Tocolytic Research Articles

Evaluation of transdermal nitroglycerine as tocolytic agent in preterm labour

Background: Preterm birth continues to be a problem for obstetricians. Preterm birth complicates 8-10% of birth. Although the causes of preterm labor are not well understood, the burden of preterm birth is clear. Aim and objectives: The aim was to study to evaluate the efficacy and safety of transdermal nitroglycerin as tocolytic agent in women with preterm labor. Subjects and methods: This prospective randomized controlled trial was conducted in obstetrics and Gynecology department, AL- HUSSIEN University Hospital. The study was carried out on total of 100 patients with preterm labour. They were randomly assigned to either the nitroglycerine patch or bed rest alone. The duration of the study ranged from 6- 12 months. Results: out of 50 women in the TNG group, a total of 47 (94.0%) women benefited from the GTN patch and the labor pains stopped within the first few hours. Only 3 (6.0%) patients could not go beyond 48 hours. Delivery was deferred for 48 to less than 72 hours, 72 to <96 hours, 96 to < 7days and more than 7 days in 4(8.0%), 11(22.0%), 4(8.0%) and 28(56.0%) respectively. Conclusion: TNG appear to be at least as effective as the commonly used tocolytics today.

Associations of GNAS and RGS Gene Polymorphisms with the Risk of Ritodrine-Induced Adverse Events in Korean Women with Preterm Labor: A Cohort Study.

Ritodrine, a β2-adrenergic receptor agonist, is among most commonly prescribed tocolytic agents. This study aimed to evaluate the associations of single nucleotide polymorphisms in GNAS, RGS2, and RGS5 with the risk of ritodrine-induced adverse events (AEs) and develop a risk scoring system to identify high-risk patients. This is the prospective cohort study conducted at the Ewha Woman’s University Mokdong Hospital between January 2010 and October 2016. Pregnant women were included if they were treated with ritodrine for preterm labor with regular uterine contractions (at least 3 every 10 min) and cervical dilation. A total of 6, 3, and 5 single nucleotide polymorphisms (SNPs) of GNAS, RGS2, and RGS5 genes were genotyped and compared in patients with and without ritodrine-induced AEs. A total of 163 patients were included in this study. After adjusting confounders, GNAS rs3730168 (per-allele odds ratio (OR): 2.1; 95% confidence interval (95% CI): 1.0–4.3) and RGS2 rs1152746 (per-allele OR: 2.6, 95% CI: 1.1–6.5) were significantly associated with ritodrine-induced AEs. According to the constructed risk scoring models, patients with 0, 1, 2, 3, 4, and 5 points showed 0%, 13%, 19%, 31%, 46%, and 100% risks of AEs. This study suggested that GNAS and RGS2 polymorphisms could affect the risk of AEs in patients treated with ritodrine.

Cost-effectiveness of antenatal corticosteroids and tocolytic agents in the management of preterm birth: A systematic review.

SummaryBackgroundPreterm birth is a leading cause of neonatal mortality and morbidity, and imposes high health and societal costs. Antenatal corticosteroids (ACS) to accelerate fetal lung maturation are commonly used in conjunction with tocolytics for arresting preterm labour in women at risk of imminent preterm birth.MethodsWe conducted a systematic review on the cost-effectiveness of ACS and/or tocolytics as part of preterm birth management. We systematically searched MEDLINE and Embase (December 2021), as well as a maternal health economic evidence repository collated from NHS Economic Evaluation Database, EconLit, PubMed, Embase, CINAHL and PsycInfo, with no date cutoff. Eligible studies were economic evaluations of ACS and/or tocolytics for preterm birth. Two reviewers independently screened citations, extracted data on cost-effectiveness and assessed study quality using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement.Findings35 studies were included: 11 studies on ACS, eight on tocolytics to facilitate ACS administration, 12 on acute and maintenance tocolysis, and four studies on a combination of ACS and tocolytics. ACS was cost-effective prior to 34 weeks’ gestation, but economic evidence on ACS use at 34-<37 weeks was conflicting. No single tocolytic was identified as the most cost-effective. Studies disagreed on whether ACS and tocolytic in combination were cost-saving when compared to no intervention.InterpretationACS use prior to 34 weeks’ gestation appears cost-effective. Further studies are required to identify what (if any) tocolytic option is most cost-effective for facilitating ACS administration, and the economic consequences of ACS use in the late preterm period.FundingUNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), a cosponsored programme executed by WHO.

