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Neurodevelopmental outcomes at 2 years in children who received sildenafil therapy in utero: The STRIDER randomised
Andrew Sharp1,2, Christine Cornforth1,3, Richard Jackson3
1Department of Women's and Children's Health, University of Liverpool, Liverpool, UK.
Insights
Sildenafil treatment did not improve outcomes for severe early-onset fetal growth restriction (FGR). This phosphodiesterase type 5 (PDE5) inhibitor did not prolong pregnancy or enhance infant neurodevelopment, and is not recommended for FGR.
Area of Science:
- Perinatal medicine
- Fetal development
- Pharmacology
Background:
- Severe early-onset fetal growth restriction (FGR) is linked to stillbirth, neonatal death, and neurodevelopmental issues.
- Poor maternal spiral artery remodeling in FGR pregnancies may be treatable with sildenafil (a PDE5 inhibitor).
Purpose of the Study:
- To evaluate the efficacy of sildenafil in improving perinatal outcomes and infant neurodevelopment in severe early-onset FGR.
- To assess if sildenafil treatment can prolong pregnancy and reduce adverse outcomes in FGR.
Main Methods:
- A superiority, double-blind, randomized controlled trial was conducted across 20 UK fetal medicine units.
- 135 pregnancies with FGR (abdominal circumference <10th centile, absent end-diastolic flow) between 22-29 weeks gestation were randomized.
- Participants received either sildenafil (25 mg three times daily) or placebo until delivery or 32 weeks gestation.
Main Results:
- Sildenafil treatment did not improve time to delivery or perinatal outcomes.
- No significant differences were observed in infant neurodevelopment or blood pressure at 2 years of age between the sildenafil and placebo groups.
- Infants treated with sildenafil showed a larger head circumference at 2 years (median difference 49.2 cm vs 47.2 cm).
Conclusions:
- Sildenafil therapy does not prolong pregnancy or improve perinatal outcomes in severe early-onset FGR.
- Sildenafil treatment did not enhance infant neurodevelopment in FGR survivors.
- Sildenafil should not be prescribed for the management of FGR.
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.
Design:
Superiority, double-blind randomised controlled trial.
Setting:
A total of 20 UK fetal medicine units.
Population:
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.
Main Outcome Measures:
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.
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