孕晚期口服小剂量米索前列醇溶液促宫颈成熟的有效性与安全性

Effectiveness and safety of low-dose oral misoprostol solution for cervical ripening in the third trimester

目的探讨口服小剂量米索前列醇溶液在孕晚期促宫颈成熟过程中的有效性和安全性。方法建立前瞻性队列,纳入2022年3月至10月在北京大学第三医院口服米索前列醇溶液促宫颈成熟的单胎初产患者396例(即口服给药组),其中单独口服用药(oral alone,OA)167例作为OA亚组,联合缩宫素/人工破膜229例作为联合口服用药(oral combination,OC)亚组。同时将本院2021年同期阴道应用米索前列醇促宫颈成熟患者218例(即阴道给药组)回顾性队列作为对照,其中单独阴道用药(vaginal alone,VA)77例作为VA亚组,联合缩宫素/人工破膜141例作为联合阴道用药(vaginal combination,VC)亚组,通过倾向性评分配对OA与VA亚组(72与73例)、OC与VC亚组(108与103例),比较多组间临床信息、住院时长、引产时限、宫缩过频、临产率、阴道分娩率、24 h分娩率、产程、不良妊娠结局及新生儿情况等。采用独立样本t检验、方差分析、非参数检验、χ^(2)检验或Fisher精确概率法对数据进行统计学分析。孕妇临产和引产失败的多因素分析采用logistic回归模型。结果口服给药组住院天数、用药至临产时限和用药至阴道分娩时限均小于阴道给药组[(5.4±2.4)与(6.5±2.6)d、(34.2±24.1)与(38.9±25.7)h、(45.8±25.8)与(53.4±27.8)h,t值分别为5.24、2.10及3.39,P值均<0.05]。口服给药组总临产率和阴道分娩率均高于阴道给药组[92.9%(368/396)与83.5%(182/218)、72.2%(286/396)与60.1%(131/218),χ^(2)值分别为13.43和9.50,P值均<0.05]。口服给药组引产失败率、宫缩过频、胎儿窘迫及宫内感染发生率均低于阴道给药组[2.0%(8/396)与6.9%(15/218)、4.3%(17/396)与17.9%(39/218)、8.8%(35/396)与14.7%(32/218)、1.3%(5/396)与3.7%(8/218),χ^(2)值分别为9.21、31.36、4.93及3.93,P值均<0.05]。OA亚组用药至临产时限和用药至阴道分娩时限均大于VA亚组[(25.8±17.0)与(17.4±10.8)h、(37.2±18.8)与(29.7±13.5)h,t值分别为3.49和2.74,P值均<0.05]。OA与VA亚组临产率、阴道分娩率、24 h内分娩率及引产失败率差异均无统计学意义(P值均>0.05),但VA亚组宫缩过频发生率大于OA亚组[19.2%(14/73)与4.2%(3/72),χ^(2)=7.89,P=0.005]。VC与OC亚组用药至临产时限和用药至阴道分娩时限差异均无统计学意义(P值均>0.05),但均大于单独用药组[VC与VA亚组:(49.7±24.6)与(17.4±10.8)h、(61.6±25.7)与(29.7±13.5)h,t值分别为5.31和5.13;OC与OA亚组:(45.3±26.6)与(25.8±17.0)h、(56.1±27.2)与(37.2±18.8)h,t值分别为10.35和9.78;P值均<0.05];OC亚组临产率、阴道分娩率、24 h内分娩率均大于VC亚组[88.9%(96/108)与77.0%(87/113)、63.0%(68/108)与47.8%(54/113)、10.3%(7/108)与0.0%(0/113),χ^(2)值分别为5.49、5.14及7.56,P值均<0.05];OC亚组宫缩过频发生率低于VC组[4.6%(5/108)与18.6%(21/113),χ^(2)=10.37,P=0.001]。Logistic回归分析发现,口服给药、孕周促进临产(OR值分别为2.18和1.43,95%CI分别为1.24~3.90和1.14~1.79),高龄影响促宫颈成熟过程中的临产(OR=0.90,95%CI:0.82~0.98);口服给药降低引产失败风险(OR=0.37,95%CI:0.14~0.91),而高龄增加引产失败风险(OR=1.21,95%CI:1.05~1.40)。结论口服小剂量米索前列醇溶液促宫颈成熟的有效性与阴道给药相仿,且住院时长更短,发生宫缩过频的风险更小,提示口服小剂量米索前列醇溶液给药较为安全,孕晚期促宫颈成熟时可作为选择。

