From the Department of Obstetrics, Wilhelmina Children's Hospital Birth Center (N.D.P., F.T., A.T.L.) and Department of Nephrology and Hypertension (J.A.J., H.G.), University Medical Center Utrecht, the Netherlands; and Department of Obstetrics, Academic Medical Center, Amsterdam, the Netherlands (W.G.).
Hypertension. 2017 Nov;70(5):998-1006. doi: 10.1161/HYPERTENSIONAHA.117.09690. Epub 2017 Sep 11.
Sildenafil is a new approach to treat fetal growth restriction (FGR) and preeclampsia. We performed a systematic meta-analysis to evaluate effects of sildenafil. Our search identified 22 animal studies (mouse, rat, rabbit, sheep, and guinea pigs) and 2 human randomized controlled trials. Data were pooled using ratio of means and mean differences with 95% confidence intervals for fetal growth and maternal blood pressure, respectively. Meta-regression analyses were performed for study-related factors that might affect efficacy of sildenafil, including the model used (healthy pregnancy versus FGR/preeclampsia) and route of administration. Dose-response curves with dose per metabolic weight (mg/kg per 24 hours) were fitted using splines. Our analyses show that sildenafil increases fetal growth during FGR/preeclampsia pregnancy compared with healthy pregnancy (1.10 [1.06-1.13] versus 1.03 [0.99-1.06]; =0.006). There was no significant effect on fetal growth in the absence of FGR/preeclampsia. Effects were similar among different species and largest after oral and continuous administration. There was a positive relation between dose and fetal growth up to a human equivalent dose of ≈450 mg/d. A significant blood pressure-lowering effect of sildenafil is present during FGR/preeclampsia pregnancy only (-19 [-25 to -13] mm Hg; <0.01), with the effect size being highly dependent on baseline blood pressure and without effect in the absence of hypertension. This meta-analysis supports that sildenafil improves fetal growth and maternal blood pressure regulation during FGR and preeclampsia pregnancy. The greatest beneficial effects on fetal growth are with dosages greater than those currently used in human studies.
西地那非是一种治疗胎儿生长受限（FGR）和子痫前期的新方法。我们进行了系统的荟萃分析来评估西地那非的效果。我们的搜索确定了 22 项动物研究（鼠、大鼠、兔、绵羊和豚鼠）和 2 项人类随机对照试验。使用均值比和均值差分别对胎儿生长和母体血压的数据进行汇总，并计算 95%置信区间。对可能影响西地那非疗效的研究相关因素进行了荟萃回归分析，包括所使用的模型（健康妊娠与 FGR/子痫前期）和给药途径。使用样条拟合了剂量与代谢体重的剂量-反应曲线（每 24 小时每代谢体重的毫克/千克）。我们的分析表明，与健康妊娠相比，西地那非在 FGR/子痫前期妊娠期间增加了胎儿生长（1.10[1.06-1.13]与 1.03[0.99-1.06]；=0.006）。在没有 FGR/子痫前期的情况下，西地那非对胎儿生长没有显著影响。不同物种之间的效果相似，口服和连续给药的效果最大。在达到约 450 毫克/天的人体等效剂量之前，剂量与胎儿生长呈正相关。只有在 FGR/子痫前期妊娠期间，西地那非才具有显著的降压作用（-19[-25 至-13]毫米汞柱；<0.01），其作用大小高度依赖于基线血压，在没有高血压的情况下没有效果。这项荟萃分析支持西地那非改善 FGR 和子痫前期妊娠期间的胎儿生长和母体血压调节。对胎儿生长的最大有益效果是在大于目前人类研究中使用的剂量下。
