April 19, 2018
JAMA Pediatrics
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.
There are very frequent uses of a couple of types of medication in infancy, among them antibiotics and acid-reducing medications such as H2-blockers or proton-pump-inhibitors. The use of both has come under scrutiny, as potential medication overuse as treatment of non-distress-causing gastroesophageal reflux is unnecessary and antibiotics are sometimes used in situations where watchful waiting may be appropriate.
However, aside from cost and creating a sense of “medication dependency,” are there downsides to using these types of medications? This retrospective cohort study was designed to assess associations between any prescribing of these pharmaceuticals and the development of various atopic conditions, including allergic rhinitis, food allergies, asthma, and more. They found statistically significant associations between use of these medications in the first 6 months of life and the development of allergic disease.
Aha! So, are clinicians to banish the use of these types of agents from their arsenal? Not so fast. It’s merely an association, and no causality can be implied from this kind of information. Given how common these conditions are, it’s entirely possible that these associations are due merely to chance. Also, given variability in the human microbiome from person to person (and over time), are there particular periods that are more susceptible to disruption by use of these types of medications? And there’s little information about dose-response relationships — is a low-dose use of acid-suppressing medication the same as a higher-dose when it comes to risk? There are too many potential variables and too little detailed information.
Finally, though their exhortation that these drugs should only be used in situations of “clear clinical benefit,” I would hope that we use any medication in only those types of situations.