The authors of the UK STRIDER trial assessing the ability of sildenafil to improve pregnancy outcomes in foetal growth restriction (FGR) have conducted a re-analysis of the study data after the Dutch STRIDER trial terminated early in response to concerns about a higher than expected neonatal mortality with sildenafil.
The UK trial has previously shown no beneficial effect of sildenafil on any outcome and no significant difference in harm when compared with placebo. The trial reaffirmed that foetuses with FGR are a very high-risk cohort, with foetal demise occurring in 43 (32%) of 135 pregnancies (30% with sildenafil and 34% with placebo), with a further 17 (18%) of 92 of infants dying in the neonatal period (20% with sildenafil and 16% with placebo).
However, the Dutch STRIDER trial has now reported higher than expected neonatal mortality (27% with sildenafil vs 14% with placebo) and high rates of persistent pulmonary hypertension of the neonate (27% vs 5%).
Writing in the Lancet Child & Adolescent Health, the UK authors say they observed no obvious differences in clinically relevant pathological or histological findings between the sildenafil or placebo groups in the UK trial in pregnancies complicated either by foetal or neonatal death. The histological and post-mortem findings were in keeping with placental disease and chronic foetal hypoxia, they conclude.
However, they add that the possibility of excess neonatal mortality and the possible reasons for these deaths warrant further study.