P1076 - Early life exposure to microbiota-altering medications is associated with childhood psychotropic medication prescriptions

Background:
The microbiota-gut-brain axis is the complex interaction between human gastrointestinal tract flora and the central nervous system. Dysbiosis affects the biochemical signal transduction cascades that modulate neurotransmitter metabolism. Many commonly prescribed medications, such as acid suppressants and antibiotics, cause significant alterations in the human gut microbiome. In vivo animal models and human database studies suggest that gut microbiome disruptions are a clinically significant risk factor for developing mental disorders. Our objective was to investigate the association of proton pump inhibitor (PPI), histamine-2 receptor antagonist (H2RA), and antibiotic prescriptions in the first two years of life with future prescriptions for psychotropic medications.

Methods:
We conducted a retrospective cohort study of infants born into the Military Health System from October 2001 to September 2012, with initial hospital stay < 7 days, enrolled past two years of age, and without psychotropic medications dispensed in the first two years of life. Psychotropic medication prescriptions are a relevant proxy for mental disorders or subthreshold mental disorders in children. Cox proportional hazards regression was used to calculate the adjusted hazard ratio (aHR) of a dispensed prescription for a psychotropic medication based on exposure to PPIs, H2RAs, and antibiotics. Patients prescribed acid-suppressants were divided into groups based on median prescription length and antibiotic patients were divided into groups based on number of classes prescribed.

Results:
There were 804,920 patients who met study inclusion criteria. A total (%) of 24,176 (3.0) children were prescribed a PPI, 79,243 (9.8) an H2RA, and 607,348 (75.5) an antibiotic during the first two years of life. The aHR of prescriptions for psychotropic medications was significantly increased among children prescribed any H2RA, PPI, or antibiotic (Table 1). The aHR of prescriptions for psychotropic medications increased commensurately with each additional antibiotic class added. Children exposed to multiple classes of medications (H2RA, PPI or antibiotics) had an increasing aHR with each additional class of medication prescribed. The aHR of psychotropic medication prescriptions was marginally higher in children prescribed longer courses of PPIs (> 64 days versus 1- 64 days), H2RAs (> 60 days versus 1 - 60 days) and multiple antibiotic classes (0, 1, 2, 3, or ≥ 4 classes) (Figure 1).

Conclusions:
This large retrospective cohort study of children found that prescriptions for acid-suppressive medications and antibiotics in the first two years of life are associated with a significant increase in future prescriptions for psychotropic medications. We found a dose-related effect, where prolonged or multiple “hits” with microbiota-altering medications are associated with a significantly increased risk of future psychotropic prescriptions. This association adds to a growing list of concerning and potentially underappreciated risks associated with early exposure to microbiota-altering medications.