Tocolyse lors des Versions par Manœuvres Externes (VME) : étude rétrospective avant/après dans une maternité de type III

ObjectiveOn January 2020, the French College of Gynecologists and Obstetricians (CNGOF) issued new Clinical Practice Guidelines (CPG) “Breech Presentation”. Since then, it is recommended to use a tocolytic agent to improve the success rate of External Cephalic Version (ECV). The aim of this study, one year after these CPG, is to compare ECV without (before CPG) and with (after CPG) tocolysis in a type III maternity hospital. We intend to assess its effects on immediate success rate of ECV and obstetrical and neonatal outcomes. Materials and methodsThis is a single-center retrospective study conducted in Nantes University Hospital. We collected patient characteristics, immediate success rate, and maternal and neonatal outcomes at delivery of all ECV over two periods: the first one during 2019 (before CPG) and the second one from June 2020 to June 2021 (after CPG). ResultsWe included 253 patients: 126 in the first period and 127 in the second period. Immediate success rate of ECV was significantly higher since the use of tocolysis: 38.6 % (period 2) vs 23.8 % (period 1) (P=0.011). However, there was not significant difference found for cephalic presentation at birth, mode of delivery or obstetrical and neonatal outcomes. ConclusionThe immediate success rate is significantly improved with the widespread use of tocolysis during ECV, with no change in obstetrical and neonatal outcomes.

Effectiveness of Nifedipine in Preterm Labour Suppression

Objective: To understand the safety and effectiveness of nifedipine as a tocolytic agent in preterm labor. Study Design: A Quasi-experimental study. Place and Duration: The study was held in the Obstetrics and Gynecology Department of Riphah International Hospital Rawalpindi for one-year duration from January 2021 to December 2021. Methodology: 90 singleton pregnancies with cervical dilatation less than 3 cm and intact membranes with preterm labour occurred between 28-34 weeks of pregnancy were included and nifedipine was given as a tocolytic agent. Results: This study was performed on 90 patients, 55(61.1%) of whom were primigravida and 35(38.9%) were multiparty. 27.1 + 5.2 years was the mean age of patients (range 20 to 45 years), 74.4% were unbooked patients compared to 25.6% were booked patients. The tocolysis was obtained successfully in 76.7% of patients. The number of days obtained in delayed delivery was analyzed (Table 1B). Overall achievement in postponing delivery over 2 and 3 days is 76.7% (69/90). 21 patients (23.3%) were considered treatment failures. Of the patients who failed treatment (21/90), 18 patients gave birth in one day and 3 patients in two-days. The mean delay in delivery &lt;2 days was 1.0 + 0.3 days, while the delay &gt;2 days was 4.31 + 9.0, which is statistically important at&gt; p 0.008. The mean heart rate prior to treatment was 83.0 + 5.0, afterwards to treatment with nifedipine it was 92.0 + 5.0, indicating a difference of 9 bpm: statistically insignificant in heart rate. Conclusion: Nifedipine was effective in suppressing preterm delivery and delaying delivery long enough to achieve therapeutic effect and transfer the mother to the 3rd degree care unit. Keywords: Tocolysis, Premature labour, Nifedipine (calcium channel blocker).

