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Journal articles on the topic 'Tocolytic'

Author: Grafiati

Published: 4 June 2021

Last updated: 15 February 2022

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1

Nasreen, Sk Zinnat Ara, Safinaz Shahreen, and Shahnaz Rahman. "Recent Update on Tocolytics for the Management of Preterm Labour." Bangladesh Journal of Obstetrics & Gynaecology 27, no. 1 (October 10, 2016): 21–26. http://dx.doi.org/10.3329/bjog.v27i1.29910.

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Tocolysis is the relaxation of the pregnant uterus to postpone delivery. Tocolytics are a wide variety of agents used to suppress uterine contraction given when delivery would result in preterm birth. Preterm birth the most important single determinant of adverse outcome in terms of both survival and quality of life of baby. Although preterm birth is defined as being before 37 completed weeks most mortality and morbidity is experienced by babies born before 34 weeks. Prevention and treatment of preterm birth is important though it is not possible when labour is too advanced, cervix is dilated for more than 4 cm and prolongation of pregnancy is hazardous because of intrauterine infection, placental abruption, IUGR, lethal congenital anomaly, severe PIH, eclampsia, active vaginal bleeding or cardiac disease 1,2. The aim of this paper is to review available data about the tocolytics. The tocolytic therapy also helpful for getting time for the administration of dexamethasone/betamethasone, a glucocorticoid drug which greatly accelerates fetal lung maturity. There is no clear first line tocolytic agent 3,4. Various types of drugs are used, with varying success rates and side effects that includes calcium-channel blockers, ? adrenergic receptor agonists, magnesium sulphate, prostaglandin-synthetase inhibitors, oxytocin receptor antagonists. Their specific effects on myometrial contractility, their safety, their efficiency, doses, route of entry, and side effects profile for the mother and the fetus are presented. The main question which tocolytic should be administrated is discussed.Bangladesh J Obstet Gynaecol, 2012; Vol. 27(1) : 21-26

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2

Coler, Brahm Seymour, Oksana Shynlova, Adam Boros-Rausch, Stephen Lye, Stephen McCartney, Kelycia B. Leimert, Wendy Xu, et al. "Landscape of Preterm Birth Therapeutics and a Path Forward." Journal of Clinical Medicine 10, no. 13 (June 29, 2021): 2912. http://dx.doi.org/10.3390/jcm10132912.

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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.

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3

Fullerton, Gail M., Mairead Black, Ashalatha Shetty, and Sohinee Bhattacharya. "Atosiban in the Management of Preterm Labour." Clinical Medicine Insights: Women's Health 4 (January 2011): CMWH.S5125. http://dx.doi.org/10.4137/cmwh.s5125.

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The purpose of this review was to look at the evidence available for the use of atosiban as a tocolytic in cases of threatened preterm labour. A Royal College of Obstetricians and Gynaecologists Green Top Guideline concluded that there was no clear evidence to show a benefit to tocolysis in reducing perinatal and neonatal morbidity and mortality. Using a systematic literature search, we summarise the evidence available on the use of atosiban for the prevention of preterm birth and compare it with other commonly used tocolytic agents in terms of efficacy, patient preference and drug safety. We conclude that although atosiban appears to be the tocolytic of choice, a clear benefit of using tocolysis in all cases of threatened preterm labour remains to be justified and clinical management should be tailored according to individual needs.

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4

Ulrich, Daniela, Verena Schneider, Gerhard Pichler, Josef Haas, Valeriu Culea, Maike Joksch, Corinna Mager, et al. "Neonatal Outcome After Hexoprenaline Compared with Atosiban After Preterm Premature Rupture of Membranes." Journal of Fetal Medicine 6, no. 4 (November 25, 2019): 171–76. http://dx.doi.org/10.1007/s40556-019-00225-7.

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AbstractPreterm premature rupture of membranes (PPROM) occurs in up to 3% of all pregnancies. Only few comparative studies have investigated potential risks and benefits between different tocolytic substances in women with PPROM. The aim of this study was to compare the neonatal short term outcome after tocolysis with Atosiban or Hexoprenaline in women with PPROM. This is a retrospective observational cohort study of women with PPROM between 24 and 32 weeks of gestation comparing neonatal and maternal outcome after tocolysis with atosiban or hexoprenaline. Outcome parameters were short term neonatal outcome, maternal tocolytic efficacy, effectiveness and tolerability and neonatal neurodevelopmental long-term outcome. Continuous variables were compared using t-Test or Mann–Whitney U test, as appropriate. For categorical variables Chi-square after Pearson and Fisher exact-test were used to compare the two groups. 93 women were included into this study with 42 women receiving hexoprenaline and 51 women receiving atosiban as primary tocolytic treatment. Mean gestational age was 29 weeks in both groups at the time PPROM. No differences were found for any short term neonatal outcome parameters, tocolytic efficacy, effectiveness and tolerability and neonatal neurodevelopmental long-term outcome. Both hexoprenaline and atosiban do not affect the short and long term neonatal outcome in women with PPROM for the time of lung maturation.

