Acid suppressants may increase risks for asthma, allergic diseases among children

The use of acid suppressants among children may increase their risks for incident asthma, atopic dermatitis and allergic rhinitis, according to a systematic review published in The Journal of Allergy and Clinical Immunology: In Practice.

These drugs therefore should be used judiciously in children, and more stringent guidelines should be developed, Harris Jun Jie Muhammad Danial Song, MBBS, of the Yong Loo Lin School of Medicine, Singapore, and colleagues wrote.

“Previous studies have established an association between the maternal use of acid suppressants and the subsequent development of allergic diseases,” Song told Healio.

“What is less certain, however, is whether or not taking these medications during childhood would also predispose a child to such risks. Hence, our team decided to undergo this study to ascertain the presence of this association,” he said.

The researchers reviewed five observational studies published across four databases through March 4, 2022, including 1,160,200 children with an average age ranging from birth through age 13 years.

Overall, patients with exposure to acid suppressants had significantly higher risks for asthma (HR = 1.44; 94% CI, 1.31-1.58) in four of the studies, AD (HR = 1.12; 95% CI, 1.1-1.14) in two of the studies and allergic rhinitis (HR = 1.4; 95% CI, 1.24-1.58) in two of the studies, compared with controls. However, the researchers indicated that there was significant heterogeneity in the studies that examined asthma and allergic rhinitis.

Significantly higher risks for asthma were associated with proton pump inhibitors (HR = 1.52; 95% CI, 1.37-1.68) in three of the included studies and with histamine-2 receptor agonists (HR = 1.4; 95% CI, 1.11-1.78) in two of the studies.

Four of the studies found significant risks for developing asthma among children who only were exposed to acid suppressants through age 6 months (HR = 1.5, 95% CI, 1.34-1.68).

One study also showed a significant risk for asthma regardless of the cumulative duration of proton pump inhibitor use, with hazard ratios of 1.52 (95% CI, 1.44-1.61) for 30 days, 1.51 (95% CI, 1.42-1.6) for 31 to 364 days, and 1.59 (95% CI, 1.25-2.02) for 365 days or more.

“Our team showed that the childhood use of acid suppressants increases one’s risks of developing asthma and allergic rhinitis by over 40%. The risk of developing atopic dermatitis increases by over 10%,” Song said. “This relationship is more significant at a younger age of exposure, particularly the first 2 years of life.”

Overall, there was not a significantly higher risk for food allergy with acid suppressant exposure (HR = 1.61; 95% CI, 0.92-2.82) based on three of the studies, although there was in a cross-sectional study that was excluded from the meta-analysis (prevalence ratio = 1.7; 95% CI, 1.1-2.5).

In one study, infants who were prescribed proton pump inhibitors or histamine-2 receptor agonists for more than 60 days before age 6 months had increased risk for developing food allergy compared with infants with up to 60 days of use of proton pump inhibitors (HR = 1.52; 95% CI, 1.32-1.74) or histamine-2 receptor agonists (HR = 1.32; 95% CI, 1.23-1.43).

After looking at patients with gastroesophageal reflux disease, two of the studies found that those who used vs. did not use acid suppressants had a higher risk for developing food allergies (HR = 1.64; 95% CI, 1.54-1.76).

hough these findings indicate a potential association between the use of acid suppressants and the development of allergic diseases, the researchers noted that the overall quality of evidence in these studies was low due to their observational nature as well as due to the low number of pooled studies that were analyzed.

Still, the researchers said, the need for caution remains.

“Doctors should be aware of this relationship and prescribe acid suppressants to the pediatric population more judiciously,” Song said. “More stringent guidelines directing the prescription of these medications should also be devised.”

Song said that more research is necessary as well.

“Future interventional studies in the form of randomized controlled trials need to be conducted to determine the causality of this relationship,” Song said.

“These studies should also determine the optimum drug dosage and duration of drug use for acid suppressants to minimize the risks of allergic disease development and maximize the benefits of symptomatic treatment of acid reflux,” he said.

For more information:

Harris Jun Jie Muhammad Danial Song, MBBS, can be reached at harris.song@u.nus.edu.