Turner Jessica, Dunn Liam, Kumar Sailesh
Mater Research Institute, University of Queensland, Level 3 Aubigny Place, Raymond Terrace, South Brisbane, Queensland, 4101, Australia; Faculty of Medicine, University of Queensland, Whitty Building, Annerley Road, South Brisbane, Queensland, 4101, Australia.
Mater Research Institute, University of Queensland, Level 3 Aubigny Place, Raymond Terrace, South Brisbane, Queensland, 4101, Australia.
Eur J Obstet Gynecol Reprod Biol. 2020 Nov;254:302-307. doi: 10.1016/j.ejogrb.2020.09.042. Epub 2020 Sep 25.
Uterine contractions during labour can result in a 60 % decline in fetoplacental perfusion, predisposing the fetus to hypoxic brain injury. Sildenafil citrate (SC) has shown promise in increasing uteroplacental perfusion as well as reducing the risk of operative birth for intrapartum fetal compromise (IFC). The aim of this study was to investigate the effect of intrapartum SC administration on fetoplacental blood flow indices.
This was a subgroup analysis from an earlier Phase II double blind randomized controlled trial; assessing the effect of intrapartum SC administration (50 mg orally 8 -hly in labour) compared to placebo for the reduction of operative birth for IFC. An ultrasound scan measuring fetoplacental Doppler indices was performed prior to and 1-4 h after the administration of the first treatment dose.
Of the 300 women randomized to the main study, pre-treatment ultrasound scans were performed in 261 participants who received the study medication; paired pre- and post-treatment scans were performed in 70 (26.8 %). SC resulted in an increase in the middle cerebral artery pulsatility index (PI) z-score [+0.08 (1.35) vs.-0.12 (1.15)], a decline in the umbilical artery-PI z-score [-0.07 (0.96) vs. + 0.04 (1.25)] and an increase in the cerebroplacental ratio [MCA-PI/UA-PI] (CPR) z-score [+0.10 (1.13) vs.-0.26 (1.14)] although these failed to reach statistical significance. Amongst those with a pre-treatment CPR above the 5th centile, SC significantly reduced the risk of operative birth for IFC compared to placebo [logrank p = 0.02; hazards ratio 0.48, 95 % CI 0.29-0.77, p = 0.003].
Although the differences in Doppler indices pre- and post- SC treatment were non-significant, there was a clear trend towards a reduction in the UA PI, a corresponding increase in the MCA PI and a rise in post treatment CPR values suggesting potential improvement in fetoplacental Dopplers with intrapartum SC treatment. However this study was limited by the small sample size. The results of this hypothesis generating study suggest that it may be possible to stratify women that would most benefit from this intervention based upon their pre-labour CPR.
分娩期间子宫收缩可导致胎儿胎盘灌注下降60%，使胎儿易发生缺氧性脑损伤。枸橼酸西地那非（SC）在增加子宫胎盘灌注以及降低因产时胎儿窘迫（IFC）而行手术分娩的风险方面已显示出前景。本研究的目的是探讨产时给予SC对胎儿胎盘血流指数的影响。
这是一项对早期II期双盲随机对照试验的亚组分析；评估产时给予SC（分娩时每8小时口服50mg）与安慰剂相比，用于降低因IFC而行手术分娩的效果。在给予首剂治疗药物之前和之后1 - 4小时进行超声扫描以测量胎儿胎盘多普勒指数。
在随机分组至主要研究的300名女性中，261名接受研究药物治疗的参与者进行了治疗前超声扫描；70名（26.8%）进行了治疗前和治疗后的配对扫描。SC导致大脑中动脉搏动指数（PI）z评分增加[+0.08（1.35）对 -0.12（1.15）]，脐动脉PI z评分下降[-0.07（0.96）对 +0.04（1.25）]，以及脑胎盘比率[MCA - PI/UA - PI]（CPR）z评分增加[+0.10（1.13）对 -0.26（1.14）]，尽管这些均未达到统计学显著性。在治疗前CPR高于第5百分位数的人群中，与安慰剂相比，SC显著降低了因IFC而行手术分娩的风险[对数秩检验p = 0.02；风险比0.48，95%置信区间0.29 - 0.77，p = 0.003]。
尽管SC治疗前后多普勒指数的差异无统计学意义，但存在明显趋势，即脐动脉PI降低，大脑中动脉PI相应增加，且治疗后CPR值升高，提示产时SC治疗可能改善胎儿胎盘多普勒情况。然而，本研究受样本量小的限制。这项探索性研究的结果表明，有可能根据分娩前的CPR对最能从该干预措施中获益的女性进行分层。