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5

Gureeva, L. V., O. M. Chistyakova, E. K. Paramonova, and O. V. Radkov. "Influence of Tocolytic Therapy with Hexoprenaline on Heart Rate Variability, Lipid Spectrum and Glycemic Level in Obese Pregnant Women." Acta Biomedica Scientifica 6, no. 1 (April 10, 2021): 7–12. http://dx.doi.org/10.29413/abs.2021-6.1.1.

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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.

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6

Snegovskikh, Denis, Konstantina Svokos, Dmitri Souza, Elizabeth Renaud, Stephen R. Carr, Mark C. Kendall, and Francois I. Luks. "Successful Anesthesia Management of Postoperative Maternal Pulmonary Edema and Uterine Hyperactivity following Open Fetal Myelomeningocele Repair." Case Reports in Anesthesiology 2021 (March 5, 2021): 1–3. http://dx.doi.org/10.1155/2021/6679845.

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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.

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7

Khoiwal, Susheela, Vandana Patidar, Radha Rastogi, and Bharat Tailor. "A comparative study between nifedipine and isoxsuprine in the suppression of preterm labor pain." International Journal of Reproduction, Contraception, Obstetrics and Gynecology 9, no. 7 (June 25, 2020): 2886. http://dx.doi.org/10.18203/2320-1770.ijrcog20202727.

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Background: A prospective study was conducted to compare the effectiveness of Nifedipine and Isoxsuprine in suppression of preterm labour pain as tocolytics drug. As preterm labour pain is major contributor for perinatal morbidity and mortality. The aims of this study were to assess the effect of nifedipine and isoxsuprine in threatened preterm labour with the aim of preventing preterm birth and its sequelae.Methods: This study was conducted on 100 patients coming to Pannadhay Rajkiya Mahila Chikitsalaya, RNT Medical College, Udaipur and attending OPD and IPD with complain of uterine contractions between 28-36 weeks of gestation.Results: Nifedipine was more effective than isoxsuprine hydrochloride as tocolytic agent.Conclusions: There is high incidence of preterm labour in India which leads to neonatal morbidity and mortality. Nifedipine is a better tocolytic drug compared to isoxsuprine hydrochloride.

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8

Lamont, Ronald F., and Jan S. Jørgensen. "Safety and Efficacy of Tocolytics for the Treatment of Spontaneous Preterm Labour." Current Pharmaceutical Design 25, no. 5 (June 3, 2019): 577–92. http://dx.doi.org/10.2174/1381612825666190329124214.

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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.

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9

Ventskovskaya, I. B., V. V. Bila, and O. S. Countryside. "Premature birth (Clinical lecture)." HEALTH OF WOMAN, no. 4(130) (May 30, 2018): 9–12. http://dx.doi.org/10.15574/hw.2018.130.9.

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The article presents modern views on the pathogenesis of preterm labor, their relevance and classification. From the perspective of evidence-based medicine methods of prevention are considered. A comparison of the main tocolytic agents, their advantages and disadvantages is presented. Key words: premature birth, perinatal and infantile mortality, tocolysis, magnesium sulfate, gestational age.

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10

Khalil, Nazma, Kazi Shafiqul Halim, and Israt Jahan Ummon. "Study on Effect of Magnesium Sulfate as Tocolytic Agent." Bangladesh Medical Journal 49, no. 2 (March 23, 2020): 25–29. http://dx.doi.org/10.3329/bmj.v49i2.55816.

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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

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11

O'Donnell, James, and Leslie Iffy. "Cardiopulmonary Adverse Effects of Oral and Subcutaneous Terbutaline for Tocolysis." Journal of Pharmacy Practice 9, no. 3 (June 1996): 181–87. http://dx.doi.org/10.1177/089719009600900305.

