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Objectives: To analyze and compare the bioelectric and mechanical activity of the uterus in pregnant women with threatening preterm delivery treated with tocolysis. Additionally, auxiliary parameters of the bioelectric signal, as registered by electrohysterography and characteristic only for this method, were measured and analyzed. Material and methods: Forty-five women with pregnancies from 24 to 36 weeks of gestation with typical clinical symptoms of threatening preterm delivery were given tocolytic therapy. Registration and analysis of bioelectric activity with electrohysterography was performed simultaneously with registration and analysis of mechanical activity with tocography. Results: After administration of tocolytic treatment, the presence of bioelectric activity was accompanied by the lack of or minimal occurrence of mechanical activity. All parameters of contraction recorded by electrohysterography had significantly greater values than those recorded by tocography. Conclusions: Measurement of bioelectric activity is more sensitive than measurement of mechanical activity of the uterus. Elevated bioelectric activity of the uterine muscle was observed despite the use of tocolysis, a lack of symptoms of threatening preterm delivery, as well as a lack of contraction in tocography. The presence of bioelectric activity may precede the occurrence of mechanical activity of the uterus, but further research is required on larger groups of patients.

"Trials evaluating tocolytic use in preterm premature rupture of membranes (PPROM) have been small and lacked adequate power to evaluate uncommon outcomes. There still is much controversy on the benefit, length of use, route, and drug of choice among clinicians treating patients with PPROM. Most professional medical societies would propose to consider the use of tocolytics for 48 hours to allow for corticosteroid administration or to allow for maternal transfer to a higher level of care. Longer treatment regimens may lead to adverse maternal and perinatal outcomes. Insufficient data are available to make stronger and more definitive recommendations."

Preterm birth remains the major cause of death and disability among children under the age of five. In developing countries antenatal preterm birth prevention clinics are set up to provide cervical length surveillance and/or treatment modalities such as cerclage or progesterone for those women with identified risk factors such as previous cervical treatment or preterm birth. However, 85% of women have no risk factors for PTB and currently there is no biomarker to screen women early in pregnancy. Women will present unexpectedly in threatened preterm labour and we have no choice but to adopt a re-active approach to their care by using predication and preparation strategies such as fetal fibronectin, tocolytic therapy and steroids. Despite these strategies approximately 15-20% of these women will give birth preterm before 34 weeks. There is a urgent need to re-design primary, secondary and tertiary prevention strategies for spontaneous preterm labour (sPTL) in singleton pregnancies aimed at identifying and addressing key gaps in clinical practice and research.

Objective: To compare the efficacy of atosiban with conventional treatment of the threatened preterm labor. Materials and methods: All the data of pregnant women with threatened preterm labor from January 1 to December 31, 2017, who received atosiban were collected. Pregnant women with conventional treatment (including β-agonists, indomethacin, magnesium sulphate and calcium channel blockers, alone or in combination) were used as control. Results: The proportion of women not requiring an alternative tocolytic treatment within 48 h and remaining undelivered was significantly higher in atosiban treatment group (89.3%; n = 25/28) compared with conventional treatment (24.2%; n = 8/33) (P

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.

[EN] Preterm birth is the leading cause of death in newborns and the survivors are prone to health complications. Threatened preterm labor (TPL) is the most common cause of hospitalization in the second half of pregnancy. The current methods used in clinical practice to diagnose preterm labor, the Bishop score or cervical length, have high negative predictive values but not positive ones. In this work we analyzed the performance of computationally efficient classification algorithms, based on electrohysterographic recordings (EHG), such as random forest (RF), extreme learning machine (ELM) and K-nearest neighbors (KNN) for imminent labor (, This work was supported by the Spanish Ministry of Economy and Competitiveness, the European Regional Development Fund (MCIU/AEI/FEDER, UE RTI2018-094449-A-I00-AR); by the Generalitat Valenciana (AICO/2019/220).

