Pentaerythrityltetranitrate (PETN) improves utero- and feto-placental Doppler parameters in pregnancies with impaired utero-placental perfusion in mid-gestation - a secondary analysis of the PETN-pilot trial

J Perinat Med. 2018 Nov 27;46(9):1004-1009. doi: 10.1515/jpm-2017-0238.

Abstract

Aim: In pregnancies complicated by impaired utero-placental perfusion, pentaeritrithyltetranitrate (PETN) has been shown to reduce the risk of severe fetal growth restriction (FGR) and perinatal death by 39%. The effect is most likely related to the vasodilatative influence of PETN. To assess its impact on utero-placental and fetal perfusion, we analyzed the Doppler parameters measured during the PETN pilot-trial.

Methods: One hundred and eleven pregnancies presenting impaired utero-placental resistance at mid-gestation were included in the trial. Fifty-four women received PETN, while 57 received a placebo. Doppler velocimetry measurements were monitored biweekly. Statistical analysis was performed using a mixed linear model.

Results: Within the first week of treatment, the mean pulsatility index (PI) of the uterine artery (UtA) dropped more prominently in the PETN group [-0.20, 95% confidence interval (CI): -0.34 to -0.05, P=0.007). The adjusted relative risk (RR) for abnormal cerebro-placental ratio (CPR) was significantly reduced by PETN [RR 0.412 (95% CI: 0.181-0.941)]. Kaplan-Meier analysis demonstrates the postponement of absent end-diastolic flow (AED), absent or reverse end-diastolic flow (ARED), brain sparing and abnormal cerebroplacental ratio (CPR) in the PETN group.

Conclusion: The demonstrated effect of PETN on utero-placental and feto-placental perfusion strengthens the evidence for a positive impact in pregnancies complicated by impaired placental perfusion and might explain the effect on neonatal outcome, as shown in the PETN-pilot trial.

Keywords: ARED; CPR; NO donor; PETN; brain sparing; fetal perfusion; impaired utero-placental perfusion; intrauterine growth retardation.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Double-Blind Method
  • Drug Monitoring / methods
  • Female
  • Fetal Growth Retardation / etiology
  • Fetal Growth Retardation / prevention & control
  • Fetus* / blood supply
  • Fetus* / diagnostic imaging
  • Gestational Age
  • Humans
  • Pentaerythritol Tetranitrate / administration & dosage*
  • Perfusion Imaging / methods
  • Placenta Diseases* / diagnosis
  • Placenta Diseases* / genetics
  • Placenta* / blood supply
  • Placenta* / diagnostic imaging
  • Pregnancy
  • Treatment Outcome
  • Ultrasonography, Prenatal / methods*
  • Umbilical Arteries / diagnostic imaging
  • Uterine Artery / diagnostic imaging
  • Uterus* / blood supply
  • Uterus* / diagnostic imaging
  • Vasodilator Agents / administration & dosage

Substances

  • Vasodilator Agents
  • Pentaerythritol Tetranitrate