Vaginal progesterone for preterm birth prevention in women with arrested preterm labor

We tested the hypothesis that administration of vaginal progesterone in women with arrested preterm labor would result in lower rates of preterm birth &lt;37 weeks compared to placebo. We performed a randomized, placebo-controlled trial comparing vaginal progesterone to placebo in women with arrested preterm labor. Our trial included women with a singleton or twin gestation at 24⁰^/7–33^6/7 weeks’ gestation who presented with preterm labor with cervical dilation ≥1 centimeter but remained undelivered. Participants were randomized to receive vaginal progesterone 200 mg daily or an identical placebo. The primary outcome was preterm birth &lt;37 weeks. We performed an updated systematic review and meta-analysis of clinical trials, including our results. We searched MEDLINE, EMBASE, CINHAL, Scopus, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov using the key terms to identify relevant trials. The risk of bias was appraised using the Cochrane risk-of-bias tool. Data were synthesized using random-effects models. Heterogeneity was assessed using Higgins <i>I</i>². The randomized trial was prematurely terminated due to slow recruitment. There were 18 women randomized to receive vaginal progesterone who had complete follow-up data and 18 women in the placebo group. The risk of preterm birth &lt;37 weeks was not significantly different in the groups (RR 1.10, 95% CI 0.63–1.19). Secondary outcomes were also similar. Thirteen trials with 1658 women (835 in the vaginal progesterone and 823 in the control groups) were included in the meta-analysis. Risk of preterm birth &lt;37 weeks was similar in women who received progesterone and those in the control group (pooled RR 1.06, 95% CI 0.83–1.35). Latency was significantly longer among women with arrested preterm labor who received vaginal progesterone (weighted mean difference: 9.2 d, 95% CI 3.2–15.1), but further analysis showed that prolonged latency was only observed in the subgroup of studies that were not placebo-controlled. This randomized controlled trial and meta-analysis do not support the use of vaginal progesterone for the prevention of preterm birth in women who present in preterm labor.

我们验证了如下假说：对于发生早产阻滞的孕妇，相较于安慰剂（placebo），给予阴道用孕激素（vaginal progesterone）可降低<37孕周的早产发生率。我们开展了一项随机安慰剂对照试验（randomized, placebo-controlled trial），对比阴道用孕激素与安慰剂在早产阻滞孕妇中的应用效果。本试验纳入孕周为24⁰/₇至33⁶/₇周的单胎或双胎妊娠孕妇，这些孕妇因早产临产就诊，宫颈扩张≥1厘米但尚未分娩。参与者被随机分配至每日接受200mg阴道用孕激素组，或外观一致的安慰剂组。本试验的主要结局指标为<37孕周的早产发生率。我们更新了一项系统综述（systematic review）并开展了荟萃分析（meta-analysis），纳入本试验的研究结果。我们通过检索MEDLINE、EMBASE、CINHAL、Scopus、Cochrane系统综述数据库以及ClinicalTrials.gov，使用关键术语筛选相关临床试验。采用Cochrane偏倚风险工具（Cochrane risk-of-bias tool）评估研究的偏倚风险。采用随机效应模型（random-effects models）对数据进行合并分析。采用Higgins I²统计量评估研究间异质性。本随机对照试验因招募进度缓慢提前终止。阴道用孕激素组共有18名孕妇完成随访并获得完整数据，安慰剂组亦有18名孕妇。两组的<37孕周早产发生率无显著差异（相对危险度RR=1.10，95%置信区间CI：0.63~1.19）。次要结局指标亦无显著组间差异。本次荟萃分析共纳入13项临床试验，涉及1658名孕妇（阴道用孕激素组835名，对照组823名）。结果显示，孕激素组与对照组孕妇的<37孕周早产发生率无显著差异（合并相对危险度pooled RR=1.06，95%置信区间CI：0.83~1.35）。接受阴道用孕激素的早产阻滞孕妇，其妊娠潜伏期显著延长（加权均数差：9.2天，95%CI：3.2~15.1），但进一步分析显示，该潜伏期延长仅在非安慰剂对照的研究亚组中被观察到。本随机对照试验与荟萃分析结果不支持在早产临产孕妇中使用阴道用孕激素预防早产。