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中国循证儿科杂志

中国循证儿科杂志 ›› 2017, Vol. 12 ›› Issue (6): 416-422.

• 论著 • 上一篇    下一篇

母孕期使用抗生素对后代患哮喘风险的Meta分析

苏艳艳1），耿刚2），付文龙2），龚财惠3），汪东海2），代继宏2）   

  1. 重庆医科大学附属儿童医院重庆，400014；1）儿童发育与疾病教育部重点实验室；2）呼吸中心；2）肺功能室
  • 收稿日期:2017-11-09 修回日期:2017-12-22 出版日期:2017-12-25 发布日期:2017-12-25
  • 通讯作者: 代继宏，E-mail: danieljh@163.com

Meta-analysis of the relationship between prenatal antibiotic use and risk of asthma in offspring

SU Yan-yan 1 ), GENG Gang 2), FU Wen-long 2), GONG Cai-hui 3), WANG Dong-hai 2), DAI Ji-hong 2)   

  1. Children’s Hospital, Chongqing Medical University, Chongqing 400014, China; 1) Key Laboratory of Developmental Diseases in Childhood of Ministry of Education, 2) Center of Respiratory Disorders, 3) Lung Function Laboratory
  • Received:2017-11-09 Revised:2017-12-22 Online:2017-12-25 Published:2017-12-25
  • Contact: DAI Ji-hong, E-mail: danieljh@163.com

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摘要： 摘要 目的：评估母亲孕期使用抗生素与儿童发生哮喘的关系。方法：检索中国知网数据库、中国维普科技期刊数据库、万方数据库以及PubMed、EMBASE、Cochrane、Ovid等数据库中关于母孕期使用抗生素与儿童哮喘的队列研究，采用 Stata12.0 软件，通过 Meta 分析方法探讨二者之间的关系。结果：纳入有儿童哮喘患病率和儿童哮喘暴露因素关联性结果（OR、RR或HR）的文献，共纳入9 项研究，均调整了母亲哮喘、吸烟等混杂因素， Meta分析结果显示:①母孕期抗生素的使用增加了儿童哮喘的风险（OR=1.14，95%CI：1.13~1.15），I2=96.5%，逐篇去除行敏感性分析，再次汇总OR =1.27（95% CI：1.17~1.38，I2=0），未对最终结果造成 明显影响；临床异质性分析：以3岁为界行亚组分析，＜3岁和≥3岁亚组文献汇总OR分别为1.85（95%CI：0.80~4.29，I2=78.8%）和1.19（95%CI：1.08~1.31，I2=96.8%）；以不同孕期行亚组分析，孕早、中和晚期OR分别为1.29（95%CI：1.23~1.34）、1.30（95%CI：1.25~1.35）和1.26（95%CI：1.21~1.31），I2均为0；以不同暴露因素获取方式行亚组分析，自我报告（采访）和来源于数据库文献汇总OR分别为1.27（95%CI：1.10~1.48，I2=71.2%）和1.20（95%CI：1.08~1.32，I2=98.6%）；以不同抗生素行亚组分析，β-内酰胺类OR=1.18（95%CI：1.08~1.30，I2=0），磺胺嘧啶OR=1.19（95%CI：0.78~1.83，I2=83.5%）。②以同胞为亚组分析，文献汇总OR=0.91（95%CI：0.79~1.06，I2=93.3%）。分别采用Begg 秩相关法和Egger直线回归法未发现明显发表偏倚。结论：本Meta分析显示母孕期使用抗生素可增加后代哮喘的风险，但同胞对照组研究显示母孕期使用抗生素与后代哮喘不关联，家庭环境、遗传等残余因素可能是重要的混杂因素，孕期抗生素使用与后代哮喘的因果关系有待进一步研究。

Abstract: AbstractObjective: To evaluate the association between the antibiotic use during pregnancy and childhood asthma. Methods: The Chinese and English databases CNKI, Wanfang Data，Chinese VIP science and technology periodical database, PubMed, EMBASE, Cochrane and ovid were searched for cohort studies on the association between the use of antibacterial agents in pregnancy and childhood asthma. This meta-analysis with Stata12.0 software explored the relationship between antibiotic and asthma.Results: There were 9 studies with the prevalence of childhood asthma and asthma exposure results related factors (OR, RR or HR) and were adjusted for maternal asthma, smoking and other confounding factors.The results of the meta-analysis showed that the use of antibacterial agents in pregnancy increased the risk of childhood asthma (OR=1.14, 95%CI: 1.13-1.15).Because of the high heterogeneity(I2=96.5%),analysis of the heterogeneity among literatures was carried out: the sensitivity analysis was made by removing each article,and the pooled risk estimates of asthma (OR=1.27, 95% CI: 1.17-1.38, I2=0）after excluding the studies of high heterogeneity that did not affect the final result;analysis of clinical heterogeneity: the subgroup analysis with the age of 3 years of asthma onset was performed ,and the pooled effect size OR of studies with < 3 years and ≥3 years respectively was 1.85(95%CI: 0.80-4.29, I2=78.8%) and OR=1.19 (95%CI: 1.08-1.31, I2=96.8%); stratified by trimesters of pregnancy, the OR was 1.29(95%CI: 1.23-1.34), 1.30(95%CI: 1.25-1.35) and 1.26(95%CI: 1.21-1.31) for the early-, mid-and late- pregnancy, respectively, and I2 =0; stratified by antibiotic assessment, the pooled OR from self reporting(interviews) and from the database was 1.27 (95%CI: 1.10-1.48, I2=71.2%), and 1.20 (95%CI:1.08-1.32, I2=98.6%) respectively; stratified by antibiotic tepy,the OR was 1.18（95%CI: 1.08-1.30，I2=0） for Beta- lactam antibiotics and 1.19（95%CI: 0.78-1.83，I2=83.5%）for Sulfonamides and trimethoprim. ②In sibling analyses, the pooled OR was 0.91 (95%CI: 0.79-1.06, I2=93.3%). There was no publication bias by the Begg rank correlation test and the Egger linear regression test.Conclusion: This meta-analysis suggested that antibiotic exposure during pregnancy may increase the risk of asthma in offspring.But in the sibling control analysis the associations disappeared, indicating the residual factors such as family environment,heredity and so on were important confounding factors that may lead to reverse causality. Therefore, the causal relationship between antibiotic use during pregnancy and risk of asthma in offspring needs further investigation.