Effectiveness of Nifedipine in Preterm Labour Suppression

Objective: To understand the safety and effectiveness of nifedipine as a tocolytic agent in preterm labor. Study Design: A Quasi-experimental study. Place and Duration: The study was held in the Obstetrics and Gynecology Department of Riphah International Hospital Rawalpindi for one-year duration from January 2021 to December 2021. Methodology: 90 singleton pregnancies with cervical dilatation less than 3 cm and intact membranes with preterm labour occurred between 28-34 weeks of pregnancy were included and nifedipine was given as a tocolytic agent. Results: This study was performed on 90 patients, 55(61.1%) of whom were primigravida and 35(38.9%) were multiparty. 27.1 + 5.2 years was the mean age of patients (range 20 to 45 years), 74.4% were unbooked patients compared to 25.6% were booked patients. The tocolysis was obtained successfully in 76.7% of patients. The number of days obtained in delayed delivery was analyzed (Table 1B). Overall achievement in postponing delivery over 2 and 3 days is 76.7% (69/90). 21 patients (23.3%) were considered treatment failures. Of the patients who failed treatment (21/90), 18 patients gave birth in one day and 3 patients in two-days. The mean delay in delivery &lt;2 days was 1.0 + 0.3 days, while the delay &gt;2 days was 4.31 + 9.0, which is statistically important at&gt; p 0.008. The mean heart rate prior to treatment was 83.0 + 5.0, afterwards to treatment with nifedipine it was 92.0 + 5.0, indicating a difference of 9 bpm: statistically insignificant in heart rate. Conclusion: Nifedipine was effective in suppressing preterm delivery and delaying delivery long enough to achieve therapeutic effect and transfer the mother to the 3rd degree care unit. Keywords: Tocolysis, Premature labour, Nifedipine (calcium channel blocker).

Clinical Factors and Perinatal Outcomes Associated With Short Latency Period in Twin Pregnancies With Preterm Premature Rupture of Membranes Before 34 Weeks: A Retrospective Study.

BackgroundThere is a lack of literature on short latency period (SLP) in twin pregnancies with preterm premature rupture of membranes (PPROM). Thus, the aim of this study was to identify the clinical factors and perinatal outcomes associated with SLP in twin pregnancies with PPROM and to establish a predictive model to identify SLP.MethodsTwin pregnancies with PPROM between 24 0/7 and 33 6/7 weeks were included and a retrospective analysis was performed. Patients were divided into two groups based on the latency period after PPROM: Group 1 ≤24 h (defined as SLP) and Group 2 >24 h (defined as long latency period, LLP), the clinical factors and perinatal outcomes were compared between the two groups. Binary logistic regression and receiver operating characteristic curve analyses were used to identify the independent clinical factors associated with latency period after PPROM and assess the predictive accuracy for SLP.Results98 and 92 pregnant women had short and long latency period, respectively. Prolonged latency significantly increased the occurrence of chorioamnionitis. Neonatal outcomes were not affected by latency duration after PPROM. Binary regression analysis revealed that higher gestational age (GA) at PPROM (P = 0.038), presence of uterine contractions (P < 0.001), Bishop score > 4 (P = 0.030), serum procalcitonin levels ≥0.05 ng/mL upon admission, and absence of use of tocolytic agents (P < 0.001) were significant independent predictors of a SLP. A predictive model developed using these predictors had an area under the curve (AUC) of 0.838, and the presence of uterine contractions alone had an AUC of = 0.711.ConclusionUterine contraction was the most important prognosticator for a SLP. A latency period of >24 h was associated with chorioamnionitis, but adverse neonatal outcomes were not observed.

The effect of celecoxib for treatment of preterm labor on fetuses during the second trimester of pregnancy: A pilot case series

ObjectiveAlthough cyclooxygenase inhibitors effectively suppress uterine contraction, constriction of the fetal ductus arteriosus (DA) and oligohydramnios are major concerns. Celecoxib, a selective cyclooxygenase 2 inhibitor, is a potential potent tocolytic agent, but there are no studies that have evaluated the beneficial or adverse effects of celecoxib use on fetuses for more than 48 hours in pregnant women. We therefore aimed to evaluate the effect of middle-long-term celecoxib administration on the fetus during the second trimester of pregnancy, particularly in terms of fetal DA and amniotic fluid volume. Materials and methodsWe retrospectively extracted and reviewed data from patients with preterm labor who received celecoxib for tocolysis for more than 48 hours between 2016 and 2020. Celecoxib was used for tocolysis only when treatment of patients with conventional tocolytic agents was ineffective. Data on the peak systolic velocity in ductus arteriosus (PSV-DA) and the maximum vertical pocket (MVP) were collected. ResultsA total of 15 patients were eligible. The median gestational age at celecoxib introduction was 22.6 weeks, and the median period of administration was 9 days (range 3–40 days). The median gestational age at delivery was 27.1 weeks, and the median duration from initial celecoxib administration to delivery was 40 days. The Z scores of PSV-DA and MVP did not change significantly after celecoxib administration. During administration, PSV-DA exceeded the 95th percentile of the corresponding normal reference range in three cases, but the levels returned to normal after reduction or discontinuation of treatment. There was no oligohydramnios during the treatment. ConclusionCelecoxib administration for more than 48 hours in the second trimester of pregnancy might be safe and tolerable in terms of fetal PSV-DA and amniotic fluid volume as long as careful ultrasound monitoring is performed. Celecoxib could be an alternative for preterm labor when conventional tocolysis is not effective.

