To Örebro University

Objective: To evaluate the association between use of proton pump inhibitors (PPIs) and risk of pneumonia in children.

Design: Nationwide register-based self-controlled case series study.

Setting: Sweden, July 2006 to December 2016.

Participants: Children aged <18 years who were treated with PPIs and had a hospitalisation or hospital emergency care visit for pneumonia within 1 year before and 2 years after PPI initiation.

Main outcomes and measures: The primary analysis examined the risk of pneumonia during the risk period (ongoing PPI treatment), the pre-exposure period (<= 30 days preceding PPI treatment) and the postexposure period (days 1-365 after PPI discontinuation), comparing to the unexposed period. Conditional Poisson regression was used to estimate incidence rate ratios (IRRs) and 95% CIs.

Results: A total of 2356 cases of pneumonia were included. Compared with the unexposed period, the risk of pneumonia was significantly increased during ongoing PPI treatment, with an adjusted IRR of 1.40 (95% CI 1.21 to 1.62). The risk of pneumonia was also increased in the pre-exposure period (adjusted IRR, 1.80, 95% CI 1.51 to 2.13), but not in the postexposure period (adjusted IRR 0.98, 95% CI 0.89 to 1.08). Dividing the risk period by time since treatment initiation, the increased risk of pneumonia was highest in the first 30 days (adjusted IRR 1.63, 95% CI 1.35 to 1.97), remained during days 31-90 (adjusted IRR 1.32, 95% CI 1.04 to 1.69), but waned in days >= 91 (IRR 1.06, 95% CI 0.79 to 1.41).

Conclusions and relevance: An increased risk of pneumonia was observed both immediately before and immediately after PPI initiation. This pattern of association can likely be explained by an underlying risk of pneumonia due to factors transiently present at the time around PPI initiation. Thus, our findings do not support a causal relationship between PPI use and risk of pneumonia.