STRIDER UK: A Randomized Controlled Trial of Sildenafil Therapy In Dismal Prognosis Early-Onset Intrauterine Growth Restriction

Early onset intrauterine growth restriction (IUGR) most commonly occurs when the placental transfer of nutrients and oxygen is impaired due to an inadequate placental implantation. The resulting fetal malnutrition and hypoxia are considered untreatable in utero. The only current option is an elective preterm delivery in order to rescue the baby from an adverse intrauterine environment. IUGR and the associated indicated preterm birth expose the fetus and neonate to significant mortality and morbidity. This diagnosis causes an important management dilemma: early delivery causes extreme prematurity with all its sequelae while delivering baby too late risks intrauterine death or morbidity secondary to critical fetal hypoxia.

Sildenafil potentiates the effect of nitric oxide (NO) and thus may cause vasodilatation of vessels responsive to NO. The incomplete remodelling of maternal spiral arteries in IUGR results in vessels with intact or partially intact muscular layers, which remain responsive to regional vascular control. Sildenafil has the potential to increase uteroplacental circulation and perfusion resulting in improved gaseous and nutrient exchange and improved fetal growth and well-being.

Use of sildenafil in an obstetric population has been limited, but several case reports and small studies now exist. Sildenafil has been used in selected cases for the treatment of maternal pulmonary arterial hypertension where there is growing data on both its safety and efficacy to improve both maternal and fetal outcomes. There is also limited data suggesting that sildenafil has the potential to increase fetal weight.

The overarching aim of the STRIDER  UK trial is to determine whether maternal treatment with oral sildenafil citrate improves perinatal outcomes in pregnancies complicated by severe early-onset IUGR without increasing risks to the mother.