Reduction of intrauterine growth retardation (IUGR) in a high-risk group with the NO-donor penterythriltetranitrat (PETN) – a prospective randomized double-blind placebo trial

Objectives: NO-donors reduce the impedance in uteroplacental vessels (Kähler et al, 2004). Lees et al's pilot study demonstrated that transdermal nitroglycerin positively influences pregnancy outcome within a high-risk collective. Currently, we present the results of a randomized, prospective, and placebo-controlled, double-blind study implemented with the aim to investigate whether the oral NO-donor Pentalong^® (PETN) is suitable as a prophylactic drug in abnormal placentation.

Methods: We included 111 pregnancies presenting with abnormal placental perfusion (bilateral notch or mean RI>0.7) between the 19^th to 24^th week of gestation (w.o.g.). Further risk factors (high-risk group: history of HELLP/preeclampsia/IUGR/IUFD/placental abruption, type I diabetes mellitus, hypertension, thrombosis/thrombophilia) were identified in 78 study participants. 53 women received PETN while 58 received placebo. Doppler velocimetry measurements of uteroplacental and fetal vessels and fetal growth scans were monitored biweekly with primary endpoints being the occurrence of, IUGR, premature birth and/or preeclampsia.

Results: Within the first week of intake, PETN improved uteroplacental perfusion significantly in comparison to placebo (mean PI 1.26±0.36 vs. 1.49±0.44; p<0.01). Premature birth <32^nd w.o.g. and IUGR <10^th percentile were reduced by 72% (3 vs. 12; p<0.05) and 36% (17 vs. 29; p<0.05) respectively. Overall frequency of preeclampsia only tended to be decreased, but the risk of developing early-onset preeclampsia <32^nd w.o.g. within the high-risk collective was almost halved (5 vs. 8, p<0.05).

Conclusion: NO-donors constitute an interesting option in the prophylaxis of adverse pregnancy outcome related to abnormal placentation.