孕期接触大环内酯类药物与自然流产风险:基于人群的回顾性队列研究。

Shani Hegger MD, MPH, Amalia Levy MPH, PhD, Gideon Koren MD, FRCPC, FACMT, Eitan Lunenfeld MD, MHA, Sharon Daniel MD, MPH, PhD
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摘要

以往评估接触大环内酯类药物后自然流产风险的研究报告结果存在争议。本研究旨在探讨孕期接触大环内酯类药物后自然流产的风险。我们通过连接三个计算机化数据库,开展了一项基于人群的回顾性队列研究:Clalit Health Services药物分配数据库、Soroka医疗中心(SMC)出生数据库和SMC住院数据库。该研究进行了多变量时变考克斯回归,并对自然流产的可疑混杂因素和已知风险因素进行了调整。计算了危险比 (HR) 和 95% 置信区间 (CI)。还进行了一项辅助分析,以评估大环内酯类药物的暴露量(按规定的日配药剂量计算)与自然流产之间的关系。研究队列包括2004年至2009年间在索罗卡医疗中心结束的65457例妊娠,其中6508例(9.9%)导致自然流产。共有825名(1.26%)孕妇在接触期间接触了大环内酯类药物。接触大环内酯类药物与自然流产无关(调整后 HR 1.00 95% CI 0.77-1.31),也与特定药物无关。没有证据表明接触大环内酯类药物与自然流产之间存在剂量反应关系。总之,这项以人群为基础的回顾性队列研究并未发现妊娠头三个月接触大环内酯类药物会增加自然流产的风险。
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Exposure to Macrolides During Pregnancy and the Risk for Spontaneous Abortions: A Population-Based Retrospective Cohort Study

Previous studies evaluating the risk of spontaneous abortions following exposure to macrolides reported controversial results. The goal of the current study was to examine the risk for spontaneous abortions following exposure to macrolides during pregnancy.

We conducted a population-based retrospective cohort study by linking three computerized databases: Clalit Health Services drug dispensation database, Soroka Medical Center (SMC) birth database, and SMC hospitalizations database. Multivariate time-varying Cox regressions were performed and adjusted for suspected confounders and known risk factors for spontaneous abortions. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated. A secondary analysis was performed to assess the association between exposure to macrolides in terms of the defined daily dose dispensed and spontaneous abortions.

The study cohort included 65,457 pregnancies that ended at Soroka Medical Center between 2004 and 2009, of which 6508 (9.9%) resulted in a spontaneous abortion. A total of 825 (1.26%) pregnancies were exposed to macrolides during the exposure period. Exposure to macrolides was not associated with spontaneous abortions as a group (adjusted HR 1.00 95% CI 0.77-1.31) or as specific medications. There was no evidence of a dose-response relationship between exposure to macrolides and spontaneous abortions.

In conclusion, this population-based retrospective cohort study did not detect an increased risk for spontaneous abortion following exposure to macrolides during the first trimester of pregnancy.

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