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Are there differences between the expected or reported adverse reactions associated with terbutaline when administered orally as opposed to the parenteral routes (such as subcutaneously or intravenously)? This is a report on a pulmonary edema and subsequent death of a laboring woman who was treated with a combination of tocolytic agents in an attempt to prolong the gestation. The agents included magnesium sulfate, and subcutaneous and oral terbutaline. The intention is to alert the reader to the cardiovascular risks associated with combining tocolytic agents, and to dispel a pervasive myth that serious adverse reactions do not occur with oral tocolysis (i.e., terbutaline).1 Until recently, the package insert sheets for both manufacturers of terbutaline restricted the attribution of serious cardiovascular risks to parenteral administration only. The clinical case will be presented, followed by a review of the published literature and the reports on file in the unpublished Food and Drug Administration MedWatch database. Finally, the comparative pharmacokinetics of the oral and parenteral terbutaline is presented to help the reader understand how these adverse events are to be expected with any route of administration of the tocolytic.

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12

Gowda, Veena Bikkolli Teekappa, and Madhubala Kalidoss. "Efficacy of oral nifedipine as a tocolytic agent." International Journal of Reproduction, Contraception, Obstetrics and Gynecology 10, no. 9 (August 26, 2021): 3450. http://dx.doi.org/10.18203/2320-1770.ijrcog20213468.

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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.

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13

Macones, George A. "Tocolytic Agents." Postgraduate Obstetrics & Gynecology 25, no. 11 (June 2005): 1–5. http://dx.doi.org/10.1097/00256406-200506010-00001.

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14

Haas, David M., Thomas F. Imperiale, Page R. Kirkpatrick, Robert W. Klein, Terrell W. Zollinger, and Alan M. Golichowski. "Tocolytic Therapy." Obstetrics & Gynecology 113, no. 3 (March 2009): 585–94. http://dx.doi.org/10.1097/aog.0b013e318199924a.

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15

Serudji, Joserizal, Rika Effendy, and Hafni Bachtiar. "PERBEDAAN RERATA KADAR IL-6 SERUM MATERNAL BERDASARKAN KEBERHASILAN PEMBERIAN TOKOLITIK PADA PARTUS PREMATURUS IMMINENS." JOURNAL OBGIN EMAS 1, no. 1 (November 28, 2019): 15–21. http://dx.doi.org/10.25077/aoj.1.1.15-21.2017.

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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

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16

Liu, Jui-Ming, Chien-Yu Liu, Ren-Jun Hsu, and Fung-Wei Chang. "Preterm Labor Using Tocolysis as a Possible Risk Factor for Postpartum Depression: A 14-Year Population-Based Study in Taiwan." International Journal of Environmental Research and Public Health 18, no. 13 (July 5, 2021): 7211. http://dx.doi.org/10.3390/ijerph18137211.

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Postpartum depression (PPD) is associated with negative physical and mental health outcomes for the mother and infant. Women often experience elevated symptoms of PPD, and the incidence of PPD has increased in recent years. There were lack of studies to investigate the effects of medications during pregnancy. Herein, we focused on the most common obstetric medical therapies used in labor and determined whether the medical therapies cause mental stress in pregnant women. This 14-year retrospective population-based nationwide study was based on the National Health Insurance Research Database. Univariate and multivariate logistic regression analyses were used to evaluate unadjusted and adjusted odds ratios and 95% confidence intervals for each tocolytic and uterotonic treatments during pregnancy and common medical illnesses. In comparing the effects of tocolytic and uterotonic medications on maternal PPD, tocolysis with the injection form of ritodrine resulted in a significantly higher risk of PPD based on multivariate analysis. This study supports existing research demonstrating an association between tocolysis with ritodrine and PPD. Ritodrine treatment for preterm labor was a significant risk factor for PPD, especially the injection form. This information provides obstetricians and health policy providers to pay attention to maternal mental health outcomes among high-risk pregnant women.

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Hubinont, C., and F. Debieve. "Prevention of Preterm Labour: 2011 Update on Tocolysis." Journal of Pregnancy 2011 (2011): 1–5. http://dx.doi.org/10.1155/2011/941057.

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The aim of this paper is to review available data about drugs for preventing preterm labour. Tocolytic therapy includesβadrenergic receptor agonists, NO donors, magnesium sulphate, prostaglandin-synthase inhibitors, oxytocin receptor antagonists, calcium-channel blockers, progesterone, 17-α-hydroxyprogesterone caproate, and antibiotics. Their specific effects on myometrial contractility, their safety, their efficiency, and side effects profile for the mother and the fetus are presented. The main question of why and for what reasons tocolysis should be administrated is discussed.