Objective To investigate the effectiveness and safety of low-dose oral misoprostol solution for cervical ripening in late gestation.Methods This was a prospective cohort study including 396 primiparas with singleton pregnancy who received low-dose oral misoprostol solution for cervical ripening(oral group)in Peking University Third Hospital from March to October 2022.They were further allocated to receive oral misoprostol alone(OA group,n=167)or oral misoprostol in combination with oxytocin/amniotomy(OC group,n=229).Moreover,218 cases who received vaginal misoprostol for cervical ripening(vaginal group)during the same period in 2021 were reviewed(a retrospective cohort).Among them,77 were given vaginal misoprostol alone(VA group)and 141 received vaginal misoprostol in combination with oxytocin/amniotomy(VC group).The OA group and VA group(72 and 73 cases)as well as the OC group and VC group(108 and 103 cases)were matched using propensity scores.Basic clinical information,hospital stay,duration of labor induction,uterine hyperstimulation,rate of labor initiation,vaginal delivery rate,rate of delivery within 24 h,duration of labor,neonatal condition,adverse pregnancy outcomes,and other information were compared between different groups.All data were statistically analyzed using independent sample t test,analysis of variance,nonparametric test,Chi-square test,or Fisher's exact probability test.Logistic regression model was used to analyze the factors affecting the labor initiation and the failure of labor induction.Results The average hospital stay,the duration from medication to labor initiation and the duration from medication to vaginal delivery were significantly shorter in the oral group than those in the vaginal group[(5.4±2.4)vs.(6.5±2.6)d,(34.2±24.1)vs.(38.9±25.7)h,(45.8±25.8)vs.(53.4±27.8)h;t=5.24,2.10 and 3.39;all P<0.05].The total labor initiation rate and vaginal delivery rate in the oral group were significantly higher than those in the vaginal group[92.9%(368/396)vs.83.5%(182/218),72.2%(286/396)vs.60.1%(131/218);χ^(2)=13.43 and 9.50;both P<0.05].The incidence of failed induction of labor,uterine hyperstimulation,fetal distress,and intrauterine infection in the oral group were lower than those in the vaginal group[2.0%(8/396)vs.6.9%(15/218),4.3%(17/396)vs.17.9%(39/218),8.8%(35/396)vs.14.7%(32/218),1.3%(5/396)vs.3.7%(8/218);χ^(2)=9.21,31.36,4.93 and 3.93;all P<0.05].The duration from medication to labor initiation and to vaginal delivery in the OA group were higher than those in the VA group[(25.8±17.0)vs.(17.4±10.8)h,(37.2±18.8)vs.(29.7±13.5)h;t=3.49 and 2.74;both P<0.05].There were no significant differences in the labor initiation rate,vaginal delivery rate,rate of delivery within 24 h or the incidence of failed induction of labor between the OA and VA groups(all P>0.05).Women in the VA group were more likely to develop uterine hyperstimulation than those in the OA group[19.2%(14/73)vs.4.2%(3/72),χ^(2)=7.89,P=0.005].There were no significant differences in the duration from medication to labor initiation or to vaginal delivery between the VC and OC groups(both P>0.05),but the duration were significantly longer than those in the corresponding medication alone group(VC vs.VA groups:(49.7±24.6)vs.(17.4±10.8)h and(61.6±25.7)vs.(29.7±13.5)h,t=5.31 and 5.13,both P<0.05;OC vs.OA groups:(45.3±26.6)vs.(25.8±17.0)h and(56.1±27.2)vs.(37.2±18.8)h,t=10.35 and 9.78,both P<0.05].The labor initiation rate,vaginal delivery rate and rate of delivery within 24 h in the OC group were higher than those in the VC group[88.9%(96/108)vs.77%(87/113),63.0%(68/108)vs.47.8%(54/113),10.3%(7/108)vs.0.0%(0/113);χ^(2)=5.49,5.14 and 7.56;all P<0.05].The incidence of uterine hyperstimulation in the OC group was 4.6%(5/108),which was lower than that in the VC group[18.6%(21/113),χ^(2)=10.37,P=0.001].Logistic regression analysis showed that oral misoprostol and gestational age were positively correlated with labor initiation[OR(95%CI):2.18(1.24-3.90)and 1.43(1.14-1.79)],while maternal age was negatively correlated with labor initiation[OR(95%CI):0.90(0.82-0.98)].Moreover,failed induction of labor was negatively correlated with oral misoprostol[OR(95%CI):0.37(0.14-0.91)],but positively correlated with maternal age[OR(95%CI):1.21(1.05-1.40)].Conclusions Oral administration of low-dose misoprostol solution is as effective as vaginal misoprostol in promoting cervical ripening.Besides,it can shorten the average hospital stay and reduce the incidence of uterine hyperstimulation,suggesting that low-dose oral misoprostol solution is relatively safer and can be used to promote cervical ripening in late gestation.