阿托西班用于双胎妊娠晚期流产及早产的临床研究

发布时间：2018-01-07 13:27

本文关键词：阿托西班用于双胎妊娠晚期流产及早产的临床研究　出处：《郑州大学》2016年硕士论文　论文类型：学位论文

更多相关文章： 双胎妊娠 早产 阿托西班 疗效 妊娠结局

【摘要】：随着辅助生殖技术的发展,双胎妊娠孕妇比例也随之增加。双胎妊娠属于高危妊娠,晚期流产及早产是双胎妊娠最主要的并发症,同时也是引起新生儿发病及死亡的主要病因。早产儿的患病率和病死率与孕周密切相关。研究表明在22~28孕周,妊娠时间每延长1天,其新生儿存活率可提高3%,若延迟妊娠至30周,则存活率可增加至90%。对于治疗晚期流产及先兆早产,使用宫缩抑制剂尽量延长妊娠时间具有重要的临床意义。据统计,目前早产率始终徘徊在15%左右,因此,早产的治疗成为研究热点。早产的原因包括:炎症及感染因素、能量代谢异常、胎儿或母亲的信号引发分娩、子宫宫颈或胎盘结构发生改变、遗传因素等。其中早产患者比同孕龄妇女具有较高的催产素敏感性和催产素受体密度,阻断催产素与受体结合,是治疗早产的一种重要途径之一。目前,最有效的催产素衍生物是阿托西班。阿托西班是对子宫有高度特异性的催产素拮抗剂,通过竞争性结合位于子宫肌层和蜕膜的缩宫素受体,阻止细胞内钙离子增加,从而在受体水平竞争性抑制由缩宫素导致的子宫收缩,使平滑肌松弛,达到治疗早产的目的。研究表明阿托西班对子宫收缩的抑制作用与缩宫素受体含量呈正相关。其对单胎妊娠的保胎效果及安全性逐渐被国内外所证实,而缺乏应用于双胎妊娠方面的数据。本研究将对阿托西班用于双胎妊娠晚期流产及早产的效果及安全性进行探讨。资料和方法1研究对象与分组1.选择2011年6月至2015年6月孕周在24~33周我院住院的有晚期流产及早产征象的双胎妊娠孕妇作为研究对象,纳入标准为:(1)宫缩持续时间≥30s、频率≥4次/30 min的规律宫缩;(2)宫颈管消退≥50%。排除标准:胎膜早破、宫口开大≥3cm、阴道出血、子痫前期、妊娠期高血压、严重的孕妇疾病、胎儿生长受限、胎儿患有染色体疾病、羊水过少、绒毛膜羊膜炎。共60例,随机分为2组,其中小疗程组30例,大疗程组30例。所有入选孕妇均无继续妊娠及使用宫缩抑制剂的禁忌证。2.经阴道超声测量宫颈长度方法:(1)排空膀胱后经阴道超声检查;(2)探头置于阴道前穹隆,避免过度用力;(3)标准矢状面,将图像放大到全屏的75%以上,测量宫颈内口至外口的直线距离,连续测量3次后取其最短值。3.阿托西班用药方案(辉凌(瑞典)制药有限公司生产):19小时方案(小疗程):首剂规格为6.75 mg,以大于1 min的速度静脉注射;然后阿托西班注射液20ml(规格:7.5mg/ml)加入0.9%氯化钠注射液或5%葡萄糖注射液180ml中,以300μg/ml的速度静脉滴注3h;然后以100μg/min直至达到预期的抑制宫缩效果,总时长约18h。44小时方案(大疗程):首剂规格为6.75 mg以大于1 min的速度静脉注射;然后阿托西班注射液40ml加入0.9%氯化钠注射液或5%葡萄糖注射液360ml中,以300μg/ml的速度静脉滴注3h;然后以100μg/min直至达到预期的抑制宫缩效果,总时长约44h。孕妇宫缩成功抑制后重新出现早产症状可给予重复的治疗。各孕妇入院即给予一个疗程的糖皮质激素治疗。4.观察指标:⑴大疗程组与小疗程组对延长孕龄48h、7d的效果及安全性的比较⑵大疗程用药方案宫颈管长度(CL)≥20mm组与CL20mm组抑制宫缩的疗效比较;小疗程用药方CL≥20mm组与CL20mm组抑制宫缩的疗效比较⑶产时、产后情况,新生儿发病率及死亡率。5.疗效及安全性判断标准有效:用药后宫缩逐渐停止,宫颈口停止扩张,继续妊娠超过48h。无效:用药后宫缩无减弱,48h内分娩。安全性:任何可能的不良反应均考虑在内,如:恶心、呕吐、颤抖、心动过速、低血压、头痛、肺水肿、出血、深静脉血栓。2统计学方法采用SPSS 17.0软件分析数据。计数资料采用百分数、χ2检验或Fisher精确检验,计量资料采用x±s表示,组间比较用t检验,以P0.05为差异有统计学意义。结果1阿托西班的治疗效果60例应用阿托西班双胎妊娠患者48h未分娩者占85.0%(51/60);7d未分娩者占63.3%(38/60)。妊娠时间最短延长15h,最长延长74d。大小疗程治疗效果比较见表2,χ2检验结果表明,大疗程组的48h和7d的抑制宫缩的有效率显著优于小疗程组,差异有统计学意义(P0.05)。2大小疗程组治疗的安全性大疗程组有1例出现头痛、恶心,1例出现心慌、胸闷,均未影响治疗。小疗程组有1例出现恶心,1例皮肤瘙痒,均未影响治疗。2组的不良反应发生率比较差异无统计学意义(P0.05)。3不同宫颈长度用药效果小疗程用药方案时CL≥20mm组的48h和7d抑制宫缩有效率显著优于CL20mm组,差异有统计学意义(P0.05);大疗程用药方案时CL≥20mm组与CL20mm组相比的48h和7d有效率差异无统计学意义(P0.05)。4妊娠结局产时子宫收缩乏力占11.7%(7/60)。无产后出血。孕周28周分娩17例,28~34周分娩29例,≥34周分娩14例。新生儿存活101例,死亡19例。结论1.阿托西班大疗程和小疗程均可有效延长双胎妊娠晚期流产及早产的妊娠时间。大疗程方案更有效。并不增加母儿的不良反应。2.双胎妊娠晚期流产及先兆早产孕妇CL20mm时大疗程用药效果更好。3.阿托西班大疗程用药并不增加母儿的不良反应,且不增加新生儿并发症的风险。
[Abstract]:With the development of assisted reproductive technology, also increased the proportion of pregnant women with twin pregnancy. Twin pregnancy belongs to high-risk pregnancy, late abortion and premature birth is the main complication of twin pregnancy, but also cause of neonatal morbidity and the major causes of death in premature infants. The incidence and death rate of disease is closely related with gestational age. The study showed that in the the 22~28 weeks of gestation, pregnancy time extended by 1 days, the survival rate can be increased by 3% to 30 weeks of pregnancy, if delayed, the survival rate can be increased to 90%. for the treatment of late abortion and preterm labor, has important clinical significance for the use of tocolytic to prolong pregnancy. According to statistics, the preterm birth rate has remained at 15% so, therefore, the treatment of preterm labor has become a research hotspot. Including the reasons of premature: inflammation and