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18

Baev, O. R., O. N. Vasilchenko, and A. O. Karapetyan. "Modern tocolysis and adverse effects of tocolytics." Gynecology 20, no. 2 (April 15, 2018): 46–50. http://dx.doi.org/10.26442/2079-5696_2018.2.46-50.

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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.

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19

Abitayeh, Georges, Vassilis Tsatsaris, Fran�ois Goffinet, and Dominique Cabrol. "New tocolytic agents." European Clinics in Obstetrics and Gynaecology 1, no. 1 (February 22, 2005): 29–35. http://dx.doi.org/10.1007/s11296-004-0009-7.

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20

Tsatsaris, Vassilis, Dominique Cabrol, and Bruno Carbonne. "Pharmacokinetics of Tocolytic Agents." Clinical Pharmacokinetics 43, no. 13 (2004): 833–44. http://dx.doi.org/10.2165/00003088-200443130-00001.

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21

Lam, Fung, and Pamela Gill. "β-Agonist Tocolytic Therapy." Obstetrics and Gynecology Clinics of North America 32, no. 3 (September 2005): 457–84. http://dx.doi.org/10.1016/j.ogc.2005.05.001.

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22

Zlatnik, Frank. "Applicability of Tocolytic Therapy." American Journal of Perinatology 9, no. 05/06 (September 1992): 494. http://dx.doi.org/10.1055/s-2007-999297.

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23

McCombs, Janet. "Update on Tocolytic Therapy." Annals of Pharmacotherapy 29, no. 5 (May 1995): 515–22. http://dx.doi.org/10.1177/106002809502900511.

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Objective: To review medications currently being used or investigated for the treatment of preterm labor. Adverse effects, pharmacoeconomic issues, and therapeutic controversies are included. Data Sources: A MEDLINE search, limited to English-language articles and publication years of 1989–1994, was used to identify pertinent literature. Additional references were identified from articles retrieved in the search. Study Selection: Studies were chosen on drugs that are available or whose approval is anticipated in the US: ritodrine, terbutaline, hexoprenaline, and magnesium sulfate. Several studies comparing indomethacin and nifedipine with currently used medications are also included. Oxytocin antagonists, now in Phase II clinical trials, are discussed. Studies focusing on adverse reactions were included because of serious concerns that these reactions raise. Data Extraction: Part of the controversy surrounding tocolytic agents involves the difficulty in comparing data from different trials, particularly because the criteria for diagnosis of preterm labor vary significantly. Therefore, no attempt was made to directly compare data from different sources; individual study data are presented. Data Synthesis: Most studies reviewed using the beta-agonists showed each to be comparable in effectiveness when given parenterally during early preterm labor. These drugs usually delay delivery for 24–48 hours. There is less evidence that they are consistently effective in the long-term treatment of preterm labor. The adverse effects vary somewhat, but all beta-agonists have been reported to cause pulmonary edema, which is the most serious adverse effect associated with the use of these medications to inhibit labor. Indomethacin and nifedipine may be alternative choices for tocolytic therapy, but each has different adverse reactions that also make them less than ideal agents. Oxytocin antagonists may provide more specific therapy and are currently being investigated. Conclusions: The beta-agonists are effective in delaying delivery for 24–48 hours in most patients; however, there are potential risks involved. Magnesium sulfate, prostaglandin synthetase inhibitors, calcium-channel blockers, and oxytocin antagonists may provide alternative choices for the treatment of preterm labor associated with neonatal morbidity and mortality. Each of the medications has advantages and disadvantages at different stages of gestation.

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KATZ, VERN L., and RICHARD M. FARMER. "Controversies in Tocolytic Therapy." Clinical Obstetrics and Gynecology 42, no. 4 (December 1999): 802. http://dx.doi.org/10.1097/00003081-199912000-00008.

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25

Altay, Mengühan Araz, Işık Görker, Rakhshanda Aslanova, Leyla Bozatlı, Nesrin Turan, and Petek Balkanlı Kaplan. "Association between Beta-Sympathomimetic Tocolysis and Risk of Autistic Spectrum Disorders, Behavioural and Developmental Outcome in Toddlers." Open Access Macedonian Journal of Medical Sciences 5, no. 6 (September 10, 2017): 730–35. http://dx.doi.org/10.3889/oamjms.2017.153.