Threatened preterm labor (TPL) is the most common cause of hospitalization in the second half of pregnancy and entails high costs for health systems. Currently, no reliable labor proximity prediction techniques are available for clinical use. Regular checks by uterine electrohysterogram (EHG) for predicting preterm labor have been widely studied. The aim of the present study was to assess the feasibility of predicting labor with a 7- and 14-day time horizon in TPL women, who may be under tocolytic treatment, using EHG and/or obstetric data. Based on 140 EHG recordings, artificial neural networks were used to develop prediction models. Non-linear EHG parameters were found to be more reliable than linear for differentiating labor in under and over 7/14 days. Using EHG and obstetric data, the &lt, 7- and &lt, 14-day labor prediction models achieved an AUC in the test group of 87.1 &plusmn, 4.3% and 76.2 &plusmn, 5.8%, respectively. These results suggest that EHG can be reliable for predicting imminent labor in TPL women, regardless of the tocolytic therapy stage. This paves the way for the development of diagnostic tools to help obstetricians make better decisions on treatments, hospital stays and admitting TPL women, and can therefore reduce costs and improve maternal and fetal wellbeing.

The efficacy of maintenance tocolytic therapy after successful arrest of preterm labor remains controversial. The purpose of this study was to evaluate the efficacy of 400 mg of daily vaginal progesterone (cyclogest) after successful parenteral tocolysis to increase latency period and improvement of neonatal outcomes in women with threatened preterm labor.In this randomized, double-blind, placebo-controlled trial, 85 participants were randomly allocated to either 400 mg daily of vaginal progesterone (Longer mean latency until delivery (53.6 ± 16.8 versus 34.5 ± 12.9) daysDaily administration of 400 mg vaginal progesterone after successful parenteral tocolysis may increase latency preceding delivery and improves cervical shortening and neonatal outcome in women with preterm labor. Further confirmatory studies are warranted.

OBJECTIVE To study the tocolytic action of nifedipine combined with sildenafil citrate (SC) and if the combination is superior to nifedipine alone in inhibiting threatened preterm labour (PTL). DESIGN Prospective randomised study. SETTING An Egyptian university hospital. POPULATION Women with threatened PTL who received either nifedipine with SC or nifedipine alone. METHODS Patients were randomly allocated to receive either (1) nifedipine 20 mg orally (stat dose), followed by 10 mg orally every 6-8 hours at the same time as vaginal administration of SC (25 mg at 8-hourly intervals) or (2) nifedipine alone. Medications were continued for 48-72 hours. MAIN OUTCOME MEASURES The percentage of women who remained undelivered during hospitalisation. RESULTS From January 2015 to November 2016, 239 women were randomised. The baseline characteristics of participants were similar. Nifedipine combined with SC was associated with more women remaining undelivered (81.8 versus 68.6%; P = 0.018) during hospitalisation. Regarding secondary outcomes, the addition of SC was also associated with fewer deliveries within 7 days of admission (9.1 versus 20.3%; P = 0.014), prolonged latency (29 versus 7 days; P = 0.002), fewer admissions to neonatal intensive care units (31.4 versus 44.1%; P = 0.043), fewer very preterm deliveries (from 28 to

As one of the main aims of obstetrics is to be able to detect imminent delivery in patients with threatened preterm labor, the techniques currently used in clinical practice have serious limitations in this respect. The electrohysterogram (EHG) has now emerged as an alternative technique, providing relevant information about labor onset when recorded in controlled checkups without administration of tocolytic drugs. The studies published to date mainly focus on EHG-burst analysis and, to a lesser extent, on whole EHG window analysis. The study described here assessed the ability of EHG signals to discriminate imminent labor ( 7 days) in women with threatened preterm labor undergoing tocolytic therapy, using both EHG-burst and whole EHG window analyses, by calculating temporal, spectral, and non-linear parameters. Only two non-linear EHG-burst parameters and four whole EHG window analysis parameters were able to distinguish the women who delivered 7 days from the others, showing that EHG can provide relevant information on the approach of labor, even in women with threatened preterm labor under the effects of tocolytic therapy. The whole EHG window outperformed the EHG-burst analysis and is seen as a step forward in the development of real-time EHG systems able to predict imminent labor in clinical praxis. Graphical abstract The ability of EHG recordings to predict imminent labor ( 7 days) was analyzed in preterm threatened patients undergoing tocolytic therapies by means of EHG-burst and whole EHG window analysis. The non-linear features were found to have better performance than the temporal and spectral parameters in separating women who delivered in less than 7 days from those who did not.

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.

