atosiban and Premature-Birth

Worldwide, nifedipine and atosiban are the two most commonly used tocolytic agents for the treatment of threatened preterm birth. The aim of this study was to evaluate the effectiveness of nifedipine and atosiban in an individual participant data meta-analysis (IPDMA).. We investigated the occurrence of adverse neonatal outcomes in women with threatened preterm birth by performing an IPDMA, and sought to identify possible subgroups in which one treatment may be preferred. We searched PubMed, Embase, and Cochrane for trials comparing nifedipine and atosiban for treatment of threatened preterm birth between 24. We detected four studies (N = 791 women), of which two provided individual participant data (N = 650 women). The composite neonatal outcome occurred in 58/364 (16%) after nifedipine versus 69/359 (19%) after atosiban (OR 0.76, 95%CI 0.47-1.23). Perinatal death occurred in 14/392 (3.6%) after nifedipine versus 7/380 (1.8%) after atosiban (OR 2.0, 95%CI 0.80-5.1). Nifedipine results in longer prolongation of pregnancy, with a 18 days to delivery compared with 10 days for atosiban (HR 0.83 (96% CI 0.69-0.99)). NICU admission occurred less often after nifedipine (46%) than after atosiban (59%), (OR 0.32, 95%CI 0.14-0.75). The sensitivity analysis revealed no difference in prolongation of pregnancy for 48 hours (OR 1.0, 95% CI 0.73-1.4) or 7 days (OR 1.3, 95% CI 0.85-5.8) between nifedipine and atosiban. There was a non-significant higher neonatal mortality in the nifedipine-exposed group (OR 1.4, 95% CI 0.60-3.4).. In this IPDMA, we found no differences in composite outcome between nifedipine and atosiban in the treatment of threatened preterm birth. However, the non-significant higher mortality after administering nifedipine warrants further investigation of the use of nifedipine as a tocolytic drug.. We conducted this study according to a prospectively prepared protocol, registered with PROSPERO (the International Prospective Register of Systematic Reviews) under CRD42016024244.

Topics: Female; Humans; Infant, Newborn; Nifedipine; Perinatal Death; Pregnancy; Premature Birth; Systematic Reviews as Topic; Tocolysis; Tocolytic Agents; Vasotocin

Preterm birth is the major cause of neonatal mortality and morbidity worldwide and a huge cost burden on healthcare. Between 22 and 26 completed weeks of gestation, for every day that delivery is delayed, survival increases by 3%.. Following a systematic review of the literature, we have provided an overview of the use of tocolytics for the prevention of preterm birth and have examined the fetal and maternal adverse effects of the various tocolytic agents currently in use.. No tocolytic currently in use was developed specifically to treat preterm labour so most have multi-organ side effects. β2-agonists are relatively safe for the fetus but have rare and potentially serious maternal adverse effects. In contrast, prostaglandin synthetase inhibitors have potentially serious side effects for the fetus and neonate but have mild maternal gastrointestinal side effects. In Europe, the choice of first line therapy is either atosiban or nifedipine. The evidence base for atosiban is much more robust than for nifedipine. While their efficacy is similar, atosiban has placebo level side effects and is safer than nifedipine but is much more expensive.

Topics: Animals; Female; Humans; Infant, Newborn; Nifedipine; Obstetric Labor, Premature; Pregnancy; Premature Birth; Tocolytic Agents; Vasotocin

In the developed world, preterm birth is in quantity and in severity the most important issue in obstetric care. Adverse neonatal outcome is strongly related to gestational age at delivery. Since the pathophysiological mechanism of preterm birth is not yet completely unraveled, the development of successful preventive strategies is hampered. When preterm labor is actually threatening, current pharmacological therapies focus on inhibition of preterm contractions. This allows for transportation of the mother to a center with a neonatal intensive care unit and administration of corticosteroids to enhance fetal lung maturation. Globally, however, large practice variation exists.. The aim of this review is to provide an overview of current pharmacological therapies for preterm labor.. For the initial tocolysis, the use of atosiban or nifedipine for 48 h is recommended based on the largest effectiveness and most favorable side effect profile. However, since data that convincingly indicate the beneficial effect of tocolytics on neonatal outcome are lacking, it might well be that tocolytics are ineffective. The role of progesterone in treatment of acute tocolysis is limited, but it might play a role in the prevention of preterm labor or as sensitizer for other tocolytic agents.

Topics: Female; Humans; Infant, Newborn; Nifedipine; Obstetric Labor, Premature; Pregnancy; Premature Birth; Progesterone; Progestins; Tocolysis; Tocolytic Agents; Vasotocin

Evidence summaries of tocolytic effectiveness assign quality levels based on a single dimension: the study design. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system takes into account several domains, including limitations of the study design and ranking the importance of outcomes.. The aim of the study was to compare the quality of evidence according to GRADE with the quality as described by existing guidelines.. A practitioner survey to rank the importance of outcomes and a systematic review were conducted. For the systematic review, we searched Medline, Embase, and DARE databases from inception to December 2010 using the terms 'tocolytics' and 'threatened preterm labour', without any language restrictions.. Inclusion criteria for the review were randomised controlled trials comparing tocolytics with either placebo or betamimetics.. The review and survey teams worked independently. Evidence ratings according to GRADE were performed.. The majority of the survey respondents thought that it was important to use tocolytics to buy the time needed for steroids to promote fetal lung maturation and to allow in utero transfer. Nearly 80% of 'high' ratings in guidelines were downgraded as a result of deficiencies identified by GRADE.. We propose a move away from the use of evidence rating systems reliant solely on study design, as they have a propensity towards strong recommendations when the underlying evidence is weak.