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AIM: To investigate whether maternal intravenous beta-mimetic tocolytic therapy increases the risk of autistic spectrum disorders (ASD) and poorer behavioural and developmental outcomes.METHOD: Our study is a prospective case-control study among 90 children between 1.5 and three years old. Cases (n = 46) were toddlers with betamimetic tocolytic exposure; control group toddlers (n = 44) were tocolytic untreated. Treated and untreated groups were also divided into subgroups: term and preterm delivered. The gestational age of tocolytic treatment start, the dose and duration of exposure in hours were obtained from obstetric medical records. The Brief Infant-Toddler Social and Emotional Assessment (BITSEA), the Modified Checklist for Autism in Toddlers (M-CHAT) and the Denver Developmental Screening Test (DDST) tests were applied for evaluation of social, emotional problems, autism and developmental disorders.RESULTS: Term and preterm born toddlers treated tocolytically in utero didn’t demonstrate a higher risk of autistic disorders or poorer behavioural and developmental results than controls. In the preterm group, the earliest start of tocolytic treatment was correlated with toddlers lower score of the Competencies Scale (p = 0.009) and a higher score of the Problems Scale (p = 0.048). Also, we concluded that preterm membrane rupture was associated with higher ASD risk in the untreated group (p = 0.043).CONCLUSION: Exposure to betamimetics during pregnancy was not associated with an increased risk of autism, behavioural and developmental disorders.

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26

Elliott, John P., and John C. Morrison. "The Evidence Regarding Maintenance Tocolysis." Obstetrics and Gynecology International 2013 (2013): 1–11. http://dx.doi.org/10.1155/2013/708023.

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Preterm delivery is a public health issue of major proportion. More than 12% of deliveries in the United States that occur at less than 37 weeks gestation preterm labor (PTL) represents the largest single reason for preterm birth (PTB). Attempts to prevent PTB have been unsuccessful. This paper of maintenance tocolytic therapy will examine the efficacy and safety of the drugs, both oral and subcutaneous, which have been utilized for prolongation of pregnancy following successful arrest of a documented episode of acute preterm labor. The evidence for oral tocolytics as maintenance therapy as well as parenteral medications for such patients is offered. Finally, the effects in the United States of the Food and Drug Administration (FDA) action on such medications are reported.

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Lee, Seung Mi, Yoomi Park, Young Ju Kim, Han-Sung Hwang, Heewon Seo, Byung-Joo Min, Kye Hwa Lee, et al. "Identifying genetic variants associated with ritodrine-induced pulmonary edema." PLOS ONE 15, no. 11 (November 9, 2020): e0241215. http://dx.doi.org/10.1371/journal.pone.0241215.

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Introduction Ritodrine is one of the most commonly used tocolytics in preterm labor, acting as a ß2-adrenergic agonist that reduces intracellular calcium levels and prevents myometrial activation. Ritodrine infusion can result in serious maternal complications, and pulmonary edema is a particular concern among these. The cause of pulmonary edema following ritodrine treatment is multifactorial; however, the contributing genetic factors remain poorly understood. This study investigates the genetic variants associated with ritodrine-induced pulmonary edema. Methods In this case-control study, 16 patients who developed pulmonary edema during ritodrine infusion [case], and 16 pregnant women who were treated with ritodrine and did not develop pulmonary edema [control] were included. The control pregnant women were selected after matching for plurality and gestational age at the time of tocolytic use. Maternal blood was collected during admission for tocolytic treatment, and whole exome sequencing was performed with the stored blood samples. Results Gene-wise variant burden (GVB) analysis resulted in a total of 71 candidate genes by comparing the cumulative effects of multiple coding variants for 19729 protein-coding genes between the patients with pulmonary edema and the matched controls. Subsequent data analysis selected only the statistically significant and deleterious variants compatible with ritodrine-induced pulmonary edema. Two final candidate variants in CPT2 and ADRA1A were confirmed by Sanger sequencing. Conclusions We identified new potential variants in genes that play a role in cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) regulation, which supports their putative involvement in the predisposition to ritodrine-induced pulmonary edema in pregnant women.

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Mathuriya, Gayatri, and Ritu Tarware. "A comparative study of magnesium sulphate and isoxsuprine as a tocolytic in preterm labour." International Journal of Reproduction, Contraception, Obstetrics and Gynecology 10, no. 3 (February 24, 2021): 950. http://dx.doi.org/10.18203/2320-1770.ijrcog20210714.

