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产前和生命早期接触抗生素与青少年特发性关节炎风险的关系:一项全国范围内基于登记的队列研究。

Antibiotic exposure in prenatal and early life and risk of juvenile idiopathic arthritis: a nationwide register-based cohort study.

机构信息

Department of Rheumatology, Oslo University Hospital, Oslo, Norway

Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.

出版信息

RMD Open. 2023 Aug;9(3). doi: 10.1136/rmdopen-2023-003333.

Abstract

OBJECTIVES

Early antibiotic exposure influences the gut microbiota which is believed to be involved in the pathogenesis of juvenile idiopathic arthritis (JIA). We aimed to investigate the association between systemic antibiotics in prenatal and early life and risk of JIA.

METHODS

We conducted a register-based cohort study including all children born in Norway from 2004 through 2012. The children were followed until 31 December 2020. Main exposures were dispensed antibiotics to the mother during pregnancy and to the child during 0-24 months of age. The outcome was defined by diagnostic codes indicating JIA. Multivariate logistic regression analyses were performed to estimate the association between antibiotic exposure and JIA.

RESULTS

We included 535 294 children and their mothers in the analyses; 1011 cases were identified. We found an association between exposure to systemic antibiotics during 0-24 months and JIA (adjusted OR (aOR) 1.40, 95% CI 1.24 to 1.59), with a stronger association for >1 course (aOR 1.50, 95% CI 1.29 to 1.74) vs 1 course (aOR 1.31, 95% CI 1.13 to 1.53). Subanalyses showed significant associations in all age periods except 0-6 months, and stronger association with sulfonamides/trimethoprim and broad-spectrum antibiotics. There was no association between prenatal antibiotic exposure and JIA.

CONCLUSIONS

The novel observation of no association with prenatal antibiotic exposure and JIA suggests that the association between antibiotics in early life and JIA is unlikely to be confounded by shared family factors. This may indicate that exposure to antibiotics in early life is an independent risk factor for JIA.

摘要

目的

早期抗生素暴露会影响肠道微生物群,而肠道微生物群被认为与青少年特发性关节炎(JIA)的发病机制有关。我们旨在研究产前和生命早期全身使用抗生素与 JIA 风险之间的关系。

方法

我们进行了一项基于登记的队列研究,纳入了 2004 年至 2012 年期间在挪威出生的所有儿童。这些儿童随访至 2020 年 12 月 31 日。主要暴露因素为母亲在怀孕期间和儿童在 0-24 个月期间使用抗生素。通过诊断代码来定义 JIA。采用多变量逻辑回归分析来估计抗生素暴露与 JIA 之间的关系。

结果

我们对 535294 名儿童及其母亲进行了分析,共发现 1011 例 JIA 病例。我们发现 0-24 个月期间全身使用抗生素与 JIA 之间存在关联(调整后的比值比[aOR] 1.40,95%置信区间 [CI] 1.24-1.59),使用>1 个疗程的关联更强(aOR 1.50,95%CI 1.29-1.74),而使用 1 个疗程的关联较弱(aOR 1.31,95%CI 1.13-1.53)。亚分析显示,除了 0-6 个月外,所有年龄段均存在显著关联,且与磺胺类药物/甲氧苄啶和广谱抗生素的关联更强。产前抗生素暴露与 JIA 之间无关联。

结论

关于产前抗生素暴露与 JIA 之间无关联的新观察结果表明,生命早期抗生素暴露与 JIA 之间的关联不太可能受到共同的家庭因素的混淆。这可能表明生命早期接触抗生素是 JIA 的一个独立危险因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffb2/10471866/7b1dc5342be3/rmdopen-2023-003333f01.jpg

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