Topics: Adrenergic beta-Agonists; Attitude of Health Personnel; Calcium Channel Blockers; Evidence-Based Medicine; Glucocorticoids; Humans; Indomethacin; Lung; Magnesium Sulfate; Nitric Oxide Donors; Practice Guidelines as Topic; Premature Birth; Research Design; Surveys and Questionnaires; Tocolytic Agents; Vasotocin

In some women, an episode of preterm labour settles and does not result in immediate preterm birth. Subsequent treatment with tocolytic agents such as oxytocin receptor antagonists may then have the potential to prevent the recurrence of preterm labour, prolonging gestation, and preventing the adverse consequences of prematurity for the infant.. To assess the effects of maintenance therapy with oxytocin antagonists administered by any route after an episode of preterm labour in order to delay or prevent preterm birth.. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2013), sought ongoing and unpublished trials by contacting experts in the field and searched the reference lists of relevant articles.. Randomised controlled trials comparing oxytocin antagonists with any alternative tocolytic agent, placebo or no treatment, used for maintenance therapy after an episode of preterm labour.. We used the standard methods of The Cochrane Collaboration and the Cochrane Pregnancy and Childbirth Group. Two review authors independently undertook evaluation of methodological quality and extracted trial data.. This review includes one trial of 513 women. When compared with placebo, atosiban did not reduce preterm birth before 37 weeks (risk ratio (RR) 0.89; 95% confidence intervals (CI) 0.71 to 1.12), 32 weeks (RR 0.85; 95% CI 0.47 to 1.55), or 28 weeks (RR 0.75; 95% CI 0.28 to 2.01). No difference was shown in neonatal morbidity, or perinatal mortality.. There is insufficient evidence to support the use of oxytocin receptor antagonists to inhibit preterm birth after a period of threatened or actual preterm labour. Any future trials using oxytocin antagonists or other drugs as maintenance therapy for preventing preterm birth should examine a variety of important infant outcome measures, including reduction of neonatal morbidity and mortality, and long-term infant follow-up. Future research should also focus on the pathophysiological pathways that precede preterm labour.

Topics: Female; Humans; Obstetric Labor, Premature; Pregnancy; Premature Birth; Randomized Controlled Trials as Topic; Receptors, Oxytocin; Tocolytic Agents; Vasotocin

Preterm birth, the leading cause of neonatal morbidity and mortality, is estimated at incidence of 12.7% of all births, which has not decreased over the last four decades despite intensive antenatal care programs aimed at high-risk groups, the widespread use of tocolytics, and a series of other preventive and therapeutic interventions. Oxytocin antagonists, namely atosiban, represent an appealing choice that seems to be effective with apparently fewer side effects than the traditional tocolytics. This article reviews the available literature on the pharmacokinetics, mode of administration, and clinical utility of oxytocin antagonists for acute and maintenance tocolysis with special emphasis on its safety profile.

Topics: Female; Hormone Antagonists; Humans; Indoles; Nifedipine; Oligopeptides; Oxytocin; Premature Birth; Pyrrolidines; Sympathomimetics; Tocolytic Agents; Vasotocin

Pregnancies with extremely preterm premature rupture of membranes (EPPROM), especially before 20 weeks of gestation, are usually considered to be a termination of pregnancy. By improvement of obstetric and neonatal care, we can prolong the pregnancy across the threshold of survival by aggressive tocolysis.. Using intrauterine insemination, a 32-year-old woman became pregnant with twins (first pregnancy). Threatened abortion occured since 9 weeks of gestation and EPPROM of the upper twin was noted at 18 weeks. Massive vaginal bleeding and vigorous uterine contractions occurred at 22 weeks. Poor control of preterm labor occurred using ritodrine and MgSO(4). Atosiban was applied to calm uterine activities. After discontinuation of atosiban at 30 weeks, the uterine contractions became severe again and an emergency cesarean section was performed to deliver two live, premature babies weighing 1,518 g and 830 g, respectively. Twin A was healthy, weighing 2,030 g at 35 days after birth and subsequently discharged. The smaller twin B was dependent on continuous positive airway pressure and died of pulmonary infection 120 days after birth.. Comparing to other tocolytic agents, Atosiban has few side effects and assisted in prolonging a pregnancy involving twins that experienced EPPROM.

Topics: Adult; Female; Fetal Growth Retardation; Fetal Membranes, Premature Rupture; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Magnesium Sulfate; Male; Pregnancy; Pregnancy, Multiple; Premature Birth; Reproductive Techniques, Assisted; Ritodrine; Tocolysis; Tocolytic Agents; Twins; Vasotocin

In some women, an episode of preterm labour settles and does not result in immediate preterm birth. Subsequent treatment with tocolytic agents such as oxytocin receptor antagonists may then have the potential to prevent the recurrence of preterm labour, prolonging gestation, and preventing the adverse consequences of prematurity for the infant.. To assess the effects of maintenance therapy with oxytocin antagonists administered by any route after an episode of preterm labour in order to delay or prevent preterm birth.. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (June 2008), sought ongoing and unpublished trials by contacting experts in the field and searched the reference lists of relevant articles.. Randomised controlled trials comparing oxytocin antagonists with any alternative tocolytic agent, placebo or no treatment, used for maintenance therapy after an episode of preterm labour.. Standard methods of the Cochrane Collaboration and the Cochrane Pregnancy and Childbirth Group were used. Two review authors independently undertook evaluation of methodological quality and extracted trial data.. This review includes one trial of 513 women. When compared with placebo, atosiban did not reduce preterm birth before 37 weeks (risk risk (RR) 0.89; 95% confidence intervals (CI) 0.71 to 1.12), 32 weeks (RR 0.85; 95% CI 0.47 to 1.55), or 28 weeks (RR 0.75; 95% CI 0.28 to 2.01). No difference was shown in neonatal morbidity, or perinatal mortality.. There is insufficient evidence to support the use of oxytocin receptor antagonists to inhibit preterm birth after a period of threatened or actual preterm labour. Any future trials using oxytocin antagonists or other drugs as maintenance therapy for preventing preterm birth should examine a variety of important infant outcome measures, including reduction of neonatal morbidity and mortality, and long-term infant follow up. Future research should also focus on the pathophysiological pathways that precede preterm labour.

