Study On The Spontaneous Preterm Labor With Progesterone

Objective Preterm birth(PB),defned as childbirth occurring between 28 and less 37 completes weeks or 196~259 days of gestation,is the most important cause of neonatal mortality and morbidity and in the global the incidence is 5% ~ 18%[1].It is estimated that around the world each year about 14.9 million(12.3~18.1million)premature births,accounting for about 11.1%[2],and in recent years,the incidence of preterm birth in almost all countries have a rising trend[3].According to different etiologies,Preterm birth is divided into spontaneous preterm labor(SPL),preterm premature rupture of membranes(PPROM)and preterm birth for medical and obstetrical indications[4].Spontaneous preterm birth,that is,uterine contracts associated with the disappearance or expansion of the cervical canal,but the integrity of the fetal membranes,accounts for 70%[5,6].Therefore,the treatment and prevention of spontaneous preterm birth has become a top priority in the prevention and treatment of preterm labor.Preterm birth is a complication of pregnancy,it is caused by a variety of reasons[7],the mechanism of premature birth,such as progesterone withdrawal, oxytocin and decidual activation and so on.Therefore,spontaneous preterm birth is not controlled by a single drug or a class of drugs.In 2014,China’s guidelines for the diagnosis and treatment of premature birth[8],such as tocolytic ritodrine hydrochloride can prevent immediate premature delivery,prolong pregnancy in the short term(2 ~ 7 days),to reduce or eliminate the symptoms of preterm labor,but did not eliminate the influence factors of preterm birth.Researches show that ritodrine hydrochloride can not improve the pregnancy outcome[9-12],and did not reduce the risk of preterm delivery and long-term complications caused by preterm birth[13-18].The guidelines also mentioned,for the history of premature delivery and other risk factors in pregnant women with preterm labor,special type of progesterone can play a role in prevention of preterm birth[8],and can be used as a continuous treatment of threatened premature symptoms after control,such as intramuscular injection with 17 alpha hydroxyprogesterone(17P)and vaginal progesterone gel or capsule.Clinical studies have found that progesterone can prolong the duration of pregnancy and reduce preterm birth 34 weeks ago,but it can not reduce perinatal mortality and neonatal morbidity[19].What or which way progesterone plays a preventive role,a preliminary study has been carried out,giving progesterone on animal model of preterm birth and found that the expression level of the zinc finger E-binding homeobox 1(Zinc finger E-box binding homeobox 1,ZEB1)m RNA increased,the expression level of oxytocin receptor(OXTR)m RNA decreased,ZEB1 m RNA can inhibit the expression of OXTR m RNA,slow down the uterine contraction[20].ZEB1 is an important member of the structure of the zinc finger transcription factor family,as a transcription inhibitory factor[21].It can be inferred that ZEB1,OXTR m RNA may be involved in the formation of human preterm labor.In this study,allylestrenol is a safe preparation of oral progesterone,belongs to 17 alpha hydroxyprogesterones,through the observation of ritodrine hydrochloride combined with allylestrenol treatment of the clinical effect of spontaneous preterm birth,analysis of therapeutic effect of combination of different gestational weeks of spontaneous preterm birth.Objective to explore the role of ZEB1 and OXTR m RNA in spontaneous preterm labor by detecting the expression of ZEB1 and OXTR m RNA in peripheral blood of pregnant women with spontaneous preterm labor.Materials and methods 1 Study population 1.1 From July 2014 to December 2015 in the Third Affiliated Hospital of Zhengzhou University hospitalized,the pregnant women who were pregnant for 28 to 33+6 weeks were randomly selected as the research objects,a total of 367 cases,according to the gestational age and medication were divided into 4 groups,including 175 cases of the control group(28~31+6 gestational weeks A1 group of 83 cases,32~33+6 gestational weeks A2 a group of 92 cases)and treatment group of 192 cases(28~31+6 gestational weeks B1 group of 91 cases,32~33+6 gestational weeks B2 group 101 cases).1.1.1 Inclusion criteria were[8]:(1)regular uterine