Changing Tocolytic Exposures among Neonatal Intensive Care Unit Admitted Preterm Infants.

Since 2010, the American College of Obstetrics and Gynecology have released three committee opinions to recommend and reaffirm the utility of magnesium sulfate for neuroprotection and later for tocolysis to achieve antenatal steroid course completion in preterm labor. We sought to determine changes in antenatal magnesium sulfate exposure and other tocolytic agents for pregnancies resulting in neonatal intensive care unit (NICU)-admitted preterm infants. Using the Pediatrix Clinical Data Warehouse, we evaluated all inborn infants delivered between 22 and 33 weeks' gestation and admitted to the intensive care units from 2009 to 2018. We classified patients based on antenatal exposure to tocolytic medications: calcium channel blockers (nifedipine and amlodipine), betamimetics (terbutaline, theophylline, and ritodrine), prostaglandin inhibitors (indomethacin), and magnesium sulfate. A total of 229,781 patients met inclusion criteria. During the study period, magnesium sulfate exposure increased from 27.6 to 57.7% of births while betamimetic exposure decreased from 10.2 to 5.2%. Increasing magnesium sulfate exposure over time was seen at all gestational ages examined and magnesium exposure was most common between 23 and 31 weeks' gestation. By 2017 to 2018, 70.5% of 24 to 29 weeks' gestation NICU infants received exposure to at least one tocolytic agent while this remained at 53.7% of 32 to 33 weeks' NICU admitted infants. Antenatal steroid exposure increased from 74.8 to 87.4% during the study period. For NICU-admitted preterm infants, prenatal exposure patterns to tocolytic agents has shifted since 2009 with prenatal magnesium sulfate exposure increasing significantly. Antenatal steroid exposure has risen concurrently. Exposure to tocolytic agents is the highest among preterm infants born between 24 and 29 weeks' gestation. · Exposure to magnesium sulfate significantly increased from 2009 to 2018 for NICU admitted infants.. · Concurrently, the use of other tocolytics decreased significantly.. · The use of antenatal steroids has been rising over time..

Acceptance of RFID Toll Payment Method by Highway Users in Malaysia

Radio frequency identification (RFID) is a wireless tracking technology for data identification, capturing and analysis. It is used in numerous business applications to overcome the drawback of collecting data manually, such as data errors, time delay and high labour cost. RFID was introduced as an alternate toll charge payment method in Malaysia highways in 2018, and the government of Malaysia aims for a full implementation by end 2023. However, up to January 2022, only 10% of highway users switched to RFID. Hence, this study aims to assess highway users’ intention level on using RFID as toll payment mode. Additionally, the study also aims to evaluate the causal relationship between users’ perception on RFID payment mode and users’ intention to use RFID. The study views users’ perception based on modified TAM theory, which consist of perceived ease of use, perceived usefulness, perceived culture’s influence and perceived privacy and security. The study is quantitative based, structured questionnaire adopted from prior studies was distributed to the targeted population, which is class 1 highway users, and 176 responded. Data collected is normally distributed and statistically reliable. Hence, data was processed further with descriptive analysis and Pearson correlation test to address the research objectives. Finding from the research reveals that users’ intention to migrate to RFID payment mode is low, which suggested additional effort is required for the full implementation of RFID by end 2023. Additionally. Result of correlation test discloses that users’ perception on the ease of use and the usefulness are significantly associated with the intention to use RFID. However, the correlation of perceived culture’s influence, privacy and security with intention is weak and insignificant. The finding implies that highway operator should focus on addressing users’ anxieties and hesitation of using RFID in order to encourage more users to migrate to RFID. Additionally, the study also contributes to the domain new technology acceptance by the introduction of users’ acceptance model for RFID based on modified TAM theory.