Topics: Female; Humans; Obstetric Labor, Premature; Pregnancy; Premature Birth; Randomized Controlled Trials as Topic; Receptors, Oxytocin; Tocolytic Agents; Vasotocin

Preterm birth is the major cause of perinatal mortality and morbidity in the developed world.. The aim of this study was to establish the importance of preterm birth and the huge healthcare costs involved and review the pathophysiology of preterm labor and the use of antepartum glucocorticoids, which are the main reason why tocolytics are used to prevent or delay preterm birth. The study also reviewed the range of tocolytics available, their mode of action and the evidence for their efficacy and fetomaternal safety.. An extensive review of the literature using well-recognized and accepted scientific search engines was employed.. The perfect tocolytic does not exist. The evidence to support the use of magnesium sulfate as a tocolytic is poor. The use of beta-agonists is decreasing worldwide as clinicians move to nifedipine or atosiban, which are as effective but much safer. Although nifedipine is cheaper than atosiban and can be administered orally, the evidence to support atosiban is much superior to that of nifedipine and there have been recent safety concerns over nifedipine.

Topics: Female; Fetus; Glucocorticoids; Health Care Costs; Humans; Magnesium Sulfate; Nifedipine; Obstetric Labor, Premature; Pregnancy; Premature Birth; Tocolytic Agents; Vasotocin

Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Cerclage, Cervical; Cesarean Section; Female; Fetal Membranes, Premature Rupture; Humans; Obstetric Labor, Premature; Pregnancy; Premature Birth; Prenatal Care; Tocolytic Agents; Vasotocin

Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Cerclage, Cervical; Cesarean Section; Female; Fetal Membranes, Premature Rupture; Humans; Obstetric Labor, Premature; Pregnancy; Premature Birth; Prenatal Care; Tocolytic Agents; Vasotocin

To compare the long-term effects of tocolysis with nifedipine or atosiban on child outcome at age 2.5-5.5 years.. The APOSTEL III trial was a multicentre randomised controlled trial that compared tocolysis with nifedipine or atosiban in 503 women with threatened preterm birth. Neonatal outcomes did not differ between both treatment arms, except for a higher incidence of intubation in the atosiban group.. Parents were asked to complete four questionnaires regarding neurodevelopment, executive function, behaviour problems and general health.. The main long-term outcome measure was a composite of abnormal development at the age of 2.5-5.5 years.. Of the 426 women eligible for follow-up, 196 (46%) parents returned the questionnaires for 115 children in the nifedipine group and 110 children in the atosiban group. Abnormal development occurred in 32 children (30%) in the nifedipine group and in 38 children (38%) in the atosiban group (OR 0.74, 95% CI 0.41-1.34). The separate outcomes for neurodevelopment, executive function, behaviour, and general health showed no significant differences between the groups. Sensitivity analysis for all children of the APOSTEL III trial, including a comparison of deceased children, resulted in a higher rate of healthy survival in the nifedipine group (64 versus 54%), but there was no significant difference in the overall mortality rate (5.4 versus 2.7%). There were no significant subgroup effects.. Outcomes on broad child neurodevelopment, executive function, behaviour and general health were comparable in both groups. Neither nifedipine nor atosiban can be considered as the preferred treatment for women with threatened preterm birth.. Nifedipine- and atosiban-exposed children had comparable long-term outcomes, including neurodevelopment, executive function and behaviour.

Topics: Child Behavior Disorders; Child, Preschool; Executive Function; Female; Follow-Up Studies; Health Status; Humans; Male; Neurodevelopmental Disorders; Nifedipine; Pregnancy; Premature Birth; Surveys and Questionnaires; Tocolysis; Tocolytic Agents; Vasotocin

To assess the cost-effectiveness of treatment with nifedipine compared with atosiban in women with threatened preterm birth.. An economic analysis alongside a randomised clinical trial (the APOSTEL III study).. Obstetric departments of 12 tertiary hospitals and seven secondary hospitals in the Netherlands and Belgium.. Women with threatened preterm birth between 25 and 34 weeks of gestation, randomised for tocolysis with either nifedipine or atosiban.. We performed an economic analysis from a societal perspective. We estimated costs from randomisation until discharge. Analyses for singleton and multiple pregnancies were performed separately. The robustness of our findings was evaluated in sensitivity analyses.. Mean costs and differences were calculated per woman treated with nifedipine or atosiban. Health outcomes were expressed as the prevalence of a composite of adverse perinatal outcomes.. Mean costs per patients were significantly lower in the nifedipine group [singleton pregnancies: €34,897 versus €43,376, mean difference (MD) -€8479 [95% confidence interval (CI) -€14,327 to -€2016)]; multiple pregnancies: €90,248 versus €102,292, MD -€12,044 (95% CI -€21,607 to € -1671). There was a non-significantly higher death rate in the nifedipine group. The difference in costs was mainly driven by a lower neonatal intensive care unit admission (NICU) rate in the nifedipine group.. Treatment with nifedipine in women with threatened preterm birth results in lower costs when compared with treatment with atosiban. However, the safety of nifedipine warrants further investigation.. In women with threatened preterm birth, tocolysis using nifedipine results in lower costs when compared with atosiban.

