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儿童时期使用抗生素与阑尾炎发病风险的关系:一项全国性队列研究

Antibiotics during childhood and development of appendicitis-a nationwide cohort study.

机构信息

Digestive Disease Centre, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark.

Centre for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.

出版信息

Aliment Pharmacol Ther. 2021 Jan;53(1):87-93. doi: 10.1111/apt.16084. Epub 2020 Sep 15.

Abstract

BACKGROUND

Appendicitis is a common disease with a lifespan risk of approximately 8%. The full range of specific causes for the disease remains elusive, but an aberrant microbiota have been identified as a potential risk factor.

AIM

To investigate if use of antibiotics in a paediatric population increases the risk of appendicitis in childhood and adolescence METHODS: We conducted a cohort study from 1 January 1995 to 31 December 2014. A total of 1 385 707 children (0-19 years of age) including 7 406 397 antibiotic prescriptions and 11 861 cases of appendicitis were included. Primary outcome was appendicitis requiring appendectomy according to previous use of antibiotics. Appendicitis and appendectomy were identified from nationwide hospital records, and exposure to antibiotics was identified from nationwide prescription register. Rate ratios (RRs) with 95% confidence intervals were estimated from Poisson and logistic regression models.

RESULTS

Children who received at least one course of antibiotics were at increased risk of developing appendicitis compared to unexposed children (adjusted RR 1.72 [95% confidence interval 1.61-1.85]), mean age of developing appendicitis was 9.8 years (SD 4.1 years). The RR of appendicitis increased by 1.04 (1.04-1.04) per antibiotic course. A higher risk of appendicitis was observed in children exposed to antibiotics within the first 6 months of life (RR 1.46 [1.36-1.56]) and children exposed to broad-spectrum antibiotics (RR 1.33 [1.27-1.39]). After adjustment for number of antibiotic courses, the association between early age of antibiotic exposure and risk of appendicitis and the association between exposure to broad-spectrum antibiotics and the risk of appendicitis both disappeared.

CONCLUSION

Children who receive antibiotics are at increased and dose-dependent risk of appendicitis. The underlying mechanisms merit further investigation.

摘要

背景

阑尾炎是一种常见疾病,其终身风险约为 8%。尽管尚未明确该病的所有具体病因,但异常的微生物群已被确定为潜在的风险因素。

目的

研究儿科人群使用抗生素是否会增加儿童和青少年阑尾炎的风险。

方法

我们进行了一项队列研究,时间范围为 1995 年 1 月 1 日至 2014 年 12 月 31 日。共纳入 1385707 名儿童(0-19 岁),包括 7406397 次抗生素处方和 11861 例阑尾炎。主要结局为根据既往使用抗生素情况确定的需要阑尾切除术的阑尾炎。阑尾炎和阑尾切除术是从全国性医院记录中确定的,抗生素暴露是从全国性处方登记处确定的。使用泊松和逻辑回归模型估计率比(RR)及其 95%置信区间。

结果

与未暴露儿童相比,至少接受过一次抗生素疗程的儿童发生阑尾炎的风险增加(调整后的 RR 1.72 [95%置信区间 1.61-1.85]),发生阑尾炎的平均年龄为 9.8 岁(标准差 4.1 岁)。每使用一个疗程抗生素,阑尾炎的风险增加 1.04(1.04-1.04)。在生命的前 6 个月暴露于抗生素的儿童(RR 1.46 [1.36-1.56])和暴露于广谱抗生素的儿童(RR 1.33 [1.27-1.39])中,阑尾炎的风险更高。在校正抗生素疗程数后,早期抗生素暴露与阑尾炎风险之间的关联以及广谱抗生素暴露与阑尾炎风险之间的关联均消失。

结论

接受抗生素治疗的儿童阑尾炎的风险增加且呈剂量依赖性。其潜在机制值得进一步研究。

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