infection, abnormal energy metabolism, signal caused by fetal or maternal childbirth, uterine cervical or placental structure Change, genetic factors. The preterm patients than the same gestational age women have high sensitivity to oxytocin and oxytocin receptor density, blocking oxytocin combined with the receptor, is an important way of treatment of preterm birth. At present, the most effective oxytocin derivatives is A Tosi Ben. A Tosi Ben is on the highly specific oxytocin antagonists by competitive binding in myometrial and decidual oxytocin receptor, prevented the increase in intracellular calcium, which at the receptor level of competitive inhibition by oxytocin induced uterine contraction, smooth muscle relaxation, to the treatment of premature. Study shows that A Tosi Ben's inhibitory effect on uterine contraction with oxytocin receptor concentrations were positively correlated. The clinical effects and safety of single pregnancy has been confirmed at home and abroad, and the lack of application in twin pregnancy data on this study. A Tosi Ben used of late abortion and premature birth of the efficacy and safety of twin pregnancy. Materials and methods: 1 subjects and groups from June 2011 to June 2015 1. gestational weeks 24~33 weeks in our hospital have twin late abortion and premature birth signs of pregnant women as the research object, the inclusion criteria: (1) sustained contractions time is more than 30s, the frequency is more than 4 times /30 min of uterine contractions; (2) the cervical canal subsided more than 50%. exclusion criteria: premature rupture of membranes, cervix than 3cm, vaginal bleeding, pre eclampsia, gestational hypertension, severe illness in pregnant women, fetal growth restriction, fetus with chromosomal diseases, oligohydramnios, villi chorioamnionitis. A total of 60 patients were randomly divided into 2 groups, the treatment group of 30 cases of small and large treatment group of 30 cases. All pregnant women were not to continue the pregnancy and use of tocolytic contraindication to.2. by transvaginal ultrasound measurement of cervical length method: (1) emptying Bladder after transvaginal ultrasound; (2) probe in the anterior vaginal fornix, to avoid excessive force; (3) the standard sagittal image to enlarge more than 75% full screen, linear distance measurement in the cervix mouth to mouth, continuous measurement after 3 times the shortest.3. regimen (Hui A Tosi Ben Ling (Sweden) pharmaceutical Co.): 19 hour plan (small course): the first agent specifications for 6.75 mg, the speed of intravenous injection of more than 1 min; then A Tosi Ben injection 20ml (size: 7.5mg/ml) with 0.9% or 5% Sodium Chloride Injection Glucose Injection 180ml, with a rate of 3H intravenous infusion of 300 g/ml; and based on 100 g/min until the desired tocolytic effect, the total time of about 18h.44 hours (of course) scheme: speed of intravenous injection of the first dose of specifications for 6.75 mg with more than 1 min; and A Tosi Ben 40ml joined Sodium Chloride Injection 0.9% injection or 5% glucose injection Liquid 360ml, with a rate of 3H intravenous infusion of 300 g/ml; and then to 100 g/min until the desired tocolytic effect, the total length of about 44h. to inhibit the contraction of pregnant women to symptoms of preterm labor can give repeated