2-year neurodevelopmental outcomes in children who received sildenafil therapy in utero: the STRIDER RCT

Abstract

Objective: severe early-onset fetal growth restriction (FGR) causes stillbirth, neonatal death and neurodevelopmental impairment. Poor maternal spiral artery remodelling maintains a vasoactive responsiveness which is susceptible to treatment with sildenafil, a phosphodiesterase type 5 inhibitor, which may improve perinatal outcomes.

Design: superiority, double-blind randomised controlled trial

Setting: 20 UK fetal medicine units

Population: FGR, defined as an abdominal circumference <10th centile with absent end diastolic flow in the umbilical artery between 22+0 and 29+6 weeks.

Methods: treatment with sildenafil (25mg three times/day) or placebo until delivery or 32 weeks.

Main outcome measures: all infants alive at hospital discharge were assessed for cardiovascular function, neuromotor, cognitive, speech and language impairment at two years of age. Primary outcome was survival without cerebral palsy or neurosensory impairment, or Bayley III composite score of >85.

Results: 135 women were randomised between November 2014 and July 2016 (70 to sildenafil, 65 to placebo). We previously published that there was no improvement in time to delivery or perinatal outcomes with sildenafil. 75 babies (55.5%) were discharged alive with 61 infants eligible for follow up (32 sildenafil and 29 placebo). One infant died (placebo), three declined and 10 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).

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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Identifiers

ORCID for Brigitte Vollmer: orcid.org/0000-0003-4088-5336

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