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Calcium channel antagonists inhibit voltage-dependent L-type calcium channels found on cardiac myocytes and peripheral vascular smooth muscle cells (primarily arteries and arterioles). By blocking calcium from entering the cell, calcium antagonists produce negative chronotropic effects (decreased heart rate), negative inotropic effects (decreased force of myocardial contraction), and negative dromotropic effects (decreased conduction velocity through the atrioventricular node). They cause direct vasodilation of peripheral vasculature and interfere with pancreatic release of insulin by blocking L-type calcium ion channels of pancreatic beta-cells. Following oral administration, absorption of calcium channel blockers is rapid and nearly complete (80–100%), although their bioavailability is limited and variable (15–94%) due to a significant first-pass metabolism in the liver. Calcium channel blockers are used in the treatment of hypertension, angina, abnormal heart rhythms (e.g., atrial fibrillation and paroxysmal supraventricular tachycardia), pulmonary hypertension, Raynaud's syndrome, cardiomyopathy and subarachnoid hemorrhage. They are also used in the prevention of migraine headaches and as a tocolytic agent (interrupt uterine contractions when premature labor occurs).

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 statementWhat 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.

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.

Objectives: This 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. Methods: This 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. Results: A 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

Prenatal repair of fetal spina-bifida in the 2nd trimester has been shown to improve neurological function after delivery of the baby. Surgery can be performed with partial delivery of the fetus through a uterine incision, or increasingly via fetoscopy. Trocars to allow surgical instrumentation are introduced either via the exteriorized uterus or percutaneously. Both approaches require maternal anesthesia, an immobile anesthetized fetus and a non-contracting uterus. This can be achieved with administration of a general anesthetic to the mother, transplacental anesthesia of the fetus and tocolytic agents as required. Transplacental anesthesia needs to balance adequate depth of anesthesia for the mother and fetus with rapidly reversible uterine atony. The anesthetist is responsible for the safety of both patients. Monitoring of cardio-respiratory parameters for the mother are well established, but the tools available to monitor fetal well-being and access for corrective therapy are limited. Cardiotocography, fetal echocardiography or ultrasound assessment of umbilical or middle cerebral artery blood flow can be monitored for fetal well-being, but interpretation can be difficult. Fetal blood pressure monitoring is not yet feasible. There is a clear need to enhance fetal monitoring and define normal parameters with clear protocols for intervention to improve fetal safety. Abandoning the procedure should be considered to avoid emergency delivery of an extremely premature fetus. More research into suitable fetal monitoring techniques are needed.

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.

Background We 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 presentation A 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. Conclusions NPPV can be safely administered in cases of tocolytic agent-induced pulmonary edema during pregnancy.

Background: Currently, the main goal for the use of tocolytic therapy is to delay the birth so as to allow the use of corticosteroids for accelerating fetal lung maturity and maternal transfer to a tertiary care center and thereby reducing neonatal morbidity and mortality. Aims and Objectives: The aims amd objectives were to compare the safety and efficacy of transdermal nitroglycerine patch with oral nifedipine as a tocolytic agent to arrest preterm labor and prevent preterm birth. Materials and Methods: Based on the selection criteria, 50 patients were selected randomly in Group A and Group B. Group A women were given transdermal nitroglycerin patch, which delivered 10 mg Nitroglycerin (NTG) over 24 h and it was applied to the woman's abdomen followed by another patch of 10 mg after 1 h if contractions persisted. After 24 h, it was replaced by a fresh patch. Group B women were given an oral loading dose of nifedipine 20 mg followed by a similar dose if contractions persisted after 1 h. A maintenance dose of 10 mg thrice daily was given if contractions were suppressed. Patients were monitored from the time of admission to the time of discharge. Results: The mean duration of prolongation of pregnancy in Group B (3.68 ± 1.91 days) was significantly more than Group A (2.78 ± 1.39 days). Headache was seen significantly more in Group A (42%) than group B (6%). Tachycardia, hypotension, and palpitation showed no statistically significant difference between them. There was no statistically significant difference in the birth weight of the babies in both the groups. Conclusion: Nifedipine is a safe and effective drug in prolonging preterm labor and has minimal maternal and neonatal side effects.

Introduction. Azanza garckeana (F.Hoffm.) Exell and Hillc. (family: Malvalceae) is traditionally used to induce or accelerate labour in pregnant women in Chongwe, Zambia, and the plant part which is commonly used are the roots. Aim. The aim of this study was to screen Azanza garckeana crude extracts for uterotonic activity on isolated Wistar rat uterine smooth muscles. The likely mechanism of action for the plant extract was also investigated. Materials and Methods. Fresh leaves and roots of the plant were collected and identified by a botanist at the University of Zambia. The methanol and cold root aqueous extracts were prepared by continuous maceration while the hot aqueous root extract was extracted using the Soxhlet method. The crude extracts of the plant were screened for uterotonic activity using uterine smooth muscles isolated from estrogenised adult nongravid female Wistar rats weighing between 160 g and 200 g. The activity of the plant was also evaluated in the presence of antagonists and tocolytic agents to determine the likely mechanism of action. Results. The hot aqueous root crude extract (22.26%) had the highest yield followed by the cold aqueous (11.32%) and methanol extracts (6.26%), respectively. The methanol crude root extract demonstrated the highest potency (EC50 = 1.28 × 10−2 mg/ml; 95% CI 6.418 × 10−3 to 2.564 × 10−2;p=0.0001), while the cold aqueous extract was the most efficacious. Salbutamol and nifedipine significantly blocked the uterotonic activity of the extract. Conclusions. This study provides scientific evidence on the uterotonic activity of Azanza garckeana with myometrial calcium mobilization as the possible mechanism of action.

