Pentaerithrityl tetranitrate (PETN) for prevention of fetal growth restriction in pregnancy: A systematic review and meta-analysis

Abstract

Background: Fetal Growth Restriction (FGR), often due to placental insufficiency, poses significant risks to perinatal outcomes. This review evaluates the efficacy of pentaerythritol tetranitrate (PETN), a nitric oxide donor, in preventing FGR. Methods: A systematic review and meta-analysis was conducted by searching PubMed, Embase, and CENTRAL up to July 2024. The inclusion criteria focused on randomized controlled trials comparing PETN to placebo in FGR prevention. Key outcomes were incidences of FGR, perinatal mortality, neonatal mortality, and intrauterine fetal demise (IUFD). Other outcomes were classified as maternal, fetal, neonatal and safety outcomes. We used Cochrane RoB 2.0 tool to assess risk of bias, and GRADE criteria for evidence quality. Results: Two eligible studies encompassing 417 pregnant women at risk of FGR were included. PETN did not significantly reduce incidence of FGR (RR 0.83, 95 % CI 0.66–1.04, 2 trials, 417 participants, low certainty) or perinatal mortality (RR 0.64, 95 % CI 0.26–1.58, 2 trials, 417 participants, very low certainty) compared to placebo. None of the studies reported neonatal mortality or IUFD. However, PETN treatment was associated with a reduction in preterm birth (RR 0.74, 95 % CI 0.58–0.93, 2 trials, 417 participants, moderate certainty). Other outcomes were similar between the groups. Conclusion: While PETN does not significantly impact FGR rates or perinatal mortality, it is associated with a reduction in preterm birth, suggesting potential benefits in high-risk pregnancies. Larger trials are necessary to substantiate these findings and clarify the role of PETN in FGR prevention.

Keywords

• Fetal Growth Restriction (FGR)
• Pentaerythritol tetranitrate (PETN)
• Placental insufficiency
• Preterm birth prevention
• Nitric oxide donors