Terstappen Fieke, Richter Anne E, Lely A Titia, Hoebeek Freek E, Elvan-Taspinar Ayten, Bos Arend F, Ganzevoort Wessel, Pels Anouk, Lemmers Petra M, Kooi Elisabeth M W
University Medical Center Utrecht, Wilhelmina Children's Hospital, Department of Obstetrics, Utrecht University, Utrecht, Netherlands.
University Medical Center Utrecht, Wilhelmina Children's Hospital and Brain Center, Department for Developmental Origins of Disease, Utrecht University, Utrecht, Netherlands.
Front Pediatr. 2020 Dec 3;8:595693. doi: 10.3389/fped.2020.595693. eCollection 2020.
Sildenafil is under investigation as a potential agent to improve uteroplacental perfusion in fetal growth restriction (FGR). However, the STRIDER RCT was halted after interim analysis due to futility and higher rates of persistent pulmonary hypertension and mortality in sildenafil-exposed neonates. This hypothesis-generating study within the Dutch STRIDER trial sought to understand what happened to these neonates by studying their regional tissue oxygen saturation (rSO) within the first 72 h after birth. Pregnant women with FGR received 25 mg placebo or sildenafil thrice daily within the Dutch STRIDER trial. We retrospectively analyzed the cerebral and renal rSO monitored with near-infrared spectroscopy (NIRS) in a subset of neonates admitted to two participating neonatal intensive care units, in which NIRS is part of standard care. Secondarily, blood pressure and heart rate were analyzed to aid interpretation. Differences in oxygenation levels and interaction with time (slope) between placebo- and sildenafil-exposed groups were tested using mixed effects analyses with multiple comparisons tests. Cerebral rSO levels were not different between treatment groups (79 vs. 77%; both = 14) with comparable slopes. Sildenafil-exposed infants ( = 5) showed lower renal rSO than placebo-exposed infants ( = 6) during several time intervals on day one and two. At 69-72 h, however, the sildenafil group showed higher renal rSO than the placebo group. Initially, diastolic blood pressure was higher and heart rate lower in the sildenafil than the placebo group, which changed during day two. Although limited by sample size, our data suggest that prenatal sildenafil alters renal but not cerebral oxygenation in FGR neonates during the first 72 post-natal hours. The observed changes in renal oxygenation could reflect a vasoconstrictive rebound from sildenafil. Similar changes observed in accompanying vital parameters support this hypothesis.
西地那非正在作为一种潜在药物进行研究，以改善胎儿生长受限（FGR）中的子宫胎盘灌注。然而，STRIDER随机对照试验在中期分析后因无效以及西地那非暴露新生儿持续性肺动脉高压和死亡率较高而停止。这项在荷兰STRIDER试验中产生假设的研究试图通过研究这些新生儿出生后72小时内的局部组织氧饱和度（rSO）来了解他们的情况。在荷兰STRIDER试验中，患有FGR的孕妇每天三次接受25毫克安慰剂或西地那非治疗。我们回顾性分析了入住两个参与试验的新生儿重症监护病房的一部分新生儿通过近红外光谱（NIRS）监测的脑和肾rSO，其中NIRS是标准护理的一部分。其次，分析血压和心率以辅助解释。使用混合效应分析和多重比较检验来测试安慰剂组和西地那非暴露组之间氧合水平的差异以及与时间的相互作用（斜率）。治疗组之间的脑rSO水平没有差异（分别为79%和77%；两组均n = 14），斜率相当。在出生第一天和第二天的几个时间段内，西地那非暴露婴儿（n = 5）的肾rSO低于安慰剂暴露婴儿（n = 6）。然而，在69 - 72小时时，西地那非组的肾rSO高于安慰剂组。最初，西地那非组的舒张压较高，心率较低，在第二天有所变化。尽管受样本量限制，但我们的数据表明，产前使用西地那非在出生后72小时内会改变FGR新生儿的肾氧合，但不会改变脑氧合。观察到的肾氧合变化可能反映了西地那非引起的血管收缩反弹。伴随的生命参数中观察到的类似变化支持这一假设。
