427. STRIDER: Sildenafil therapy in dismal prognosis early-onset fetal growth restriction – A systematic review with individual participant data

Abstract

In pregnancies complicated by early-onset extreme fetal growth restriction (FGR), there is a high risk of preterm birth and an overall dismal fetal prognosis. The underlying cause is uteroplacental insufficiency. There is ample evidence from in vitro models, and animal models that sildenafil ameliorates this pathological process. Preliminary data in human pregnancies complicated by FGR has also suggested that Sildenafil improves outcomes. A group of international collaborators originating from the Global Obstetrics Network (GONet) launched a joint initiative to fund clinical multicenter studies in research networks in the United Kingdom, The Netherlands, Canada and New Zealand/Australia. Within each country, stand-alone randomised clinical trials are being or have been conducted within the national network. Synchronization of study design and definitions, central data collection and a pro-active design of a meta-analysis with aggregate data and Individual Participant Data (IPD) have been agreed upon from the start. The primary outcome for babies is being alive at term gestation without evidence of serious adverse neonatal outcome. An important secondary outcome is age-adequate performance on the two-year Bayley scales of infant and toddler development-III (composite cognitive score and composite motor score). IPD meta-analysis allows meaningful subgroup and sensitivity analyses including assessment of the influence of several patient characteristics: an abnormal serum level of placental growth factor, absent/reversed umbilical arterial end-diastolic flow at commencement of treatment, and other patient characteristics available at baseline such as gestational age and estimated fetal weight. Conclusion: The concerted effort in the design and conduct of these large international studies provides an efficient use of scarce resources and will optimise speedy resolution of the underlying research questions, in addition to facilitating adequate power for subgroup analyses.