Viagra for Babies: Increasing Placental Blood Flow During Labour Using Sildenafil Citrate

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Perkins, Anthony V

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Holland, Olivia J

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Labour is a stressful time for the mother and increases pressure on the fetus, amplifying the risk of adverse fetal outcomes. During labour, blood flow to the fetus becomes restricted due to contractions and can decrease by up to 60% (Wray et al., 2021), posing substantial risk, associated with both short and long term health consequences. Complications during gestation may result in small for gestational age babies (SGA), or fetal growth restriction (FGR), which is when the fetus fails to reach its full growth potential. Such babies are at increased risk of poor intrapartum or perinatal outcomes compared to healthy pregnancies. For high risk pregnancies such as preeclampsia, there are more severe consequences during labour, enhancing the pre-existing fetal distress. Fetal distress arises from the hypoxia experienced when placental blood flow decreases, causing hypoxic injury, leading to severe impairments, neonatal encephalopathy, Cerebral Palsy (CP) and even death. Therefore, by investigating placental dysfunction, more specifically, increasing placental blood flow during labour, fetal outcomes may be improved, and rates of debilitating conditions and neonatal death may decrease. When fetal distress is present, the only way to improve pregnancy outcomes is by emergency caesarean section (CS) or instrumental vaginal delivery. Both procedures pose significant risks to both the mother and fetus. Sildenafil Citrate (SC), also known as Viagra, has been shown to increase blood flow through vasodilation of the pelvic vessels, and may be a possible treatment to increase oxygen supply to the fetus during labour and fetal distress. This may be an effective therapy to lessen the burden of such serious adverse outcomes such as neonatal encephalopathy and CP, and lessen the need for emergency interventions. Additionally, using SC to increase placental blood flow, may potentially be an acute therapy for pregnancy conditions such as preeclampsia. Evidence suggests that increasing time spent in the intrauterine environment can significantly heighten chances for better fetal outcomes, and lower neonatal intensive care unit (NICU) admissions (Turbeville & Sasser, 2020). SC has been studied in women in labour in the RIDSTRESS 1 RCT. It was found to reduce the risk for emergency operative birth by 51%, and reduce the rate of pathological heart rates by 43% (Turner et al., 2020). In this research project, we used maternal and fetal plasma samples from RIDSTRESS 1, and measured key biomarkers of hypoxia, oxidative stress and inflammation. Levels of these biomarkers were correlated with key physiological outcomes for both mother and neonate. Biomarkers were analysed using ELISA, qPCR, Multiplex cytokine assays, and cell culture studies were conducted with SC drug treatment to examine direct effects of SC on mitochondrial O2 usage. No significant differences were detected in hypoxia biomarkers between the treatment groups, in both maternal and cord blood samples. Antioxidant capacity assays suggest no significant differences between the treatment and placebo group. Further investigation through Multiplex cytokine assay overall displays no significant changes in selected inflammatory cytokines with the use of sildenafil. Through multiple comparisons of maternal pre- and post- treatment and cord blood samples, some changes were highlighted, although the validity of such comparisons are questionable and discussed further throughout the discussion. Mitochondrial respirometry demonstrates that at a high concentration of 120μM of Sildenafil citrate, oxygen flux within the Swan-71 cells is significantly higher. Fetal outcomes were overall improved with the use of Sildenafil citrate, although this was not reflected through the analyses conducted in this research project. It is critical that further investigation takes place to validate the use of Sildenafil during labour and expand the limited therapies available for hypoxia during labour.

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Thesis (Masters)

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Master of Medical Research (MMedRes)


School of Pharmacy & Med Sci

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