黄体酮软胶囊联合阿托西班对高龄先兆早产患者血清学指标及母婴结局的影响

Effect of progesterone softgel combined with atosiban on serum index levels and maternal and infant outcome in patients of advanced maternal age with threatened premature delivery

目的探究黄体酮软胶囊联合阿托西班对高龄先兆早产患者血清基质金属蛋白酶抑制剂-1(TIMP-1)、一氧化氮(NO)、前列腺素E_(2)(PGE_(2))水平及母婴结局的影响。方法回顾性分析2021年1月至2023年12月扬州大学附属医院收治的102例高龄先兆早产患者的临床资料,根据治疗方案分为联合组(45例)和对照组(57例)。对照组采用常规支持治疗及硫酸镁治疗,联合组在常规支持治疗基础上采用黄体酮软胶囊联合阿托西班,两组均随访至妊娠结束。比较两组临床症状缓解时间,治疗前、治疗10 d后血清学指标,母婴结局,治疗期间的安全性。结果联合组腹痛、腰酸、出血缓解的时间[分别为(3.23±0.68)、(6.31±0.79)、(5.29±0.87)d]均短于对照组[分别为(4.88±0.77)、(7.73±0.88)、(6.87±0.82)d],差异均有统计学意义(t=11.307,8.461,9.406,均P<0.05)。治疗10 d后,两组血清TIMP-1水平较治疗前升高,且联合组[(132.70±11.91)pg·mL^(-1)]高于对照组[(112.53±13.23)pg·mL^(-1)],差异有统计学意义(t=7.986,P<0.05)。治疗10 d后,两组NO、PGE_(2)水平较治疗前降低,且联合组[分别为(23.05±3.61)μmol·L^(-1)、(41.75±5.20)pg·mL^(-1)]均低于对照组[分别为(27.76±3.55)μmol·L^(-1)、(51.43±5.21)pg·mL^(-1)],差异均有统计学意义(t=6.604,9.325,均P<0.05)。治疗后,联合组保胎成功率、新生儿体质量、Apgar评分、分娩孕周[分别为100.00%(45/45)、(2.89±0.38)kg、(9.35±0.19)分、(38.91±1.78)周]均高于对照组[分别为87.72%(50/57)、(2.27±0.33)kg、(8.77±0.38)分、(37.89±1.21)周],差异均有统计学意义(χ^(2)=4.151,t=8.811,9.351,3.438,均P<0.05);联合组早产率为4.44%(2/45),低于对照组的17.54%(10/57),差异有统计学意义(χ^(2)=4.157,P<0.05)。在治疗期间,对照组总不良反应发生率为13.33%(6/45),与联合组的7.02%(4/57)比较,差异无统计学意义(χ^(2)=1.156,P=0.282)。结论黄体酮软胶囊联合阿托西班可使高龄先兆早产患者症状缓解,改善母婴结局,改善血清TIMP-1、NO、PGE_(2)水平,安全性良好。

Objective To investigate the effect of progesterone softgel combined with atosiban on serum levels of matrix metalloproteinase inhibitor-1(TIMP-1),nitric oxide(NO),prostaglandin E_(2)(PGE_(2))and maternal and infant outcomes in patients of advanced maternal age with threatened premature delivery.Methods Clinical data of 102 patients of advanced maternal age with threatened premature delivery admitted to Yangzhou University Affiliated Hospital from January 2021 to December 2023 were retrospectively analyzed.These patients were divided into the combination group(n=45)and the control group(n=57)according to the treatment plan.The patients in the control group received conventional supportive treatment and magnesium sulfate treatment while those in the combination group received treatment with progesterone softgel combined with atosiban in addition to the usual supportive care.All the patients in both groups were followed up to pregnancy.The clinical symptom remission time,serum indexes before treatment and 10 days after treatment,maternal and infant outcomes and safety during treatment were compared between the two groups.Results The relief time of symptoms(abdominal pain,lumbar acid,bleeding relief)in the combination group was(3.23±0.68)d,(6.31±0.79)d,(5.29±0.87)d respectively,which was significantly shorter than that of(4.88±0.77)d,(7.73±0.88)d,(6.87±0.82)d in the control(t=11.307,8.461,9.406,all P<0.05).After 10 days of treatment,the serum level of TIMP-1 was increased in both groups,and it was remarkably higher in the combination group than in the control((132.70±11.91)pg·mL^(-1) vs(112.53±13.23)pg·mL^(-1))(t=7.986,P<0.05).The levels of NO and PGE_(2)were decreased in both groups,and they were significantly lower in the combination group than in the contol((23.05±3.61)μmol·L^(-1) vs(27.76±3.55)μmol·L^(-1),(41.75±5.20)pg·mL^(-1) vs(51.43±5.21)pg·mL^(-1))(t=6.604,9.325,both P<0.05).Meanwhile,the success rate of fetal protection,neonatal body weight,Apgar score,gestational weeks of delivery were 100.00%(45/45),(2.89±0.38)kg,(9.35±0.19)points,(38.91±1.78)weeks in the combination group,which were all higher than those of 87.72%(50/57),(2.27±0.33)kg,(8.77±0.38)min,(37.89±1.21)weeks in the control(χ^(2)=4.151,t=8.811,9.351,3.438,all P<0.05).The preterm birth rate in the combination group was 4.44%(2/45),which was lower than that of 17.54%(10/57)in the control,showing statistically significant difference(χ^(2)=4.157,P<0.05).No significant difference was found in the incidence of adverse reactions between the two groups(13.33%(6/45)vs 7.02%(4/57))(χ^(2)=1.156,P=0.282).Conclusion Progesterone softgel combined with atosiban can alleviate symptoms and improve maternal and infant outcomes in patients of advance maternal age with threatened preterm delivery since it can improve the regulation of serum TIMP-1,NO and PGE_(2)levels.Furthermore,it is of high safety.