Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial
Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial
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DOI：
10.1002/uog.9017
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发表时间：
2011-07-01
影响因子：
7.1
通讯作者：
Creasy, G. W.
中科院分区：
文献类型：
--
作者：
Hassan, S. S.;Romero, R.;Creasy, G. W.
目的：妊娠中期超声检查显示宫颈短的女性早产风险增加。本研究旨在确定使用微粒化阴道孕酮凝胶对超声检查显示宫颈短的女性降低早产风险及相关新生儿并发症的有效性和安全性。
方法：这是一项多中心、随机、双盲、安慰剂对照试验，纳入了妊娠19 + 0至23 + 6周、单胎妊娠且超声检查显示宫颈短（10 - 20毫米）的无症状女性。从20至23 + 6周开始，女性被随机分配每日接受阴道孕酮凝胶或安慰剂治疗，直至36 + 6周、胎膜破裂或分娩（以先发生者为准）。随机分组序列根据研究中心和既往早产史进行分层。主要终点是妊娠33周前早产。采用意向性治疗分析。
结果：在随机分组的465名女性中，7人失访，458人（阴道孕酮凝胶组n = 235；安慰剂组n = 223）纳入分析。分配接受阴道孕酮治疗的女性在33周前早产的发生率低于分配接受安慰剂的女性（8.9%（n = 21）对16.1%（n = 36）；相对风险（RR），0.55；95%置信区间，0.33 - 0.92；P = 0.02）。在对协变量进行调整后，该效应仍然显著（调整后的RR，0.52；95%置信区间，0.31 - 0.91；P = 0.02）。阴道孕酮还与28周前早产发生率显著降低（5.1%对10.3%；RR，0.50；95%置信区间，0.25 - 0.97；P = 0.04）以及35周前早产发生率显著降低（14.5%对23.3%；RR，0.62；95%置信区间，0.42 - 0.92；P = 0.02）、呼吸窘迫综合征发生率显著降低（3.0%对7.6%；RR，0.39；95%置信区间，0.17 - 0.92；P = 0.03）、任何新生儿发病或死亡事件发生率显著降低（7.7%对13.5%；RR，0.57；95%置信区间，0.33 - 0.99；P = 0.04）以及出生体重<1500克的发生率显著降低（6.4%（15/234）对13.6%（30/220）；RR，0.47；95%置信区间，0.26 - 0.85；P = 0.01）相关。两组之间治疗相关不良事件的发生率无差异。
结论：在妊娠中期对超声检查显示宫颈短的女性使用阴道孕酮凝胶与妊娠33周前早产发生率降低45%以及新生儿结局改善相关。版权所有（C）2011国际妇产科超声学会。由约翰威立父子有限公司出版。
Objectives Women with a sonographic short cervix in the mid-trimester are at increased risk for preterm delivery. This study was undertaken to determine the efficacy and safety of using micronized vaginal progesterone gel to reduce the risk of preterm birth and associated neonatal complications in women with a sonographic short cervix.Methods This was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled asymptomatic women with a singleton pregnancy and a sonographic short cervix (10-20 mm) at 19 + 0 to 23 + 6 weeks of gestation. Women were allocated randomly to receive vaginal progesterone gel or placebo daily starting from 20 to 23 + 6 weeks until 36 + 6 weeks, rupture of membranes or delivery, whichever occurred first. Randomization sequence was stratified by center and history of a previous preterm birth. The primary endpoint was preterm birth before 33 weeks of gestation. Analysis was by intention to treat.Results Of 465 women randomized, seven were lost to follow-up and 458 (vaginal progesterone gel, n = 235; placebo, n = 223) were included in the analysis. Women allocated to receive vaginal progesterone had a lower rate of preterm birth before 33 weeks than did those allocated to placebo (8.9% (n = 21) vs 16.1% (n = 36); relative risk (RR), 0.55; 95% CI, 0.33-0.92; P = 0.02). The effect remained significant after adjustment for covariables (adjusted RR, 0.52; 95% CI, 0.31-0.91; P = 0.02). Vaginal progesterone was also associated with a significant reduction in the rate of preterm birth before 28 weeks (5.1% vs 10.3%; RR, 0.50; 95% CI, 0.25-0.97; P = 0.04) and 35 weeks (14.5% vs 23.3%; RR, 0.62; 95% CI, 0.42-0.92; P = 0.02), respiratory distress syndrome (3.0% vs 7.6%; RR, 0.39; 95% CI, 0.17-0.92; P = 0.03), any neonatal morbidity or mortality event (7.7% vs 13.5%; RR, 0.57; 95% CI, 0.33-0.99; P = 0.04) and birth weight < 1500 g (6.4% (15/234) vs 13.6% (30/220); RR, 0.47; 95% CI, 0.26-0.85; P = 0.01). There were no differences in the incidence of treatment-related adverse events between the groups.Conclusions The administration of vaginal progesterone gel to women with a sonographic short cervix in the mid-trimester is associated with a 45% reduction in the rate of preterm birth before 33 weeks of gestation and with improved neonatal outcome. Copyright (C) 2011 ISUOG. Published by John Wiley & Sons, Ltd.