Background: Preterm labour is a major cause of maternal mortality in our country. Hypomagnesaemia during pregnancy could be an indirect cause of preterm labour. Magnesium has a role on uterine smooth muscle relaxation, which is the basis for the use of magnesium sulphate as a tocolytic agent. Objective: This study was done to see the effect of magnesium sulfate to prevent preterm labour and perinatal outcome. Materials and Methods: This study was carried out in Comilla Medical College & Hospital, from December 2011 to May 2012. Fifty pregnant women, both primi and multi with preterm labour were selected for the study. Results: Study showed labour delayed >24 hours in 86% cases. And the majority of newborn (96%) had Apgar score in 5 minute was 8-10, 4% had Apgar score 7-8. The mode of delivery was vaginal in 70% cases and by c/s in 16% cases; among subject whose labour delayed more than 24 hours. Conclusion: Intravenously administration of magnesium sulfate is safe, well tolerated and effective tocolytic agent for prolongation of pregnancy in preterm labour. It produces minimal harmful effects on mother and fetus. KYAMC Journal Vol. 11, No.-3, October 2020, Page 145-149

We face many problems in diagnosis, monitoring and adopting treatment policy.There are very limited studies about preterm labour prevention in our country and few national data are available about the incidence of preterm labour. Acute tocolysis prevents preterm labor for 48 hours, which is the critical period for antenatal steroid administration or maternal transfer to perinatal centers to improve neonatal outcomes. This prospective study was conducted. To determine the effectiveness of magnesium sulfate as tocolytic agent in preterm labour to arrest the premature onset of labour. A total of 90 primigravid and multigravid with preterm labour was included in this study at 250 Beded General Hospital Tangail from January 2012 to December 2015. The mean age of the respondents was 24.13±4.67 year. The mean systolic and diastolic blood pressure were 122.47±12.64 and 71.67±12.67 mm of Hg respectively. Gestational age did not influence on the outcome of treatment with Tocolytic regime. Out of 90 pregnant women, 70% were anemic, 53.3% had vaginal bleeding and 76.7% had abdominal pain. Among 90 respondents only 6 women had premature rupture of membrane and about 40% had inadequate amniotic fluid. The three treatment regime (Antibiotic+ Tocolytic+ steroid) was found indifferent in terms of affectivity. Preterm labour is not a very uncommon pregnancy-related complication. This study evaluates, the effect of magnesium sulphate as tocolytic agent. Bangladesh Med J. 2020 May; 49(2) : 25-29

Despite safety concerns, β2-sympathomimetics are still widely used as tocolytic agents. β-Blockers in turn are used to treat vasculo-proliferative diseases of the newborn such as retinopathy of prematurity (ROP), which may lead to visual impairment and blindness. The scope of this study was to investigate whether antenatal exposure to the β2-sympathomimetic fenoterol contributes to the development of ROP. For this single-center retrospective case–control study of prospectively collected clinical data, all infants born before 32 weeks of gestation between 2001 and 2012 were included. The association of prenatal exposure to fenoterol and the development of ROP were analyzed by multivariate logistic regression. n = 1134 infants

Background: Vitamin D receptors (VDR) are expressed in many reproductive tissues indicating a potential role of vitamin D3-VDR in the regulation of reproductive functions. Nevertheless, the data about the effect of vitamin D3 in the uterus are scarce.Aim of Study: This study was designed to evaluate the potential effects of vitamin D3 on spontaneous, KCl-induced and oxytocin-induced contractions in the rat uterus in vitro.Material and Methods: The study was conducted on 10 healthy adult female albino non-pregnant rats. Full-thickness longitudinal muscle strips were dissected from each non-pregnant rat and then myometrial tension was recorded. The strips were mounted vertically in organ baths and exposed to vitamin D3 and different uterotonic agents to delineate the potential action of vitamin D3 on the rat myometrial contrac-tility. Spontaneous contractions were recorded using mechan-ical activity recording system. We evaluated the effects of 3 different dosed of vitamin D3 on spontaneous uterine contrac-tions; then on concentrated KCl-induced uterine contractions and oxytocin (OT)-induced uterine contractions. Furthermore, the effects of vitamin D3 on spontaneous uterine contractions pretreated with nifedipine; a voltage-gated L-type Ca2+ channel antagonist were investigated.Results: Vitamin D3 significantly inhibited the spontaneous uterine contractions in a dose dependent manner. Moreover, vitamin D3 inhibited the uterine contractions whether induced by oxytocin or concentrated KCl. Administration of nifedipine resulted in a significant decline in the force amplitude of spontaneous uterine contractions. In the presence of vitamin D3, the uterine relaxant effect of nifedipine was significantly augmented.Conclusions: The inhibitory effects of the in vitro admin-istration of vitamin D3 on rat uterus may yield novel insights into its therapeutic use. Further, it may be recommended to be used as a novel tocolytic agent for preventing unwanted uterine contractions in early pregnancy and relieving pain related to dysmenorrhea.

