Tocolytic treatment and childhood allergic disorders: The Japan Environment and Children’s Study

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.

Landscape of Preterm Birth Therapeutics and a Path Forward

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

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

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.

Short-Term Outcomes of Atosiban in the Treatmentof Preterm Labour at the Sultan Qaboos University Hospital, Muscat, Oman

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 <12 hours. Failure to delay delivery by ≥48 hours was significantly lower among women with normal versus abnormal cervical findings (11.1% versus 25.6%; P = 0.023). Only 9.4% of women experienced minor side-effects. Mean birth weight (2,724.55 versus 1,707.59 g; P <0.001) and Apgar scores at 5 minutes (9.66 versus 8.28; P <0.001) were significantly higher among neonates delivered at ≥48 versus <48 hours post-atosiban, whereas the rate of neonatal respiratory distress syndrome was significantly lower (18.4% versus 81.6%; P <0.001). Conclusion: Atosiban was highly effective in delaying delivery by ≥48 hours and resulted in few adverse maternal side-effects and neonatal outcomes. To the best of the authors’ knowledge, this is the first study conducted in Oman to evaluate the effectiveness of atosiban in preventing preterm labour. Keywords: Preterm Labor; Atosiban; Tocolytic Agents; Treatment Outcome; Patient Outcome Assessment; Oman.

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

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.

Successful Anesthesia Management of Postoperative Maternal Pulmonary Edema and Uterine Hyperactivity following Open Fetal Myelomeningocele Repair

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.

The Uterotonic Screening of the Root Extract of Azanza garckeana (Malvaceae) on Isolated Wistar Rat Uterine Smooth Muscles

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.

Experiences with High Success Rate of External Cephalic Version and Comparisons of Different Tocolysis for Risk-effective version based on a bayesian network meta-analysis

Background: External cephalic version (ECV) has been proved effectively in reducing the cesarean section rates, but the success rates of the procedure are uneven. Experiences of ECV with high success rate were concluded in this paper. And in order to evaluate the efficiency of the applied tocolytic agents, a corresponding bayesian-network meta-analysis was conducted.Methods: Through retrospective analysis of eighty-four single pregnant women with breech presentation near or at term who received ECV from Dalian Maternal and Child Health Care Hospital from April 2017 to November 2019, influence factors associated with the success rate of ECV were analyzed. Meanwhile, a bayesian-network meta-analysis including sixteen eligible randomized controlled trials (RCTs) about comparisons of five common tololytic agents and placebo with 3468 participants searched from Pubmed, Cochrane library and Embase databases until May 20, 2019 was conducted to identify the efficiency of ritodrine and terbutaline applied in the authors’ procedures. Results: The ECV procedures were conducted by a skilled obstetrician through strict selection of the candidates. Oral ritodrine, intravenous terbutaline in combination with epidual analgesia were applied as interventions. Success rate of ECV reached 90.48% (76/84) and the overall vaginal delivery rate is up to 88.16% (67/76). Only one patient reverted to breech presentation due to loose of the bellyband. Among the possible variables, amniotic fluid index were identified to have significantly relationship with the success rate of ECV. As the bayesian network meta-analysis proved: terbutaline, salbutamol and ritodrine played more important roles than nitroglycerine and nifedipine on the success rate of ECV. But salbutamol was found to have more common side effects than terbutaline and ritodrine.Conclusions: We conclude that factors influencing the success rate of ECV mainly include: 1. characteristics of the mothers and fetuses, 2. interventions, 3. skills of the surgeon. During ECV process, selection of patients with enough amniotic fluid and proper stature with no contraindications is essential. And a more detailed scoring standard according to the possible influence indicators of the mothers and fetuses for the feasibility of ECV should be set up in the future. Besides, application of terbutaline and ritodrine as tocolytic agents during ECV procedure were considered to be effective for increasing successful versions.