Pentaerithrityl tetranitrate (PETN) for secondary prevention of intrauterine growth restriction (PETN Trial)

胎儿宫内发育迟缓(IUGR)是围产儿死亡和发病的最重要原因，影响10%的妊娠。IUGR被定义为胎儿宫内供应的病理性限制和胎儿无法实现其生长潜力。此外，作为成人疾病的发育源，宫内营养不良会造成终生后果。在母亲中，IUGR与血管病变、胎盘受损和蜕膜螺旋动脉重塑失败有关，导致胎盘灌注受损。因此，在妊娠中期通过双功超声发现的异常子宫血流，以及与血管健康受损相关的母体状况，包括既往的IUGR，表明在怀孕期间发生IUGR的风险。NO供体如季戊四氮酯(PETN)可降低子宫胎盘血管的阻抗，并已被证明对血管内皮细胞具有保护作用。一项随机的单中心初步研究显示，在PETN干预组中，IUGR或围产儿死亡的相对风险降低了38%(CI 95%：-1%至63%)，32周前早产的风险降低了70%(CI 95%：9%至92%)。这些数据有力地表明，PETN是一种可行的药物，可以显著改善因胎盘功能不全而受损的妊娠结局。为了证实PETN对妊娠结局的影响，325名有可能发生IUGR的孕妇将参加一项前瞻性、多中心、随机、双盲、安慰剂对照、平行分组的干预试验。

Affecting 10% of pregnancies, intrauterine growth restriction (IUGR) is the most important cause of perinatal mortality and morbidity. IUGR is defined as the pathologic restriction of intrauterine supply and the failure of the fetus to achieve its growth potential. Furthermore intrauterine malnutrition causes lifelong consequences as developmental origin of adult diseases. In the mother, IUGR is associated with vascular pathology, impaired placentation and the failure of decidual spiral artery remodelling, leading to impaired placental perfusion. Consequently, abnormal uterine flow, identified by duplex sonography at mid gestation, as well as maternal conditions associated with impaired vascular health, including previous IUGR, signifies the risk of developing IUGR during pregnancy. NO-donors as pentaerithrityl tetranitrate (PETN) reduce the impedance in the uteroplacental vessels and have been demonstrated to possess protecting effects on the endothelium. A randomized mono-center pilot study revealed a 38% relative risk reduction for IUGR or perinatal death (CI 95%: -1% to 63%) and a 70% reduction of preterm birth before 32 weeks of gestation (CI 95%: 9% to 92%) in the PETN intervention group. These data strongly suggest that PETN is a feasible drug to significantly improve the outcome in pregnancies compromised by placental insufficiency. To confirm the effects of PETN on pregnancy outcome 325 pregnant women at risk to develop IUGR will be enrolled into a prospective, multicenter, randomized, double-blind, placebo controlled, parallel group, interventional trial.