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Thursday 10 May 2018
Acid-Suppressive Medications, Antibiotics and Allergic Diseases in Early Childhood

The article WAidid suggests this week, "Association Between Use of Acid-Suppressive Medications and Antibiotics During Infancy and Allergic Diseases in Early Childhood", was published last month on JAMA Pediatrics and tackles the issue of children microbiome alterations caused by medications. 

The cumulative prevalence of allergic diseases and asthma has risen over the past several decades. An area of environmental change, which may be contributing to the rise of allergic diseases, is the increasing use of medications, in particular gastric acid–suppressive medications and antibiotics that alter the development of the human microbiome, causing dysbiosis. Moreover, acid suppressive medications, which reduce protein digestion, can affect how ingested antigens are processed in the intestinal tract. Furthermore, acid suppression has been associated with food and medication allergy, probably through the increase immunoglobulin E production.
The authors reported the data of the largest retrospective cohort study in which, using the TRICARE Management Activity Military Health System database, they evaluated the increased risk of childhood allergic diseases, after the exposure to either acid-suppressive medications or antibiotics during infancy. To be included in the study, children must have had a birth medical record in the database between October 2001 and September 2013, and continued enrollment from within 35 days of birth until at least age 1 year. Children, who were diagnosed with any of the outcome allergic conditions within the first 6 months of life, were excluded. 
The medications involved were: histamine-2 receptor antagonist (H2RA), proton pump inhibitor (PPI), or antibiotic. Allergic disease outcomes were defined using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic codes.
A total of 792130 children were selected: during the first 6 months of life, 60209 children (7.6%) were prescribed an H2RA, 13687 (1.7%) a PPI, and 131708 (16.6%) an antibiotic. Of all children, 12546 (1.6%) received H2RAs and antibiotics, 5520 (0.7%) received H2RAs and PPIs, 1590 (0.2%) received PPIs and antibiotics, and 2549 (0.3%) received all 3 medications. The most frequently used H2RA was ranitidine (95.1%), followed by nizatidine and famotidine. Lansoprazole was the most commonly prescribed PPI (75.5%). Median days of antibiotics prescribed was 10. The most common classes were penicillin (65.3%), followed by cephalosporin (14.2%), and macrolides (10.1%).
A greater percentage of boys was prescribed an H2RA, 2RA than girls (P<.001 for all comparisons). Premature infants were more likely to be prescribed H2RAs and PPIs than full-term infants (P<.001 for both comparisons). There was no significant difference in the percentage of children born prematurely given antibiotics compared with full-term infants.
24514 were diagnosed with a food allergy: peanut allergy was the most common, followed by cow’s milk allergy and egg allergy. With regard to other allergic diseases, the 2 most common diagnoses were allergic rhinitis and contact dermatitis, followed by atopic dermatitis, asthma, and urticaria. 
All covariates analyzed exhibited a statistically significant association with allergic disease. A greater percentage of boys developed an allergic condition than girls (P<.001). Children born by cesarean delivery and those born prematurely also demonstrated an increased risk of allergic disease compared with children without those conditions (P<.001 for both).
Every allergic disease assessed exhibited a significantly increased risk in children who had received H2RAs or PPIs, except for seafood allergy. Risk of food allergy, after treatment with acid-suppressive medications, exhibited a dose-dependent effect.
All nonfood allergic diseases studies also were found to be significantly associated with the use of acid-suppressive medication therapy: medication allergy, allergic rhinitis, anaphylaxis, asthma, allergic conjunctivitis, and urticaria. 
Prescriptions for antibiotics were significantly associated with an increased risk of allergic diseases: Hazard Ratio (HR) for development of any food allergy was 1.14.
While neither peanut allergy nor seafood allergy exhibited significantly increased risk, antibiotic use was associated with an increased risk of both cow’s milk allergy and egg allergy. Antibiotics did not demonstrate a dose-dependent risk for development of food allergy.
Several nonfood allergic diseases were significantly increased in children who had received antibiotics: asthma (more than 2-fold risk), anaphylaxis, allergic conjunctivitis, medication allergy, atopic dermatitis, allergic rhinitis, contact dermatitis, and urticaria.
The authors concluded that acid-suppressive medications were associated with a greater risk of food allergy than antibiotic use, highlighting the importance of paying attention especially to H2RAs and PPIs, which are generally considered safe and commonly prescribed for children younger than 1 year.

AUTHORS: Mitre E, Susi A, Kropp LE, Schwartz DJ, Gorman GH, Nylund CM.