Hofmeyr G J, Gülmezoglu A M, Alfirevic Z
Department of Obstetrics and Gynaecology, Coronation Hospital and University of the Witwatersrand, South Africa.
Br J Obstet Gynaecol. 1999 Aug;106(8):798-803. doi: 10.1111/j.1471-0528.1999.tb08400.x.
To determine, from the best available evidence, the effectiveness and safety of misoprostol administered vaginally or orally for third trimester cervical ripening or induction of labour.
Clinical trials of misoprostol used for cervical ripening or labour induction in the third trimester were identified from the register of randomised trials maintained by the Cochrane Pregnancy and Childbirth Group. All identified trials were considered for inclusion in the review according to a prespecified protocol. Primary outcomes were chosen to address clinical effectiveness (delivery within 24 hours) and safety (uterine hyperstimulation, caesarean section, serious maternal and neonatal morbidity) and were determined a priori. All meta-analyses were based on the intention-to-treat principle. In the absence of heterogeneity the summary statistics have been expressed as typical relative risk (RR) and 95% confidence interval (CI).
Vaginal misoprostol: one small study showed that the use of misoprostol results in more effective cervical ripening and reduced need for oxytocin when compared with placebo. When compared with oxytocin, vaginal misoprostol was more effective for labour induction. The relative risk of failure to achieve vaginal delivery within 24 hours was 0.48 (95% CI 0.35 to 0.66). However, the relative risks for uterine hyperstimulation with and without fetal heart rate abnormalities were 2.54 (95% CI 1.12 to 5.77) and 2.96 (95% CI 2.11 to 4.14), respectively. In three out of four trials which studied women with intact membranes and unfavourable cervices, failure to achieve vaginal delivery within 24 hours was reduced with misoprostol when compared with other prostaglandins (RR 0.71, 95% CI 0.62 to 0.81). Vaginal misoprostol was associated with increased uterine hyperstimulation both without fetal heart rate changes (RR 1.67, 95% CI 1.30 to 2.14) and with associated fetal heart rate changes (RR 1.45, 95% CI 1.04 to 2.04). There was also an increase in meconium stained amniotic fluid following vaginal misoprostol (RR 1.38, 95% CI 1.06 to 1.79). Oral misoprostol: one small trial suggests that, when compared with placebo, oral misoprostol reduces the need for oxytocin and shortens the time between induction and delivery. Compared with other prostaglandins one small trial showed a reduced need for oxytocin with oral misoprostol. Two trials compared oral with vaginal misoprostol using different doses. No significant differences were evident.
Overall, misoprostol appears to be more effective than conventional methods of cervical ripening and labour induction. Although no differences in perinatal outcome were shown, the studies were not sufficiently large to exclude the possibility of uncommon serious adverse effects. In particular the increase in uterine hyperstimulation with fetal heart rate changes following misoprostol is a matter for concern. It is possible that, if sufficient numbers are studied, an unacceptably high number of serious adverse events including uterine rupture and asphyxial fetal deaths may occur. The data at present are not robust enough to address the issue of safety. Thus, though misoprostol shows promise as a highly effective, inexpensive and convenient agent for labour induction, it cannot be recommended for routine use at this stage. Lower dose misoprostol regimens should be investigated further.
基于现有最佳证据，确定阴道或口服米索前列醇用于孕晚期宫颈成熟或引产的有效性和安全性。
从Cochrane妊娠与分娩小组维护的随机试验登记册中识别出用于孕晚期宫颈成熟或引产的米索前列醇临床试验。根据预先指定的方案，所有识别出的试验均被考虑纳入综述。选择主要结局以解决临床有效性（24小时内分娩）和安全性（子宫过度刺激、剖宫产、严重母婴发病率）问题，并预先确定。所有荟萃分析均基于意向性治疗原则。在不存在异质性的情况下，汇总统计数据以典型相对风险（RR）和95%置信区间（CI）表示。
阴道用米索前列醇：一项小型研究表明，与安慰剂相比，使用米索前列醇可使宫颈成熟更有效，并减少催产素的使用需求。与催产素相比，阴道用米索前列醇引产更有效。24小时内未实现阴道分娩的相对风险为0.48（95%CI 0.35至0.66）。然而，伴有和不伴有胎儿心率异常的子宫过度刺激的相对风险分别为2.54（95%CI 1.12至5.77）和2.96（95%CI 2.11至4.14）。在四项研究胎膜完整且宫颈条件不佳的女性的试验中，有三项试验表明，与其他前列腺素相比，米索前列醇可降低24小时内未实现阴道分娩的发生率（RR 0.71，95%CI 0.62至0.81）。阴道用米索前列醇与不伴有胎儿心率变化的子宫过度刺激增加相关（RR 1.67，95%CI 1.30至2.14），也与伴有胎儿心率变化的子宫过度刺激增加相关（RR 1.45，95%CI 1.04至2.04）。阴道用米索前列醇后羊水胎粪污染也有所增加（RR 1.38，95%CI 1.06至1.79）。口服米索前列醇：一项小型试验表明，与安慰剂相比，口服米索前列醇可减少催产素的使用需求，并缩短引产与分娩之间的时间。与其他前列腺素相比，一项小型试验表明口服米索前列醇可减少催产素的使用需求。两项试验比较了不同剂量的口服米索前列醇与阴道用米索前列醇。未发现明显差异。
总体而言，米索前列醇似乎比传统的宫颈成熟和引产方法更有效。尽管未显示围产期结局存在差异，但研究规模不足以排除罕见严重不良反应的可能性。特别是米索前列醇后伴有胎儿心率变化的子宫过度刺激增加令人担忧。如果研究数量足够多，可能会发生包括子宫破裂和胎儿窒息死亡在内的高得不可接受的严重不良事件。目前的数据不够有力，无法解决安全性问题。因此，尽管米索前列醇有望成为一种高效、廉价且方便的引产药物，但现阶段不推荐常规使用。应进一步研究低剂量米索前列醇方案。
