Groom K M, McCowan L M, Stone P R, Chamley L C, McLintock C
Department of Obstetrics and Gynaecology, Faculty of Medical Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
National Women's Health, Auckland City Hospital, Private Bag 92024, Auckland, New Zealand.
BMC Pregnancy Childbirth. 2016 Nov 22;16(1):367. doi: 10.1186/s12884-016-1162-y.
Preeclampsia and intrauterine fetal growth restriction (IUGR) are two of the most common causes of maternal and perinatal morbidity and mortality. Current methods of predicting those at most risk of these conditions remain relatively poor, and in clinical practice past obstetric history remains the most commonly used tool. Aspirin and, in women at risk of preeclampsia only, calcium have been demonstrated to have a modest effect on risk reduction. Several observational studies and randomised trials suggest that low molecular weight heparin (LMWH) therapy may confer some benefit.
METHODS/DESIGN: This is a multicentre open label randomised controlled trial to determine the effect of the LMWH, enoxaparin, on the prevention of recurrence of preeclampsia and/or IUGR in women at high risk due to their past obstetric history in addition to standard high risk care for all participants.
A singleton pregnancy >6 and <16 weeks gestation with most recent prior pregnancy with duration >12 weeks having; (1) preeclampsia delivered <36 weeks, (2) Small for gestational age (SGA) infant <10 customised birthweight centile delivered <36 weeks or, (3) SGA infant ≤3 customised birthweight centile delivered at any gestation. Randomisation is stratified for maternal thrombophilia status and women are randomly assigned to 'standard high risk care' or 'standard high risk care' plus enoxaparin 40 mg from recruitment until 36 weeks or delivery, whichever occurs sooner. Standard high risk care includes the use of aspirin 100 mg daily and calcium 1000-1500 mg daily (unless only had previous SGA with no preeclampsia). The primary outcome is preeclampsia and/or SGA <5 customised birthweight centile. Analysis will be by intention to treat.
The EPPI trial has more focussed and clinically relevant inclusion criteria than other randomised trials with a more restricted composite primary outcome. The inclusion of standard use of aspirin (and calcium) for all participants will help to ensure that any differences observed in outcome are likely to be related to enoxaparin use. These data will make a significant contribution to future meta-analyses and systematic reviews on the use of LMWH for the prevention of placental mediated conditions.
ACTRN12609000699268 Australian New Zealand Clinical Trials Registry. Date registered 13/Aug/2009 (prospective registration).
子痫前期和胎儿宫内生长受限（IUGR）是孕产妇和围产期发病及死亡的两个最常见原因。目前预测这些疾病高危人群的方法仍然相对较差，在临床实践中，既往产科病史仍然是最常用的工具。阿司匹林以及仅针对有子痫前期风险的女性使用的钙，已被证明在降低风险方面有一定作用。多项观察性研究和随机试验表明，低分子量肝素（LMWH）治疗可能有益。
方法/设计：这是一项多中心开放标签随机对照试验，旨在确定LMWH依诺肝素除了为所有参与者提供标准的高危护理外，对预防有既往产科病史的高危女性子痫前期和/或IUGR复发的效果。
单胎妊娠，孕周>6周且<16周，最近一次既往妊娠持续时间>12周，且有以下情况之一：（1）子痫前期在<36周分娩；（2）小于胎龄（SGA）婴儿<第10百分位定制出生体重且在<36周分娩；或（3）SGA婴儿≤第3百分位定制出生体重在任何孕周分娩。根据母亲血栓形成倾向状态进行分层随机分组，女性被随机分配到“标准高危护理”组或“标准高危护理”加依诺肝素40mg组，从招募开始直至36周或分娩（以先到者为准）。标准高危护理包括每天使用100mg阿司匹林和1000 - 1500mg钙（除非既往仅有SGA且无子痫前期）。主要结局是子痫前期和/或SGA<第5百分位定制出生体重。分析将按意向性治疗进行。
与其他随机试验相比，EPPI试验有更聚焦且临床相关的纳入标准，主要复合结局更受限。所有参与者均使用标准剂量的阿司匹林（和钙）将有助于确保观察到的结局差异可能与依诺肝素的使用有关。这些数据将对未来关于使用LMWH预防胎盘介导疾病的荟萃分析和系统评价做出重大贡献。
澳大利亚新西兰临床试验注册中心ACTRN12609000699268。注册日期：2009年8月13日（前瞻性注册）。
