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对于疑似有胎儿窘迫的早产婴儿,立即分娩与延迟分娩以改善结局的比较。

Immediate versus deferred delivery of the preterm baby with suspected fetal compromise for improving outcomes.

作者信息

Stock Sarah J, Bricker Leanne, Norman Jane E, West Helen M

机构信息

MRC Centre for Reproductive Health, University of Edinburgh Queen's Medical Research Centre, Edinburgh, UK, EH16 4TJ.

出版信息

Cochrane Database Syst Rev. 2016 Jul 12;7(7):CD008968. doi: 10.1002/14651858.CD008968.pub3.

Abstract

BACKGROUND

Immediate delivery of the preterm fetus with suspected compromise may decrease the risk of damage due to intrauterine hypoxia. However, it may also increase the risks of prematurity.

OBJECTIVES

To assess the effects of immediate versus deferred delivery of preterm babies with suspected fetal compromise on neonatal, maternal and long-term outcomes.

SEARCH METHODS

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2016) and reference lists of retrieved studies.

SELECTION CRITERIA

Randomised trials comparing a policy of immediate delivery with deferred delivery or expectant management in preterm fetuses with suspected in utero compromise. Quasi-randomised trials and trials employing a cluster-randomised design were eligible for inclusion but none were identified.

DATA COLLECTION AND ANALYSIS

Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy.

MAIN RESULTS

We included one trial of 548 women (588 babies) in the review. Women with pregnancies between 24 and 36 weeks' gestation took part. The study took place in 13 European countries, between 1993 and 2001. The difference in the median randomisation to delivery interval between immediate delivery and deferred delivery was four days (median: 0.9 (inter-quartile range (IQR) 0.4 to 1.3) days for immediate delivery, median: 4.9 (IQR 2.0 to 10.8) days in the delay group).There was no clear difference in the primary outcomes of extended perinatal mortality (risk ratio (RR) 1.17, 95% confidence interval (CI) 0.67 to 2.04, one trial, 587 babies, moderate-quality evidence) or the composite outcome of death or disability at or after two years of age (RR 1.22, 95% CI 0.85 to 1.75, one trial, 573 babies, moderate-quality evidence) with immediate delivery compared to deferred delivery. The results for these outcomes are consistent with both appreciable benefit and harm. More babies in the immediate delivery group were ventilated for more than 24 hours (RR 1.54, 95% CI 1.20 to 1.97, one trial, 576 babies). There were no differences between the immediate delivery and deferred delivery groups in any other infant mortality outcome (stillbirth, neonatal mortality, postneonatal mortality > 28 days to discharge), individual neonatal morbidity or markers of neonatal morbidity (cord pH less than 7.00, Apgar less than seven at five minutes, convulsions, interventricular haemorrhage or germinal matrix haemorrhage, necrotising enterocolitis and periventricular leucomalacia or ventriculomegaly).Some important outcomes were not reported, in particular infant admission to neonatal intensive care or special care facility, and respiratory distress syndrome. We were not able to calculate composite rates of serious neonatal morbidity, even though individual morbidities were reported, due to the risk of double counting infants with more than one morbidity.More children in the immediate delivery group had cerebral palsy at or after two years of age (RR 5.88, 95% CI 1.33 to 26.02, one trial, 507 children). There were, however, no differences in neurodevelopment impairment at or after two years (RR 1.72, 95% CI 0.86 to 3.41, one trial, 507 children), death at or after two years of age (RR 1.04, 95% CI 0.66 to 1.63, one trial, 573 children), or death or disability in childhood (six to 13 years of age) (RR 0.82, 95% CI 0.48 to 1.40, one trial, 302 children). More women in the immediate delivery group had caesarean delivery than in the deferred delivery group (RR 1.15, 95% CI 1.07 to 1.24, one trial, 547 women, high-quality evidence). Data were not available on any other maternal outcomes.There were several methodological weaknesses in the included study, and the level of evidence for the primary outcomes was graded high for caesarean section and moderate for extended perinatal mortality and death or disability at or after two years. The evidence was downgraded because the CIs for these outcomes were wide, and were consistent with both appreciable benefit and harm. Bias may have been introduced by several factors: blinding was not possible due to the nature of the intervention, data for childhood follow-up were incomplete due to attrition, and no adjustment was made in the analysis for the non-independence of babies from multiple pregnancies (39 out of 548 pregnancies). This study only included cases of suspected fetal compromise where there was uncertainty whether immediate delivery was indicated, thus results must be interpreted with caution.

AUTHORS' CONCLUSIONS: Currently there is insufficient evidence on the benefits and harms of immediate delivery compared with deferred delivery in cases of suspected fetal compromise at preterm gestations to make firm recommendations. There is a lack of trials addressing this question, and limitations of the one included trial means that caution must be used in interpreting and generalising the findings. More research is needed to guide clinical practice.Although the included trial is relatively large, it has insufficient power to detect differences in neonatal mortality. It did not report any maternal outcomes other than mode of delivery, or evaluate maternal satisfaction or economic outcomes. The applicability of the findings is limited by several factors: Women with a wide range of obstetric complications and gestational ages were included, and subgroup analysis is currently limited. Advances in Doppler assessment techniques may diagnose severe compromise more accurately and help make decisions about the timing of delivery. The potential benefits of deferring delivery for longer or shorter periods cannot be presumed.Where there is uncertainty whether or not to deliver a preterm fetus with suspected fetal compromise, there seems to be no benefit to immediate delivery. Deferring delivery until test results worsen or increasing gestation favours delivery may improve the outcomes for mother and baby.There is a need for high-quality randomised controlled trials comparing immediate and deferred delivery where there is suspected fetal compromise at preterm gestations to guide clinical practice. Future trials should report all important outcomes, and should be adequately powered to detect differences in maternal and neonatal morbidity and mortality.

