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Published on: June 29, 2013
Short-term outcomes of phosphodiesterase type 5 inhibitors for fetal growth restriction: a study protocol for a
Jessica Liauw1, Katie Groom2, Wessel Ganzevoort3
1Department of Obstetrics and Gynaecology, University of British Columbia, Room C420-4500 Oak Street, Vancouver, British Columbia, V6H 3N1, Canada. Jessica.liauw@phsa.ca.
Insights
This systematic review will analyze phosphodiesterase type 5 (PDE-5) inhibitors for treating fetal growth restriction. The goal is to determine if these drugs improve infant survival and reduce neonatal complications.
Area of Science:
- Perinatal medicine
- Pharmacology
- Clinical trials
Background:
- Early onset fetal growth restriction (FGR) poses significant risks to maternal and neonatal health.
- Phosphodiesterase type 5 (PDE-5) inhibitors show potential in preclinical and small trials for FGR, but evidence is limited.
- The STRIDER Consortium has conducted trials on sildenafil for FGR.
Purpose of the Study:
- To systematically review and meta-analyze data from randomized trials of PDE-5 inhibitors for early onset FGR.
- To evaluate the effect of PDE-5 inhibitors on neonatal morbidity and mortality.
Main Methods:
- A comprehensive search of multiple databases (MEDLINE, EMBASE, CENTRAL) and clinical trial registries.
- Inclusion of randomized trials investigating PDE-5 inhibitors in singleton pregnancies with FGR.
- Primary outcome: infant survival without serious adverse neonatal outcome. Secondary outcomes: gestational age and birth weight z-scores.
- Data analysis will include aggregate and individual participant data meta-analysis, Trial Sequential Analysis, and bias assessment using Cochrane Risk of Bias 2 tool. Certainty of evidence assessed with GRADE.
Main Results:
- This section is not applicable as the abstract describes a protocol for a systematic review and meta-analysis, not the results of the study itself.
Conclusions:
- This pre-defined protocol aims to minimize bias and provide robust evidence on the efficacy of PDE-5 inhibitors for treating early onset fetal growth restriction.
- The findings will inform clinical practice regarding the use of PDE-5 inhibitors in managing FGR.
Background:
Early onset fetal growth restriction secondary to placental insufficiency can lead to severe maternal and neonatal morbidity and mortality. Pre-clinical studies and a few small randomised clinical trials have suggested that phosphodiesterase type 5 (PDE-5) inhibitors may have protective effects against placental insufficiency in this context; however, robust evidence is lacking. The STRIDER Consortium conducted four randomised trials to investigate the use of a PDE-5 inhibitor, sildenafil, for the treatment of early onset fetal growth restriction. We present a protocol for the pre-planned systematic review with individual participant data meta-analysis, aggregate meta-analysis, and trial sequential analysis of these and other eligible trials. The main objective of this study will be to evaluate the effects of PDE-5 inhibitors on neonatal morbidity compared with placebo or no intervention among pregnancies with fetal growth restriction.
Methods:
We will search the following electronic databases with no language or date restrictions: OVID MEDLINE, OVID EMBASE, the Cochrane Controlled Register of Trials (CENTRAL), and the clinical trial registers Clinicaltrials.gov and World Health Organisation International Clinical Trials Registry Platform (ICTRP). We will identify randomised trials of PDE-5 inhibitors in singleton pregnancies with growth restriction. Two reviewers will independently screen all citations, full-text articles, and abstract data. Our primary outcome will be infant survival without evidence of serious adverse neonatal outcome. Secondary outcomes will include gestational age at birth and birth weight z-scores. We will assess bias using the Cochrane Risk of Bias 2 tool. We will conduct aggregate meta-analysis using fixed and random effects models, Trial Sequential Analysis, and individual participant data meta-analysis using one- and two-stage approaches. The certainty of evidence will be assessed with GRADE.
Discussion:
This pre-defined protocol will minimise bias during analysis and interpretation of results, toward the goal of providing robust evidence regarding the use of PDE-5 inhibitors for the treatment of early onset fetal growth restriction.
Systematic Review Registration:
PROSPERO (CRD42017069688).
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