A Proof of Principle Randomised Placebo-Controlled Trial for Use of Statins to Ameliorate Early Onset Preeclampsia

先兆子痫(PE)是一种潜在的妊娠危险状态，母亲S血压高于正常水平，且尿液中有蛋白质。大约每100名妇女中就有1人在怀孕32周前经历先兆子痫。唯一有效的治疗方法是早产，但这会给婴儿带来严重的后果。警惕的等待通常在临床上被用来让婴儿S的肺成熟，这可能会导致母亲病情的恶化。迫切需要一种廉价而有效的治疗方法来预防子痫前期并发症。目前尚不清楚先兆子痫的原因，但最近一些已知影响血流的血液分子(称为抗血管生成因子)在PE患者中升高。当给怀孕的动物服用这些抗血管生成因子时，它们会模仿先兆子痫。他汀类药物可以降低胆固醇，从而降低这些分子的水平。目前尚不清楚他汀类药物是否可以降低子痫前期的严重程度和并发症。我们将测试他汀类药物可以降低妊娠32周前先兆子痫妇女的这些分子并降低先兆子痫的严重程度的想法。来自六家医院的医生将寻求这些女性的同意。那些适合并同意的人，将被随机分为两组。其中一组将获得每日剂量的他汀类药物。另一位将得到一颗假糖丸(安慰剂)。我们希望招募128名女性。这些妇女和她们的医生都不知道她们属于哪个群体。这样，我们就可以确信，两组之间的任何差异都是由于治疗造成的。妇女将留在医院接受密切监测，如果先兆子痫恶化，她们的婴儿将分娩。这项试验是独一无二的，因为它是第一次测试他汀类药物是否可以降低先兆子痫的严重程度，而且他汀类药物通常不会开给孕妇。有些人担心他汀类药物可能会导致婴儿的先天性缺陷，但我们没有找到令人信服的证据来支持这一点。此外，我们认为，一旦婴儿S的器官已经发育，在怀孕后期给予他汀类药物是安全的。然而，所有副作用和并发症都将受到密切监测。如果这项小型试验表明先兆子痫的严重程度有所减轻，并且副作用很少，将组织一项更大规模的试验，以确定他汀类药物是否可以延长妊娠时间，减少早产数量。

Preeclampsia (PE) is a potentially dangerous condition of pregnancy in which the mother?s blood pressure is higher than normal and there is protein in the urine. About 1 in 100 women experience preeclampsia before 32 weeks of pregnancy. The only effective treatment is to deliver the baby prematurely, but this has serious consequences for the baby. Watchful waiting, often employed clinically to allow the baby?s lungs to mature, risks progression of disease severity in the mother. A cheap and effective therapy for prevention of preeclampsia complications is urgently needed.It is not known what causes preeclampsia but recently some blood molecules (called anti-angiogenic factors) known to affect blood flow are higher in women with PE. These anti-angiogenic factors when given to pregnant animals mimic preeclampsia. Drugs called statins, which lower cholesterol, reduce the levels of these molecules. It is not known whether statins can reduce the severity and complications of preeclampsia.We will test the idea that statins can reduce these molecules in preeclamptic women before 32 weeks of pregnancy and decrease the severity of preeclampsia. Doctors from six hospitals will seek consent from these women. Those who are suitable and agree, will be randomly divided into two groups. One group will get a daily dose of statin. The other will get a dummy sugar pill (placebo). We hope to recruit 128 women. Neither the women nor their doctors will know what group they are in. In this way, we can be confident that any differences between the two groups are due to treatment. Women will stay in hospital and be closely monitored, and if the preeclampsia gets worse, their baby will be delivered.This trial is unique because it is the first to test whether statins can reduce the severity of preeclampsia and because statins are not prescribed normally to pregnant women. There is some concern that statins may cause congenital defects in the baby, but we have found no convincing evidence to support this. Furthermore, we believe it is safe to give statins later in pregnancy once the baby?s organs have already developed. However, all side effects and complications will be closely monitored.If this small trial shows that the severity of preeclampsia is reduced, and there are few side effects, a bigger trial will be organised to determine if statins can increase the length of pregnancy and reduce the number of premature deliveries.