Topics: Cost-Benefit Analysis; Female; Humans; Nifedipine; Pregnancy; Pregnancy, Multiple; Premature Birth; Prenatal Care; Tocolytic Agents; Vasotocin

Brain injury in neonates born prematurely is associated strongly with poor neurodevelopmental outcome. The aim of this study was to evaluate whether tocolysis with nifedipine or atosiban in women with threatened preterm birth can reduce the incidence of overall brain injury in neonates born prematurely.. This was a secondary analysis of the APOSTEL-III trial (Dutch Clinical Trial Registry, no. NTR2947), a randomized clinical trial in which women with threatened preterm labor between 25 and 34 weeks of gestation were allocated to treatment with nifedipine or atosiban. In this secondary analysis, women delivered at ≤ 32 weeks of gestational age in the two main contributing centers were included. Primary outcome was the presence of neonatal brain injury, which was defined as presence of abnormalities on ultrasound investigation and classified into mild and severe. To evaluate type and severity of brain injury, all neonatal ultrasounds performed during neonatal intensive and medium care admission were analyzed. To test the robustness of our results, a sensitivity analysis was performed assessing differences in baseline or known risk factors for brain injury.. A total of 117 neonates (from 102 women) were studied, of which 51 had been exposed to nifedipine and 66 to atosiban. Brain injury was observed in 22 (43.1%) neonates in the nifedipine group compared with 37 (56.1%) in the atosiban group (OR, 0.60; 95% CI, 0.29-1.24). Presence of mild brain injury was comparable between the nifedipine (33.3%) and atosiban (48.5%) groups (OR, 0.53; 95% CI, 0.25-1.13). Severe brain injury was also comparable between the groups, observed in 9.8% of neonates in the nifedipine vs 7.6% of those in the atosiban group (OR, 1.33; 95% CI, 0.36-4.85). Intraventricular hemorrhage (≥ Grade I) was the most frequently seen ultrasound abnormality, observed in 18 (35.3%) neonates in the nifedipine group vs 25 (37.9%) in the atosiban group (OR, 0.90; 95% CI, 0.42-1.91). The sensitivity analysis, with adjustment for maternal age and gestational age at randomization, showed no statistical difference between the groups for presence of brain injury (OR, 0.58; 95% CI, 0.27-1.27).. In children born before 32 weeks of gestation after the use of tocolytics, the prevalence of brain injury was high. No significant differences were found with respect to overall brain injury between neonates exposed to nifedipine and those exposed to atosiban. However, as this study was a secondary analysis of the APOSTEL III trial, it was underpowered for brain injury. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Topics: Administration, Intravenous; Adult; Brain Injuries; Female; Gestational Age; Humans; Infant, Newborn; Male; Nifedipine; Pregnancy; Pregnancy Outcome; Premature Birth; Tocolytic Agents; Treatment Outcome; Vasotocin

In women with threatened preterm birth, delay of delivery by 48 h allows antenatal corticosteroids to improve neonatal outcomes. For this reason, tocolytics are often administered for 48 h; however, there is no consensus about which drug results in the best maternal and neonatal outcomes. In the APOSTEL III trial we aimed to compare the effectiveness and safety of the calcium-channel blocker nifedipine and the oxytocin inhibitor atosiban in women with threatened preterm birth.. We did this multicentre, randomised controlled trial in ten tertiary and nine teaching hospitals in the Netherlands and Belgium. Women with threatened preterm birth (gestational age 25-34 weeks) were randomly assigned (1:1) to either oral nifedipine or intravenous atosiban for 48 h. An independent data manager used a web-based computerised programme to randomly assign women in permuted block sizes of four, with groups stratified by centre. Clinicians, outcome assessors, and women were not masked to treatment group. The primary outcome was a composite of adverse perinatal outcomes, which included perinatal mortality, bronchopulmonary dysplasia, sepsis, intraventricular haemorrhage, periventricular leukomalacia, and necrotising enterocolitis. Analysis was done in all women and babies with follow-up data. The study is registered at the Dutch Clinical Trial Registry, number NTR2947.. Between July 6, 2011, and July 7, 2014, we randomly assigned 254 women to nifedipine and 256 to atosiban. Primary outcome data were available for 248 women and 297 babies in the nifedipine group and 255 women and 294 babies in the atosiban group. The primary outcome occurred in 42 babies (14%) in the nifedipine group and in 45 (15%) in the atosiban group (relative risk [RR] 0·91, 95% CI 0·61-1·37). 16 (5%) babies died in the nifedipine group and seven (2%) died in the atosiban group (RR 2·20, 95% CI 0·91-5·33); all deaths were deemed unlikely to be related to the study drug. Maternal adverse events did not differ between groups.. In women with threatened preterm birth, 48 h of tocolysis with nifedipine or atosiban results in similar perinatal outcomes. Future clinical research should focus on large placebo-controlled trials, powered for perinatal outcomes.. ZonMw (the Netherlands Organisation for Health Research and Development).

Topics: Administration, Intravenous; Administration, Ophthalmic; Adult; Belgium; Calcium Channel Blockers; Female; Humans; Infant, Newborn; Netherlands; Nifedipine; Perinatal Mortality; Pregnancy; Pregnancy Outcome; Premature Birth; Tocolytic Agents; Treatment Outcome; Vasotocin

The purpose of this study was to identify the effects of abdominal breathing on state anxiety, stress and tocolytic dosage for pregnant women in preterm labor.. The participants were 60 pregnant women in preterm labor who were hospitalized from April to July, 2009. Thirty participants were assigned to the experimental group and 30 to the control group. None of them had any other complications except preterm labor. The modified Mason's breathing technique was used with the experimental group 3 times a day for 3 days. Data were collected using a self-report questionnaire and chart review, and analyzed with the SPSS 13.0 WIN program.. "State anxiety of the experimental group will be lower than that of the control group" was supported. "Stress of the experimental group will be lower than that of the control group" was supported. "The Ritodrine dosage for the experimental group will be lower than that of the control group" was supported. "The Atosiban dosage for the experimental group will be lower than that of the control group" was supported.. These results indicate that abdominal breathing is an effective nursing intervention for pregnant women in preterm labor.

