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.
Versailles Saint-Quentin-en-Yvelines University, Versailles, France.
JAMA Pediatr. 2023 Oct 1;177(10):1028-1038. doi: 10.1001/jamapediatrics.2023.2900.
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.
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.
PPI exposure over time.
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.
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).
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.
质子泵抑制剂 (PPI) 的使用可能通过改变微生物群或直接作用于免疫系统导致感染。然而，只有少数研究在儿童中进行，结果存在冲突。
评估质子泵抑制剂的使用与儿童严重感染之间的关联，总体以及按感染部位和病原体进行评估。
设计、地点和参与者：这项全国性队列研究基于法国健康数据系统 (SNDS) 构建的母婴 EPI-MERES 注册数据库。我们纳入了 2010 年 1 月 1 日至 2018 年 12 月 31 日期间出生的所有接受治疗胃食管反流病或其他胃酸相关疾病的儿童，治疗方法包括质子泵抑制剂、组胺 2 受体拮抗剂或抗酸剂/藻酸盐。索引日期定义为首次开具这些药物的日期。对儿童进行随访，直至因严重感染、失访、死亡或 2019 年 12 月 31 日住院治疗。
质子泵抑制剂的时间暴露情况。
使用 Cox 模型评估严重感染与质子泵抑制剂使用之间的关联，采用调整后的危险比 (aHR) 和 95%置信区间 (CI)。质子泵抑制剂的使用被视为时间变化。应用 30 天的滞后时间以最小化反向因果关系。模型根据社会人口统计学数据、妊娠特征、儿童合并症和医疗保健利用情况进行调整。
研究人群包括 1 262 424 名儿童（中位 [IQR] 随访时间，3.8 [1.8-6.2] 岁），其中 606 645 名儿童接受了质子泵抑制剂（323 852 名男性 [53.4%]；索引日期的中位 [IQR] 年龄，88 [44-282] 天），655 779 名儿童未接受质子泵抑制剂（342 454 名男性 [52.2%]；中位 [IQR] 年龄，82 [44-172] 天）。质子泵抑制剂的暴露与严重感染的总体风险增加相关（aHR，1.34；95%CI，1.32-1.36）。在消化道感染（aHR，1.52；95%CI，1.48-1.55）；耳、鼻、喉（aHR，1.47；95%CI，1.41-1.52）；下呼吸道（aHR，1.22；95%CI，1.19-1.25）；肾脏或泌尿道（aHR，1.20；95%CI，1.15-1.25）；神经系统（aHR，1.31；95%CI，1.11-1.54），以及细菌性感染（aHR，1.56；95%CI，1.50-1.63）和病毒性感染（aHR，1.30；95%CI，1.28-1.33）方面，观察到风险增加。
在这项研究中，质子泵抑制剂的使用与儿童严重感染的风险增加相关。在该人群中，质子泵抑制剂不应在没有明确适应证的情况下使用。
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