The objective is aimed to Assessing risk factors for unsuccessful rate of uterus contraction inhibition in pregnant women 240/7-336/7 weeks of gestation in Maharat Nakhon Ratchasima Hospital The retrospective cohort study approved by the Research Ethics committee of, Maharat Hospital, Nokhon Ratchasima Province Thailand studying pregnant women who were diagnosed with preterm labor pain with gestrational age of 240/7-336/7 weeks at the delivery ward of Maharat Nakhon Ratchasima Hospital and received Dexamethasone(corticosteroid) for the first time in every case between 1 January 2016 – 31 December 2018. From 361 pregnant women with preterm labor pain, 169 women were successful inhibition which was 54.29%. The group with failure inhibition were 165 women which was 45.71%. The factors relating to unsuccessful inhibition of uterus contraction were ANC less than 5 times, Adjusted odd ratios(AORs) 1.74; 95%CI 1.01-3.03, multiple pregnancy AORs 4.42 ; 95%CI 1.96-9.97 Cervical dilatation ≥3 cm AORs 5.93; 95%CI 3.44-10.22, the Effacement ≥ 80%, AORs 3.39; 95%CI 2.07-5.55, transfer from another hospital AORs 13.96; 95%CI 5.24-37.19. The research concludes that the factors relating to unsuccessful inhibition of uterus contraction were ANC less than 5 times, multiple pregnancy, Cervical dilatation ≥3 centimeters, Effacement ≥ 80%,and pregnant women referred from Secondary care center

Background: This study aimed to evaluate differences in maternal characteristics and obstetric and childhood outcomes between term births according to the use of tocolytic treatment. Methods: This study analyzed the data of the participants enrolled in the Japan Environment and Children’s Study between 2011 and 2014. Data of 63,409 women with singleton births after 37 weeks of gestation were analyzed. We compared maternal characteristics, obstetric outcomes, and childhood outcomes between term births with tocolytic treatment and those without tocolytic treatment. Multiple logistic regression was used to calculate adjusted odds ratios for childhood outcomes with significant between-group differences in the univariable analysis for term births with tocolytic agents, with term births without tocolytic agents as the reference group. Results: In term births with tocolytic agents, participants had significantly younger age, leaner body mass index, higher oxidative stress during pregnancy, shorter pregnancy period, lighter neonatal birth weight, lower incidence of gestational diabetes mellitus, higher incidence of preterm premature rupture of membrane, higher rates of cesarean section, lower incidence of meconium-stained amniotic fluid during pregnancy, and higher incidence of childhood allergic disorders. The incidence of childhood developmental disorders showed no significant between-group differences. The adjusted odds ratio for childhood allergic disorders in term births with tocolytic agents was 1.09 (95% confidence interval, 1.04-1.14). Conclusions: This study found no significant association between tocolytic treatment and the incidence of childhood developmental disorders in children with term births. However, tocolytic treatment showed an association with a slightly increased incidence of childhood allergic disorders.

Preterm labor needs to be prevented, one of the prevention methods is by tocolytic administration which could prevent labor thus providing a chance for lung maturation. Preterm Pregnancy is associated with increased concentrations of cytokines such as Interleukin (IL). The increasing concentration of maternal serum IL-6 can be used to predict preterm labor. This research uses the design Cross-Sectional Comparative to determine differences in means of maternal serum levels of IL-6 based on the success of the administration of a tocolytic agent on preterm labor. This study was performed on pregnant women who come to the obstetric emergency room of DR. MA. Hanafiah Batusangkar Hospital within August-November 2015. The total number which was included in statistical analysis was 34 pregnant women which were divided into 2 groups, 17 people in the group of patients who failed in tocolytic agent administration, and 17 people in the group who success in managed with a tocolytic agent. Statistical analysis was performed to analyze the validity using the T-test. There are significant differences in the average rate of maternal serum IL-6 in patients who failed to treat with a tocolytic agent and successful to treat with a tocolytic agent. Seen from the p-value 0.000. Levels of maternal serum IL-6 in patients who failed to treat with a tocolytic agent were higher than successful to treat with a tocolytic agent.Keywords: IL-6, Tocolytic, Preterm labor

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 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.

Objective The aim of the study is to obtain insights on the short and long-term safety and effectiveness of isoxsuprine hydrochloride as a tocolytic agent in the management of PTL. Study Design In this prospective, single-center, noncomparative study, patients (with preterm labor at gestational age of 24–37 weeks) were administered intravenous (IV) infusion of 40-mg isoxsuprine hydrochloride until uterine quiescence, followed by intramuscular (IM) injection of isoxsuprine hydrochloride 10 mg/4-hourly for first 24 hours and maintained with retard 40-mg sustained release capsule (two times a day) till the time of delivery or 37 completed weeks of pregnancy. Results All patients (n = 50) achieved successful tocolysis in 24 hours and 48 hours postadministration of isoxsuprine hydrochloride (IV/IM/oral). Mean (±SD) gestation age at the time of delivery was 39.8 ± 2.1 weeks, with latency period of 58.5 ± 18.7 days. Pregnancy outcomes were normal in all the patients and no congenital anomaly/fetal infection was reported. Mean (±SD) fetal birth weight was 2.7 ± 0.3 kg; mean (±SD) Apgar score at 1 and 5 minutes were 7.5 ± 0.6 and 9.2 ± 0.4, respectively. Maternal tachycardia and vomiting (8.0% each) were the commonly reported adverse drug reactions, which were resolved with dose adjustment. Conclusion Isoxsuprine was found to be an effective and well-tolerated tocolytic agent in arresting PTL, in turn resulting in the overall improvement in maternal and perinatal outcomes.

