Department of Medical and Surgical Science of the Infant and Adult, University of Modena and Reggio Emilia, Modena, Italy.
Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
PLoS One. 2023 Feb 22;18(2):e0277563. doi: 10.1371/journal.pone.0277563. eCollection 2023.
Prevention of preterm birth (PTB) with progestogens after an episode of threatened preterm labour is still controversial. As different progestogens have distinct molecular structures and biological effects, we conducted a systematic review and pairwise meta-analysis to investigate the individual role played by 17-alpha-hydroxyprogesterone caproate (17-HP), vaginal progesterone (Vaginal P) and oral progesterone (Oral P).
The search was performed in MEDLINE, ClinicalTrials.gov and the Cochrane Central Register of Controlled Trials (CENTRAL) up to 31 October 2021. Published RCTs comparing progestogens to placebo or no treatment for maintenance tocolysis were considered. We included women with singleton gestations, excluding quasi-randomized trials, studies on women with preterm premature rupture of membrane, or receiving maintenance tocolysis with other drugs. Primary outcomes were preterm birth (PTB) < 37 weeks' and < 34 weeks'. We assessed risk of bias and evaluated certainty of evidence with the GRADE approach.
Seventeen RCTs including 2152 women with singleton gestations were included. Twelve studies tested vaginal P, five 17-HP, and only 1 oral P. PTB < 34 weeks' did not differ among women receiving vaginal P (RR 1.21, 95%CI 0.91 to 1.61, 1077 participants, moderate certainty of evidence), or oral P (RR 0.89, 95%CI 0.38 to 2.10, 90 participants, low certainty of evidence) as opposed to placebo. Instead, 17-HP significantly reduced the outcome (RR 0.72, 95% CI 0.54 to 0.95, 450 participants, moderate certainty of evidence). PTB < 37 weeks' did not differ among women receiving vaginal P (RR 0.95, 95%CI 0.72 to 1.26, 8 studies, 1231 participants, moderate certainty of evidence) or 17-HP (RR 0.86, 95%CI 0.60 to 1.21, 450 participants, low certainty of evidence) when compared to placebo/no treatment. Instead, oral P significantly reduced the outcome (RR 0.58, 95% CI 0.36 to 0.93, 90 participants, low certainty of evidence).
With a moderate certainty of evidence, 17-HP prevents PTB < 34 weeks' gestation among women that remained undelivered after an episode of threatened preterm labour. However, data are insufficient to generate recommendations in clinical practice. In the same women, both 17-HP and vaginal P are ineffective in the prevention of PTB < 37 weeks'.
对于曾有早产先兆的患者，使用孕激素预防早产（PTB）仍存在争议。由于不同的孕激素具有不同的分子结构和生物学效应，我们进行了系统评价和成对荟萃分析，以研究 17-α-羟孕酮己酸酯（17-HP）、阴道孕酮（Vaginal P）和口服孕酮（Oral P）各自的作用。
我们在 MEDLINE、ClinicalTrials.gov 和 Cochrane 对照试验中心注册库（CENTRAL）中进行了检索，检索时间截至 2021 年 10 月 31 日。纳入了比较孕激素与安慰剂或无治疗用于维持保胎治疗的随机对照试验。我们纳入了单胎妊娠的女性，排除了半随机试验、有早产胎膜早破的女性、或接受其他药物维持保胎治疗的女性。主要结局为 37 周前早产（PTB）和 34 周前早产。我们使用 GRADE 方法评估了偏倚风险和证据质量。
共纳入了 17 项 RCT，涉及 2152 名单胎妊娠女性。12 项研究测试了阴道 P，5 项研究测试了 17-HP，只有 1 项研究测试了口服 P。与安慰剂相比，阴道 P 组（RR 1.21，95%CI 0.91 至 1.61，1077 名参与者，证据质量为中等）或口服 P 组（RR 0.89，95%CI 0.38 至 2.10，90 名参与者，证据质量为低）的 34 周前早产率没有差异。相反，17-HP 显著降低了该结局（RR 0.72，95%CI 0.54 至 0.95，450 名参与者，证据质量为中等）。与安慰剂/无治疗相比，阴道 P 组（RR 0.95，95%CI 0.72 至 1.26，8 项研究，1231 名参与者，证据质量为中等）或 17-HP 组（RR 0.86，95%CI 0.60 至 1.21，450 名参与者，证据质量为低）的 37 周前早产率没有差异。相反，口服 P 显著降低了该结局（RR 0.58，95%CI 0.36 至 0.93，90 名参与者，证据质量为低）。
中等质量证据表明，对于曾有早产先兆的患者，在经历早产先兆后仍未分娩的患者中，17-HP 可预防 34 周前早产。然而，数据不足以在临床实践中提出建议。在这些女性中，17-HP 和阴道 P 均不能预防 37 周前早产。
