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婴幼儿中耳炎和其他呼吸道感染的抗生素治疗与 1 型糖尿病风险相关:一项基于全国登记的研究和同胞分析。

Early Childhood Antibiotic Treatment for Otitis Media and Other Respiratory Tract Infections Is Associated With Risk of Type 1 Diabetes: A Nationwide Register-Based Study With Sibling Analysis.

机构信息

Molecular Epidemiology, Department of Medical Sciences, and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.

出版信息

Diabetes Care. 2020 May;43(5):991-999. doi: 10.2337/dc19-1162. Epub 2020 Mar 4.

Abstract

OBJECTIVE

The effect of early-life antibiotic treatment on the risk of type 1 diabetes is debated. This study assessed this question, applying a register-based design in children up to age 10 years including a large sibling-control analysis.

RESEARCH DESIGN AND METHODS

All singleton children ( = 797,318) born in Sweden between 1 July 2005 and 30 September 2013 were included and monitored to 31 December 2014. Cox proportional hazards models, adjusted for parental and perinatal characteristics, were applied, and stratified models were used to account for unmeasured confounders shared by siblings.

RESULTS

Type 1 diabetes developed in 1,297 children during the follow-up (median 4.0 years [range 0-8.3]). Prescribed antibiotics in the 1st year of life (23.8%) were associated with an increased risk of type 1 diabetes (adjusted hazard ratio [HR] 1.19 [95% CI 1.05-1.36]), with larger effect estimates among children delivered by cesarean section ( for interaction = 0.016). The association was driven by exposure to antibiotics primarily used for acute otitis media and respiratory tract infections. Further, we found an association of antibiotic prescriptions in pregnancy (22.5%) with type 1 diabetes (adjusted HR 1.15 [95% CI 1.00-1.32]). In general, sibling analysis supported these results, albeit often with statistically nonsignificant associations.

CONCLUSIONS

Dispensed prescription of antibiotics, mainly for acute otitis media and respiratory tract infections, in the 1st year of life is associated with an increased risk of type 1 diabetes before age 10 years, most prominently in children delivered by cesarean section.

摘要

目的

关于早期抗生素治疗对 1 型糖尿病风险的影响存在争议。本研究通过在 10 岁以下儿童中应用基于登记的设计,包括一项大型的同胞对照分析,评估了这一问题。

研究设计和方法

所有于 2005 年 7 月 1 日至 2013 年 9 月 30 日期间在瑞典出生的单胎儿童(=797318)均被纳入研究,并随访至 2014 年 12 月 31 日。应用 Cox 比例风险模型,根据父母和围产期特征进行调整,并使用分层模型来解释同胞间未测量的混杂因素。

结果

在随访期间,797318 名儿童中有 1297 名(中位数为 4.0 年[范围 0-8.3])发展为 1 型糖尿病。在生命的第 1 年中开具的抗生素(23.8%)与 1 型糖尿病的风险增加相关(校正后的风险比[HR]1.19[95%CI 1.05-1.36]),剖宫产分娩的儿童的估计值更大(交互检验 P=0.016)。这种关联主要是由用于急性中耳炎和呼吸道感染的抗生素暴露引起的。此外,我们发现妊娠期间开具的抗生素处方(22.5%)与 1 型糖尿病相关(校正后的 HR 1.15[95%CI 1.00-1.32])。总体而言,同胞分析支持这些结果,但通常关联的统计学意义不显著。

结论

生命的第 1 年中开具的抗生素处方(主要用于急性中耳炎和呼吸道感染)与 10 岁以下儿童 1 型糖尿病的风险增加有关,在剖宫产分娩的儿童中最为明显。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca84/7171951/448556ffcdad/dc191162f1.jpg

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