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婴儿期反复接触抗生素:是幼年特发性关节炎的诱发因素,还是该群体对感染更易感性的一种表现?

Repeated exposure to antibiotics in infancy: a predisposing factor for juvenile idiopathic arthritis or a sign of this group's greater susceptibility to infections?

作者信息

Arvonen Miika, Virta Lauri J, Pokka Tytti, Kröger Liisa, Vähäsalo Paula

机构信息

From the Department of Pediatrics, Kuopio University Hospital, Kuopio, and University of Eastern Finland, Kuopio; Research Department, Social Insurance Institution, Turku; Medical Research Center Oulu, Department of Pediatrics, Oulu University Hospital and University of Oulu, Oulu, Finland.M. Arvonen, MD, PhD, Department of Pediatrics, Kuopio University Hospital, University of Eastern Finland, and Medical Research Center Oulu, Department of Pediatrics, Oulu University Hospital, University of Oulu; L.J. Virta, MD, PhD, Research Department, Social Insurance Institution; T. Pokka, MSc, Medical Research Center Oulu, Department of Pediatrics, Oulu University Hospital, and University of Oulu; L. Kröger, MD, PhD, Department of Pediatrics, Kuopio University Hospital, and University of Eastern Finland; P. Vähäsalo, MD, PhD, Medical Research Center Oulu, Department of Pediatrics, Oulu University Hospital, and University of Oulu.

出版信息

J Rheumatol. 2015 Mar;42(3):521-6. doi: 10.3899/jrheum.140348. Epub 2014 Oct 15.

Abstract

OBJECTIVE

Previous exposure to antibiotics has been associated with the pathogenesis of several autoimmune diseases. Our objective was to explore whether childhood exposure to antibiotics would be associated with the risk of developing juvenile idiopathic arthritis (JIA).

METHODS

The material was collected from national registers containing all children born in 2000-2010 in Finland and diagnosed with JIA by the end of December 2012 (n = 1298) and appropriate controls (n = 5179) matched for age, sex, and place of birth. All purchases of antibiotics were collected from birth until the index date (i.e., the date of special reimbursement for JIA medications). A conditional logistic regression was performed to evaluate the association between the exposure to antibiotics and the risk of JIA.

RESULTS

The risk of JIA increased with the number of antibiotic purchases from birth to the index date: for ≥ 1 purchases versus none, OR 1.6, 95% CI 1.3-1.9 with an upward trend in OR (p < 0.001). Antibiotic groups lincosamides and cephalosporins showed the strongest association with JIA (OR 6.6, 95% CI 3.7-11.7, and OR 1.6, 95% CI 1.4-1.8, respectively). Overall exposure to antibiotics before 2 years of age was associated with an increased risk of JIA (OR 1.4, 95% CI 1.2-1.6), with the trend test of OR (p < 0.001).

CONCLUSION

Previous early and repeated exposure to antibiotics may predispose individuals to develop JIA. Alternatively, the apparent association may reflect shared susceptibility to infections and JIA.

摘要

目的

既往接触抗生素与多种自身免疫性疾病的发病机制有关。我们的目的是探讨儿童期接触抗生素是否与幼年特发性关节炎(JIA)的发病风险相关。

方法

研究材料取自芬兰国家登记册,其中包含2000年至2010年出生且在2012年12月底前被诊断为JIA的所有儿童(n = 1298)以及按年龄、性别和出生地匹配的适当对照(n = 5179)。收集从出生到索引日期(即JIA药物特殊报销日期)的所有抗生素购买记录。进行条件逻辑回归以评估抗生素暴露与JIA风险之间的关联。

结果

从出生到索引日期购买抗生素的数量越多,患JIA的风险越高:≥1次购买与未购买相比,比值比(OR)为1.6,95%置信区间(CI)为1.3 - 1.9,且OR呈上升趋势(p < 0.001)。林可酰胺类和头孢菌素类抗生素与JIA的关联最强(OR分别为6.6,95%CI为3.7 - 11.7,以及OR为1.6,95%CI为1.4 - 1.8)。2岁前总体接触抗生素与JIA风险增加相关(OR为1.4,95%CI为1.2 - 1.6),OR趋势检验(p < 0.001)。

结论

既往早期和反复接触抗生素可能使个体易患JIA。或者,这种明显的关联可能反映了对感染和JIA的共同易感性。

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