Early Use of Proton Pump Inhibitors Increases Risk of Upper Respiratory Tract Infections in Children: A Birth Cohort Study

Objectives Proton pump inhibitors (PPI) are frequently prescribed in infancy for functional gastrointestinal disorders such as colic and gastroesophageal reflux, despite limited evidence of benefit and potential risk. We aimed to examine the association between early PPI exposure and respiratory tract infections (RTIs) in a birth cohort. Methods In the ARIES cohort (Santiago, Chile), 200 of 265 children with complete data were followed from birth to 24 months. Early PPI exposure was defined as any use during the first 6 months, while any exposure encompassed the first 24 months. Clinical data were collected via parental questionnaires and medical records. Associations were assessed using logistic regressions. Results Sixteen infants (8%) received PPIs during the first 6 months and 22 (11%) during the first 2 years. By age two, otitis media occurred in 12%, viral croup in 18%, bronchiolitis in 36%, pneumonia in 2.5%, RTI‐related hospitalization in 3%, and RTI‐related antibiotic use in 38%. Early PPI exposure was independently associated with otitis media (adjusted odds ratio [aOR] 9.5, 95% CI 2.1−42.5), viral croup (aOR 4.8, 95% CI 1.5−15.2), RTI‐related hospitalization (aOR 19.3, 95% CI 1.6−225.8), and antibiotic use (aOR 9.9, 95% CI 2.5−38.6). Any PPI exposure also increased odds of otitis media (aOR 5.4, 95% CI 1.4−21.0), viral croup (aOR 3.0, 95% CI 1.1−8.1), RTI‐related hospitalization (aOR 17.5, 95% CI 1.5−205.0), and antibiotic use (aOR 8.9, 95% CI 2.9−27.1). No significant associations were observed with lower RTIs. Conclusions Early PPI exposure in infancy is associated with higher risk of upper RTIs, RTI‐related hospitalization and antibiotic prescriptions. These findings underscore the importance of cautious PPI prescribing in early life, a critical period for immune and microbiota development.