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

Objectives: To 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 methods: Relevant databases were searched from inception up to June 2021. The randomeffects 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. Results: Seven 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. Conclusion: PDE-5 inhibitors administration, especially sildenafil, may improve uteroplacental, but not fetal cerebral blood perfusion in pregnancies complicated by FGR. (C) 2021 Elsevier B.V. All rights reserved.