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Updated: Feb 16, 2026

Comprehensive Evaluation of the Effectiveness and Safety of Placenta-Targeted Drug Delivery Using Three Complementary Methods
Published on: September 10, 2018
Pentaerythrityltetranitrate (PETN) improves utero- and feto-placental Doppler parameters in pregnancies with impaired
Sandy Bowkalow1, Ekkehard Schleussner1, Christiane Kähler2
1Department of Obstetrics, University Hospital Jena, Friedrich Schiller University, Jena, Germany.
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.

