Mater Research Institute, The University of Queensland, Queensland, Australia; Faculty of Medicine, The University of Queensland, Queensland, Australia.
Mater Research Institute, The University of Queensland, Queensland, Australia.
Am J Obstet Gynecol. 2020 May;222(5):401-414. doi: 10.1016/j.ajog.2020.01.025. Epub 2020 Jan 21.
Sildenafil citrate is a vasodilator used in erectile dysfunction and pulmonary hypertension. We tested whether it reduces emergency operative births for fetal compromise and improves fetal or uteroplacental perfusion in labor in a phase 2 double-blind randomized controlled trial.
Women at term in early labor or undergoing scheduled induction of labor at Mater Mother's Hospital, Brisbane, Australia, were randomly allocated 50 mg of sildenafil citrate orally 8 hourly up to 150 mg or placebo. Intrapartum fetal monitoring followed Royal Australian and New Zealand College of Obstetricians and Gynaecologists guidelines. Primary outcomes were (1) emergency operative birth (by cesarean delivery or instrumental vaginal birth) for intrapartum fetal compromise and (2) mean indices of fetal and uteroplacental perfusion using Doppler ultrasound. Analysis was by intention-to-treat.
ANZCTRN12615000319572 RESULTS: Between September 2015 and January 2019, 300 women were randomized equally to sildenafil citrate or placebo. Sildenafil citrate reduced the risk of emergency operative birth by 51% (18% vs 36.7%; relative risk, 0.49, 95% confidence interval, 0.33-0.73, P=.0004, number needed to treat = 5 [3-11]). There was no difference in indices of fetal and uteroplacental perfusion, but these were ascertained in only 71 women. Sildenafil citrate reduced the risk of meconium-stained liquor or pathologic fetal heart rate patterns by 43% (25.3% vs 44.7%; relative risk, 0.57, 95% confidence interval, 0.41-0.79, P=.0005), but its effects on fetal scalp sampling rates (2.0% vs 6.7%; relative risk, 0.30, 95% confidence interval, 0.08-1.07, P=.06) and adverse neonatal outcome (20.7% vs 21.3%; relative risk, 0.97, 95% confidence interval, 0.62-1.50, P=.89) were inconclusive. Only 3.6% of maternal levels of sildenafil citrate or its metabolite were detected in cord blood. No differences in maternal adverse events were seen.
Sildenafil citrate reduced operative birth for intrapartum fetal compromise, but much larger phase 3 trials of its effects on mother and child are needed before it can be routinely recommended.
枸橼酸西地那非是一种血管扩张剂，用于治疗勃起功能障碍和肺动脉高压。我们在一项 2 期双盲随机对照试验中测试了它是否能减少因胎儿窘迫而行的紧急剖宫产分娩，并改善分娩时的胎儿或胎盘灌注。
在澳大利亚布里斯班的 Mater Mothers' Hospital，处于分娩早期或计划行引产的足月妇女，被随机分配口服 50mg 枸橼酸西地那非，每 8 小时一次，最大剂量 150mg，或安慰剂。产时胎儿监测遵循澳大利亚和新西兰皇家妇产科学院的指南。主要结局为（1）因产时胎儿窘迫而行的紧急剖宫产分娩（经剖宫产或器械助产）；（2）使用多普勒超声测量胎儿和胎盘灌注的平均指数。分析为意向治疗。
ANZCTRN12615000319572
2015 年 9 月至 2019 年 1 月，300 名妇女被随机平均分配至枸橼酸西地那非或安慰剂组。枸橼酸西地那非降低了 51%的紧急剖宫产分娩风险（18%对 36.7%；相对风险，0.49，95%置信区间，0.33-0.73，P=0.0004，需要治疗的人数=5[3-11]）。胎儿和胎盘灌注的指数没有差异，但仅在 71 名妇女中确定了这些指数。枸橼酸西地那非降低了胎粪污染羊水或病理性胎心监护图形的风险 43%（25.3%对 44.7%；相对风险，0.57，95%置信区间，0.41-0.79，P=0.0005），但其对胎儿头皮取样率（2.0%对 6.7%；相对风险，0.30，95%置信区间，0.08-1.07，P=0.06）和新生儿不良结局（20.7%对 21.3%；相对风险，0.97，95%置信区间，0.62-1.50，P=0.89）的影响尚无定论。仅在 3.6%的脐血中检测到枸橼酸西地那非或其代谢物的母体内水平。未见母亲不良事件的差异。
枸橼酸西地那非降低了因胎儿窘迫而行的剖宫产分娩，但需要更大规模的 3 期试验来确定其对母婴的影响，然后才能常规推荐。
