CRADLE-4: Can Reduction of Adverse pregnancy outcomes occur with planned DeLivery vs.Expectant management in pre-eclampsia?

先兆子痫影响大约二十五分之一的孕妇，当母亲出现高血压和尿中蛋白质时，医生会诊断出先兆子痫。这种疾病的并发症可能非常严重。先兆子痫，特别是当它发生在怀孕早期，可能会导致严重的问题，为母亲，如适合，出血，甚至可能导致她的死亡。婴儿可能会受到胎盘功能不良的影响，这会导致血流减少，营养不足和氧气供应不足，从而导致生长减缓，因此婴儿可能出生时体重不足，甚至可能死亡。婴儿死亡是常见的，当疾病没有及时识别时，常见于LMIC环境中。及时分娩可以预防许多并发症，但也会增加婴儿早产和不成熟的风险。对于那些在怀孕结束时出现血压升高或轻度先兆子痫的妇女，分娩已被证明可以降低母亲出现问题的风险，也可以降低剖腹产率，而不会增加婴儿的风险。当先兆子痫发生在怀孕早期，在怀孕的第34周之前，婴儿早产的风险很高。在这种情况下，最好不要分娩，除非母亲或婴儿恶化。在怀孕第34周到第37周之间常规分娩婴儿的风险/益处尚不清楚。大约三分之一的先兆子痫女性出现在这个窗口期，并且病情比足月时更严重。分娩可以预防母亲的并发症，但与足月分娩相比，可能会增加婴儿的风险。如果妇女生活在资源较少的国家，那里的医生、助产士、护士、医疗用品和医院病床较少，而且文化价值观不同，这一决定就更加复杂。在这项试验中，我们的目标是确定识别和准确诊断与分娩（在48小时内分娩或剖腹产）或“观察和等待”管理是否对生活在印度和赞比亚的妊娠第34周至第37周的先兆子痫妇女及其婴儿更好。“观察和等待”，医学专业人士称之为“期待管理”，意味着孕妇将被密切观察，只有在母亲或婴儿出现任何并发症，或者怀孕达到第37周时才能分娩。为了测试这一点，使用我们的CRADLE VSA设备诊断为先兆子痫的孕妇，在怀孕第34周至第37周之间进入医院或诊所，但不需要立即分娩，将由计算机分配（即随机分配，就像扔硬币一样）到分娩或期待管理。如果她们被分配分娩，她们可能不得不前往当地医院，那里有分娩设施。如果他们被分配到预期管理，他们将继续得到同样的照顾，他们通常会有。这可能包括留院观察或到诊所进行定期检查。如果我们采取立即分娩的政策，我们将发现母亲的并发症是否减少。这项研究还将发现这种策略是否会导致更少的婴儿入院，更少的婴儿重症监护室入院，以及与“等待和观察”组的妇女所生的婴儿相比，这组婴儿的死亡率是否更低。我们选择在印度和赞比亚进行这项试验，因为他们有不同的医疗保健系统和挑战。我们将确保了解该战略在每个国家的影响以及妇女及其家庭的经历，以便我们的结果与许多其他国家相关。

Pre-eclampsia affects approximately one in twenty-five pregnancies and is diagnosed by doctors when the mother develops high blood pressure and protein in her urine. The complications of this disorder are potentially very serious. Pre-eclampsia, particularly when it occurs early on in pregnancy, can result in severe problems for the mother such as fits, bleeding, and may even result in her death. The baby can be affected by a poorly functioning placenta, which leads to reduced blood flow, inadequate nutrition and poor oxygen supply which can result in reduced growth so that the infant may be born with a low birthweight and may even die. Death of the baby is common when the disease is not recognized in a timely fashion, common in a LMIC setting. Timely delivery of the baby will prevent many of these complications, but can also increase the risk of problems for the baby related to premature birth and immaturity.In women who develop raised blood pressure or mild pre-eclampsia at the end of pregnancy, bringing on labour has been shown to reduce the risk of problems to the mother and also lower the caesarean section rate, without any increased risk to the baby. When pre-eclampsia occurs in early pregnancy, before the 34th week of pregnancy, the risk to the baby of being born early is high. In this case it is better not to deliver unless the mother or baby deteriorate. The risk/benefit of routinely delivering the baby between the 34th and 37th week of pregnancy is less clear. Approximately a third of women with pre-eclampsia present in this window, and the disease in more severe than at term. Delivery may prevent complications in the mother but might increase risks to the baby compared with delivery at term. This decision is even more complicated when women live in countries with less resources where there are fewer doctors, midwives, nurses, medical supplies and hospital beds and different cultural values. In this trial we would aim to determine whether recognition and accurate diagnosis with delivery (bringing on labour within 48 hours or caesarean) or 'watch and wait' management is better for women with pre-eclampsia living in India and Zambia between the 34th and 37th week of pregnancy and their babies. 'Watch and wait', which medical professionals call 'expectant management', means that pregnant women will be closely observed and only be delivered if any complications arise in either the mother or the baby, or if the 37th week of pregnancy is reached. To test this, pregnant women that have been diagnosed with pre-eclampsia using our CRADLE VSA device, who come into hospital or clinic between the 34th and 37th week of pregnancy but do not require immediate delivery, will be allocated by a computer (i.e. by chance, like tossing a coin) to delivery or expectant management. If they are allocated to delivery they may have to travel to a local hospital where they have the facilities for this. If they are allocated to expectant management they will continue to have the same care they would usually have had. This may include staying in hospital for observation or coming to clinic for regular check ups. We will find out if there are fewer complications in the mother if we adopt the policy of immediate delivery. The study will also find out if this strategy leads to fewer babies being admitted to hospital, less frequent admission to a baby intensive care unit and if there are fewer deaths in this group when compared to those babies born to women in the 'wait and watch' group.We have chosen to run this trial in India and Zambia as they have different health care systems and challenges. We will ensure we find out about how the strategy is affected in each country and about the experiences of women and their families so our results will be relevant to many other countries.