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抗生素暴露与儿童自身免疫性疾病的发展:基于登记的病例对照研究。

Antibiotic exposures and the development of pediatric autoimmune diseases: a register-based case-control study.

机构信息

Faculty of Medicine and Health Technology (MET), Tampere University, Tampere, Finland.

Folkhälsan Research Center, Helsinki, Finland.

出版信息

Pediatr Res. 2023 Mar;93(4):1096-1104. doi: 10.1038/s41390-022-02188-4. Epub 2022 Jul 19.

Abstract

BACKGROUND

Antibiotics have been associated with several individual autoimmune diseases (ADs). This study aims to discover whether pre-diagnostic antibiotics are associated with the onset of ADs in general.

METHODS

From a cohort of 11,407 children, 242 developed ADs (type 1 diabetes, autoimmune thyroiditis, juvenile idiopathic arthritis (JIA), or inflammatory bowel diseases) by a median age of 16 years. Antibiotic purchases from birth until the date of diagnosis (or respective date in the matched controls n = 708) were traced from national registers.

RESULTS

Total number of antibiotic purchases was not related to the onset of ADs when studied as a group. Of specific diagnoses, JIA was associated with the total number of antibiotics throughout the childhood and with broad-spectrum antibiotics before the age of 3 years. Intriguingly, recent and frequent antibiotic use (within 2 years before diagnosis and ≥3 purchases) was associated with the onset of ADs (OR 1.72, 95% CI 1.08-2.74). Regardless of frequent use in childhood (40% of all antibiotics), penicillin group antibiotics were not related to any ADs.

CONCLUSIONS

Use of antibiotics was relatively safe regarding the overall development of ADs. However, broad-spectrum antibiotics should be used considerately as they may associate with an increased likelihood of JIA.

IMPACT

Increasing numbers of antibiotic purchases before the age of 3 years or throughout childhood were not associated with the development of pediatric autoimmune diseases. Broad-spectrum antibiotics were related to the development of autoimmune diseases, especially juvenile idiopathic arthritis in children, while penicillin group antibiotics were not. The use of broad-spectrum antibiotics in children should be cautious as they may carry along a risk for autoimmune disease development.

摘要

背景

抗生素与几种自身免疫性疾病(AD)有关。本研究旨在探讨诊断前使用抗生素是否与 AD 的发病有关。

方法

从 11407 名儿童的队列中,有 242 名儿童在中位年龄为 16 岁时患上了 AD(1 型糖尿病、自身免疫性甲状腺炎、幼年特发性关节炎(JIA)或炎症性肠病)。从国家登记处追溯了从出生到诊断日期(或相应对照病例的 708 名)的抗生素购买情况。

结果

当作为一个整体进行研究时,抗生素购买的总数与 AD 的发病无关。在特定诊断中,JIA 与整个儿童期的抗生素总数以及 3 岁前的广谱抗生素有关。有趣的是,最近和频繁的抗生素使用(在诊断前 2 年内和≥3 次购买)与 AD 的发病有关(OR 1.72,95%CI 1.08-2.74)。无论在儿童期(40%的所有抗生素)中是否频繁使用,青霉素类抗生素与任何 AD 均无关。

结论

抗生素的使用在总体上对 AD 的发展相对安全。然而,广谱抗生素的使用应慎重,因为它们可能与 JIA 的发生几率增加有关。

意义

在 3 岁之前或整个儿童期增加抗生素的使用次数与儿科自身免疫性疾病的发展无关。广谱抗生素与自身免疫性疾病的发生有关,尤其是儿童 JIA,而青霉素类抗生素则无关。儿童应谨慎使用广谱抗生素,因为它们可能会增加自身免疫性疾病的发病风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee15/10033398/fe7df9f09440/41390_2022_2188_Fig1_HTML.jpg

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