Role of Tocolytics in Preterm

Tocolytics are the drugs that are used to prolong the time of child birth, for a short period - up to 2 days. If the labour starts too early during pregnancy also termed as preterm birth, which is supposed to be one of the major cause of neonatal mortality and morbidity, all over the world. Administration of tocolytic agents can help in preterm labour to delay the preterm labour by 48 hours. Tocolytics temporarily slow the contractions and hence it is possible to transport the patient to a hospital, where specialized care can be provided to premature baby and also corticosteroids can be administered, which help mature the baby’s lungs. Different class of drugs are studied as tocolytics. Beta-Adrenergic receptor agonists like Terbutaline, Ritodrine, Fenoterol, Metaproterenol, Hexoprenaline, Albuterol, Orciprenaline, Nylidrin. Calcium channel blockers like Nicardipine and Nifedipine. Magnesium Sulfate. Nonsteroidal anti-inflammatories or prostaglandin inhibitors like Indomethacin, and Oxytocin inhibitors like Atosiban were found effective in different studies with some side effects, are discussed here briefly. Some Nitrates, alcohol, Progesterone have also been tried with not much significant effect. Calcium channel blocker specially Nifedipine is most studied and found to be safer and effective for tocolysis. Individual uterine relaxant therapy should take into account individual differences in metabolism and response to drugs.. Short term use of tocolytics has been proven more effective and safer than longer use of it for pre-term labour.

Active ageing policy in challenging production environments: a case study involving social partners in Spain

In recent years, due to population ageing, the European Union has promoted active ageing policies as a means to encourage workers to delay labour market exit. Our paper explores what active ageing means to social partners (employers, managers and workers) in Spain and also the viability of implementing an active ageing culture in organizations. We used a qualitative case study methodology to identify perceptions regarding obstacles and facilitators in the adoption of an active ageing culture in different production sectors, as well as responses to active ageing policies. Data-generating workshops were held with employees and managers of four types of companies located in the south of the country. Perceived obstacles to active ageing were more organizational than individual in nature. Some of these obstacles gave rise to a kind of forced active ageing in a context in which the previous predominant message had been to retire as early as possible. Job adaptation was perceived as both an obstacle and a facilitator. Increasing recognition of older workers and raising their motivation to extend their working lives were found to be important pending tasks. In contexts of high unemployment, active ageing often remains largely unknown within productive organizations, and the idea of retiring as soon as possible continues to guide many workers. In these circumstances, the implementation of top-down, uniform active ageing policies has proven to be of limited efficacy. Awareness campaigns and initiatives aimed at improving older workers’ health and abilities should be launched as complementary active ageing strategies.

Effects of acute tocolysis using ritodrine hydrochloride on foetal heart rate patterns in intrauterine foetal resuscitation: a retrospective, single-centre observational study

No consistent recommendations concerning the preferred tocolytic agents for intrauterine foetal resuscitation are available. We evaluated the effects of acute tocolysis (AT) using ritodrine hydrochloride on foetal heart rate (FHR) patterns and neonatal outcomes. We retrospectively analysed the data of patients undergoing emergency caesarean section because of non-reassuring foetal status indicated by foetal scalp electrodes. Patients were classified into AT (ritodrine hydrochloride approximately 500 µg/min) and control groups with 15 and 12 participants, respectively. FHR patterns, Apgar scores, umbilical arterial analysis, and neonatal admission were compared. All participants had FHR category II; decelerations disappeared in all foetuses in the AT group, with no significant difference in neonatal outcomes. The AT group had a higher baseline FHR and lower short-term FHR variability than the control group, indicating foetal autonomic responses. Further studies are needed to clarify the effects of AT on FHR patterns, neonatal outcomes, and foetal and neonatal autonomic responses. Impact statement What is already known on this subject? The usefulness of acute tocolysis using ritodrine hydrochloride has been well-documented in several studies; however, such an application often induces side effects, such as maternal tachycardia, palpitations, and tremors. What the results of this study add? The short-term administration of ritodrine hydrochloride eliminated decelerations, with no significant difference in neonatal outcomes in pregnant women with foetal heart rate category II. Meanwhile, there were higher foetal heart rate and lower short-term foetal heart rate variability in pregnant women administered with ritodrine hydrochloride, indicating foetal autonomic responses. What the implications are of these findings for clinical practice and/or further research? Ritodrine hydrochloride administration, even for short-term, appears to be associated with foetal autonomic responses. Further studies with stratification of patient groups based on the severity and aetiology of non-reassuring foetal status, including pregnant women with foetal category III, would elucidate the risk and benefit of acute tocolysis using ritodrine hydrochloride, based on foetal heart rate patterns, neonatal outcomes, and foetal and neonatal autonomic responses.