treatment. Glucocorticoid treatment.4. observation indexes of all pregnant women admitted to a course the large and small group: treatment group treatment of prolonged gestational age 48h, compared to the treatment regimen of cervical high efficacy and safety of 7D tube length (CL) than the curative effect comparison of 20mm group and CL20mm group tocolytic treatment with prescription; small CL = 20mm group and CL20mm group to compare the efficacy of the product inhibition of contraction when postpartum and neonatal morbidity and mortality of.5. efficacy and safety criteria: effective medication uterine cervix gradually stop, stop the expansion, to continue the pregnancy more than 48h. medication invalid: uterine contraction without weakening, 48h delivery security: any. Adverse reaction are considered, such as nausea, vomiting, shivering, tachycardia, hypotension, headache, pulmonary edema, hemorrhage, deep venous thrombosis.2 statistical methods using SPSS 17 software to analyze data. Count data using chi square test or 2 percentage, Fisher exact test, measurement data using the X + s group. Compared with t test, with P0.05 as the difference was statistically significant. The treatment effect of 60 cases of the application results of the 1 A Tosi Ben A Tosi Ben twin pregnancy 48h delivery accounted for 85% (51/60); 7d delivery accounted for 63.3% (38/60) of pregnancy. The shortest time extension of 15h, the longest extended treatment effect size of 74d. treatment see Table 2, 2 test results showed that the inhibition of contraction large treatment group of 48h and 7d was significantly better than the small group, the difference was statistically significant (P0.05).2 treatment group safety treatment group with 1 cases of headache, nausea, 1 cases Palpitation, chest tightness, did not affect the treatment. Small treatment group had 1 cases of nausea, 1 cases of skin itching, did not affect the occurrence of adverse reactions in the treatment group.2 rate had no significant difference (P0.05) of.3 in different cervical length medication effect of drug treatment for small CL = 20mm group 48h and 7d with inhibition of contraction the efficiency was higher than that of CL20mm group, the difference was statistically significant (P0.05); large drug treatment scheme CL = 20mm group compared with CL20mm group 48h and 7d there was no significant difference in efficiency (P0.05).4 pregnancy outcome uterine atony accounted for 11.7% (7/60). No postpartum hemorrhage. 28 weeks gestation delivery 17 example, 28~34 weeks delivery 29 cases over 34 weeks in 14 cases of delivery. Neonatal survival in 101 cases, 19 cases died. Conclusion the 1. big and small atosiban can effectively prolong the course of treatment of late abortion and premature birth of twin pregnancy pregnancy time. Large treatment regimen was more effective. The mother does not increase Good response to.2., twin pregnancy, late pregnancy, and threatened premature delivery of pregnant women had better effect when they were treated with CL20mm for a large period of time..3. A Tosi Ben did not increase the adverse reaction of mother and child, and did not increase the risk of neonatal complications.

【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R714.21

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