Background:Effective screening for term preeclampsia is provided by a combination of maternal factors with measurements of mean arterial pressure, serum placental growth factor, and serum soluble fms-like tyrosine kinase-1 at 35 to 37 weeks of gestation, with a detection rate of ≈75% at a screen-positive rate of 10%. However, there is no known intervention to reduce the incidence of the disease.Methods:In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1120 women with singleton pregnancies at high risk of term preeclampsia to receive pravastatin at a dose of 20 mg/d or placebo from 35 to 37 weeks of gestation until delivery or 41 weeks. The primary outcome was delivery with preeclampsia at any time after randomization. The analysis was performed according to intention to treat.Results:A total of 29 women withdrew consent during the trial. Preeclampsia occurred in 14.6% (80 of 548) of participants in the pravastatin group and in 13.6% (74 of 543) in the placebo group. Allowing for the effect of risk at the time of screening and participating center, the mixed-effects Cox regression showed no evidence of an effect of pravastatin (hazard ratio for statin/placebo, 1.08 [95% CI, 0.78–1.49]; P=0.65). There was no evidence of interaction between the effect of pravastatin, estimated risk of preeclampsia, pregnancy history, adherence, and aspirin treatment. There was no significant between-group difference in the incidence of any secondary outcomes, including gestational hypertension, stillbirth, abruption, delivery of small for gestational age neonates, neonatal death, or neonatal morbidity. There was no significant between-group difference in the treatment effects on serum placental growth factor and soluble fms-like tyrosine kinase-1 concentrations 1 and 3 weeks after randomization. Adherence was good, with reported intake of ≥80% of the required number of tablets in 89% of participants. There were no significant between-group differences in neonatal adverse outcomes or other adverse events.Conclusions:Pravastatin in women at high risk of term preeclampsia did not reduce the incidence of delivery with preeclampsia.Registration:URL: https://www.isrctn.com; Unique identifier ISRCTN16123934.

中文翻译：

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普伐他汀与安慰剂在足月先兆子痫高风险妊娠中的比较

背景：妊娠期 35 至 37 周时，将母体因素与平均动脉压、血清胎盘生长因子和血清可溶性 fms 样酪氨酸激酶-1 的测量值相结合，可有效筛查足月子痫，检出率为≈75%，筛查阳性率为 10%。然而，目前还没有已知的干预措施可以降低该疾病的发病率。方法：在这项多中心、双盲、安慰剂对照试验中，我们随机分配了 1120 名患有足月先兆子痫高风险的单胎妊娠妇女接受一定剂量的普伐他汀治疗。从妊娠 35 到 37 周到分娩或 41 周，每天服用 20 毫克/天或安慰剂。主要结果是随机分组后任何时间发生先兆子痫的分娩。根据治疗意向进行分析。结果：共有 29 名女性在试验期间撤回同意。普伐他汀组 14.6%（548 人中的 80 人）和安慰剂组 13.6%（543 人中的 74 人）发生先兆子痫。考虑到筛选和参与中心时的风险影响，混合效应 Cox 回归显示没有证据表明普伐他汀有影响（他汀类药物/安慰剂的风险比，1.08 [95% CI，0.78–1.49]；磷=0.65）。没有证据表明普伐他汀的作用、估计的先兆子痫风险、妊娠史、依从性和阿司匹林治疗之间存在相互作用。任何次要结局的发生率均无显着组间差异，包括妊娠期高血压、死产、早剥、小于胎龄儿的分娩、新生儿死亡或新生儿发病率。随机分组后 1 周和 3 周，治疗对血清胎盘生长因子和可溶性 fms 样酪氨酸激酶 1 浓度的影响没有显着的组间差异。依从性良好，据报道，89% 的参与者摄入≥80% 的所需片剂。新生儿不良结局或其他不良事件无显着组间差异。结论：普伐他汀对足月先兆子痫高风险女性的治疗并未降低先兆子痫分娩的发生率。注册：网址：https://www.isrctn.com；唯一标识符 ISRCTN16123934。