Background: Preterm labor (PTL) is a serious emergency wherein robust management is imperative for achieving improved outcome. Objective: To evaluate the efficacy and safety of nifedipine alone vs nifedipine with vaginal progesterone in managing threatened PTL. Materials and Methods: This comparative study was carried out at the Pakistan Institute of Medical Sciences, Islamabad over a 2-year’ period, from September, 2013 to August, 2015. The study included 276 patients with threatened PTL. Half of them were allocated to nifedipine alone group whereas the remainder half to the additional progesterone group. In nifedipine alone group (group A), all the patients were given 20mg of rapid release nifedipine orally. If uterine contraction continued, a 10mg dose was repeated every 20 min with a maximum of 40mg within the first hour. After completing the first hour, 20mg was given every 4–6 hr for 72 hr. In the additional vaginal progesterone group (group B), following successful tocolysis with nifedipine, additional - maintenance tocolysis was ensured with vaginal progesterone 200mg daily. Results: Successful acute tocolysis was achieved with nifedipine among 86.23% patients. Mean pregnancy prolongation was 11.13 ± 5.08 days in group A while 29.73 ± 3.10 days in group B. (p0.001). Conclusion: Acute tocolytic therapy with nifedipine was successful in the majority of our patients. The additional daily use of vaginal progesterone suppositories resulted in significant prolongation of pregnancy as well as reduction in the rate of low birth weight and neonatal ICU admissions. Key words: Preterm labor, Tocolytics, Nifedipine, Progesterone.

Background: The objective of this study was to assess the maternal and neonatal outcomes in patients with preterm labor pains and also to correlate threatened abortion with preterm pains.Methods: The study conducted was a prospective observational study. 100 cases of preterm labor admitted to JK hospital, Bhopal over a period of 2 years with singleton gestation between 28 to 36+6 weeks were included.Results: Maximum preterm deliveries were in the late preterm group (80%). Correlation of preterm labor with threatened abortion was not significant (OR=1.03; p>0.05). 42% cases delivered vaginally and 58% by LSCS. Prolongation of pregnancy after tocolytic therapy was upto 12 hours in 35% cases, 12-24 hours in 40% cases and >24 hours in only 15% cases. The most commonly encountered neonatal complication was RDS, 37%, out of which 9% required resuscitation at birth and 8% required ventilator support followed by jaundice in 23%, sepsis in 3% cases and NEC in 4% cases. The association between gestational age and requirement of resuscitation at birth (X2=19.9; p=0.00), need of ventilator (X2=12.6; p=0.002) and neonatal RDS (X2=6.9; p=0.031) was found to be significant.Conclusions: Preterm births are major obstetric problem that have an extensive impact on neonatal morbidity and mortality.

Introduction: Tocolytics may cause changes in fetal heart rate (HR) pattern, while fetal heart rate variability (HRV) is an important marker of fetal well-being. We aim to systematically review the literature on how tocolytic drugs affect fetal HRV.Materials and methods: We searched CENTRAL, PubMed and EMBASE up to June 2016. Studies published in English, using computerized or visual analysis to describe the effect of tocolytics on HRV in human fetuses were included. Studies describing tocolytics during labor, external cephalic version, pre-eclampsia and infection were excluded. Eventually, we included six studies, describing 169 pregnant women.Results: Nifedipine, atosiban and indomethacin administration show no clinically important effect on fetal HRV. Following administration of magnesium sulfate decreased variability and cases of bradycardia are described. Fenoterol administration results in a slight increase in fetal HR with no changes in variability. After ritodrine administration increased fetal HR and decreased variability is seen. The effect of co-administration of corticosteroids should be taken into account.Conclusion: In order to prevent iatrogenic preterm labor, the effects of tocolytic drugs on fetal HRV should be taken into account when monitoring these fetuses.Keywords: Tocolytic therapy, calcium channel blocker, oxytocin receptor antagonist, prostaglandin antagonist, beta-adrenergic agonist, fetal heart rate variability

Background: Currently preterm labour is one of the most challenging problem faced by both obstetricians and perinatologists, this episode in the course of woman’s pregnancy takes a heavy tool for perinatal mortality which accounts for approximately 50-75%. The incidence of preterm labour is estimated to be 5-10% of all pregnancies.Methods: It was a prospective randomize control trail over a period of 3 year at department of obstetrics and gynecology, tertiary care hospital Pune, Maharashtra, India. Total 100 subjects were randomized into two groups with group one receiving vaginal micronized progesterone and group two control group receiving only tocolytics and steroids. Subsequently authors compared the safety and efficacy of vaginal micronized progesterone versus placebo as a maintenance therapy in preventing preterm labour.Results: This analysis showed that women who randomized to progesterone prophylaxis had a significantly increase in duration of pregnancy. The mean of birthweight in Group A and Group B was 2963±36 gm and 2567±49 gm and respectively which confirmed the positive effects of progesterone on increasing infants’ weights at birth.Conclusions: Authors concluded that progesterone therapy had acceptable efficacy in the prevention of preterm labor in terms of prolongation of delivery and by increasing gestational age at delivery.