Background:Preterm birth is the major cause of perinatal mortality and morbidity worldwide. Attempts to reduce the burden may be proactive using biochemical or biophysical prediction and preventative measures. If these efforts fail, then the approach may have to be reactive using tocolytics to inhibit spontaneous preterm labour.Objective:We have reviewed the evidence concerning the safety and efficacy of various classes of tocolytic agents.Results:The evidence to support the use of magnesium sulfate or nitric oxide donors as a tocolytic is poor. Compared to placebo or no treatment, there is evidence to support the efficacy of calcium channel blockers (mainly nifedipine), prostaglandin synthetase inhibitors (mainly indomethacin and sulindac), oxytocin receptor antagonists (mainly atosiban) and β2-agonists (mainly ritodrine, terbutaline, salbutamol and fenoterol). Maternal safety concerns have reduced the use of β2-agonists. Fetal safety and gestational age restrictions have largely condemned prostaglandin synthetase inhibitors to second-line therapy. First-line therapy in Europe and other parts of the world outside the USA and Australia is limited to calcium channel blockers and oxytocin receptor antagonists. With respect to efficacy, atosiban and nifedipine are similar, but the robustness of the evidence favours atosiban. With respect to safety, atosiban is clearly the safest tocolytic as there are fetomaternal concerns with nifedipine, particularly in high daily doses.Conclusion:The perfect tocolytic that is uniformly effective and safe does not exist. Cost, licensing and informed consent are considerations involved in the choice. Efforts continue to develop and introduce other or better agents, including novel compounds such as progesterone, PGF2α antagonists and statins.

Despite considerable progress in the field of perinatal care, infectious diseases, especially when caused by gram negative bacteria, remain a major reason for neonatal morbidity and mortality. Notably infants born prematurely and those with very low birth weight are at risk due to their immature and deficient immune system and their prolonged hospitalization which promotes nosocomial infections. In case of impending preterm birth, betamethasone is given to induce lung maturation and tocolytic agents like indomethacin or fenoterol are administered to suppress premature labor. The aim of this study was to analyze the effects of these drugs on the immune system of mothers and neonates. Therefore, mononuclear cells from cord blood and peripheral maternal blood were stimulated with Escherichia coli and incubated with betamethasone, indomethacin and fenoterol. Subsequently the effect of the treatment on cytokine production was determined. Betamethasone alone and in combination with tocolytic agents inhibited the production of pro- and anti-inflammatory cytokines. Not only does betamethasone dampen the immune response by reducing the production of cytokines, it also has a variety of other detrimental short- and long-term effects on the neonate. In conclusion we would recommend using biological markers to determine if premature labor actually leads to preterm birth and subsequently administer betamethasone only to mothers giving birth prematurely.

MgSO 4 is used as a tocolytic agent. It is considered to be a calcium channel antagonist, but a different mechanism of its action might be involved. The aim of this study was to examine the contribution of calcium concentrations and potassium channels in the mechanism of MgSO 4 -mediated uterine relaxation. Isolated uteri from female Wister rats were treated with increasing MgSO 4 concentrations (0.1-30 mM). MgSO 4 induced dose-dependent inhibition of spontaneous activity. Addition of Ca 2+ (6 mM and 12 mM) stimulated uterine contractile activity and attenuated the inhibitory activity of MgSO 4 . In order to analyze the role of different subtypes of potassium channels, Ca 2+ -stimulated uteri were pretreated with glibenclamide (Glib), a selective ATP-sensitive potassium channel inhibitor (K ATP ), tetraethylammonium (TEA), a non-specific inhibitor of large conductance calcium-activated potassium channels (BK Ca ), and 4-aminopyridine (4-AP), a voltage-sensitive potassium channel inhibitor (Kv), at concentrations that had no effect per se . Pretreatment with 4-AP had no effect on MgSO 4 -mediated relaxation of Ca 2+ -stimulated uteri. The relaxing effect of MgSO 4 was potentiated by pretreatment with glibenclamide. Pretreatment with TEA attenuated the MgSO 4 -mediated decrease in frequency. Our results suggest that MgSO 4 acts as a general calcium antagonist that influences Ca 2+ -mediated potassium channels. Furthermore, it seems that MgSO 4 uterine relaxation activity is partially mediated by selective ATP-sensitive potassium channels, suggesting an ATP-dependent role. https://doi.org/10.2298/ABS180615031S Received: June 15, 2018; Revised: July 6, 2018; Accepted: July 6, 2018; Published online: July 16, 2018 How to cite this article: Sokolovic D, Drakul D, Orescanin-Dusic Z, Tatalovic N, Pecelj M, Milovanovic S, Blagojevic D. The role of potassium channels and calcium in the relaxation mechanism of magnesium sulfate on the isolated rat uterus. Arch Biol Sci. 2019;71(1):5-11.

