Department of Gynecology and Obstetrics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Department of Epidemiology, School of Public Health, Iran University of Medical Sciences, P.O. Box: 22431993, Tehran, Iran.
Arch Gynecol Obstet. 2020 Jul;302(1):5-22. doi: 10.1007/s00404-020-05569-4. Epub 2020 May 14.
This systematic review and meta-analysis of observational studies were conducted to assess the association between antibiotics use during pregnancy and spontaneous miscarriage.
A systematic search of online databases as well as reference lists of retrieved studies were performed up to September 2018 to identify observational studies that investigated the association between antibiotics use and spontaneous miscarriage. The retrieved studies were assessed for methodological quality. Pooled relative risk (RR) and 95% confidence intervals were calculated using DerSimonian and Laird method. Random-effects meta-analysis was used to account for conceptual heterogeneity. Sensitivity analysis was performed to assess the robustness of pooled estimates using Stata software.
Of 1435 retrieved studies, 89 were reviewed in depth and 12 (8 prospective cohort and 4 population-based case-control studies) met the criteria for inclusion in a systematic review with 1,084,792 participants and 7015 cases of spontaneous miscarriage. Finally, 11 studies were included in the meta-analysis (one study was not included in the meta-analysis owing to methodological issues and low-quality score). Overall percentage of miscarriage in women who received antibiotics was 2.6%. After adjusting for important potential confounders, use of macrolides (RR: 1.42; 95% CI 1.04, 1.93), quinolones (RR: 2.48; 95% CI 1.46, 4.20), and tetracyclines (RR: 2.57; 95% CI 1.95, 3.38) during pregnancy were significantly associated with spontaneous miscarriage. In macrolides class, a significant positive association was found between clarithromycin and spontaneous miscarriage (RR: 1.98; 95% CI 1.46, 2.70). Sensitivity analysis demonstrated the consistency of the results, indicating that the meta-analysis model was robust.
Findings support a significant positive association between use of macrolides (especially clarithromycin), quinolones, and tetracyclines during pregnancy and spontaneous miscarriage, although it should be interpreted with caution in the context of limitations of the available data.
International register for systematic reviews; PROSPEROCRD42018093465.
本系统评价和荟萃分析观察性研究旨在评估妊娠期间使用抗生素与自然流产之间的关联。
系统检索在线数据库以及检索研究的参考文献列表，以确定调查抗生素使用与自然流产之间关联的观察性研究。对检索到的研究进行方法学质量评估。使用 DerSimonian 和 Laird 方法计算汇总相对风险 (RR) 和 95%置信区间。使用随机效应荟萃分析来解释概念异质性。使用 Stata 软件进行敏感性分析，以评估汇总估计值的稳健性。
在 1435 篇检索到的研究中，有 89 篇进行了深入审查，其中 12 篇（8 项前瞻性队列研究和 4 项基于人群的病例对照研究）符合系统评价的标准，共有 1084792 名参与者和 7015 例自然流产。最终，有 11 项研究纳入荟萃分析（由于方法学问题和低质量评分，有 1 项研究未纳入荟萃分析）。接受抗生素治疗的女性流产的总体百分比为 2.6%。在调整重要潜在混杂因素后，妊娠期间使用大环内酯类（RR：1.42；95%CI 1.04，1.93）、喹诺酮类（RR：2.48；95%CI 1.46，4.20）和四环素类（RR：2.57；95%CI 1.95，3.38）与自然流产显著相关。在大环内酯类药物中，发现克拉霉素与自然流产之间存在显著正相关（RR：1.98；95%CI 1.46，2.70）。敏感性分析表明结果一致，表明荟萃分析模型稳健。
研究结果支持妊娠期间使用大环内酯类（尤其是克拉霉素）、喹诺酮类和四环素类与自然流产之间存在显著正相关，但鉴于现有数据的局限性，应谨慎解释这些发现。
国际系统评价注册库；PROSPEROCRD42018093465。
