Research Summary

Intrapartum Sildenafil Fails to Improve Perinatal Outcomes in Large Multicenter Trial

Kate Young

Key Highlights:

  • In a large multicenter randomized clinical trial, intrapartum oral sildenafil citrate did not reduce adverse perinatal outcomes related to fetal hypoxia.
  • The composite outcome occurred in approximately 5% of both sildenafil and placebo groups.
  • Subgroup analyses revealed no differential treatment effect across participant characteristics.

In a large, randomized clinical trial involving over 3200 participants, the use of intrapartum oral sildenafil citrate showed no benefit in reducing adverse perinatal outcomes potentially associated with fetal hypoxia when compared with placebo. The incidence of the composite primary outcome was nearly identical between the intervention and control groups, with no statistically significant difference observed.

Sildenafil citrate has been considered a potential intervention to enhance uteroplacental blood flow, thereby improving oxygen delivery to the fetus during labor. However, evidence supporting its role in reducing perinatal complications from intrapartum hypoxia has been inconclusive, prompting this rigorous evaluation.

This placebo-controlled trial was conducted across 13 Australian hospitals between September 2021 and June 2024. Eligible participants included women aged 18 years or older with term singleton or dichorionic twin pregnancies planning vaginal delivery, either spontaneous or induced. Participants were randomly assigned to receive 50 mg of oral sildenafil citrate every 8 hours (up to 150 mg total) or a matching placebo. The primary composite outcome included a range of perinatal complications indicative of intrapartum hypoxia, such as low Apgar score, neonatal seizures, and persistent pulmonary hypertension of the newborn.

Among the 3257 women enrolled, 1626 were assigned to sildenafil and 1631 to placebo. Baseline characteristics, including maternal age and gestational age, were similar across groups. The primary composite outcome occurred in 5.1% of the sildenafil group and 5.2% of the placebo group (RR, 1.02; 95% CI, 0.75–1.37). No significant differences were found for emergency cesarean or instrumental deliveries due to fetal distress, or for any individual components of the composite outcome. Subgroup analyses confirmed no evidence of effect modification based on participant characteristics.

“Sildenafil citrate did not result in a lower incidence of adverse perinatal outcomes potentially related to intrapartum hypoxia,” the study authors concluded.

Reference:
Kumar S, Tarnow-Mordi W, Mol BW, et al. Intrapartum Sildenafil to Improve Perinatal Outcomes: A Randomized Clinical Trial. JAMA. Published online June 9, 2025. doi:10.1001/jama.2025.7710