Birth asphyxia, defined by the WHO as failure to establish spontaneous breathing at birth, accounts for nearly 1 million neonatal deaths annually.^1,2  Birth asphyxia is the second most common cause of neonatal mortality worldwide.^1,2 The primary cause of birth asphyxia is poor perfusion of the fetus by the placenta during labor, which may lead to non-reassuring fetal status (fetal distress), hypoxic injury, or death.  Currently, there are no evidence-based therapies to improve fetal perfusion during labor in cases of severe fetal compromise.  Urgent operative delivery is the only option to restore gas exchange to the baby.  In low-resource settings, intrapartum fetal monitoring may not be available to detect fetal distress and access to urgent operative delivery to relieve distress may be limited.  Thus, a high burden of death due to birth asphyxia is carried in the developing world. 

Feasible therapies for use in low-resource settings to reduce deaths from birth asphyxia are urgently needed.  Sildenafil citrate is a novel approach to reduce fetal distress during labor

Introduction - birth asphyxia remain a leading cause of neonatal mortality and morbidity in Kenya. The primary cause of birth asphyxia is poor perfusion of the fetus by the placenta during labor, which may lead to non-reassuring fetal status (fetal distress), hypoxic injury, or death.  Currently, there are no evidence-based therapies to improve fetal perfusion during labor in cases of severe fetal compromise.  In low-resource settings, intrapartum fetal monitoring may not be available to detect fetal distress and access to urgent operative delivery to relieve distress may be limited.  Feasible therapies for use in low-resource settings to reduce deaths from birth asphyxia are urgently needed.  Sildenafil citrate is a novel approach to reduce fetal distress during labor.  Sildenafil citrate is a phosphodiesterase type-5 inhibitor that acts as a vasodilator that is known to increase uteroplacental blood flow. It is unknown if intrapartum sildenafil citrate would be feasible or effective in low-resource settings. We hypothesize that treatment with sildenafil citrate during labor will decrease stillbirth and early neonatal mortality in low-resource settings, but, first, a feasibility trial to inform the design of a definitive trial appropriate for low-resource settings is necessary.  The specific aims correspond to feasibility objectives that will inform the design and implementation of a large randomized controlled trial of intrapartum sildenafil citrate.

Objective: To assess the feasibility of drug administration during early labor, patient acceptance of the intervention, and to confirm the safety of sildenafil citrate in pregnant women in a low-resource setting

Study design: Double blinded, placebo-controlled randomized feasibility trial

Study Setting; Nakuru county and referral hospital in the Mother and Baby unit

Methods: Pregnant women aged 18 to 50years who present to the study health care facilities in early labor will be screened for study eligibility. Eligible women who consent  and if husbands are available have consented for the study will be randomized to receive sildenafil 50 mg orally every 8 hours up to a total of 3 doses or a placebo every 8 hours up to a total of 3 doses during the course of labor. All additional care of the mother and infant will provided according to the local standard of care.  The number and timing of sildenafil doses as well as length of labor in participants will be reported.  The intervention will be considered acceptable if 50% of eligible women enroll.  All enrolled women will be monitored by clinical treatment team for symptoms presenting potential side effects of sildenafil occurring from the time of dose administration to 8 hours following the last dose.  All enrolled neonates will be monitored for neonatal hypoxemia. NICU admission rates in all participants will also be recorded and features of hypoxic ischemic injury will be determined using Sarnat examination. Data will be analyzed using SPSS version 24