Background Placenta praevia refers to a placenta located in the lower segment of the uterus. This abnormal location predisposes the placenta to abnormal bleeding with an increased risk of premature labour. The merits of tocolytic drugs (tocolysis) to calm uterine contractions and prolong pregnancy in women with placenta praevia are uncertain. Objectives The primary objective is to determine the effects of tocolysis versus no tocolysis on pregnancy prolongation. Secondary objectives include to determining the effects of tocolysis versus no tocolysis on gestational age at delivery, maternal hospitalisations, recurrent vaginal bleeding, prematurity, admissions into neonatology, and perinatal deaths. Methods We searched MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, reference lists of pertinent articles and trial registries for randomised controlled trials comparing tocolysis to no tocolysis or placebo in patients with placenta praevia. Risk of bias and data extraction was done independently by two reviewers. We pooled data using a random-effects model. We used the GRADE system to assess the certainty of evidence for each outcome. Main results There is no significant difference in pregnancy prolongation with the use of tocolysis in cases of placenta praevia (mean difference [MD] 11.51 days; 95% CI, − 1.75, 24.76; 3 trials, 253 participants; low certainty evidence). Tocolysis has no significant effect on gestational age at delivery (MD 0.33 weeks [95% CI − 1.53, 2.19]: 2 trials, 169 participants, moderate certainty evidence), birthweight (MD 0.12 kg [95% CI − 0.26, 0.5 kg]: 2 trials, 169 participants, moderate certainty evidence), risk of premature delivery (risk ratio [RR] 1.04; 95% CI 0.56, 1.94): 2 trials, 169 participants, low certainty evidence), risk of repeat vaginal bleeding (RR 1.05 [95% CI 0.73, 1.51]: 2 trials, 169 participants, moderate certainty evidence). Tocolysis has no significant effect on the risk of perinatal death (risk difference [RD]: 0.00 [95% CI − 0.04, 0.03]: 2 trials, 169 women; low certainty evidence), number of days of maternal hospitalisation (MD 0.60 days [95% CI − 0.79, 1.99]: 1 trial, 109 women; low certainty evidence), risk of fetal admissions into neonatology (RR 1.30 [95% CI 0.80, 2.12]: 1 trial, 109 participants, low certainty evidence) and on the duration of stay in neonatology units (MD 0.70 days [95% CI − 5.26, 6.66]: 1 trial, 109 participants, low certainty evidence). Conclusion In women with symptomatic placenta praevia, there is no significant effect on pregnancy prolongation with the use of tocolysis. Tocolysis has no significant effect on other prenatal, perinatal, neonatal and maternal outcomes among women with symptomatic placenta praevia. Systematic review registration PROSPERO CRD42018091513 Electronic supplementary material The online version of this article (10.1186/s13643-018-0923-2) contains supplementary material, which is available to authorized users.

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.

BACKGROUND Premature labor is an important cause of infant death and long-term disability. This study aimed to explore the safety and effectiveness of combining the tocolytic agents atosiban and ritodrine to extend gestation. MATERIAL AND METHODS The study included 52 patients with late threatened abortion and threatened premature labor between 20⁰⸍⁷ and 33⁶⸍⁷ weeks' gestation who were administrated continuous tocolytic agents for 48 h. Patients were divided into a research group receiving ritodrine combined with atosiban, owing to having no response to ritodrine alone (n=30), and a control group receiving ritodrine alone (n=22). The mean infusion rate and duration of tocolytic administration, gestation extension, pregnancy outcomes, and adverse effects were recorded. Routine blood tests, including C-reactive protein, and cultures for leukorrhea, candida, and mycoplasma were performed before and 1 week after treatment. RESULTS Patients receiving ritodrine with atosiban had a mean gestation extension of 42.53±31.70 days. The extension of gestation of the research group was statistically shorter than that of the control group (P0.05). The fetal loss rate, newborn birth weight, and Apgar score at 1 min were similar between the 2 groups (all, P0.05). The research group had a lower incidence of palpitations than the control group (P0.05). CONCLUSIONS For patients with late threatened abortion or threatened premature labor not controlled with ritodrine alone, ritodrine combined with atosiban extends gestation and improves pregnancy outcomes. For patients with abnormal uterine contractions, routine testing for reproductive tract infection should be performed. When infection is present, anti-infective therapy should be administered.

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.

Effective tocolysis is essential after fetal myelomeningocele repair and is associated with the development of pulmonary edema. The increased uterine activity in the immediate postoperative period is commonly treated with magnesium sulfate. However, other tocolytic agents such as nitroglycerine, nifedipine, indomethacin, terbutaline, and atosiban (outside the US) have also been used to combat uterine contractility. The ideal tocolytic regimen which balances the risks and benefits of in-utero surgery has yet to be determined. In this case report, we describe a unique case of fetal myelomeningocele repair complicated by maternal pulmonary edema and increased uterine activity resistant to magnesium sulfate therapy.

Tocolytic agents, commonly used for inhibiting preterm labor, pose the risk of uterine atony, leading to postpartum hemorrhage. This study elucidated the effects of different tocolytic agents on postoperative hemorrhage among women in preterm labor undergoing Cesarean delivery (CD). Data from Taiwan National Health Insurance Research Database were analyzed. The risk (adjusted hazard ratio [aHR] and 95% confidence intervals [CI]) of postoperative hemorrhage in CD women with preterm labor diagnosis using tocolytic agents (Tocolysis group) comparing to CD women not using tocolytic agents (Control group) were determined. Impacts of different tocolytic agents in this regard were also investigated. Our data revealed that the incidence (11.7% vs 2.6%, P

Background Currently 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)]. Objective This 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. Methods Human 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. Results The 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. Conclusion A 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.

Ajumbise is a polyherbal used by women in southeast Nigeria to enhance labor, expel retained placenta and blood clots after delivery, relief postpartum and menstrual pains and promote involution of the uterus. In this study, the effect of the polyherbal on uterine smooth muscles function was evaluated to scientifically validate its traditional uterotonic use. The polyherbal so obtained was physically separated into six different plant parts and identified. Extracts were prepared from the whole material and the six plant materials. Matured female albino rats previously primed with stilboesterol (1 mg/kg body weight) for 24 h were used for the study. Uterine horn from each rat was suspended in a 30 ml organ bath containing Dejalon solution maintained at 37°C and continuously bubbled with air. Effects of administered drugs were recorded on a digital physiograph by means of an isometric force transducer. Results obtained showed that Ajumbise extract as a whole significantly caused contractions of the isolated uterine tissue when compared with basal rhythmic contractions (P Spondias mombin > Barteria fistulosa > Napoleona vogelli > Euphorbia convolvuloids. While the contractile responses elicited by the whole extract were lower than those of standard agents (oxytocin and acetylcholine). The contractile effect of Ajumbise as a whole may be the difference in activities between one uterotonic agent and five tocolytic agents. We therefore conclude that components of Ajumbise may be a potential source of uterotonic and tocolytic agents.