contraction(more than 4 times/20 min or greater than or equal to 8 times/60 min);(2)cervical length(CL)measurements(transvaginal ultrasound)less than 20 mm,the cervix has not been expanded.Exclusion criteria[8]: ritodrine tocolysis taboo,serious medical and hematological diseases,abnormal thyroid function in pregnancy,severe hypertension,diabetes mellitus,twin pregnancy and multiple pregnancy,abnormal amniotic fluid volume,placental dysfunction,premature rupture of membranes(PPROM),cervical cerclage,or congenital fetal chromosomal abnormalities abnormal development.1.1.2 The cervical length measured by transvaginal ultrasound method[8]: first bladder emptying,the ultrasonic probe is placed in the anterior vaginal fornix,to avoid excessive force,in the standard sagittal position,magnified images to screen more than 75%,measuring cervical internal to the straight line distance outside the mouth,3 times in a row,the minimum value.1.2 30 cases of healthy singleton pregnancy women were randomly selected from the Third Affiliated Hospital of Zhengzhou University during the period of gestational age from 28 to 33+6 weeks of gestation,and extraction of peripheral blood 5ml in EDTA tubethe.(blank control group)30 cases were randomly selected from the above(1.1)treatment group(n=192),before progesterone and 48 hours after administration and extraction of peripheral blood 5ml in EDTA tubethe respectively(before treatment group,after treatment group).The specimens were used to study the changes of OXTR,ZEB1 m RNA expression in the peripheral blood of pregnant women with threatened preterm labor.All the pregnant women were informed consent,and in line with the requirements of the Third Affiliated Hospital of Zhengzhou University ethics committee.2 Treatment plan The control group: Ritodrine Hydrochloride Injection(An Bao,sindong biotechnology Limited by Share Ltd production)100mg in 5% glucose solution,infusion pump,pump start into the dose of 0.05 mg /min,10 min 0.05 mg /min(i.e.every increase add 5 drops of /min)to achieve the desired effect,until,generally maintained at 0.15 ~ 0.35 mg /min(or 15 to 35 drops of /min),to continue to stop after uterine infusion of at least 12 ~ 18 h,the total treatment time of less than 48 h.The treatment group: according to the method of administration and the matters needing attention given ritodrine hydrochloride and given oral progesterone(Allylestrenol Tablets,Duolimu,Changzhou siyao Pharmaceutical Co.Ltd.production),5 to 20 mg daily,until delivery(< 36 weeks)or 36 gestational weeks.3 Method Using Real-time PCR we detected the expression expression levels of the OXTR and ZEB1 m RNA in the peripheral blood of pregnant women.4 Observation 4.1(1)Pregnant women in each group after the treatment of pregnancy to extend the efficiency of 48 h and 7d,the average length of pregnancy;(2)The incidence of preterm birth,the average gestational age of delivery and the incidence of low birth weight and the average birth weight;(3)Neonatal morbidity and mortality in the control and treatment groups;(4)Adverse reactions were observed in the control group and the treatment group 4.2 Efficacy criteria: Effective: Uterine gradually stop after treatment,to continue the pregnancy more than 48 h or 7d.Invalid: uterine contraction without reducing medication,in 48 h or 7d in delivery.4.3 To observe the changes of OXTR and ZEB1 m RNA expression in peripheral blood of pregnant women before and after progesterone treatment.5 Statistical analysis The data were analysed using SPSS 21.0 software.The OXTR,ZEB1 m RNA expression of compared with the least significant difference method(LSD).The counting data were represented as percentages and χ2 test.The measurement datas of the normal distribution were represented as (?)