Topics: Adult; Anxiety; Breathing Exercises; Female; Gestational Age; Humans; Obstetric Labor, Premature; Pregnancy; Premature Birth; Ritodrine; Stress, Psychological; Tocolytic Agents; Vasotocin

The choice of first-line tocolytic agent is a topic of worldwide debate. The oxytocin receptor antagonist atosiban and the calcium antagonist nifedipine appear to be effective in postponing delivery. However, information is lacking on their possible effects on the fetal biophysical profile.. To study the direct fetal effects of tocolysis with atosiban or nifedipine combined with a course of betamethasone.. We performed a randomised controlled study including women with preterm labour requiring tocolytic treatment. Primary outcome measures were the effects on fetal heart rate (FHR) and its variation. Secondary endpoints were the effects on fetal movement and blood flow (pulsatility index - PI) of the umbilical (UA) and medial cerebral arteries (MCA).. One-hour recordings of FHR and fetal movements were made on each of five successive days (days 0-4). Fetal blood flow velocity patterns were studied daily by Doppler ultrasound. Baseline characteristics of 31 women who had not delivered at day 0 and needed no escape tocolysis did not differ between the study groups. Multilevel analysis showed no significant effect of either tocolytic on FHR and movement parameters over the 5-day study period. The use of tocolytics also did not significantly alter the time courses of PI-values for UA (p = 0.37) and MCA (p = 0.62).. This study demonstrates for the first time the direct effects of atosiban on fetal movement, heart rate and blood flow. Tocolysis with either atosiban or nifedipine combined with betamethasone administration appears to have no direct fetal adverse effects.

Topics: Adult; Algorithms; Betamethasone; Drug Combinations; Female; Fetal Blood; Fetal Movement; Heart Rate, Fetal; Humans; Infant, Newborn; Nifedipine; Placental Circulation; Pregnancy; Pregnancy Outcome; Premature Birth; Tocolytic Agents; Vasotocin

There is a lack of FDA-approved tocolytics for the management of preterm labor (PL). In prior drug discovery efforts, we identified mundulone and mundulone acetate (MA) as inhibitors of in vitro intracellular Ca

Topics: Animals; Biological Products; Female; Humans; Infant, Newborn; Mice; Mifepristone; Nifedipine; Obstetric Labor, Premature; Premature Birth; Tocolytic Agents

Objective To evaluate the impact of atosiban as a tocolytic agent in patients treated with the fetoscopic endotracheal occlusion (FETO) procedure due to congenital diaphragmatic hernia (CDH). As premature birth after fetoscopy remains a serious concern, an effort to reduce prematurity is required. Methods A total of 43 patients with severe CDH treated with FETO were enrolled in this study. The study group consisted of 22 patients who received atosiban during the FETO procedure and a control group of 21 patients who did not receive atosiban during the FETO procedure. Demographic data, gestational age (GA) at delivery, cervical length and GA at premature rupture of membranes (PROM) were evaluated. Results The GA at delivery was significantly different between the two groups studied. The median GA at delivery was 32.6 and 34.5 weeks in the no-atosiban vs. atosiban groups, respectively (P = 0.013). The median cervical length was 29.9 and 31.2 mm for the no-atosiban and atosiban groups, respectively, and was not statistically significant (P = 0.28). There were no significant correlations between groups for the occurrence of PROM, GA at the time of PROM, duration of the procedures, parity, maternal body mass index (BMI) or age. In the univariate linear regression model, the only factor independently associated with GA at delivery was the use of atosiban during FETO procedures (β = 0.375; P < 0.013). Conclusion In cases of severe CDH treated with FETO, the use of atosiban as a tocolytic agent during the procedure prolonged pregnancy by 2 weeks. Cervical length, duration of FETO or maternal characteristics were not associated with GA at delivery.

Topics: Adult; Female; Fetoscopy; Follow-Up Studies; Gestational Age; Hernias, Diaphragmatic, Congenital; Humans; Infant, Newborn; Linear Models; Pregnancy; Premature Birth; Retrospective Studies; Tocolytic Agents; Treatment Outcome; Vasotocin

The herbal medicine Bryophyllum pinnatum has been used as a tocolytic agent in anthroposophic medicine and, recently, in conventional settings alone or as an add-on medication with tocolytic agents such as atosiban or nifedipine. We wanted to compare the inhibitory effect of atosiban and nifedipine on human myometrial contractility in vitro in the absence and in the presence of B. pinnatum press juice (BPJ).. Myometrium biopsies were collected during elective Caesarean sections. Myometrial strips were placed under tension into an organ bath and allowed to contract spontaneously. Test substances alone and at concentrations known to moderately affect contractility in this setup, or in combination, were added to the organ bath, and contractility was recorded throughout the experiments. Changes in the strength (measured as area under the curve (AUC) and amplitude) and frequency of contractions after the addition of all test substances were determined. Cell viability assays were performed with the human myometrium hTERT-C3 and PHM1-41 cell lines.. BPJ (2.5 μg/mL), atosiban (0.27 μg/mL), and nifedipine (3 ng/mL), moderately reduced the strength of spontaneous myometrium contractions. When BPJ was added together with atosiban or nifedipine, inhibition of contraction strength was significantly higher than with the tocolytics alone (p = 0.03 and p < 0.001, respectively). In the case of AUC, BPJ plus atosiban promoted a decrease to 48.8 ± 6.3% of initial, whereas BPJ and atosiban alone lowered it to 70.9 ± 4.7% and to 80.9 ± 4.1% of initial, respectively. Also in the case of AUC, BPJ plus nifedipine promoted a decrease to 39.9 ± 4.6% of initial, at the same time that BPJ and nifedipine alone lowered it to 78.9 ± 3.8% and 71.0 ± 3.4% of initial. Amplitude data supported those AUC data. The inhibitory effects of BPJ plus atosiban and of BPJ plus nifedipine on contractions strength were concentration-dependent. None of the test substances, alone or in combination, decreased myometrial cell viability.. BPJ enhances the inhibitory effect of atosiban and nifedipine on the strength of myometrial contractions, without affecting myometrium tissue or cell viability. The combination treatment of BPJ with atosiban or nifedipine has therapeutic potential.