[EN] Although research studies using electrohysterography on women without tocolytic therapy have shown its potential for preterm birth diagnosis, tocolytics are usually administered in emergency rooms at the first sign of threatened preterm labor (TPL). Information on the uterine response during tocolytic treatment could prove useful for the development of tools able to predict true preterm deliveries under normal clinical conditions. The aim of this study was thus to analyze the effects of Atosiban on Electrohysterogram (EHG) parameters and to compare its effects on women who delivered preterm (WDP) and at term (WDT). Electrohysterograms recorded in different Atosiban therapy stages (before, during and after drug administration) on 40 WDT and 27 WDP were analyzed by computing linear, and non-linear EHG parameters. Results reveal that Atosiban does not greatly affect the EHG signal amplitude, but does modify its spectral content and reduces the energy associated with the fast wave high component in both WDP and WDT, with a faster response in the latter. EHG signal complexity remained constant in WDT, while it increased in WDP until it reached similar values to WDT during Atosiban treatment. The spectral and complexity parameters were able to separate (p < 0.05) WDT and WDP prior to and during tocolytic treatment and before and after treatment, respectively. The results pave the way for developing better and more reliable medical decision support systems based on EHG for preterm delivery prediction in TPL women in clinical scenarios., This work received financial support from the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (DPI2015-68397-R), VLC/Campus (UPV-FE-2018-B03) and by Conselleria de Educación, Investigación, Cultura y Deporte, Generalitat Valenciana (GV/2018/104).

This chapter discusses preterm labor. It lists the risk factors and various tocolytic therapies. It discusses specific tocolytic drugs and contraindications to these drugs.

The article provides a comparative evaluation of different methods of treatment of preterm labor. It analyzed the effectiveness of therapy, and outcomes of 45 pregnant women who are in therapy as preterm labor carried an acute intravenous tocolysis, and then move on to maintenance tocolysis in combination with the intravaginal application of micronized natural progesterone. A control group comprised 42 patients, who spend only acute tocolysis. We believe that the preferred replacement of pregnant women with acute tocolysis to tocolytic therapy to supportive tablet form while using micronized form of progesterone.

Aim: To elucidate factors associated with a poor neonatal prognosis in preterm placental abruption. Methods: A multicenter retrospective study was conducted. A total of 247 cases with preterm placental abruption during 2009, derived from an electronic database constructed by the Japan Society of Obstetrics and Gynecology, were investigated as the subjects of this study, and were divided into three groups: very preterm (VPT, n=66) was delivered at 28 to 31 gestational weeks, preterm (n=56) was at 32 and 33 weeks, and late preterm (LPT, n=125) was at 34 to 36 weeks. Risk factors, clinical course, and neonatal/infantile outcomes were compared. Poor neonatal outcome was defined as stillbirth, or neonatal and infantile death, or cases with neurological disability at 2 years of age. Results: The number of subjects who received tocolytic therapy was significantly higher in the VPT group as compared with the LPT group. It was higher in the VPT group even after excluding the 57 stillbirths. Multiple logistic regression analysis revealed that poor prognostic factors were umbilical arterial pH (Δ=0.1) (0.17 [0.069-0.417], p

In the United States, the generally accepted indication for tocolytic therapy centers on suppression of preterm labor. This may be in the form of preventative therapy with progesterone in women with prior spontaneous preterm birth or as an acute intervention to suppress established uterine contractions associated with cervical change occurring at less than 37 weeks gestation. This article seeks to apply this perspective to tocolytic therapy. Here, we provide a review of current tocolytic options and what the last decade of discovery has revealed about the regulation of myometrial excitability and quiescence. Moving forward, we must incorporate the emerging molecular data that is amassing in order to develop novel and effective tocolytic therapeutic options to prevent preterm labor and spontaneous preterm birth (sPTB).

ispartof: INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA vol:34 pages:113-114 ispartof: location:Netherlands status: published

This article touches upon the most important problem of obstetrics and neonatology - preterm birth. This article provides an analysis of the literature on the pathogenesis, etiology preterm birth, the role of modern therapy used in the treatment of preterm birth. Efficacy and safety this therapy for the mother and fetus. We analyzed various modes of tocolytic therapy, which used in modern obstetrics now. We provided data of foreign studies on the subject.