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Background: Preterm birth is a significant health problem across the world because of associated neonatal mortality and short-and long-term morbidity in later life. The incidence in India is higher than developed countries.Methods: The present study conducted in the Department of Obstetrics and Gynaecology, MGM Medical College and M. Y. Hospital. Indore, (Madhya Pradesh). The patients selected from labour rooms.100 antenatal women of gestational age between 28 weeks to 37 weeks presenting with preterm labor, 50 in each group. Group A consisted women receiving magnesium sulphate, group B had women receiving isoxsuprine. Efficacy of the two tocolytics, prolongation of pregnancy and neonatal outcome in preterm labour was assessed.Results: Intravenous magnesium sulphate was much effective in postponement of preterm labour for at least 48 hours (74%) as compared to isoxsuprine (50%). As a cervical dilatation, effacement increased the success rate of both the drugs came down. Magnesium sulphate side effects were better monitored clinically and tolerated. Also, better neonatal outcome and lesser perinatal mortality were noticed in this group (24%) compared to isoxsuprine (54%).Conclusions: Prematurity is the one of the major risk factor determing perinatal outcome. There is no ideal tocolytic, short term prolongation till steroid coverage for lung maturit with minimum side effects and to achieve better perinatal outcome recommended. The number of nursery admissions of preterm babies with better perinatal outcome were observed with magnesium sulphate. Also, the number of nursery admissions of preterm babies were less when treated with magnesium sulphate as tocolytic (also found to have neuroprotective effects in various studies), as compared to isoxsuprine.

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Hack, Maureen, and Dinesh Shah. "Periventricular haemorrhage and tocolytic therapies." Lancet 359, no. 9302 (January 2002): 185–86. http://dx.doi.org/10.1016/s0140-6736(02)07464-0.

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Maduro, Maria Rosa. "A Potentially New Tocolytic Agent." Reproductive Sciences 25, no. 11 (October 16, 2018): 1529–30. http://dx.doi.org/10.1177/1933719118802730.

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ALLEN, STEVEN R. "Tocolytic Therapy in Preterm PROM." Clinical Obstetrics and Gynecology 41, no. 4 (December 1998): 842–48. http://dx.doi.org/10.1097/00003081-199812000-00008.

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Vermillion, Stephen T., and Charles N. Landen. "Prostaglandin inhibitors as tocolytic agents." Seminars in Perinatology 25, no. 4 (August 2001): 256–62. http://dx.doi.org/10.1053/sper.2001.27549.

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Parsons, M. T., C. A. Owens, and W. N. Spellacy. "Thermic Effects of Tocolytic Agents." Obstetric Anesthesia Digest 7, no. 3 (October 1987): 119. http://dx.doi.org/10.1097/00132582-198710000-00033.

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Spirlet, Marina de, Jean-Marc Treluyer, Sylvie Chevret, Elisabeth Rey, Michel Tournaire, Dominique Cabrol, and Gerard Pons. "Tocolytic effects of intravenous nitroglycerin." Fundamental and Clinical Pharmacology 18, no. 2 (April 2004): 207–17. http://dx.doi.org/10.1111/j.1472-8206.2003.00231.x.

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Caritis, Steve. "Adverse effects of tocolytic therapy." BJOG: An International Journal of Obstetrics & Gynaecology 112 (February 16, 2005): 74–78. http://dx.doi.org/10.1111/j.1471-0528.2005.00590.x.

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Bruner, Joseph P., T. Angel Bruner, and Albert P. Sarno. "Long-Term Intravenous Tocolytic Therapy." Military Medicine 162, no. 8 (August 1, 1997): 555–59. http://dx.doi.org/10.1093/milmed/162.8.555.

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Haas, D. M., D. M. Caldwell, P. Kirkpatrick, J. J. McIntosh, and N. J. Welton. "Tocolytic Therapy for Preterm Delivery." Obstetric Anesthesia Digest 33, no. 4 (December 2013): 193. http://dx.doi.org/10.1097/01.aoa.0000436304.63295.b4.

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BN, Seema, and Tejaswi V. Pujar. "Comparison of safety, efficacy and perinatal outcome of isoxsuprine and nifedipine in women with preterm labour." International Journal of Reproduction, Contraception, Obstetrics and Gynecology 6, no. 2 (January 31, 2017): 400. http://dx.doi.org/10.18203/2320-1770.ijrcog20164845.