Topics: Adult; Drug Antagonism; Female; Humans; In Vitro Techniques; Kalanchoe; Myometrium; Nifedipine; Plant Extracts; Pregnancy; Premature Birth; Tocolytic Agents; Uterine Contraction; Vasotocin; Young Adult

Topics: Cost-Benefit Analysis; Female; Humans; Infant, Newborn; Nifedipine; Pregnancy; Premature Birth; Vasotocin

Oxytocin is a hormone involved in the mechanism of breastfeeding, uterine contractions, and social relationships. Atosiban (competitive oxytocin antagonist) is one of the most commonly used tocolytics for the threat of preterm labor in Europe. The aim of this study is to determinate if the administration of atosiban has any influence in the type of feeding in the term newborn at discharge. The secondary objective is to verify its effectiveness for the prevention of preterm delivery and in the possibility of applying treatment to complete lung maturation.. Retrospective cohort study carried out in a tertiary University Hospital distinguished by WHO-UNICEF as a Baby-Friendly Hospital Initiative. The analysis included 264 women exposed to atosiban during a period of 4 years. One hundred met inclusion criteria. Unexposed infants born right after and before the exposed ones were selected as the not exposed subgroup (n = 200).. Among women treated with atosiban, 82% maintained exclusively breastfed (EBF), 8% had mixed breastfeeding, and 10% had formula feeding at discharge. In the nonexposed group, 82% maintained EBF, 9.5% had mixed breastfeeding, and 8.5% had formula feeding at discharge (p = 0.84). 97.5% of pregnant women treated with atosiban received corticosteroid for lung maturation, and 49.5% completed gestation with term newborns.. There were no significant differences in the type of feeding at discharge between the atosiban group and the nonexposed group. In most cases, the administration of tocolytic therapy allowed to complete lung maturation.

Topics: Adult; Breast Feeding; Female; Humans; Infant, Newborn; Milk, Human; Pregnancy; Premature Birth; Prenatal Exposure Delayed Effects; Receptors, Oxytocin; Retrospective Studies; Term Birth; Tocolytic Agents; Treatment Outcome; Vasotocin

Preterm labor caused by uterine contractions is a major contributor to neonatal morbidity and mortality. Treatment intended to reduce uterine contractions include tocolytic agents, such as indomethacin. Unfortunately, clinically used tocolytics are frequently inefficient and cross the placenta causing fetal side effects. Here we show for the first time in obstetrics the use of a targeted nanoparticle directed to the pregnant uterus and loaded with a tocolytic for reducing its placental passage and sustaining its efficacy. Nanoliposomes encapsulating indomethacin and decorated with clinically used oxytocin receptor antagonist were designed and evaluated in-vitro, ex-vivo and in-vivo. The proposed approach resulted in targeting uterine cells in-vitro, inhibiting uterine contractions ex-vivo, while doubling uterine drug concentration, decreasing fetal levels, and maintaining the preterm birth rate in vivo in a pregnant mouse model. This promising approach opens new horizons for drug development in obstetrics that could greatly impact preterm birth, which currently has no successful treatments.

Topics: Animals; Disease Models, Animal; Drug Compounding; Female; Gene Expression; Hormone Antagonists; Humans; Indomethacin; Liposomes; Mice; Molecular Targeted Therapy; Nanostructures; Obstetric Labor, Premature; Placenta; Pregnancy; Premature Birth; Protein Binding; Receptors, Oxytocin; Tocolytic Agents; Uterine Contraction; Uterus; Vasotocin

While tocolytic therapy may not be indicated in all cases of spontaneous preterm labor (SPTL), the evidence that they are superior to placebo is robust. The perfect tocolytic that is 100% efficacious and 100% safe does not exist and efforts should continue to develop and introduce safer and more effective agents. A reduction in the rate of neonatal mortality and morbidity using tocolysis has not been shown but no tocolytic study has been powered by numbers sufficient to demonstrate such an effect. Tocolytics can delay delivery long enough to administer a course of antepartum glucocorticoids and arrange in utero transfer to a center with neonatal intensive care facilities, both of which reduce neonatal mortality and morbidity. Few tocolytics (β₂-agonists and atosiban) are licensed for use as tocolytics and only one was developed specifically to treat preterm labor (atosiban). Accordingly, most tocolytics have multi-organ adverse effects. Currently, based on the evidence of safety and efficacy, atosiban should be the first-choice tocolytic for the treatment of SPTL to prevent or delay preterm birth.

Topics: Adrenergic beta-Agonists; Female; Glucocorticoids; Humans; Infant, Newborn; Nifedipine; Obstetric Labor, Premature; Pregnancy; Premature Birth; Tocolysis; Tocolytic Agents; Vasotocin

The objective of this study was to compare the safety and efficacy of atosiban and ritodrine in the treatment of threatened preterm labour (TPL) and to analyse the predictive factors of preterm delivery. We retrospectively sampled data on 380 women hospitalised for TPL (24-35 weeks' gestation), in our clinic between 2004 and 2007. All were subjected to tocolysis with ritodrine and/or atosiban. Data were analysed using R (version 2.12.1), considering p < 0.05 as significant. We had 69 women treated with atosiban, 242 treated with ritodrine and 69 treated with ritodrine changed for atosiban, if adverse effects occurred. In the multivariate logistic regression, the use of atosiban vs ritodrine does not play any role in delaying delivery after 48 h or 7 days, whereas the cervical change at the digital examination, high contractions pre/post-therapy ratio, pPROM, cervical length and fibronectin result as predictive factors for both delivery before 48 h or 7 days. Maternal adverse drug effects were significantly more frequent in patients treated with ritodrine, and one single case of pulmonary oedema was observed. We found fewer side-effects in the atosiban than in the ritodrine group and no difference in efficacy. Moreover, the most predictive factors for preterm delivery were fibronectin test, pPROM, digital vaginal examination and uterine contraction persistence. We believe that predictive capacity of these tests could give the opportunity for targeting therapy and limiting drug side-effects and cost.

