背景:孕激素和环扎术在高危妊娠早产预防中单独有效。然而,国家和国际指南都缺乏数据来评论环扎术后同步使用孕激素治疗的潜在益处.迄今为止,有关孕激素并发环扎的益处的研究很少,结果参差不齐,这给最佳临床实践带来了不确定性。
目的:本研究旨在评估孕激素环扎术在预防单胎妊娠自发性早产方面是否优于单独环扎术。
方法:这是一项单胎妊娠的国际回顾性队列研究,没有重大异常或非整倍性,并在2016年6月至2020年6月期间在美国和哥伦比亚的10个不同机构进行环扎。排除标准是缺乏关于孕激素是否处方的文件,不可用的交付结果,妊娠16周前终止妊娠(自发或诱导)。感兴趣的暴露是使用孕激素与环扎放置,其中包括那些继续使用孕激素或环扎后开始使用孕激素的人。对照组包括环扎放置后不使用孕激素的人,其中包括那些在整个怀孕期间没有使用孕激素的人,或者那些开始使用孕激素,然后在环扎放置后停止使用孕激素的人。孕激素类型,环扎指征,母体基线特征,收集产妇/新生儿结局.主要结果是<37周时的自发性早产。次要结局是<34周时的自发性早产,分娩时的胎龄,和复合新生儿结局,包括≥1以下:围产期死亡率,确诊脓毒症,III或IV级脑室内出血,早产儿视网膜病变,呼吸窘迫综合征,支气管肺发育不良.根据环扎适应症计划进行亚组分析,孕激素类型(阴道孕酮vs17-羟孕酮己酸),早产史,和网站。连续变量在调整后的分析中与协方差分析进行了比较,和分类变量与多变量逻辑回归进行比较,用调整后的比值比调整潜在的混杂因素。生成Cox回归存活曲线以比较潜伏期与自发分娩,37周后审查。
结果:在研究期间,共有699例患者符合纳入标准:孕激素环扎组561例,单用环扎组138例.基线特征相似,孕激素组先前自发性早产的可能性较高(61%vs41%;P<.001)。在孕激素组中,52%的人每周服用17-羟孕酮己酸酯,44%的阴道孕酮每日服用,每天口服孕酮3%。孕激素环扎与自发性早产<37周的频率显着降低相关(31%vs39%;调整后的比值比,0.59[0.39-0.89];P=0.01)和<34周(19%对27%;调整后的赔率比,0.55[0.35-0.87];P=.01),自发分娩的潜伏期增加(自发性早产的风险比<37周,0.66[0.49-0.90];P=.009),围产期死亡的频率较低(7%对16%;调整后的比值比,0.37[0.20-0.67];P=.001)。在计划的亚组分析中,在阴道孕酮治疗的患者中,早产<37周的几率降低的相关性仍然存在,那些以前没有早产的人,那些有超声或检查指示的环扎,那些在环扎前开始孕激素治疗的人,以及仅限于美国的网站。
结论:与单用环扎相比,使用孕激素并环扎可降低自发性早产和早期自发性早产的发生率。尽管这项研究不足以进行亚组分析,对于那些有超声或检查指示的环扎术的人来说,获益的证据强度最大,还有阴道孕酮.
Both progestogens and cerclage are individually effective in preterm birth prevention in high risk pregnancies. However, national and international guidelines cite a lack of data available to comment on the potential benefit of concurrent progestogen therapy after cerclage has been placed. Studies to date have been small with mixed results regarding benefit of concurrent
progestogen with cerclage leaving uncertainty regarding best clinical practice.
This study aimed to evaluate whether cerclage with
progestogen therapy was superior to cerclage alone in the prevention of spontaneous preterm birth in singleton pregnancies.
This is an international retrospective cohort study of singleton pregnancies, without major anomaly or aneuploidy, and with cerclage placed at 10 different institutions in the United States and Colombia from June 2016 to June 2020. Exclusion criteria were lack of documentation regarding whether
progestogen was prescribed, unavailable delivery outcome, and pregnancy termination (spontaneous or induced) before 16 weeks\' gestation. The exposure of interest was progestogen use with cerclage placement, which included those who continued to use
progestogen or who started
progestogen after cerclage. The comparison group consisted of those without progestogen use after cerclage placement, which included those who had no
progestogen use during the entire pregnancy or who initiated
progestogen and then stopped it after cerclage placement. Progestogen type, cerclage indication, maternal baseline characteristics, and maternal/neonatal outcomes were collected. The primary outcome was spontaneous preterm birth at <37 weeks. The secondary outcomes were spontaneous preterm birth at <34 weeks, gestational age at delivery, and a composite neonatal outcome including ≥1 of the following: perinatal mortality, confirmed sepsis, grade III or IV intraventricular hemorrhage, retinopathy of prematurity, respiratory distress syndrome, and bronchopulmonary dysplasia. There were planned subgroup analyses by cerclage indication, progestogen type (vaginal progesterone vs 17-hydroxyprogesterone caproate), preterm birth history, and site. Continuous variables were compared in adjusted analyses with analysis of covariance, and categorical variables were compared with multivariable logistic regression, adjusting for potential confounders with adjusted odds ratio. A Cox regression survival curve was generated to compare latency to spontaneous delivery, censored after 37 weeks.
During the study period, a total of 699 singletons met the inclusion criteria: 561 in the progestogen with cerclage group and 138 with cerclage alone. Baseline characteristics were similar, except the higher likelihood of previous spontaneous preterm birth in the progestogen group (61% vs 41%; P<.001). Within the progestogen group, 52% were on 17-hydroxyprogesterone caproate weekly, 44% on vaginal progesterone daily, and 3% on oral progesterone daily. Progestogen with cerclage was associated with a significantly lower frequency of spontaneous preterm birth <37 weeks (31% vs 39%; adjusted odds ratio, 0.59 [0.39-0.89]; P=.01) and <34 weeks (19% vs 27%; adjusted odds ratio, 0.55 [0.35-0.87]; P=.01), increased latency to spontaneous delivery (hazard ratio for spontaneous preterm birth <37 weeks, 0.66 [0.49-0.90]; P=.009), and lower frequency of perinatal death (7% vs 16%; adjusted odds ratio, 0.37 [0.20-0.67]; P=.001). In planned subgroup analyses, association with reduced odds of preterm birth <37 weeks persisted in those on vaginal progesterone, those without a previous preterm birth, those with ultrasound- or examination-indicated cerclage, those who started progestogen therapy before cerclage, and in sites restricted to the United States.
Use of progestogen with cerclage was associated with reduced rates of spontaneous preterm birth and early spontaneous preterm birth compared with cerclage alone. Although this study was not sufficiently powered for subgroup analysis, the strength of evidence for benefit appeared greatest for those with ultrasound- or examination-indicated cerclage, and with vaginal progesterone. El resumen está disponible en Español al final del artículo.