AIMS Magnesium sulfate has neuroprotective effects in preterm infants. Whether other antepartum treatments interfere with the neuroprotective actions is not well known. This study aims to explore the impacts of antenatal administration of Magnesium sulfate or beta-2 adrenergic agonists as tocolytic agents on the developing brain in premature infants. METHODS This is a retrospective cohort study in four tertiary perinatal centers in Japan. We collected data of pregnant women and infants born between 28 and 36 weeks for tocolytic agents, gestational age, sex, antenatal corticosteroid, fetal growth restriction, pathological chorioamnionitis, low umbilical arterial pH values (

The hepatic hydatid cyst is a major public health concern in endemic areas. It presents a therapeutic challenge when it occurs in pregnant women and exposes the mother and the fetus to a high mortality risk in the case of complications. The main complication is communication with the biliary tree, which fortunately is rare. A multi-center retrospective study was conducted spanning 7 years, from January 2009 to December 2015. In 17 departments of surgery across Tunisia, 24 cases were identified of pregnant women who were treated for complicated hepatic hydatid cyst. The data on their treatment and outcome were retrieved from the medical records. The age range of the 24 patients was 23 to 40 years, median 30 years. The median gestational age was 15 weeks (range 5 to 29 weeks).The patients complained of a variety of symptoms, mainly abdominal pain (87.5%), fever (50%), jaundice (50%) and vomiting (21%). The laboratory examination showed leukocytosis (54.2%), cholestasis (41.7%), elevated liver enzymes (12%), and positive blood culture (6%). On abdominal ultrasound (U/S), dilatation of the common bile duct was observed in 41% of the cases, dilatation of the intra-hepatic bile ducts in 50%, and hydatid material in the duct in 12% of the cases. Most of the cysts were located in the right lobe of the liver, in the hepatic dome. All of the patients were treated surgically, by one of three types of intervention: Largot intervention (18 cases), internal transfistulary drainage (4 cases), and the Perdromo procedure (2 cases). Postoperative follow-up was complication-free for 20 patients. In the remaining four, complications included: purulent retention (1 case), biliary fistula (2 cases), pneumonia (1 case). There was no maternal death. A tocolytic agent was administered to 16 women and 21 had a live full-term birth. One spontaneous miscarriage and 2 neonatal deaths occurred. Complicated hydatid cyst in pregnancy is a serious condition which can be life-threatening for the mother and the fetus. The treatment is surgical, and patient management requires close collaboration between the surgeon, the anesthesiologist and the obstetrician-gynecologist.

β2-sympathomimetics are used in obstetrics as tocolytic agents, despite a remarkable profile of side effects. Recently, the β2-sympathomimetic tocolytic drug hexoprenaline was identified as an independent risk factor for the development of infantile hemangioma (IH) in preterm infants. The aim of this study was to evaluate whether this observed effect was applicable to other β2-mimetic tocolytic agents like fenoterol. Clinical prospectively collected data of all infants born between 2001 and 2012 and admitted to the neonatal intensive care unit (NICU) at Heidelberg University Hospital and respective maternal data were merged. For the current retrospective cohort study, cases (IH) were matched to controls (no IH) at a ratio of 1:4, adjusting for birth weight, gestational age, gender and multiple gestations. Prenatal exposure to fenoterol and perinatal outcome were analyzed in the total cohort and in subgroups. N = 5070 infants were admitted to our neonatal department, out of which n = 172 infants with IH were identified and compared to n = 596 matched controls. Exposure to fenoterol was not associated with a higher rate of IH in the total matched population (OR 0.926, 95% CI 0.619–1.384) or in a subgroup of neonates

Aim of Work: To assess effect of nifedipine administration as a tocolytic agent on placental and fetal cerebral blood flow as well as on fetal cardiac function by measuring Pulsatility Index (PI) of the umbilical artery, Middle Cerebral Arteries (MCA) and Ductus Venosus (DV) twice, immediately before initial nifedipine dose and 24 hours after the therapy.Methods: Prospective, observational, analytic cohort, clinical trial involved 70 women with single viable fetus between 24-35 weeks undergoing tocolysis by nifedipine. Pulsatility Index (PI) of the umbilical artery, Middle Cerebral Arteries (MCA) and Ductus Venosus (DV) was assessed twice, immediately before initial nifedipine dose and 24 hours after the therapy.Results: The mean age of pregnant participants was (28.6± 3.1), mean Body Mass Index (BMI) was (22.2±1.3). There was no significant effect of nifedipine on Hemodynamic parameters (maternal heart rate, systolic blood pressure and diastolic blood pressure). There was no statistically significant difference of Pulsatility Index (PI) of the umbilical artery, Middle Cerebral Arteries (MCA) and Ductus Venosus (DV) before and after treatment.Conclusion: Oral nifedipine is a safe tocolytic agent on placental and fetal cerebral blood flow as well as on fetal cardiac function when used in pregnant women at risk of preterm delivery during the first 24 hours.