Topics: Adult; Female; Humans; Italy; Pregnancy; Premature Birth; Retrospective Studies; Risk Factors; Ritodrine; Tocolysis; Tocolytic Agents; Vasotocin

Premature birth poses a real problem of public health. As the principal cause of foetal ill-health and perinatal mortality, it generates high healthcare costs. By seeking to prevent early labour and to deal with its causes, a good obstetrical practice can reduce its negative impact, both medical and financial, on society. This article describes the results of a study of threatened preterm delivery admissions at the Citadelle hospital in Liege during the year 2012. The findings are compared to international guidelines with a view to identify aspects that could be improved.

Topics: Academic Medical Centers; Female; Guideline Adherence; Hospitals, Maternity; Humans; Infant, Newborn; Internationality; Practice Guidelines as Topic; Practice Patterns, Physicians'; Pregnancy; Pregnancy, High-Risk; Premature Birth; Retrospective Studies; Vasotocin

The purpose of this study was to investigate the effect of atosiban (Tractocile; Ferring, Limhamn, Sweden), an oxytocin receptor antagonist, on uterine electrical activity in women with preterm labor and to determine whether this information can assist in the prediction of preterm delivery.. Uterine electrical activity was recorded prospectively in 21 women with preterm labor before and during treatment with Tractocile and, for purpose of comparison, in 4 pregnant women without uterine contractions to set the baseline of uterine electrical activity in a quiescent uterus. Uterine activity was recorded with a noninvasive, 9-channel recorder with an electromyography amplifier and a 3-dimensional position sensor with an automatic data analyzer. Uterine electrical activity was quantified by an electrical uterine monitor (EUM) and measured in microwatts per second (μW/s).. The overall pre-Tractocile EUM index was 3.43 ± 0.58 μW/s, which was significantly higher than baseline uterine activity in women without preterm contractions (2.3 ± 0.11 μW/s; P = .001). During the administration of Tractocile, the EUM index gradually decreased in a relatively constant rate from 3.43 ± 0.58 μW/s to 2.56 ± 0.88 μW/s after 330 minutes of continuous therapy (P < .001). The peak effect of Tractocile was observed 4 hours after the initiation of treatment and was followed by a relative plateau. Women with a latency of <7 days from treatment to delivery were characterized by a distinct EUM-pattern in response to Tractocile, compared with women with a latency of ≥7 days (P < .001). A similar EUM-pattern after the administration of Tractocile was also observed for women who delivered at <37 weeks of gestation compared with the women who delivered at term.. Tractocile reduces uterine electrical activity in women with preterm labor. This information can provide more insight into the effects of tocolytic agents and to aid in the risk stratification of preterm delivery in women with preterm contractions.

Topics: Adult; Case-Control Studies; Electromyography; Female; Humans; Obstetric Labor, Premature; Pregnancy; Premature Birth; Prospective Studies; Receptors, Oxytocin; Tocolytic Agents; Treatment Outcome; Uterus; Vasotocin; Young Adult

Preterm delivery results in neonatal morbidity and mortality. We set out to estimate the difference in rates of preterm delivery in two institutions, serving a single population, with differing policies regarding use of tocolytic drugs for the prevention of preterm delivery.. A retrospective study comparing preterm delivery rates between 2002 and 2007 in two large tertiary hospitals serving a single urban population with similar risk factor profile located less than 2 miles from each other. During the study period Hospital A routinely used tocolytic therapy, Hospital B operates a policy of never using any tocolytic drugs. Rates of delivery prior to 26, 30, 34 and 37 weeks were compared for each hospital.. During the study period there were 90,843 deliveries between the two hospitals. The overall rates of preterm delivery at less than 37 weeks gestation were comparable with 6.62% (2794/42,232) in Hospital A and 6.15% (2989/48,611) in Hospital B (p = 0.99). There was no significant difference in the numbers delivering at less than 34 weeks, 995/42,232 (2.36%) versus 1134/48,611 (2.33%), p = 0.59, less than 30 weeks, 403/42,232 (0.95%) versus 429/48,611 (0.88%), p = 0.87 or prior to 26 weeks, 126/42,232 (0.29%) versus 121/48,611 (0.25%), p= 0.08.. In this large population routine use of tocolytic drugs in the treatment of threatened preterm labor does not alter rates of early or late preterm delivery. While this study is limited by its retrospective nature, it calls into question the practice of tocolysis.

Topics: Cohort Studies; Female; Gestational Age; Hospitals, Urban; Humans; Infant, Newborn; Infant, Premature, Diseases; Obstetric Labor, Premature; Practice Guidelines as Topic; Pregnancy; Premature Birth; Professional Practice; Retrospective Studies; Tocolysis; Tocolytic Agents; Urban Population; Vasotocin

To analyse the expression of 15 genes encoding receptors and enzymes associated with the molecular mechanism of the tocolytic drugs atosiban (oxytocin receptor antagonist), nifedipine (calcium channel blocker) and celecoxib (selective cyclo-oxygenase-2 inhibitor) in preterm labor patients with premature rupture of fetal membranes in relation to symptoms of intrauterine infection and preterm labor risk factors.. Experimental molecular study.. Tertiary obstetric care center.. Myometrial samples were obtained during cesarean sections from 35 patients who delivered preterm with unverified symptoms of intrauterine infection, 35 patients who delivered preterm without symptoms of intrauterine infection and 90 women who delivered at term.. The Micro Fluidic Profiling Card analytic system was used to evaluate mRNA expression of the genes of interest.. The relative quantification values for mRNA expression.. The median oxytocin receptor and cyclo-oxygenase-2 mRNA expression in preterm patients with clinical symptoms of intrauterine infection was significantly higher than in preterm patients without symptoms. The median mRNA expression of β(1) , β(3) and β(4) subunits of the L-type calcium channel and prostaglandin E(2) receptor was significantly higher in preterm patients compared with term patients.. The mRNA expression of hormones, enzymes and their receptors associated with tocolytic actions can differ in various clinical conditions. The expression of these genes is regulated at different levels and can be modified by inflammatory factors, which affect their functions.