Aim: Our aim is to evaluate the effect of nifedipine on fetoplacental hemodynamic parameters. Methods: A retrospective study was conducted at a tertiary center with 30 patients for whom nifedipine treatment was used as a tocolytic therapy for preterm labor. Initiation of this treatment was at 31.6±2.5 weeks of gestation. We combined the pulse Doppler imaging parameters with grayscale imaging via the Bernoulli theorem, which is called the “continuity equation”, to get the fetoplacental perfusion (FPP). Evaluated parameters were the resistance index (RI), the pulsatility index (PI), systole/diastole ratios (S/D), the velocity-time integral of the umbilical artery (VTI), the radius of the umbilical artery, the peak systolic velocity and the mean pressure gradient in the umbilical artery. From these parameters, the FPP was acquired. Results: We found that the RI, the PI and the S/D ratio did not change after treatment with nifedipine. The mean pressure gradient, the VTI and the peak systolic velocity increased after treatment with nifedipine. Nifedipine increases FPP from 166±73.81 beat.cm3/min to 220±83.3 beat.cm3/min. Discussion: Although nifedipine had no effect on the PI, the RI or the S/D, it increased the mean pressure gradient, the VTI and FPP.

Ritodrine hydrochloride has been widely used for tocolysis, although serious side-effects have been reported. We report two cases of agranulocytosis induced by ritodrine hydrochloride, which probably occurred by different mechanisms. Two patients were hospitalized because of preterm labor and were given intravenous ritodrine hydrochloride. The nadir of neutrocytes was 199/mm(3) and 13/mm(3) in the two cases, respectively. The total dose of ritodrine hydrochloride was calculated to be 7800 mg for 26 days and 2500 mg for 22 days, respectively. The total doses were heavier and administration duration was longer in Case 1, which suggested a toxic mechanism of agranulocytosis, while in Case 2, they were smaller and shorter, suggesting an immunological mechanism. For patients receiving ritodrine hydrochloride, the white blood cell count should be checked frequently regardless of the duration of therapy and a drug lymphocyte stimulation test should be performed.

Organized uterine contractions, including those necessary for parturition, are dependent on calcium entry through voltage-gated calcium channels in myometrial smooth muscle cells. Recent evidence suggests that small-conductance Ca2+-activated potassium channels (KCa2), specifically isoforms KCa2.2 and 2.3, may control these contractions through negative feedback regulation of Ca2+ entry. We tested whether selective pharmacologic activation of KCa2.2/2.3 channels might depress uterine contractions, providing a new strategy for preterm labor intervention. Western blot analysis and immunofluorescence microscopy revealed expression of both KCa2.2 and KCa2.3 in the myometrium of nonpregnant (NP) and pregnant (gestation day 10 and 16; D10 and D16, respectively) mice. Spontaneous phasic contractions of isolated NP, D10, and D16 uterine strips were all suppressed by the KCa2.2/2.3-selective activator CyPPA in a concentration-dependent manner. This effect was antagonized by the selective KCa2 inhibitor apamin. Whereas CyPPA sensitivity was reduced in D10 and D16 versus NP strips (pIC50 5.33 ± 0.09, 4.64 ± 0.03, 4.72 ± 0.10, respectively), all contractions were abolished between 30 and 60 μM. Blunted contractions were associated with CyPPA depression of spontaneous Ca2+ events in myometrial smooth muscle bundles. Augmentation of uterine contractions with oxytocin or prostaglandin F2α did not reduce CyPPA sensitivity or efficacy. Finally, in an RU486-induced preterm labor model, CyPPA significantly delayed time to delivery by 3.4 h and caused a 2.5-fold increase in pup retention. These data indicate that pharmacologic stimulation of myometrial KCa2.2/2.3 channels effectively suppresses Ca2+-mediated uterine contractions and delays preterm birth in mice, supporting the potential utility of this approach in tocolytic therapies.

