The effect of phosphodiesterase-5 inhibitors on uteroplacental and fetal cerebral perfusion in pregnancies with fetal growth restriction: A systematic review and meta-analysis

Abstract

ObjectivesTo evaluate the effect of phosphodiesterase-5 (PDE-5) inhibitors on uteroplacental and fetal cerebral perfusion in pregnancies complicated with fetal growth restriction (FGR). Material and methodsRelevant databases were searched from inception up to June 2021. The random-effects model was used to pool the weighted mean differences (WMDs) and the corresponding 95% confidence intervals (CIs). The primary outcomes were the effect of PDE-5 inhibitors on uterine (UtA-PI), umbilical (UA-PI) and middle cerebral artery (MCA-PI) pulsatility indices. Subgroup analyses were also performed based on the type of PDE-5 inhibitor medication, the dosage of medication, duration of treatment, sample size and onset of FGR. ResultsSeven clinical trials were eligible, 6 trials using sildenafil, and one using tadalafil. The random-effects models indicated PDE-5 inhibitors significantly decrease UtA-PI (WMD = −0.28, 95% CI = −0.46,−0.11) and UA-PI (WMD = −0.07, 95% CI = −0.13, −0.01); however it failed to show a significant effect on MCA-PI (WMD = 0.24, 95% CI = −0.63, 1.11). Subgroup analyses showed similar significant effects of sildenafil on UtA-PI and UA-PI; however, no significant effect was observed after treatment with tadalafil. ConclusionPDE-5 inhibitors administration, especially sildenafil, may improve uteroplacental, but not fetal cerebral blood perfusion in pregnancies complicated by FGR.