±s,and the comparison between the groups was performed using the t test.Difference with P<0.05 were considered to be statistically significant.Results 1 control group and treatment group The control group A1 63.9%(53/83)of the women did not deliver within 48 hours and 54.2%(45/83)of the women did not deliver within 7 days,the average pregnancy length(24.27±22.12)d;treatment group B1 80.2%(73/91)of the women did not deliver within 48 hours and 74.7%(68/91)of the women did not deliver within 7 days,the average pregnancy length(35.59±21.64)d.The above results compared with the control group,the differences were statistically significant(P<0.05).The control group A2 75.0%(69/92)of the women did not deliver within 48 hours and 65.2%(60/92)of the women did not deliver within 7 days,the average pregnancy length(27.46±22.51)d;treatment group B2 96%(97/101)of the women did not deliver within 48 hours and 87.1%(88/101)of the women did not deliver within 7 days,the average pregnancy length(42.89±15.62)d.The above results compared with the control group,the differences were statistically significant(P<0.05).And the treatment group B2 in the extended 48 h and 7d efficiency and prolong the average duration of pregnancy was higher than the treatment group B1,the differences were statistically significant(P<0.05).2 Mean gestational age and neonatal outcome The control group of A1 the mean gestational weeks of pregnant women was(33.60±3.15)weeks,premature birth rate was 57.8%(48/83),the average birth weight was(2318.91±711.25)g,the incidence of low birth weight was 51.8%(43/83),the incidence rate of neonatal respiratory distress syndrome(NRDS)was 50.6%(42/83),the incidence of intracranial hemorrhage was 39.8%(33/83);the treatment group of B1 the mean gestational weeks of pregnant women was(35.09±3.53)weeks,premature birth rate was 36.3%(33/91),the average birth weight was(2702.08±805.62)g,the incidence of low birth weight infants was 32.0%(30/91),the incidence of NRDS was 34.1%(31/91),and the incidence of intracranial hemorrhage was 20.9%(19/91).The differences between the control group and the treatment group were statistically significant(P<0.05).The control group of A2 the mean gestational weeks of pregnant women was(36.86±3.22)weeks,premature birth rate was 46.7%(43/92),the average birth weight(2644.34±571.14)g,the incidence of low birth weight 45.6%(42/92);the treatment group of B2 the mean gestational weeks of pregnant women was(38.96±2.33)weeks,premature birth rate was 21.8%(22/101),the average birth weight(3049.40±577.02)g,the incidence of low birth weight 24.7%(25/101).The results of the treatment group and the control group,the differences were statistically significant(P<0.05).The incidence of NRDS in the treatment group B2 was 11.9%(12/101),the incidence of intracranial hemorrhage was 5.9%(6/101),and compared with that of B1 the differences between the two groups was statistically significant(P<0.05).There were 4 cases of necrotizing enterocolitis in the control group A1,and 4 cases of the neonatal death.In the treatment group B1,there were 1 cases of neonatal septicemia and 2 cases of neonatal death.3 Medication safety in the control group and the treatment group Pregnant women in the control group there were 2 cases with chest discomfort,3 cases of headache,3 cases of elevated blood glucose,5 cases of tachycardia;in treatment group of pregnant women there were 4 cases of headache,2 cases of tachycardia,6 cases of elevated blood glucose,and they did not affect the subsequent treatment.There were no significant differences(P>0.05).4 Expression of OXTR and ZEB1 m RNA in peripheral blood of pregnant women The dissolution curves of different PCR products were single peak,no non-specific amplification.The peripheral blood of maternal were detected in OXTR,ZEB1 m RNA and,β-actin m RNA the detection rate was 100%.5 Comparison of OXTR and ZEB1 m RNA expression in peripheral blood of pregnant women The OXTR m RNA expression of before treatment group were higher than the blank control group and after treatment group in the peripheral blood of pregnant women(P<0.001),ZEB1 m RNA expression were lower than the blank control group and the after treatment group(P<0.001),blank control group and treatment group OXTR,ZEB1 m RNA expression(P>0.05).Conclusions1.The effects of the pregnant women with preterm labor with ritodrine hydrochloride combined with allylestrenol are better than single with ritodrine,which donnot increase the adverse reactions of pregnant women,and the treatment effects are more significant with the gestational weeks over 32 weeks.2.The expression of ZEB1 m RNA in peripheral blood of pregnant women with spontaneous preterm labor after progesterone treatment elevated and the expression of OXTR m RNA decreased,which are both close to the normal pregnant women.It can be inferred that ZEB1,OXTR m RNA maybe related to spontaneous preterm birth.