1. Use of histamine 2 receptor antagonists (H2RA) or proton pump inhibitors (PPIs) during the first 6 months of life was associated with increased risk of allergic disease and asthma.
2. Use of antibiotics in early life was also linked to increased risk of allergic disease and anaphylaxis.
Evidence Rating Level: 2 (Good)
Study Rundown: The rate of allergic disease is rising amongst children in the United States and other countries. There has been some evidence that exposure to certain medications may be associated with the development of allergic disease. Antibiotics in early life have been implicated in altering the development of the human microbiome which may influence antigen exposure and tolerance. Acid suppressing medications alter protein digestion and antigen exposure as well as influencing the microbiome development. This retrospective cohort study estimated the risk of allergic disease in children exposed to acid suppressing medications or antibiotics in the first 6 months of life. The study found that allergic disease was increased for children exposed to either of these classes of medications.
The main strength of the study is its large, modern cohort, but the retrospective design and reliance on dispensed prescriptions as an estimation of exposure can be a sourcees of bias. Symptoms of food allergy may be misdiagnosed as reflux symptoms leading to an increased use of anti-acid medications for these patients.
In-Depth [retrospective cohort]: This study used the TRICARE Management Activity Military Health Systems database of military service members and their dependents. Children were included in the cohort if they were born between 2001 and 2013 with enrollment from within 35 days of birth to at least 1 year of age. Children were excluded if they had been diagnosed with an allergic disease within the first 6 months of life, had incomplete enrollment data, or had an initial birth stay greater than 7 days. Patients were considered exposed to a medication if they had any dispensed prescription for H2RA, PPIs, or an antibiotic within 6 months of birth. Allergic disease diagnosis from 6 months of age to study end or end of enrollment were determined using International Classification of Diseases (ICD) diagnostic codes.
Of the 792 130 children included in the study, 7.6% were exposed to an H2RA, 1.7% were given a PPI, and 16.6% were prescribed an antibiotic. The use of H2RA was linked to a risk of food allergy (adjusted hazard ratio 2.18 [95%CI, 2.04-2.33]), medication allergy (aHR 1.70 [95%CI, 1.60-1.80]), anaphylaxis (aHR 1.51 [95%CI, 1.38-1.66]), rhinitis (1.50 [95%CI, 1.46-1.54]), and asthma 1.25 (95%CI, 1.21-1.29). Use of PPI was also linked to increased risk of food allergy (2.59 [95%CI, 2.25-3.00]), medication allergy (1.84 [95%CI, 1.56-2.17]), anaphylaxis (1.45 [95%CI, 1.22-1.73]), rhinitis (1.44 [95%CI, 1.36-1.52]) and asthma (1.41 [95%CI, 1.31-1.52]). Antibiotic use was linked to increased risk of asthma (aHR 2.09 [95%CI, 2.05-2.13]), rhinitis (1.75 [95%CI, 1.72-1.78]), and anaphylaxis (1.51 [95%CI, 1.38-1.66]).
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