Antenatal Sildenafil Citrate for Fetal Growth Restriction: Updated Evidence on Fetoplacental Pulsatility Indices and Perinatal Outcomes — Systematic Review and Meta-analysis
DOI:
https://doi.org/10.22225/wmj.11.1.14507.39-53Keywords:
Fetal Growth Restriction, Sildenafil Citrate, Fetoplacental Pulsatility IndicesAbstract
The aim of this study is to evaluate the impact of antenatal sildenafil citrate on fetoplacental pulsatility indices and perinatal outcomes in pregnancies complicated by FGR. A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. PubMed, Scopus, and Web of Science were searched up to October 2025. Randomized controlled trials (RCTs) comparing sildenafil citrate with placebo in FGR pregnancies were included. Primary outcomes included umbilical artery (UA) and middle cerebral artery (MCA) pulsatility indices, birth weight, gestational age at delivery, and stillbirth rate. Secondary outcomes included neonatal mortality, major morbidity, and NICU admission. Random-effects models were used to calculate pooled mean differences (MDs) or risk ratios (RRs) with 95% confidence intervals (CIs). Twelve RCTs involving a total of 1,083 pregnant women with FGR were analyzed. Sildenafil citrate significantly reduced UA-PI (MD = ?0.22; 95% CI ?0.33 to ?0.11; p < 0.0001) and increased mean birth weight (MD = 178.39 g; 95% CI 61.48–295.30; p = 0.003). However, it showed no significant effects on MCA-PI, gestational age, stillbirth, neonatal mortality, severe intraventricular hemorrhage, or NICU admission. Conversely, an increased risk of persistent pulmonary hypertension of the newborn (PPHN) was observed (OR = 4.37; 95% CI 1.49–12.80; p = 0.007). Antenatal sildenafil citrate may improve selected fetoplacental hemodynamic parameters and birth weight in FGR pregnancies, but its association with increased PPHN risk warrants caution. Further large-scale RCTs are needed to confirm efficacy and neonatal safety.
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