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.

OBJECTIVE: For the first line tocolysis, calcium channel blockers (CCB)--oral nifedipine (Adalate®) or intravenous nicardipine (Loxen®)--are frequently used in France. No study compared nifedipine and nicardipine in management of threatened preterm delivery. From data of a French observational study, we compared factors associated with the use of nifedipine and nicardipine. Efficacy and tolerance of the two treatments were also compared. METHODS: It was a secondary analysis of EVAPRIMA study, a practice survey describing management of threatened preterm delivery in 107 French maternity units. Only women who received calcium channel blockers in their first line tocolytic therapy were included. We studied obstetrical factors associated with the choice of nifedipine or nicardipine. We also analyzed factors associated with a delivery within seven days following admission using univariate and multivariate analysis. Adverse secondary effects were compared between women who received nifedipine or nicardipine. RESULTS: Three hundred and four women received calcium channel blockers for their first line tocolytic therapy, in 73 maternity units: 93 (30.6%) women received oral nifedipine and 211 (69.4%) intravenous nicardipine. The same CCB was always prescribed in 69 maternity units. Admission after in utero transfer was less frequent among women who received nifedipine (6.5% versus 17.1%, P=0.01). Premature rupture of the membranes was also less frequent among women who received nifedipine (4.3% versus 13.7%, P=0.02), in comparison with women who received nicardipine. Median duration between admission for threatened preterm labor and delivery was longer when nifedipine was used (44 days versus 36 days, P=0.04). After adjustment on obstetrical factors, the risk to have a delivery within 7 days following admission was not significantly different between nifedipine and nicardipine groups (adjusted OR=0.5 [0.2-1.2]). Among women who received nifedipine only two cases (2.1%) of adverse event were reported with only one case needing a switch of treatment. Thirteen (6.2%) cases of adverse event were reported among women who received nicardipine (P=0.16); in three cases it motivated a switch. However, due to bias and limits inherent in such studies, our results should be interpreted cautiously. CONCLUSION: Nicardipine is the first choice for French obstetricians in management of severe threatened preterm delivery. However, intravenous nicardipine does not increase gestational duration in comparison with oral nifedipine.

Transport of women in preterm labour in Western Australia is conducted in small fixed wing aircraft over distances up to 2,000 km (1,200 miles). In recent years β-sympathomimetic inhibition of uterine activity has been employed to reduce the risk of delivery during transfer. This study reports the outcome of routine use of this therapy in which at times classical contraindications have not been observed. During 1983 and 1984, 99 consecutive maternal aerial transfers for preterm labour using β-sympathomimetic drugs by infusion resulted in only 1 case of pulmonary oedema and 2 of maternal hyperglycaemia. There were no deliveries during the flights. The results of this study suggest β-sympathomimetic inhibition of uterine activity for women in preterm labour is safe and efficacious therapy for long distance aeromedical evacuation in small aircraft.

Tocolytic treatment with fenoterol and additional administration of betamethasone and acetyl salicylic acid to a 19-year-old girl caused irreversible and finally fatal pulmonary changes. The clinical course in this and that of other published cases indicates a causal relationship between the tocolytic treatment and the onset of pulmonary oedema. The pulmonary arterial pressures in this patient, the poor therapeutic response and the shock-lung picture without corresponding myocardial changes suggest a non-cardiogenic cause of pulmonary oedema. Any of the three drugs administered could have been responsible.

Objective: The object of this study was to determine the effects of maternal tocolysis with glycerol trinitrate (GTN) patches on the neurodevelopment of infants. Study design: This was a randomized, multicenter, controlled trial comparing the efficacy of GTN patches with standard beta 2 agonist as tocolytic therapy. The previously reported outcomes of this study indicated no difference in neonatal mortality or morbidity to hospital discharge. One hundred fifty-six surviving infants from 2 Australian centers were psychometrically assessed using the Griffiths Mental development Scales (revised) at 18 months of age. Results: There was no difference in psychometric performance between those infants enrolled in either the GTN (81 infants) or beta 2 agonist (75 infants) arm of the study. Conclusion: This randomized trial supports no significant difference between GTN patches in comparison with standard beta 2 agonist for tocolytic therapy. The results underscore the association between premature labor and adverse infant outcomes. (c) 2006 Mosby, Inc. All rights reserved.

