Sildenafil citrate therapy for severe early-onset intrauterine growth restriction

Abstract

Please cite this paper as: von Dadelszen P, Dwinnell S, Magee LA, Carleton BC, Gruslin A, Lee B, Lim KI, Liston RM, Miller SP, Rurak D, Sherlock RL, Skoll MA, Wareing MM, Baker PN, for the Research into Advanced Fetal Diagnosis and Therapy (RAFT) Group. Sildenafil citrate therapy for severe early‐onset intrauterine growth restriction. BJOG 2011;118:624–628. Currently, there is no effective therapy for severe early‐onset intrauterine growth restriction (IUGR). Sildenafil citrate vasodilates the myometrial arteries isolated from women with IUGR‐complicated pregnancies. Women were offered Sildenafil (25 mg three times daily until delivery) if their pregnancy was complicated by early‐onset IUGR [abdominal circumference (AC) < 5th percentile] and either the gestational age was <25+0 weeks or an estimate of the fetal weight was <600 g (excluding known fetal anomaly/syndrome and/or planned termination). Sildenafil treatment was associated with increased fetal AC growth [odds ratio, 12.9; 95% confidence interval (CI), 1.3, 126; compared with institutional Sildenafil‐naive early‐onset IUGR controls]. Randomised controlled trial data are required to determine whether Sildenafil improves perinatal outcomes for early‐onset IUGR‐complicated pregnancies.

Long-term increase in uterine blood flow is achieved by local overexpression of VEGF-A165 in the uterine arteries of pregnant sheep

“…Sildenafil citrate (Viagra), a phosphodiesterase-5 inhibitor known to improve blood flow via cyclic guanosine monophosphate (cGMP)-mediated endothelial relaxation of blood vessels, enhanced vasodilatation of myometrial small arteries from women with FGR. 6 Oral or subcutaneous sildenafil citrate in randomized controlled trials in human FGR and PET have shown no maternal or neonatal benefit, 17 although a recent small nonrandomized study did show significantly increased abdominal circumference in severe early-onset FGR 18 but no benefit on fetal outcome. It is concerning that in pregnant ewes carrying growth-restricted fetuses, intravenous infusion of sildenafil citrate decreased uterine blood flow causing fetal hypoxia, probably because of a systemic reduction in vascular resistance and consequent blood flow 'steal' from the uteroplacental circulation to the systemic vascular circuit.…”

Sildenafil Citrate Improves Ultrasound Doppler Velocimetry Indices in Foetal Growth Restriction – A Randomised Controlled Trial At A Tertiary Care Teaching Hospital in South India.

“…al. [19]. These effects could be explained with improvement of foetal perfusion and the resultant nutrient availability.…”

Study of effect of sildenafil citrate in pregnant women with intrauterine growth restriction/oligohydramnios

“…At present we don't have effective evidence based treatment for pregnancies with IUGR. Non-specific interventions include maternal lifestyle modifications, low dose aspirin, drugs which release nitric oxide, complete bed rest, hospital admission and surveillance or pregnancy termination 3 . These widely practiced interventions are not based on evidence from randomized control trials.…”