Effects of Bryophyllum pinnatum Administration on Wistar Rat Pregnancy: Biochemical and Histological Aspects

Introduction: Bryophyllum pinnatum is widely used in folk medicine. It has neuropharmacological, anti-inflammatory, immunomodulatory, antidiabetic, hepatoprotective, and nephroprotective effects, among others. It also acts on uterine contractility. It is prescribed by practitioners of anthroposophic medicine for preterm labor, insomnia, and emotional disorders, and has other potential uses in obstetrics. As all drugs currently used in preterm labor have side effects, new tocolytic agents remain an area of active research. Objective: To evaluate the effect of B. pinnatum mother tincture (MT) on albino rats and their offspring throughout pregnancy from a biochemical and histological standpoint. Methods: Longitudinal, prospective, randomized controlled bioassay. This is the second stage of a trial that investigated 60 animals distributed across six equal groups: controls C1 and C2, which received 1 and 25 times the vehicle dose (30% ethanol), B1 and B2 (1- and 25-fold doses of B. pinnatum MT), and B3 and B4 (which received 50- and 100-fold doses of B. pinnatum concentrate). At this stage, blood chemistry parameters (glucose, alanine aminotransferase [ALT], aspartate aminotransferase [AST], creatinine, and blood urea nitrogen) were measured in dams, as well as histological aspects of dam liver, kidney, placenta, and uterine tissue and fetal liver, kidney, heart, and brain. Results: No differences were found between group B1 (therapeutic dose) and its control C1 in relation to glucose, AST, ALT, and creatinine. Group B2 exhibited lower glucose levels than groups C1, B3, and B4. There was no difference in AST across groups. Groups B3 and B4 exhibited higher ALT levels than groups C1 and B1. Groups B1–B4 exhibited higher urea nitrogen levels than group C1. Creatinine levels were higher in groups B2 and B3 than group C1. On morphological evaluation, fatty infiltration of the liver was observed in the alcoholic vehicle control groups (C1 and C2). Conclusions: Daily administration of B. pinnatum at therapeutic doses (group B1) to pregnant albino rats appears to be safe, with reduced glucose at dose B2, elevated ALT at doses B3 and B4, and increased urea at doses B1 to B4 and creatinine at B2 and B3, but never exceeding the normal reference range. It was not associated with histological changes in specimens of the maternal or fetal structures of interest.

Landscape of Preterm Birth Therapeutics and a Path Forward.

Preterm birth (PTB) remains the leading cause of infant morbidity and mortality. Despite 50 years of research, therapeutic options are limited and many lack clear efficacy. Tocolytic agents are drugs that briefly delay PTB, typically to allow antenatal corticosteroid administration for accelerating fetal lung maturity or to transfer patients to high-level care facilities. Globally, there is an unmet need for better tocolytic agents, particularly in low- and middle-income countries. Although most tocolytics, such as betamimetics and indomethacin, suppress downstream mediators of the parturition pathway, newer therapeutics are being designed to selectively target inflammatory checkpoints with the goal of providing broader and more effective tocolysis. However, the relatively small market for new PTB therapeutics and formidable regulatory hurdles have led to minimal pharmaceutical interest and a stagnant drug pipeline. In this review, we present the current landscape of PTB therapeutics, assessing the history of drug development, mechanisms of action, adverse effects, and the updated literature on drug efficacy. We also review the regulatory hurdles and other obstacles impairing novel tocolytic development. Ultimately, we present possible steps to expedite drug development and meet the growing need for effective preterm birth therapeutics.