摘要

背景

对于疑似有危险的早产胎儿,立即分娩可能会降低因宫内缺氧造成损害的风险。然而,这也可能增加早产的风险。

目的

评估对于疑似有危险的早产婴儿,立即分娩与延迟分娩对新生儿、母亲及长期预后的影响。

检索方法

我们检索了Cochrane妊娠与分娩组试验注册库(2016年4月30日)以及检索到的研究的参考文献列表。

选择标准

随机对照试验,比较对于疑似宫内有危险的早产胎儿采取立即分娩策略与延迟分娩或期待治疗策略的效果。半随机试验和采用整群随机设计的试验符合纳入标准,但未检索到此类试验。

数据收集与分析

两位综述作者独立评估试验是否符合纳入标准及偏倚风险,提取数据并检查其准确性。

主要结果

本综述纳入了一项试验,涉及548名女性(588名婴儿)。妊娠24至36周的女性参与了该研究。研究于1993年至2001年在13个欧洲国家进行。立即分娩组与延迟分娩组随机化至分娩间隔的中位数差异为4天(立即分娩组中位数:0.9天(四分位间距(IQR)0.4至1.3天),延迟组中位数:4.9天(IQR 2.0至10.8天))。与延迟分娩相比,立即分娩在围产期延长死亡率(风险比(RR)1.17,95%置信区间(CI)0.67至2.04,一项试验,587名婴儿,中等质量证据)或两岁及以后死亡或残疾的复合结局(RR 1.22,95%CI 0.85至1.75,一项试验,573名婴儿,中等质量证据)这些主要结局方面无明显差异。这些结局的结果既显示出明显益处也显示出危害。立即分娩组中有更多婴儿接受了超过24小时的通气治疗(RR 1.54,95%CI 1.20至1.97,一项试验,576名婴儿)。立即分娩组与延迟分娩组在任何其他婴儿死亡结局(死产、新生儿死亡、出生后28天至出院后的新生儿后期死亡)、个体新生儿发病率或新生儿发病率指标(脐动脉血pH值低于7.00、5分钟时阿氏评分低于7分、惊厥、脑室内出血或生发基质出血、坏死性小肠结肠炎以及脑室周围白质软化或脑室扩大)方面均无差异。一些重要结局未被报告,特别是婴儿入住新生儿重症监护或特殊护理机构以及呼吸窘迫综合征。尽管报告了个体发病率,但由于存在一种以上发病率的婴儿可能被重复计算的风险,我们无法计算严重新生儿发病率的综合发生率。立即分娩组中两岁及以后患脑瘫的儿童更多(RR 5.88,95%CI 1.33至26.02,一项试验,507名儿童)。然而,在两岁及以后的神经发育障碍(RR 1.72,95%CI 0.86至3.41,一项试验,507名儿童)、两岁及以后的死亡(RR 1.04,95%CI 0.66至1.63,一项试验,573名儿童)或儿童期(6至13岁)死亡或残疾(RR 0.82,95%CI 0.48至1.40,一项试验,302名儿童)方面无差异。立即分娩组中剖宫产的女性比延迟分娩组更多(RR 1.15,95%CI 1.07至1.24,一项试验,547名女性,高质量证据)。未获得任何其他母亲结局的数据。纳入的研究存在几个方法学上的弱点,剖宫产主要结局的证据等级为高,围产期延长死亡率以及两岁及以后死亡或残疾的证据等级为中等。证据被降级是因为这些结局的置信区间较宽,且既显示出明显益处也显示出危害。可能由几个因素引入了偏倚:由于干预措施的性质无法进行盲法,由于失访儿童期随访数据不完整,并且在分析中未对来自多胎妊娠的婴儿的非独立性进行调整(548例妊娠中有39例)。本研究仅纳入了疑似胎儿有危险且不确定是否应立即分娩的病例,因此结果必须谨慎解释。

作者结论

目前对于早产时疑似胎儿有危险的情况,与延迟分娩相比,立即分娩的利弊证据不足,无法做出确切推荐。缺乏针对此问题的试验,且纳入的一项试验存在局限性,这意味着在解释和推广研究结果时必须谨慎。需要更多研究来指导临床实践。尽管纳入的试验规模相对较大,但检测新生儿死亡率差异的效能不足。除了分娩方式外,未报告任何母亲结局,也未评估母亲满意度或经济结局。研究结果的适用性受到几个因素的限制:纳入了各种产科并发症和不同孕周的女性,且目前亚组分析有限。多普勒评估技术的进展可能更准确地诊断严重危险情况,并有助于做出分娩时机的决策。不能假定延长或缩短延迟分娩时间的潜在益处。当不确定是否应分娩疑似有危险的早产胎儿时,立即分娩似乎没有益处。延迟分娩直至检测结果恶化或孕周增加有利于分娩可能会改善母婴结局。需要高质量的随机对照试验来比较早产时疑似胎儿有危险情况下的立即分娩和延迟分娩,以指导临床实践。未来的试验应报告所有重要结局,并有足够的效能检测母亲和新生儿发病率及死亡率的差异。

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