Relevance. Toсolytic therapy is the only method that is used in the treatment of pregnant women with preterm labor. However, the effectiveness and safety of this therapy is still a matter of debate. One of the least studied issues of this problem is the safety of therapy, which is primarily manifested by the frequency of side effects. The aim is to carry out a comparative study of the safety of the most common tocolytic agents - atosiban, nifedipine and hexoprenaline sulfate. Material and methods. The study included 173 pregnant women with threatening premature births in a period of 28 to 34 weeks. In 54 cases, tocolysis with nifedipinum, 57 with atosiban, 62 with hexoprenaline was performed. To assess the effectiveness of tocolysis, clinical and instrumental methods of control (ultrasound with cervicometry) were used. The primary outcome points were the frequency of prolongation of pregnancy at 48 h and the incidence of side effects, including those requiring the termination of tocolysis. Results. Prolongation of pregnancy at 48 h was achieved in groups of nifedipine, atosiban and hexoprenaline sulfate, respectively in 46 (85.19%), 55 (96.49%) and 53 (77.40%) pregnant. Atosiban showed significantly higher efficacy. In 8 cases of tocolysis with nifedipine and 3 - hexoprenaline, the tocolysis protocol was not performed due to intolerance of treatment. In these observations, the highest frequency of preterm labor occurred. After excluding these observations from the analysis of differences in the frequency of prolongation of pregnancy was not. The overall frequency of adverse events in the groups was 38.9, 12.3 and 82.3%, and was significantly lower in the atosiban group than nifedipine and hexoprenaline sulfate. Conclusions. The effectiveness of tocolysis is affected by the tolerability of the drugs. Atosiban showed the best of the three drug safety profile. With comparable efficacy, atosiban has proven to be a drug that, to a greater extent than nifedipine and hexoprenaline sulfate, meets the current requirements for tocolytic drugs.

The aim of the study was to compare the efficacy and safety of tocolytic agents - atosiban and hexoprenaline.Patients and methods: The study included 119 pregnant women with threatening preterm labour between 28 to 34 weeks of gestation. Sixty two pregnant received 62 tocolysis by hexoprenaline and fifty seven - atosiban. There were no differences in the clinical condition of pregnant women and features of preterm labour among groups before start of the tocolysis.The degree of effectiveness is determined by the duration of the pregnancy prolongation (48 hours, 7 days, more than 14 days).Results: 9 women of 62 that received hexoprenaline tocolysis (22,6%), and 2 – atosiban (3.5%) failed to prolong the pregnancy for more than 48 hours (p < 0,05). Additionally, 5 women of the hexoprenaline group had premature labour within the first week from the treatment start and eight within 7-14 days. In the group of women with an effective atosiban tocolysis all births took place in a range of more than 7 days from the beginning of tocolysis. Four woman in hexoprenaline group received one repeated course of therapy with this drug (without a loading dose) for 24 hours. In atosiban group full repeated course was conducted in the two cases. Full-term gestation births occurred in 14 women (22.6%) after hexoprenaline tocolysis and in 19 (33.3%) – atosiban (p > 0,05%). On average, atosiban tocolysis allowed to prolong pregnancy by 6.5 days longer than hexoprenaline (p < 0,05).Conclusion: The results of study has shown that atosiban is more effective than hexoprenaline in pregnancy prolongation for more than 48 hours in threatening preterm labor.

Preterm birth (PTB) is the leading cause of neonatal mortality and morbidity. Although the severity of neonatal outcomes is inversely correlated with gestational age, all PTBs can lead to potentially life-threatening neonatal outcomes and major lifelong health complications. Because advances in neonatal care have substantially decreased neonatal mortality, the incidence of PTB and its complications is unabatedly rising. PTB currently affects more than 10% of births worldwide, with similar numbers in developed countries. Correspondingly, improving neonatal outcome is a key objective of the World Health Organization. The recently approved (in Europe) tocolytics drug, Atosiban, used to prolong preterm gestation, has not been shown to improve neonatal outcome, nor have other tocolytic agents used in clinic. Thus, PTB remains an unmet medical need. Recent evidence shows that most, if not all, PTBs are associated with (overt or occult) inflammatory processes in gestational tissues, independent of infection. Pro- inflammatory cytokines are produced from maternal and fetal cells in response to sterile or infectious stressors. These seem to orchestrate a multi-tissue response including myometrial contractility, cervical ripening, and weakening/rupture of fetal membranes, leading to the onset of preterm labor. This integrated system might have been conserved through mammalian evolution due to increased maternal and/or fetal survival when gestation is terminated in specific settings, such as infection. Hence, inflammation may be a common pathway to the numerous aetiologies of PTB. Most importantly, recent evidence suggests that inflammation is transmitted to the fetus, thereby inducing organ injuries that may underlie the development of major neonatal diseases. Targeting inflammation prenatally instead of myometrial contraction could be a more successful and safe approach for the management of PTB, as suggested by recent animal studies. RésuméLa naissance prématurée est la principale cause de mortalité et de morbidité néonatale. Bien que la sévérité des issus néonataux soit inversement corrélée avec l’âge gestationnel à la naissance, toutes les naissances prématurées peuvent mener à des issus néonataux potentiellement mortels et à des complications avec répercussions s’échelonnant sur toute la vie. Étant donné que la mortalité néonatale a considérablement diminuée avec les récentes avancées en néonatalogie, l’incidence de la naissance prématurée et de ses complications sont en hausse. La naissance prématurée affecte présentement plus de 10% des naissances à travers le monde, avec des taux similaires dans les pays développés. Conséquemment, d’améliorer l’issu néonatal est un objectif clé de l’Organisation Mondiale de la Santé. Le tocolytique Atosiban récemment approuvé (en Europe) pour prolonger les gestations pré- maturées n’a pas démontré d’efficacité pour améliorer les issus néonataux, tout comme les autres tocolytiques utilisés en clinique, et la naissance prématurée demeure un besoin médical non-atteint. Des données récentes démontrent que la plupart, sinon toutes les naissances prématurées sont associées avec des processus inflammatoires (francs ou silencieux) dans les tissus gestationnels, indépendamment de l’infection. Les cytokines pro-inflammatoires sont produites dans les cellules maternelles et fœtales en réponse à des stresseurs stériles ou infectieux, et semblent orchestrer une réponse multi-tissulaire incluant la contractilité myométriale, la préparation cervicale, et l’affaiblissement/rupture des membranes fœtales, menant au commencement du travail préterme. Ce système intégré pourrait avoir été conservé durant l’évolution mammifère à cause d’une survie accrue de la mère et/ou du fœtus lorsque la gestation est terminée dans un contexte spécifique, comme l’infection. Donc, l’inflammation pourrait constituer une voie commune finale pour les nombreuses causes de la naissance prématurée. De façon importante, des données récentes sug- gèrent que cette inflammation est transmise au fœtus et en retour induit des dommages aux organes qui pourraient sous-tendre le développement de maladies néonatales majeures. De cibler l’inflammation en prénatal plutôt que les contractions myométriales pourrait constituer une approche sécuritaire et plus efficace, comme suggéré par de récentes études animales.