Short-Term Outcomes of Atosiban in the Treatment of Preterm Labour at the Sultan Qaboos University Hospital, Muscat, Oman: A tertiary care experience.

ObjectivesThis study aimed to generate baseline evidence regarding the effectiveness of atosiban in delaying delivery by ≥48 hours among pregnant women presenting with threatened preterm labour (TPL). The secondary objective was to assess the relationship between atosiban success and various perinatal factors and neonatal outcomes.MethodsThis retrospective study was conducted between June 2008 and May 2018 at the Sultan Qaboos University Hospital, Muscat, Oman. The medical records of all pregnant women who received atosiban between 24–34 gestational weeks for TPL during this period were reviewed.ResultsA total of 159 women were included in the study. Atosiban was successful in delaying delivery by ≥48 hours in 130 cases (81.8%). Approximately half of the women (50.9%) achieved uterine quiescence in <12 hours. Failure to delay delivery by ≥48 hours was significantly lower among women with normal versus abnormal cervical findings (11.1% versus 25.6%; P = 0.023). Only 9.4% of women experienced minor side-effects. Mean birth weight (2,724.55 versus 1,707.59 g; P <0.001) and Apgar scores at 5 minutes (9.66 versus 8.28; P <0.001) were significantly higher among neonates delivered at ≥48 versus <48 hours post-atosiban, whereas the rate of neonatal respiratory distress syndrome was significantly lower (18.4% versus 81.6%; P <0.001).ConclusionAtosiban was highly effective in delaying delivery by ≥48 hours and resulted in few adverse maternal side-effects and neonatal outcomes. To the best of the authors’ knowledge, this is the first study conducted in Oman to evaluate the effectiveness of atosiban in preventing preterm labour.

Influence of Tocolytic Therapy with Hexoprenaline on Heart Rate Variability, Lipid Spectrum and Glycemic Level in Obese Pregnant Women

Background. Obesity is associated with the risk of spontaneous preterm birth. Hexoprenaline is the effective and most widely used tocolytic agent, possessing however a significant number of side effects. The effect of hexoprenaline tocolysis on heart rate variability, lipid spectrum and glycaemia level in obese pregnant women remain unexplored.Aim of the research. To study the effect of tocolytic therapy with hexoprenaline on heart rate variability, lipid spectrum and glycemic level in obese pregnant women.Materials and methods. The study included two groups of pregnant women with threatened preterm labor who received tocolysis with hexoprenaline. One group consisted of 68 obese patients, the other – 72 non-obese pregnant women (control group). Patients underwent Holter monitoring. Fasting serum glucose and lipids spectrum were measured before starting tocolytic therapy and after 24 hours of tocolysis.Results. In obese pregnant women with hexoprenaline infusion, the heart rate, the 24-hours number of supraventricular extrasystoles and ventricular extrasystoles during the day are significantly higher. Frequency domain parameters, very low frequency during the day, low frequency at night and 24-hours high frequency were significantly decreased than in control group. After a day of tocolysis in obese pregnant women, the level of total cholesterol, low density lipoproteins, triglycerides, and glucose significantly increases when compared with the results before therapy. For patients in the control group treated with hexoprenaline, only the concentration of high-density lipoproteins is increased.Conclusion. Obesity in pregnant women receiving hexoprenaline tocolysis is associated with low heart rate variability and an increase in the number of cardiac arrhythmias, as well as lipid disorders and an increase in glucose level.