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Background: Over the last 50 years, extensive research has been conducted with the objective of preventing, predicting and optimizing the outcome of patients with preterm labour. Currently, the therapeutic foundation for treating preterm labour involves the use of tocolysis. An attempt is made to study the tocolytic effect of Isoxsuprine and nifedipine in suppression of preterm labour.Methods: This is a prospective study, carried out in the department of Obstetrics and Gynaecology of S S institute of medical sciences and research centre, Davangere, over a period of 15 months- from October 2014 to January 2016.Results: 60 antenatal cases with 28-36 weeks of gestation with painful intermittent uterine contractions were considered for the study. Subjects were randomly allotted into two groups - Group A (Isoxsuprine) and Group B (Nifedipine) 30 patients each. Main outcomes include prolongation of pregnancy, maternal side effects and neonatal outcome were compared. Baseline characteristics were well matched in both study groups. Mean prolongation of pregnancy was 31.68 days in Nifedipine and 27.54 days in Isoxsuprine group which was statistically significant. Success rate with Nifedipine was found to be 96% as compared to Isoxsuprine which was 75%. Maternal side effects like hypotension (13.33%) and tachycardia (6.66%) were common in Isoxsuprine group, while facial flushing was seen in16.66% patients in Nifedipine group. Neonatal outcome was similar in the both groups.Conclusions: Nifedipine is a safe and effective tocolytic agent than Isoxsuprine with less maternal complications.

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Nakajima, Yoshiyuki, and Naoki Masaoka. "Evaluation of Creatine Kinase, Lactate Dehydrogenase, and Amylase Concentrations in Umbilical Blood of Preterm Infants after Long-Term Tocolysis." Obstetrics and Gynecology International 2014 (2014): 1–8. http://dx.doi.org/10.1155/2014/278379.

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Creatine kinase (CK), lactate dehydrogenase (LDH), and amylase levels of preterm infants following long-term tocolysis in pregnant women are limited. The objective of this study was to determine if the tocolytic therapy affects CK, LDH, and amylase levels in the umbilical blood. This study included 215 preterm infants born to women treated with and without ritodrine hydrochloride. CK, LDH, and amylase levels in the umbilical blood at delivery were determined. Infants were divided according to the ritodrine tocolysis, as follows: Group A (n=91), not exposed to ritodrine; Group B (n=44), IV ritodrine for <1 week; Group C (n=80), IV ritodrine for ≥1 week. The CK concentration in cord blood of Group C (198.8±14.2 IU/L) was significantly higher in comparison with Group A (155.0±7.3 IU/L,P<0.05). There was no significant difference in LDH and amylase levels in the three groups. The CK significantly correlated with gestational age (r=0.42,P<0.01) and birth weight (r=0.38,P<0.01). LDH and amylase levels did not change with gestational age nor birth weight. In conclusion, long-term ritodrine tocolysis leads to increased umbilical blood CK level.

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Proklova, G. F., R. A. Chilova, E. A. Sokova, R. E. Kazakov, E. V. Zhukova, K. O. Akopov, and N. S. Trifonova. "Effect of ADRB2 gene polymorphism on the efficacy and safety of tocolytic therapy with β2-adrenergic agonists in preterm birth." Russian Journal of Woman and Child Health 3, no. 3 (2020): 194–97. http://dx.doi.org/10.32364/2618-8430-2020-3-3-194-197.

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This paper reviews the effects of ADRB2 gene polymorphism on the efficacy of tocolytic therapy in preterm birth. Statistically, prematurity accounts for 70% to 75% of neonatal and infant mortality while stillbirths are 13 times more common in preterm birth compared to full-term birth. Despite modern diagnostic and treatment options to manage threatened preterm labor, its rate does not reduce. Meanwhile, pregnancy prolongation even by 48 hours is often enough to prevent newborn respiratory distress syndrome thereby improving perinatal outcomes, saving many lives of preterm babies, and preventing disability. That is why it is so important to initiate early maximally efficient and safe for a fetus tocolytic therapy aimed at prolonging the pregnancy. It was demonstrated that individual genetic variations determining intranatal phenotype exist. However, the associations between genetic characteristics and the rate of labor activity were currently demonstrated only for single genes. This is particularly true for a gene encoding β2-adrenergic receptors whose stimulation in the uterus and cervix by endogenous and exogenous agonists relaxes smooth muscles.KEYWORDS: preterm birth, perinatal outcome, tocolytic therapy, ADRB2 gene polymorphism, β2-adrenergic receptors, single nucleotide polymorphism.FOR CITATION: Proklova G.F., Chilova R.A., Sokova E.A. et al. Effect of ADRB gene polymorphism on the efficacy and safety of tocolytic therapy with β2-adrenergic agonists in preterm birth. Russian Journal of Woman and Child Health. 2020;3(3):194–197. DOI: 10.32364/2618-8430-2020-3-3-194-197.

