Proton Pump Inhibitor Use and Risk of Serious Infections in Young Children
Marion Lassalle1, Mahmoud Zureik1,2, Rosemary Dray-Spira1
1EPI-PHARE, Epidemiology of Health Products (French National Agency for the Safety of Medicines and Health Products [ANSM], and French National Health Insurance [CNAM]), Saint-Denis, France.
Insights
Proton pump inhibitor (PPI) use in children is linked to a higher risk of serious infections. These findings suggest careful consideration of PPI prescriptions for pediatric patients.
Area of Science:
- Pediatric Gastroenterology
- Infectious Diseases
- Pharmacovigilance
Background:
- Proton pump inhibitors (PPIs) may increase infection risk by altering gut microbiota or affecting immune function.
- Limited research exists on PPIs and serious infections in children, with conflicting findings.
Purpose of the Study:
- To evaluate the association between proton pump inhibitor (PPI) use and serious infections in children.
- To analyze these associations by infection site and pathogen type.
Main Methods:
- Nationwide cohort study using the French Health Data System (SNDS) from 2010-2019.
- Included over 1.2 million children, analyzing PPI exposure and serious infection events.
- Used Cox models with time-varying PPI exposure and a 30-day lag to assess risks.
Main Results:
- Proton pump inhibitor (PPI) use was associated with a 34% increased risk of serious infections in children (aHR, 1.34).
- Elevated risks were observed for digestive, ENT, respiratory, urinary, and nervous system infections.
- Increased risks were noted for both bacterial (aHR, 1.56) and viral infections (aHR, 1.30).
Conclusions:
- Proton pump inhibitor (PPI) use is associated with significantly increased risks of serious infections in young children.
- These findings highlight the need for cautious prescribing of PPIs in pediatric populations, emphasizing clear indications.
Importance:
Proton pump inhibitor (PPI) use may lead to infections through alteration of the microbiota or direct action on the immune system. However, only a few studies were conducted in children, with conflicting results.
Objective:
To assess the associations between PPI use and serious infections in children, overall and by infection site and pathogen.
Design, Setting, And Participants:
This nationwide cohort study was based on the Mother-Child EPI-MERES Register built from the French Health Data System (SNDS). We included all children born between January 1, 2010, and December 31, 2018, who received a treatment for gastroesophageal reflux disease or other gastric acid-related disorders, namely PPIs, histamine 2 receptor antagonists, or antacids/alginate. The index date was defined as the first date any of these medications was dispensed. Children were followed up until admission to the hospital for serious infection, loss of follow-up, death, or December 31, 2019.
Exposure:
PPI exposure over time.
Main Outcomes And Measures:
Associations between serious infections and PPI use were estimated by adjusted hazard ratios (aHRs) and 95% CIs using Cox models. PPI use was introduced as time-varying. A 30-day lag was applied to minimize reverse causality. Models were adjusted for sociodemographic data, pregnancy characteristics, child comorbidities, and health care utilization.
Results:
The study population comprised 1 262 424 children (median [IQR] follow-up, 3.8 [1.8-6.2] years), including 606 645 who received PPI (323 852 male [53.4%]; median [IQR] age at index date, 88 [44-282] days) and 655 779 who did not receive PPI (342 454 male [52.2%]; median [IQR] age, 82 [44-172] days). PPI exposure was associated with an increased risk of serious infections overall (aHR, 1.34; 95% CI, 1.32-1.36). Increased risks were also observed for infections in the digestive tract (aHR, 1.52; 95% CI, 1.48-1.55); ear, nose, and throat sphere (aHR, 1.47; 95% CI, 1.41-1.52); lower respiratory tract (aHR, 1.22; 95% CI, 1.19-1.25); kidneys or urinary tract (aHR, 1.20; 95% CI, 1.15-1.25); and nervous system (aHR, 1.31; 95% CI, 1.11-1.54) and for both bacterial (aHR, 1.56; 95% CI, 1.50-1.63) and viral infections (aHR, 1.30; 95% CI, 1.28-1.33).
Conclusions And Relevance:
In this study, PPI use was associated with increased risks of serious infections in young children. Proton pump inhibitors should not be used without a clear indication in this population.
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