Noninvasive positive-pressure ventilation in pregnancy to treat acute pulmonary edema induced by tocolytic agents: a case report

BackgroundWe report a case of pulmonary edema induced by tocolytic agents that was successfully managed with noninvasive positive-pressure ventilation (NPPV) and resulted in extended gestation.Case presentationA 36-year-old Japanese pregnant woman received tocolytic therapy with ritodrine hydrochloride, magnesium sulfate, nifedipine, and betamethasone from 28 weeks of gestation. She developed respiratory failure. and her chest X-ray showed enlarged pulmonary vascular shadows. At 29 weeks and 1 day of gestation, she was diagnosed with pulmonary edema induced by tocolytic agents. Because respiratory failure worsened 2 days after ritodrine hydrochloride and magnesium sulfate were stopped, NPPV was initiated. Her respiratory status improved and she was weaned off of NPPV after 3 days. She underwent cesarean section because of breech presentation at 30 weeks and 0 days of gestation due to initiation of labor pains.ConclusionsNPPV can be safely administered in cases of tocolytic agent-induced pulmonary edema during pregnancy.

Anoctamin 1 antagonism potentiates conventional tocolytic-mediated relaxation of pregnant human uterine smooth muscle

BackgroundCurrently available tocolytic agents are not effective treatment for preterm labor beyond 48 h. A major reason is the development of maternal side effects which preclude the maintenance of an effective steady-state drug concentration. One strategy that can mitigate these side effects is utilizing synergistic drug combinations to reduce the drug concentrations necessary to elicit a clinical effect. We have previously shown that three anoctamin 1 (ANO1) antagonists mediate potent relaxation of precontracted human uterine smooth muscle (USM). In this study, we aimed to determine whether a combination of sub-relaxatory doses of tocolytic drugs in current clinical use [the L-type voltage-gated calcium channel (VGCC) blocker, nifedipine (NIF); and the β2-adrenergic (β2AR) agonist, terbutaline (TRB)] will potentiate USM relaxation with two ANO1 antagonists [benzbromarone (BB) and MONNA (MN)].ObjectiveThis study sought to examine the synergistic potency and mechanistic basis of two ANO1 antagonists with currently available tocolytic drugs. Functional endpoints assessed included relaxation of pre-contracting pregnant human USM tissue, inhibition of intracellular calcium release, and reduction of spontaneous transient inward current (STIC) recordings in human uterine smooth muscle cells.MethodsHuman myometrial strips and primary human USM cells were used in organ bath and calcium flux experiments with different combinations of sub-threshold doses of ANO1 antagonists and terbutaline or nifedipine to determine if ANO1 antagonists potentiate tocolytic drugs.ResultsThe combination of sub-threshold doses of two ANO1 antagonists and current tocolytic drugs demonstrate a significant degree of synergy to relax human pregnant USM compared to the effects achieved when these drugs are administered individually.ConclusionA combination of sub-threshold doses of VGCC blocker and β2AR agonist with ANO1 antagonists potentiates relaxation of oxytocin-induced contractility and calcium flux in human USM ex vivo. Our findings may serve as a foundation for novel tocolytic drug combinations.

Bryophyllum pinnatum Compounds Inhibit Oxytocin-Induced Signaling Pathways in Human Myometrial Cells.

Bryophyllum pinnatum has been used in the treatment of premature labor, first in anthroposophic hospitals and, recently, in conventional settings as an add-on medication. In vitro work with hTERT human myometrial cells showed that B. pinnatum leaf press juice inhibits the increase of intracellular free calcium concentration induced by oxytocin, a hormone known to play a role in labor. Our aim was to identify fractions/compounds in B. pinnatum press juice that contribute to this inhibitory effect, and to investigate their effect on oxytocin-driven activation of the MAPK cascade. Several fractions/compounds from B. pinnatum press juice led to a concentration-dependent decrease of oxytocin-induced increase of intracellular free calcium concentration, but none of them was as strong as B. pinnatum press juice. However, the combination of a bufadienolide and a flavonoid-enriched fraction was as effective as B. pinnatum press juice, and their combination had a synergistic effect. B. pinnatum press juice inhibited oxytocin-driven activation of MAPKs SAPK/JNK and ERK1/2, an effect also exerted by the bufadienolide-enriched fraction. The effect of B. pinnatum press juice on oxytocin-induced signaling pathways was comparable to that of the oxytocin-receptor antagonist and tocolytic agent atosiban. Our findings further substantiate the use of B. pinnatum press juice preparations in the treatment of preterm labor.