With the advent of preterm birth prevention programs, increasing numbers of patients are now considered candidates for tocolytic management. Tocolysis' chief benefit is significantly prolonging pregnancy in the hope of avoiding or ameliorating the sequelae of preterm delivery. Three principal indications dominate the use of tocolysis in the treatment of preterm labor: (1) prophylaxis, (2) acute therapy, and (3) maintenance.

The rationale for using tocolytics in preterm labour is to enable transfer of the mother to a tertiary centre and to prolong pregnancy sufficiently so that glucocorticoids can be administered to the mother. There is little question that these short term objectives can be achieved with contemporary tocolytics. Whether tocolytics can maintain pregnancy for sufficient periods to enable in utero maturation to occur remains an unresolved question. When a decision is made to use tocolytics, the clinician is faced with a multitude of choices with side effects, efficacy and ease of administration generally being the most important considerations. Placebo-controlled studies suggest that the beta-agonists, prostaglandin inhibitors and atosiban are effective in prolonging pregnancy for 24-48 hours. Of these three agents, atosiban has the best safety profile. There are no placebo-controlled studies with calcium channel blockers or nitric oxide donors. However, because of their ease of use and efficacy compared with the beta-agonists, calcium channel blockers are widely used. Calcium channel blockers appear to have a better safety profile than the beta-agonists, but there are still significant cardiovascular side effects associated with their use. Indomethacin, although proven to be efficacious, has a safety profile that limits its utility for other than short courses. Magnesium sulphate is the most commonly used tocolytic in the United States, despite a lack of evidence for its efficacy. Although magnesium sulphate appears to have a good safety profile, serious side effects have been reported with its use. The choice of tocolytics is commonly based on personal preference. Whichever tocolytic is chosen, the fundamental parturitional process is not reversed by contemporary treatment, rather a reduction in uterine response to a stimulant; thus, the expectations of tocolytic treatment need to be reconsidered.

The purpose of this study was to evaluate the effect of acute tocolysis on severely pathological cardiotocographic (CTG) readings during the first stage of labor. Seventy-three consecutive parturients with full-term pregnancy were treated by acute tocolysis with a beta-mimetic agent after recognition of severe CTG abnormality in the first stage of labor. The main outcome measures were normalization or persistence of the CTG pattern after tocolysis. Risk factors with regard to CTG effect of tocolysis were also evaluated. In 67% of cases the CTG pattern normalized at a mean of 4 minutes after the beginning of intravenous tocolysis. No characteristic feature of the parturient, labor course, CTG abnormality, or the parameters of uterine contractive activity was found to be a predictive factor with regard to the CTG effect of tocolysis. No adverse effects of tocolytic therapy were found. Tocolysis with a beta-mimetic agent is an effective method to normalize the CTG pattern during the first stage of labor, even in cases without uterine hypertonicity.

The ultimate goal of treating preterm labor is to prolong the pregnancy long enough to decrease the incidence of neonatal mortality and morbidity associated with prematurity, while minimizing maternal and fetal risks. There are many controversies in treating preterm labor. Much of this controversy stems from the difficulty in establishing efficacy and safety of interventions and uncertainty of the diagnosis of preterm labor. This article outlines conventional measures and tocolytic therapy directed at prolonging the pregnancy. A review of the effect of tocolytic agents, administration, side effects, and nursing interventions is included. Key words: preterm labor treatment

In addition to questions raised about the efficacy of many tocolytics, appropriate concern has been voiced about the safety of these potent drugs. Although some degree of risk for adverse effects with drugs promising a strong therapeutic effect can be accepted, caution needs to be exercised when benefits are marginal or unproven. Unfortunately, some of the tocolytics, most notably the betamimetics and magnesium sulfate, have been found to have considerable potential for adverse maternal cardiovascular and respiratory effects. Although less clearly established, the use of indomethacin appears to be associated with increased fetal and neonatal risks. Concerning magnesium sulfate, in addition to the well-known maternal effects, the accumulating evidence showing an increased frequency of adverse outcomes in the fetus and neonate has led to the recommendations to abandon its use entirely as a tocolytic. Given the limitations of our current state of knowledge, nifedipine would appear to be among the more efficacious and safer tocolytics available to use when properly indicated.

