April 03, 2018
3 min read

Acid-suppressor, antibiotic use in infancy tied to later allergic disease

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Infants who are prescribed acid suppressors, such as a histamine-2 receptor antagonist or a proton pump inhibitor, or antibiotics within their first 6 months of life may be more likely to develop allergic disease in early childhood, according to findings published in JAMA Pediatrics. However, significant concerns have been raised about the study’s methodology and conclusions (see Perspective, below).

“Both gastric acid-suppressive medications and antibiotics have been implicated as factors that may enhance the development of allergic diseases,” Edward Mitre, MD, from the department of microbiology and immunology at the F. Edward Hébert School of Medicine in the Uniformed Services University of the Health Sciences, and colleagues wrote. “Use of these medications, which can directly cause intestinal dysbiosis, is of concern in light of increasing evidence that alterations in the human microbiome can increase the risk for allergy development.”

“Furthermore, acid-suppressive medications, which reduce protein digestion, can affect how ingested antigens are processed in the intestinal tract,” the researchers continued.

To examine whether treating infants 6 months of age or younger with antibiotics or acid-suppressive medications is associated with allergic disease in early childhood, Mitre and colleagues conducted a retrospective cohort study that included infants who were labeled as beneficiaries through the Department of Defense TRICARE. All infants included had a birth medical record stored within the Military Healy System and were born between Oct. 1, 2001, and Sept. 30, 2013.

Additionally, the infants included in this study must have been enrolled in the program within 35 days of birth until at least 1 year of age. Children were excluded from the study if they stayed in the hospital for more than 7 days following birth or received a diagnosis of food allergy, anaphylaxis, asthma, atopic dermatitis, allergic rhinitis, allergic conjunctivitis, urticaria, contact dermatitis, medication allergy or other allergy within the first 6 months of life.

Researchers found little evidence to support the efficacy of histamine-2 receptor antagonist in infants, and reported that trials have not found clinical benefit of proton pump inhibitor therapy in infants with symptoms attributed to gastroesophageal reflux.

Of the 792,130 children included in the study (49.9% female), 7.6% were prescribed a histamine-2 receptor antagonist (H2RA) and 1.7% were prescribed a proton pump inhibitor (PPI) within the first 6 months of life. Antibiotics also were prescribed for 16.6% of infants included in the study during this time. Mitre and colleagues noted that data continued to be collected on these infants for a median of 4.6 years.

When children were prescribed an H2RA, the researchers noted adjusted HRs of 2.18 (95% CI, 2.04-2.33) for food allergy, 1.70 (95% CI, 1.60-1.80) for medication allergy, 1.51 (95% CI, 1.38-1.66) for anaphylaxis, 1.50 (95% CI, 1.46-1.54) for allergic rhinitis and 1.25 (95% CI, 1.21-1.29) for asthma.

Infants who were prescribed PPIs had comparable aHRs, which the researchers observed at 2.59 (95% CI, 2.25-3.00) for food allergy, 1.84 (95% CI, 1.56-2.17) for medication allergy, 1.45 (95% CI, 1.22-1.73) for anaphylaxis and 1.44 (95% CI, 1.36-1.52) for asthma.

Mitre and colleagues also calculated the aHRs related to later allergic disease in children who were prescribed antibiotics within the first 6 months of life. They observed these rates at 2.09 (95% CI, 2.05-2.13) for asthma, 1.75 (95% CI, 1.72-1.78) for allergic rhinitis, 1.51 (95% CI, 1.38-1.66) for anaphylaxis and 1.42 (95% CI, 1.34-1.50) for allergic conjunctivitis.

“While there has been increasing recognition of the potential risks of antibiotic use during infancy, H2RAs and PPIs are considered to be generally safe and are commonly prescribed for children younger than 1 year,” Mitre and colleagues wrote. “… These medications are frequently given to infants who regurgitate food and appear to be fussy. For most infants, however, regurgitation of gastric contents is not a disease but rather is a developmentally normal process.”

“A systematic review found little evidence to support the efficacy of H2RAs in infants, and trials have not found clinical benefit of PPI therapy in infants with symptoms attributed to gastroesophageal reflux,” the researchers added. – by Katherine Bortz

Disclosures: The authors report no relevant financial disclosures.

Editor’s note: This article has been revised to reflect concerns over the study’s findings.