Association Between Use of Acid-Suppressive Medications and Antibiotics During Infancy and Allergic Diseases in Early Childhood

Abstract

<div class="section"> <a class="named-anchor" id="ab-poi180013-1"> <!-- named anchor --> </a> <h5 class="section-title" id="d5534818e297">Question</h5> <p id="d5534818e299">Does use of medications that disturb the microbiome in infancy increase subsequent risk of developing allergic diseases? </p> </div><div class="section"> <a class="named-anchor" id="ab-poi180013-2"> <!-- named anchor --> </a> <h5 class="section-title" id="d5534818e302">Findings</h5> <p id="d5534818e304">In this cohort study of 792 130 children, the hazard of developing an allergic disease was significantly increased in those who had received acid-suppressive medications or antibiotics during the first 6 months of life. </p> </div><div class="section"> <a class="named-anchor" id="ab-poi180013-3"> <!-- named anchor --> </a> <h5 class="section-title" id="d5534818e307">Meaning</h5> <p id="d5534818e309">Exposure to acid-suppressive medications or antibiotics in the first 6 months of life may increase risk of allergic disease development. </p> </div><div class="section"> <a class="named-anchor" id="ab-poi180013-4"> <!-- named anchor --> </a> <h5 class="section-title" id="d5534818e313">Importance</h5> <p id="d5534818e315">Allergic diseases are prevalent in childhood. Early exposure to medications that can alter the microbiome, including acid-suppressive medications and antibiotics, may influence the likelihood of allergy. </p> </div><div class="section"> <a class="named-anchor" id="ab-poi180013-5"> <!-- named anchor --> </a> <h5 class="section-title" id="d5534818e318">Objective</h5> <p id="d5534818e320">To determine whether there is an association between the use of acid-suppressive medications or antibiotics in the first 6 months of infancy and development of allergic diseases in early childhood. </p> </div><div class="section"> <a class="named-anchor" id="ab-poi180013-6"> <!-- named anchor --> </a> <h5 class="section-title" id="d5534818e323">Design, Setting, and Participants</h5> <p id="d5534818e325">A retrospective cohort study was conducted in 792 130 children who were Department of Defense TRICARE beneficiaries with a birth medical record in the Military Health System database between October 1, 2001, and September 30, 2013, with continued enrollment from within 35 days of birth until at least age 1 year. Children who had an initial birth stay of greater than 7 days or were diagnosed with any of the outcome allergic conditions within the first 6 months of life were excluded from the study. Data analysis was performed from April 15, 2015, to January 4, 2018. </p> </div><div class="section"> <a class="named-anchor" id="ab-poi180013-7"> <!-- named anchor --> </a> <h5 class="section-title" id="d5534818e328">Exposures</h5> <p id="d5534818e330">Exposures were defined as having any dispensed prescription for a histamine-2 receptor antagonist (H ₂RA), proton pump inhibitor (PPI), or antibiotic. </p> </div><div class="section"> <a class="named-anchor" id="ab-poi180013-8"> <!-- named anchor --> </a> <h5 class="section-title" id="d5534818e336">Main Outcomes and Measures</h5> <p id="d5534818e338">The main outcome was allergic disease, defined as the presence of food allergy, anaphylaxis, asthma, atopic dermatitis, allergic rhinitis, allergic conjunctivitis, urticaria, contact dermatitis, medication allergy, or other allergy. </p> </div><div class="section"> <a class="named-anchor" id="ab-poi180013-9"> <!-- named anchor --> </a> <h5 class="section-title" id="d5534818e341">Results</h5> <p id="d5534818e343">Of 792 130 children (395 215 [49.9%] girls) included for analysis, 60 209 (7.6%) were prescribed an H ₂RA, 13 687 (1.7%) were prescribed a PPI, and 131 708 (16.6%) were prescribed an antibiotic during the first 6 months of life. Data for each child were available for a median of 4.6 years. Adjusted hazard ratios (aHRs) in children prescribed H ₂RAs and PPIs, respectively, were 2.18 (95% CI, 2.04-2.33) and 2.59 (95% CI, 2.25-3.00) for food allergy, 1.70 (95% CI, 1.60-1.80) and 1.84 (95% CI, 1.56-2.17) for medication allergy, 1.51 (95% CI, 1.38-1.66) and 1.45 (95% CI, 1.22-1.73) for anaphylaxis, 1.50 (95% CI, 1.46-1.54) and 1.44 (95% CI, 1.36-1.52) for allergic rhinitis, and 1.25 (95% CI, 1.21-1.29) and 1.41 (95% CI, 1.31-1.52) for asthma. The aHRs after antibiotic prescription in the first 6 months of life were 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. </p> </div><div class="section"> <a class="named-anchor" id="ab-poi180013-10"> <!-- named anchor --> </a> <h5 class="section-title" id="d5534818e352">Conclusions and Relevance</h5> <p id="d5534818e354">This study found associations between the use of acid-suppressive medications and antibiotics during the first 6 months of infancy and subsequent development of allergic disease. Acid-suppressive medications and antibiotics should be used during infancy only in situations of clear clinical benefit. </p> </div><p class="first" id="d5534818e357">This cohort study examines the association between development of childhood allergies and use of histamine-2 receptor antagonists, proton pump inhibitors, or antibiotics during infancy. </p>