Proton Pump Inhibitor Use and Risk of Serious Infections in Young Children

{ 'indexed': {'date-parts': [[2024, 9, 23]], 'date-time': '2024-09-23T06:43:38Z', 'timestamp': 1727073818939}, 'reference-count': 43, 'publisher': 'American Medical Association (AMA)', 'issue': '10', 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'published-print': {'date-parts': [[2023, 10, 1]]}, 'abstract': '<jats:sec id="ab-poi230045-4"><jats:title>Importance</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec ' 'id="ab-poi230045-5"><jats:title>Objective</jats:title><jats:p>To assess the associations ' 'between PPI use and serious infections in children, overall and by infection site and ' 'pathogen.</jats:p></jats:sec><jats:sec id="ab-poi230045-6"><jats:title>Design, Setting, and ' 'Participants</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec ' 'id="ab-poi230045-7"><jats:title>Exposure</jats:title><jats:p>PPI exposure over ' 'time.</jats:p></jats:sec><jats:sec id="ab-poi230045-8"><jats:title>Main Outcomes and ' 'Measures</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec ' 'id="ab-poi230045-9"><jats:title>Results</jats:title><jats:p>The study population comprised ' '1\u202f262\u202f424 children (median [IQR] follow-up, 3.8 [1.8-6.2] years), including ' '606\u202f645 who received PPI (323\u202f852 male [53.4%]; median [IQR] age at index date, 88 ' '[44-282] days) and 655\u202f779 who did not receive PPI (342\u202f454 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).</jats:p></jats:sec><jats:sec ' 'id="ab-poi230045-10"><jats:title>Conclusions and Relevance</jats:title><jats:p>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.</jats:p></jats:sec>', 'DOI': '10.1001/jamapediatrics.2023.2900', 'type': 'journal-article', 'created': {'date-parts': [[2023, 8, 14]], 'date-time': '2023-08-14T15:01:13Z', 'timestamp': 1692025273000}, 'page': '1028', 'source': 'Crossref', 'is-referenced-by-count': 23, 'title': 'Proton Pump Inhibitor Use and Risk of Serious Infections in Young Children', 'prefix': '10.1001', 'volume': '177', 'author': [ { 'given': 'Marion', 'family': 'Lassalle', 'sequence': 'first', 'affiliation': [ { 'name': 'EPI-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'}]}, { 'given': 'Mahmoud', 'family': 'Zureik', 'sequence': 'additional', 'affiliation': [ { 'name': 'EPI-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'}, { 'name': 'Versailles Saint-Quentin-en-Yvelines University, Versailles, ' 'France'}]}, { 'given': 'Rosemary', 'family': 'Dray-Spira', 'sequence': 'additional', 'affiliation': [ { 'name': 'EPI-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'}]}], 'member': '10', 'reference': [ { 'issue': '3', 'key': 'poi230045r1', 'doi-asserted-by': 'publisher', 'first-page': '516', 'DOI': '10.1097/MPG.0000000000001889', 'article-title': 'Pediatric gastroesophageal reflux clinical practice guidelines: joint ' 'recommendations of the North American Society for Pediatric ' 'Gastroenterology, Hepatology, and Nutrition and the European Society ' 'for Pediatric Gastroenterology, Hepatology, and Nutrition.', 'volume': '66', 'author': 'Rosen', 'year': '2018', 'journal-title': 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