目的:严重的早发性胎儿生长受限(FGR)导致死胎,新生儿死亡和神经发育障碍。不良的母体螺旋动脉重塑可维持血管活性反应性,但对西地那非治疗敏感,5型磷酸二酯酶(PDE5)抑制剂,这可能会改善围产期结局。
方法:优越性,双盲随机对照试验。
方法:共20个英国胎儿医学单位。
方法:受FGR影响的怀孕,定义为在妊娠220至296周之间,脐动脉舒张末期血流缺乏,腹围低于十分之一。
方法:用西地那非(25mg,3次/天)或安慰剂治疗直至分娩或妊娠32周。
方法:评估所有出院时存活的婴儿的心血管功能和认知功能,2岁时的言语/语言和神经运动障碍。主要结果是无脑瘫或神经感觉障碍的生存,或Bayley-III综合评分>85.
结果:总计,在2014年11月至2016年7月期间,对135名女性进行了随机分组(西地那非70人,安慰剂65人)。我们以前发表过,西地那非在分娩时间或围产期结局方面没有改善。总之,75名婴儿(55.5%)存活出院,61名婴儿符合随访条件(32名西地那非和29名安慰剂)。一名婴儿死亡(安慰剂),三名母亲拒绝,十名母亲无法联系。使用西地那非治疗后,神经发育或血压没有差异。接受西地那非治疗的婴儿在2岁时头围较大(中位数差异49.2cm,IQR46.4-50.3,vs47.2厘米,95%CI44.7-48.9厘米)。
结论:西地那非治疗不能延长妊娠或改善围产期结局,也不能改善FGR幸存者的婴儿神经发育。因此,西地那非不应用于这种情况。
OBJECTIVE: Severe early-onset fetal growth restriction (FGR) causes stillbirth, neonatal death and neurodevelopmental impairment. Poor maternal spiral artery remodelling maintains vasoactive responsiveness but is susceptible to treatment with sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, which may improve perinatal outcomes.
METHODS: Superiority, double-blind randomised controlled
trial.
METHODS: A total of 20 UK fetal medicine units.
METHODS: Pregnancies affected by FGR, defined as an abdominal circumference below the tenth centile with absent end-diastolic flow in the umbilical artery between 22+0 and 29+6 weeks of gestation.
METHODS: Treatment with sildenafil (25 mg three times/day) or placebo until delivery or 32 weeks of gestation.
METHODS: All infants alive at hospital discharge were assessed for cardiovascular function and cognitive, speech/language and neuromotor impairment at 2 years of age. The primary outcome was survival without cerebral palsy or neurosensory impairment, or a Bayley-III composite score of >85.
RESULTS: In total, 135 women were randomised between November 2014 and July 2016 (70 to sildenafil and 65 to placebo). We previously published that there was no improvement in time to delivery or perinatal outcomes with sildenafil. In all, 75 babies (55.5%) were discharged alive, with 61 infants eligible for follow-up (32 sildenafil and 29 placebo). One infant died (placebo), three mothers declined and ten mothers were uncontactable. There was no difference in neurodevelopment or blood pressure following treatment with sildenafil. Infants who received sildenafil had a larger head circumference at 2 years of age (median difference 49.2 cm, IQR 46.4-50.3, vs 47.2 cm, 95% CI 44.7-48.9 cm).
CONCLUSIONS: Sildenafil therapy did not prolong pregnancy or improve perinatal outcomes and did not improve infant neurodevelopment in FGR survivors. Therefore, sildenafil should not be prescribed for this condition.