrote in the study.

Data were derived from Robinson LB, et al. J Allergy Clinic Immunol Pract. 2022;doi:10.1016/j.2022.07.013.

“Prenatal exposure to acid suppressant medications (ASMs) has been associated with increased risk of childhood asthma, but less is known about the risks of exposure in early infancy,” Robinson told Healio. “We performed this study to better understand these associations.”

There is little evidence for their efficacy and the American Academy of Pediatrics recommends limited use, according to the researchers, but ASMs such as proton pump inhibitors and histamine-2 receptor agonists often are administered to infants for gastroesophageal reflux and GERD.

The study involved 920 participants (30% aged younger than 2 months; 40% girls; 43% non-Hispanic white) in the ongoing 35th Multicenter Airway Research Collaboration multicenter cohort study enrolled during a hospitalization for bronchiolitis during the winters of 2011 through 2014.

According to the researchers, 202 (22%) were exposed to ASMs during infancy. Of them, 178 had data on their exposure duration, with a median duration of ASM use of 13.7 weeks (interquartile range [IQR]4-31).

Also, 177 of the 202 infants with ASM exposure had a documented GERD diagnosis during their first year of life. A greater percentage of exposed vs. unexposed infants were non-Hispanic white, privately insured and exposed to ASM prenatally.

Overall, 289 (32%) of 913 participants developed recurrent wheeze by age 3 years, including 84 of 195 (43%) exposed to ASM during infancy and 205 of 718 (29%) without exposure.

Infants exposed to ASM experienced a significantly higher rate of developing recurrent wheeze by age 3 years in the unadjusted model (HR = 1.65; 95% CI, 1.28-2.12), with a persistent association following adjustment (adjusted HR = 1.58; 95% CI , 1.2-2.08).

Among 610 participants analyzed for allergen sensitization, 29% developed food sensitization, 27% developed aeroallergen sensitization and 42% were sensitized to a food or aeroallergen. Incidence of sensitization to a food or aeroallergen appeared comparable between the ASM exposure and nonexposure groups (40% vs. 42%).

When they analyzed the cohort for asthma, the researchers found that 239 (28%) of 861 participants had developed asthma by age 6 years, including 64 of 189 (34%) exposed to ASM in infancy and 175 of 672 (26%) who were not exposed.

In the unadjusted model, those exposed to ASMs experienced significantly higher odds for developing asthma by age 6 years than those who had not been exposed (OR = 1.45; 95% CI, 1.09-1.94), with an association that persisted after adjustment (adjusted OR = 1.66; 95% CI, 1.22-2.27).

“In our study, infants exposed to acid suppressant medications had a significantly increased risk of developing recurrent wheeze and asthma in childhood. We did not, however, find an association with development of allergic sensitization,” Robinson said. “This is an interesting finding that warrants additional study including study of the underlying mechanism of these associations.”

The researchers noted that the mechanism behind the associations between ASM exposure and risks for recurrent wheeze and asthma are unknown. Risk for allergen sensitization and deleterious alterations in the airway and gut microbiota could play a role, they continued, although the lack of increased allergen sensitization suggests that development of sensitization in early childhood might not be the underlying mechanism.

“In line with pediatric guidelines, doctors should use caution when prescribing acid suppressant medications during infancy. As always, doctors should carefully consider the potential risks and benefits of the therapy,” Robinson said.

The researchers intend to continue their studies.

“The next steps include confirming the results in patient populations including healthy children and determining the underlying mechanism of this association,” Robinson said.

For more information:

Lacey B. Robinson, MD, MPH, can be reached at laceybrobinson@gmail.com.

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