Department of Women and Children's Health, School of Life Course Sciences, King's College London, London, UK.
Birmingham Clinical Trials Unit, University of Birmingham, UK.
Lancet. 2019 Sep 28;394(10204):1181-1190. doi: 10.1016/S0140-6736(19)31963-4. Epub 2019 Aug 28.
In women with late preterm pre-eclampsia, the optimal time to initiate delivery is unclear because limitation of maternal disease progression needs to be balanced against infant complications. The aim of this trial was to determine whether planned earlier initiation of delivery reduces maternal adverse outcomes without substantial worsening of neonatal or infant outcomes, compared with expectant management (usual care) in women with late preterm pre-eclampsia.
In this parallel-group, non-masked, multicentre, randomised controlled trial done in 46 maternity units across England and Wales, we compared planned delivery versus expectant management (usual care) with individual randomisation in women with late preterm pre-eclampsia from 34 to less than 37 weeks' gestation and a singleton or dichorionic diamniotic twin pregnancy. The co-primary maternal outcome was a composite of maternal morbidity or recorded systolic blood pressure of at least 160 mm Hg with a superiority hypothesis. The co-primary perinatal outcome was a composite of perinatal deaths or neonatal unit admission up to infant hospital discharge with a non-inferiority hypothesis (non-inferiority margin of 10% difference in incidence). Analyses were by intention to treat, together with a per-protocol analysis for the perinatal outcome. The trial was prospectively registered with the ISRCTN registry, ISRCTN01879376. The trial is closed to recruitment but follow-up is ongoing.
Between Sept 29, 2014, and Dec 10, 2018, 901 women were recruited. 450 women (448 women and 471 infants analysed) were allocated to planned delivery and 451 women (451 women and 475 infants analysed) to expectant management. The incidence of the co-primary maternal outcome was significantly lower in the planned delivery group (289 [65%] women) compared with the expectant management group (338 [75%] women; adjusted relative risk 0·86, 95% CI 0·79-0·94; p=0·0005). The incidence of the co-primary perinatal outcome by intention to treat was significantly higher in the planned delivery group (196 [42%] infants) compared with the expectant management group (159 [34%] infants; 1·26, 1·08-1·47; p=0·0034). The results from the per-protocol analysis were similar. There were nine serious adverse events in the planned delivery group and 12 in the expectant management group.
There is strong evidence to suggest that planned delivery reduces maternal morbidity and severe hypertension compared with expectant management, with more neonatal unit admissions related to prematurity but no indicators of greater neonatal morbidity. This trade-off should be discussed with women with late preterm pre-eclampsia to allow shared decision making on timing of delivery.
National Institute for Health Research Health Technology Assessment Programme.
对于患有晚期早产先兆子痫的女性，分娩时机尚不清楚，因为需要平衡母体疾病进展的限制与婴儿并发症。本试验旨在确定与期待管理（常规护理）相比，计划提前分娩是否可以减少母体不良结局，而不会对新生儿或婴儿结局造成实质性恶化，适用于 34 至不足 37 周妊娠且单胎或双绒毛膜双胎妊娠的晚期早产先兆子痫女性。
在英格兰和威尔士的 46 个产科单位进行的这项平行组、非盲、多中心、随机对照试验中，我们比较了计划分娩与期待管理（常规护理）在 34 至不足 37 周妊娠且单胎或双绒毛膜双胎妊娠的晚期早产先兆子痫女性中的情况，随机分组。主要的母体结局是复合母体发病率或记录的收缩压至少为 160mmHg，采用优势假设。主要围产期结局是围产期死亡或新生儿入住新生儿重症监护病房至婴儿出院的复合结局，采用非劣效性假设（发病率差异 10%的非劣效性边界）。分析采用意向治疗，同时对围产期结局进行方案分析。该试验在 ISRCTN 注册中心进行了前瞻性注册，ISRCTN01879376。该试验已停止招募，但随访仍在继续。
2014 年 9 月 29 日至 2018 年 12 月 10 日期间，共招募了 901 名女性。450 名女性（448 名女性和 471 名婴儿进行了分析）被分配到计划分娩组，451 名女性（451 名女性和 475 名婴儿进行了分析）被分配到期待管理组。计划分娩组的主要母体结局发生率明显低于期待管理组（289 [65%]名女性）（调整后的相对风险 0.86，95%CI 0.79-0.94；p=0.0005）。按意向治疗分析，计划分娩组的主要围产期结局发生率明显高于期待管理组（196 [42%]名婴儿）（159 [34%]名婴儿；1.26，1.08-1.47；p=0.0034）。方案分析的结果相似。计划分娩组有 9 例严重不良事件，期待管理组有 12 例。
有强有力的证据表明，与期待管理相比，计划分娩可降低母体发病率和严重高血压，与早产相关的新生儿重症监护病房入院人数增加，但新生儿发病率无明显增加。应该与患有晚期早产先兆子痫的女性讨论这种权衡，以允许在分娩时机上进行共同决策。
英国国民保健制度卫生技术评估计划。
