STRIDER NZAus: A multicentre randomised controlled trial of sildenafil therapy in early-onset fetal growth restriction.

OBJECTIVE: To assess the effect of maternal sildenafil therapy on fetal growth in pregnancies with early-onset fetal growth restriction. DESIGN: A randomised placebo-controlled trial. SETTING: Thirteen maternal-fetal medicine units across New Zealand and Australia. POPULATION: Women with singleton pregnancies affected by fetal growth restriction at 22+0 to 29+6 weeks. METHODS: Women were randomised to oral 25mg sildenafil citrate or visually matching placebo three times daily until 32+0 weeks, birth or fetal death (whichever occurred first). MAIN OUTCOME MEASURES: The primary outcome was the proportion of pregnancies with an increase in fetal growth velocity. Secondary outcomes included livebirth, survival to hospital discharge free of major neonatal morbidity and preeclampsia. RESULTS: Sildenafil did not affect the proportion of pregnancies with an increase in fetal growth velocity; 32/61 (52.5%) sildenafil-treated 39/57 (68.4%) placebo-treated, adjusted OR 0.49, 95% CI 0.23-1.05 and had no effect on abdominal circumference Z-scores (p=0.61). Sildenafil use was associated with a lower mean uterine pulsatility index after 48 hours treatment (1.56 vs 1.81 p=0.02). The livebirth rate was 56/63 (88.9%) sildenafil-treated 47/59 (79.7%) placebo-treated, adjusted OR 2.50 (95%CI 0.80-7.79); survival to hospital discharge free of major neonatal morbidity was 42/63 (66.7%) sildenafil-treated 33/59 (55.9%) placebo-treated, adjusted OR 1.93 (0.84-4.45); and new-onset preeclampsia was 9/51 (17.7%) sildenafil-treated and 14/55 (25.5%) placebo-treated, OR 0.67 (95%CI 0.26-1.75). CONCLUSIONS: Maternal sildenafil use had no effect on fetal growth velocity. Prospectively planned meta-analyses will determine whether sildenafil exerts other effects on maternal and fetal/neonatal wellbeing.