Fenoterol is a widely used anti-asthmatic and tocolytic agent, but high plasma concentrations of fenoterol may lead to severe and even fatal adverse reactions. We studied whether heritable deficiency of the liver organic cation transporter 1 (OCT1), a trait observed in 3% of Europeans and white Americans, affects fenoterol plasma concentrations and toxicity. OCT1 transported fenoterol with high affinity, and OCT1 inhibition in human hepatocytes reduced fenoterol uptake threefold. After administration of 180 µg of fenoterol to 39 healthy individuals, the OCT1-deficient individuals (zero active OCT1 alleles; n = 5) showed 1.9-fold greater systemic fenoterol exposure (P = 4.0 × 10−5) and 1.7-fold lower volume of distribution (P = 8.0 × 10−5). Correspondingly, the OCT1-deficient individuals had a 1.5-fold stronger increase in heart rate (P = 0.002), a 3.4-fold greater increase in blood glucose (P = 3.0 × 10−5), and significantly lower serum potassium levels. In conclusion, heritable OCT1 deficiency significantly increases plasma concentrations of fenoterol and may be an important factor underlying the excess mortality associated with fenoterol.

Globally, preterm birth rates are rising and have a significant impact on neonatal morbidity and mortality. Preterm birth remains difficult to prevent and a number of strategies for preterm birth prevention (progesterone, cervical pessaries, cervical cerclage, tocolytics, and antibiotics) have been identified. While some of these show more promise, there is a paucity of evidence regarding the long-term effects of these strategies on childhood outcomes. Strategies used to improve the health of babies if born preterm, such as antenatal magnesium sulfate for fetal neuroprotection and antenatal corticosteroids for fetal lung maturation, show evidence of short-term benefit but lack large-scale follow-up data of long-term childhood outcomes. Future research on preterm birth interventions should include long-term follow-up of the children, ideally with similar outcome measures to allow for future meta-analyses.

Background: Preterm birth is defined as birth at less than 37 weeks period of gestation, is the most important single determinant of adverse infant outcome in terms of both survival and quality of life. The need for tocolysis in terms of safety and efficacy is necessary to decrease perinatal mortality and morbidity in preterm labour. This study was aimed to evaluate the effectiveness of nifedipine as a tocolytic for inhibiting uterine contraction in threatened preterm labour.Methods: It was a prospective, nonblinded, single centred, randomized control trial. This study included 100 cases of preterm labour admitted in department of obstetrics and gynaecology, KIMSH, Bangalore, who satisfied the inclusion and exclusion criteria and were administered with nifedipine tocolysis.Results: 100 cases of preterm were evaluated for the prolongation of pregnancy for more than 48 hours. Prolongation of pregnancy till term was observed in 88% of the cases administered with nifedipine tocolysis. The mean gestational age in each group was 32.58±1.95 weeks. Nifedipine had very few side effects, namely tachycardia and headache and no changes in fetal heart rate.Conclusions: In this study oral nifedipine was found to be efficacious in prolongation of pregnancy for more than 48 hours with the ease of oral administration and with minimal dose tocolytic effect was achieved. It had minimal maternal and neonatal side effects and eliminate the need for intensive maternal monitoring.

Background: Tocolytic agents are used to reduce preterm deliveries. Very few studies documenting the comparison of tocolytic agents viz. nifedipine, nitroglycerin dermal patches and isoxsuprine. Other drugs are not used due to their adverse effects. Objective was to study and compare the safety efficacy of nifedipine, nitroglycerin dermal patches and isoxsuprine as tocolytic agents in suppression of preterm labour 1 year study.Methods: This was a prospective case control study was conducted for a period of 1 year. Total 90 cases selected to study were randomly distribute in to three treatment groups viz. A, B, and C nifedipine, nitroglycerin and isoxsuprine respectively. Subjects in all three groups were evaluated for maternal pulse rate, palpitation uterine contractions and fetal heart rate in order to assess efficacy of each drug under investigation.Results: There was no statistically significant difference in age of woman’s in three different groups. Among (100%) subjects, majority of the cases i.e. (27.8%) primi gravida followed by multi (72.2%). Side effects of nifedipine was less when compared to nitroglycerine dermal patch and isoxsuprine i/v/o of headache (8.9%), nausea (1.1%), vomiting (1.1%), tachycardia (3.3%), palpitation (3.3%), hypotension (1.1%). side effects were statistically significant different between the treatment groups. There was no statistically significant difference with respect to APGAR score at 1 minute and 5 minutes.Conclusions: Oral nifedipine was found to be superior and efficacious as tocolytic agent as compared to transdermal nitroglycerin and intravenous isoxsuprine.