Maki Shintaro, Takakura Sho, Tsuji Makoto, Magawa Shoichi, Tamaishi Yuya, Nii Masafumi, Kaneda Michiko, Yoshida Kenta, Toriyabe Kuniaki, Kondo Eiji, Ikeda Tomoaki
Department of Obstetrics and Gynecology, Mie University Graduate School of Medicine, Tsu 514-8507, Mie, Japan.
Biomedicines. 2024 Apr 4;12(4):804. doi: 10.3390/biomedicines12040804.
Fetal growth restriction (FGR) is a major concern in perinatal care. Various medications have been proposed as potential treatments for this serious condition. Nonetheless, there is still no definitive treatment. We studied tadalafil, a phosphodiesterase-5 inhibitor, as a therapeutic agent for FGR in clinical studies and animal experiments. In this review, we summarize our preclinical and clinical data on the use of tadalafil for FGR. Our studies in mouse models indicated that tadalafil improved FGR and hypertensive disorders of pregnancy. A phase II trial we conducted provided evidence supporting the efficacy of tadalafil in prolonging pregnancy (52.4 vs. 36.8 days; = 0.03) and indicated a good safety profile for fetuses and neonates. Fetal, neonatal, and infant mortality was significantly lower in mothers receiving tadalafil treatment than that in controls (total number: 1 vs. 7, respectively; = 0.03), and no severe adverse maternal events associated with tadalafil were observed. Although further studies are needed to establish the usefulness of tadalafil in FGR treatment, our research indicates that the use of tadalafil in FGR treatment may be a paradigm shift in perinatal care.
胎儿生长受限（FGR）是围产期护理中的一个主要问题。各种药物已被提议作为这种严重病症的潜在治疗方法。尽管如此，仍然没有确定的治疗方法。我们在临床研究和动物实验中研究了磷酸二酯酶-5抑制剂他达拉非作为FGR的治疗药物。在这篇综述中，我们总结了关于他达拉非用于FGR的临床前和临床数据。我们在小鼠模型中的研究表明，他达拉非改善了FGR和妊娠高血压疾病。我们进行的一项II期试验提供了证据，支持他达拉非在延长孕期方面的疗效（52.4天对36.8天；P = 0.03），并表明对胎儿和新生儿具有良好的安全性。接受他达拉非治疗的母亲的胎儿、新生儿和婴儿死亡率显著低于对照组（总数分别为1例对7例；P = 0.03），且未观察到与他达拉非相关的严重不良母体事件。尽管需要进一步研究来确定他达拉非在FGR治疗中的有效性，但我们的研究表明，他达拉非用于FGR治疗可能是围产期护理的一个范式转变。