Topics: Adult; Calcium Channel Blockers; Calcium Channels, L-Type; Celecoxib; Cyclooxygenase 2 Inhibitors; Dinoprostone; Endometritis; Female; Fetal Membranes, Premature Rupture; Gene Expression Profiling; Gene Expression Regulation, Developmental; Humans; Nifedipine; Obstetric Labor, Premature; Oxytocics; Pregnancy; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Premature Birth; Pyrazoles; RNA, Messenger; Sulfonamides; Term Birth; Tocolytic Agents; Vasotocin

Preterm delivery is a significant cause of neonatal morbidity and mortality. Pregnant women, with symptoms and signs consistent with preterm labor, can be treated with various tocolytic drugs. Atosiban is one of many drugs indicated to arrest imminent preterm labor. Various studies show that the efficacy of atosiban is similar to other tocolytic drugs. The main advantage of atosiban is a relativeLy low incidence of adverse maternal reactions. Its considerable shortcoming is the financial cost, compared to other available drugs.. In view of its cost, we have decided to implement a strict protocol to direct the use of atosiban, with the intent to reduce costs, without hampering quality of care.. The protocol was implemented from July 2009, and it outlines the medical and procedural terms to use atosiban. We compared similar time periods before and after implementation of the protocol. The outcomes compared included: treatment success, rates of preterm deliveries and financial costs.. Within the timeframe that the protocol was implemented, we have been able to demonstrate a 40% reduction in atosiban related costs, compared to a parallel period, when the clinical guidelines were not implemented. This translates into savings of about NIS 40,000 (New Israeli Shekel) (approximately $10,000). This was achieved without an increase in the rate of preterm deliveries.. Implementing and enforcing a simple protocol of supervision on the use of atosiban enables a considerable reduction of financial costs related to atosiban, without hampering medical care.

Topics: Cost Savings; Female; Humans; Israel; Obstetric Labor, Premature; Practice Guidelines as Topic; Pregnancy; Premature Birth; Quality of Health Care; Tocolytic Agents; Treatment Outcome; Vasotocin

Preterm birth is still the major cause of neonatal mortality and morbidity despite major improvements in neonatal care in the developed countries. Among survivors, the risk of severe consequences is inversely related to the gestational age at delivery. Appropriate antenatal intervention should delay delivery long enough to reduce perinatal consequences related to prematurity. Efficacy of tocolysis varies with gestational age and by the underlying cause of the preterm labour. In this paper we evaluate the use of not steroid anti-inflammatory drugs (NSAIDs) and other tocolytic agents in premature labor as optimal acute first-line treatment. We'll then discuss the use of medical therapy in order to delay delivery beyond 48 hours in selected cases. In a ongoing prospectic randomised trial we consider the association Atosiban - Progesterone to treat spontaneous preterm labor. Our preliminary data suggest that vaginal administration of Progesterone after arrest of uterine activity by atosiban administration could be able to prolong pregnancy in subjects with short cervix.

Topics: Administration, Intravaginal; Adrenergic beta-Agonists; Anti-Inflammatory Agents, Non-Steroidal; Clinical Trials as Topic; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Italy; Pregnancy; Premature Birth; Progesterone; Prospective Studies; Ritodrine; Tocolytic Agents; Vasotocin

Topics: Bias; Fetal Mortality; Humans; Premature Birth; Receptors, Oxytocin; Tocolytic Agents; Vasotocin

A synthetic oxytocin analogue, barusiban, was shown to potently inhibit oxytocin-induced activity of myometrium from term pregnant women. The responsiveness to vasopressin was not influenced by the compound.. To test the effect of barusiban and a reference compound, atosiban, on oxytocin-induced activity of myometrium from women at preterm pregnancy in comparison to myometrium from women at term.. Fifteen preterm (30-36 gestational weeks) and 12 term pregnant women (38-41 weeks) who underwent cesarean delivery donated myometrial tissue for the study. Concentration-response curves following oxytocin administration to isolated myometrial strips were recorded in control experiments, in the presence of barusiban at concentrations of 2.5, 25, and 250 nM, and of atosiban at concentrations of 25, 250, and 750 nM. Effective concentration 50% (EC50) and pA2 values were calculated.. Both antagonists in higher concentrations increased the EC50 values to oxytocin. The median pA2 value for preterm myometrium with barusiban was 9.76 and with atosiban 7.86. For term myometrium the corresponding pA2 results were 9.89 and 7.81, respectively. None of these pA2 values differed to any statistically significant degree.. The selective oxytocin antagonist, barusiban, concentration-dependently inhibits oxytocin-induced myometrial contractions of both preterm and term myometrium at least as potently as atosiban. It remains to be determined if the selectivity of barusiban for the oxytocin receptor confers an advantage over atosiban as a tocolytic in preterm labor.

Topics: Adult; Dose-Response Relationship, Drug; Female; Humans; In Vitro Techniques; Myometrium; Oxytocin; Pregnancy; Premature Birth; Uterine Contraction; Vasotocin