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D., Rita, and V. Haripriya. "Comparative study of efficacy of nifedipine, nitroglycerin dermal patches and isoxsuprine as tocolytic agents in suppression of preterm labour 1-year study at navodaya medical college hospital and research centre Raichur." International Journal of Reproduction, Contraception, Obstetrics and Gynecology 10, no. 7 (June 28, 2021): 2806. http://dx.doi.org/10.18203/2320-1770.ijrcog20212672.

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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.

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Proklova, G. F., E. A. Sokova, R. E. Kazakov, R. A. Chilova, E. V. Zhukova, and K. O. Akopov. "Polymorphism of the ADRB2 gene as a predictor of preterm birth." Voprosy ginekologii, akušerstva i perinatologii 20, no. 2 (2021): 5–12. http://dx.doi.org/10.20953/1726-1678-2021-2-5-12.

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Tocolytic therapy with the use of β2-agonist hexoprenaline is used to prolong pregnancy. Polymorphisms of the ADRB2 gene can affect the efficacy and safety of this drug, including missense mutations associated with the Gly16Arg and Gln27Glu substitutions. Objective. To study the role of the ADRB2 gene polymorphism in preterm birth, as well as the efficiency and safety of tocolytic therapy with hexoprenaline. Patients and methods. 120 pregnant women were examined. The main group included 60 pregnant women who were at risk of preterm birth and to whom intravenous tocolytic therapy with hexoprenaline was performed. In the control group (n = 60), there was a woman whose pregnancy was not accompanied by the threat of preterm birth, and delivery itself was emergency and spontaneous. The identification of the Gly16Arg and Gln27Glu polymorphisms of the ADRB2 gene was carried out by the PCR-RFLP method. Results. In pregnant women with the threat of premature labor, the 16Arg allele (p = 0.028) was less common, and the 16Gly/Gly genotype (p = 0.027) of the ADRB2 gene was reliably more common. Adverse reactions to hexoprenaline occured in 53% of pregnant women: in 47%, it was tachycardia, in 6% – headache. Their incidence was not associated with the ADRB2 gene polymorphism. Conclusion. The effectiveness of hexoprenaline is lower in the carriers of genotypes indicating high or low expression of β2-adrenoreceptors. Key words: hexoprenaline, genotyping, single-nucleotide polymorphisms, preterm birth, tocolytic therapy, ADRB2

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Pisani, Richard J. "Pulmonary Edema Associated with Tocolytic Therapy." Annals of Internal Medicine 110, no. 9 (May 1, 1989): 714. http://dx.doi.org/10.7326/0003-4819-110-9-714.

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&NA;. "Potassium channel activators - potential tocolytic agents?" Inpharma Weekly &NA;, no. 920 (January 1994): 10. http://dx.doi.org/10.2165/00128413-199409200-00019.

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Wischnik, Arthur. "Risk-Benefit Assessment of Tocolytic Drugs." Drug Safety 6, no. 5 (1991): 371–80. http://dx.doi.org/10.2165/00002018-199106050-00007.

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Mahomed, Kassam, Paul Garner, and Lelia Duley. "Tocolytic magnesium sulphate and paediatric mortality." Lancet 351, no. 9098 (January 1998): 293. http://dx.doi.org/10.1016/s0140-6736(05)78237-4.

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Mittendorf, Robert, Nancy Roizen, Mark Siegler, Babak Khoshnood, and Kwang-Sun Lee. "Tocolytic magnesium sulphate and paediatric mortality." Lancet 351, no. 9098 (January 1998): 293. http://dx.doi.org/10.1016/s0140-6736(05)78238-6.

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Grether, Judith, Deborah Hirtz, Donald McNellis, Karin Nelson, and Dwight J. Rouse. "Tocolytic magnesium sulphate and paediatric mortality." Lancet 351, no. 9098 (January 1998): 292. http://dx.doi.org/10.1016/s0140-6736(05)78239-8.

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Leveno, Kenneth J. "Tocolytic magnesium sulphate and paediatric mortality." Lancet 351, no. 9098 (January 1998): 291–92. http://dx.doi.org/10.1016/s0140-6736(05)78240-4.

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Crowther, Caroline, Janet Hiller, Lex Doyle, Judith Lumley, and John Carlin. "Tocolytic magnesium sulphate and paediatric mortality." Lancet 351, no. 9098 (January 1998): 291. http://dx.doi.org/10.1016/s0140-6736(05)78241-6.

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