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

Abstract

Importance: 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.

Objective: 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.

Design, setting, and participants: 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.

Exposures: Exposures were defined as having any dispensed prescription for a histamine-2 receptor antagonist (H2RA), proton pump inhibitor (PPI), or antibiotic.

Main outcomes and measures: 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.

Results: Of 792 130 children (395 215 [49.9%] girls) included for analysis, 60 209 (7.6%) were prescribed an H2RA, 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 H2RAs 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.

Conclusions and relevance: 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.

Figure 1.. Patient Selection

Patients were selected on the basis of having 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. Exclusion criteria included initial birth stay of greater than 7 days, diagnosis of any of the outcome allergic conditions within the first 6 months of life, and incomplete enrollment and demographic data sets.

Figure 2.. Incidence of Food Allergy and Duration of Histamine-2 Receptor Antagonist (H₂RA), Proton Pump Inhibitor (PPI), and Antibiotic Prescribed During the First 6 Months of Life

Incidence for H₂RA (A), PPI (B), and antibiotic (C) therapy prescribed. Inset table reports adjusted hazard ratios (aHRs) for development of food allergy determined by duration of medicine prescribed. Duration is defined in Results section.