Summary Preterm labour (PTL) is a major contributor to preterm delivery (PTD) but delivery is often not preventable by current therapies. We conducted this study to determine the proportion of women with PTL who were and who were not candidates for tocolytic therapy. The cohort comprised residents of Olmsted County, Minnesota who delivered at >20 weeks’ gestation in 1985–94 and who experienced PTL. Medical records were abstracted to identify episodes of PTL, its treatment and outcome. We developed an algorithm that accounted for gestation at delivery and pregnancy complications to determine the proportion of pregnancies complicated by PTL that were candidates for tocolytic therapy. Of 651 pregnancies complicated by PTL, a 50% probability sample, stratified by delivery year, were selected and abstracted. The cumulative incidence of PTL ranged from 3.6 to 6.4 per 100 deliveries of live or stillborn infants. Tocolysis was not contraindicated for 49.4% of all women with PTL and for a third of women with only one PTL episode. Delivery was delayed to >35 weeks in 53.8% of candidates for tocolysis. Only an additional 11.7% of women with one or more PTL episodes could have had their PTD delayed beyond 35 weeks if a perfect tocolytic therapy had been available. Many pregnancies complicated by PTL occurred at ≥35 weeks or involved maternal or obstetric factors that contraindicated tocolytic medications. The maximum incremental benefit that could be expected of a new safe and efficacious tocolytic therapy would be to reduce current PTD rates resulting from PTL by about 12%.

A variety of fetal disorders are now accessible to treatment in utero due to the rapid advances in diagnostic and therapeutic possibilities. Different surgical techniques, such as open or endoscopic fetal procedures, require special anaesthesiological management because the anaesthesiologist has to care for two patients—the mother and the fetus. This chapter describes currently performed fetal interventions and outlines anaesthesiological features. We describe the pros and cons of regional and general anaesthesia for this highly specialized surgical field, as well as different treatment modalities in post-operative pain and tocolytic therapy. Ethical issues arise because fetal surgery is a relatively new sector and deals with unborn life. Although, currently, only a few centres carry out fetal surgical interventions, this medical field is expanding. This chapter offers some support to the anaesthesiologists who have to care for these patients in the future.

This study was performed prospectively on 144 randomly selected women carrying singleton uncomplicated pregnancies of 20 to 36 gestational weeks and 60 women with preterm labour matched for gestational age to determine the predictive value of transvaginal cervical measurements for evaluation of the response to tocolytic therapy. Cervical length and width and width of the cervical canal were measured and funnelling of internal os of the cervical canal was evaluated by transvaginal ultrasonography in each case. These measurements did not reveal any change depending on the gestational age in the control group. The mean values for cervical length and width, and width of cervical canal were 45.05+/-6.52 mm, 38.75+/-4.11 mm, 7.01+/-2.76 mm, respectively. Mean cervical length+/-standard deviations of the control group were used as cut-off values for the prediction of preterm delivery in the preterm labour group. When the cut-off value of the cervical length was accepted as 38.53 mm (-1 SD of the control group), the sensitivity, specificity, positive and negative predictive values for prediction of preterm delivery were 80.9%, 72.2%, 87.2%, 61.9%, respectively; whereas when this cut-off value was used in combination with the funnelling of the internal cervical os, the sensitivity and negative predictive value decreased to 40.5% and 41.9%, respectively; but the positive predictive value and specificity became 100.0% and 100.0%, respectively.

Preterm birth accounts for the majority of neonatal morbidity and mortality not associated with congenital anomalies. Its incidence has remained relatively unchanged over the past 15 to 20 years. Tocolytic therapy has been shown to be ineffective in the prevention of preterm labor but can delay delivery by approximately 48 hours. Four major drug groups are currently available. The article reviews each drug group, including mechanism of action, pharmacology, side effects, efficacy, and nursing implications.

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.

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

Preterm birth continues to be a global public health burden. Most neonatal deaths occur as a result of prematurity, and among those who survive, a substantial proportion develop disability during childhood. Preterm birth usually follows spontaneous preterm labour, preterm prelabour rupture of membranes, or iatrogenic preterm delivery. Short-term tocolysis is generally indicated to arrest labour in order for corticosteroids to be given, or for the woman to be transferred to a higher level of neonatal care. Hexoprenaline was the cornerstone of such therapy in South Africa for many years. A wide variety of tocolytic drugs have been in clinical use around the world, yet the evidence that they confer benefit to the infant remains open to debate. Some tocolytic drugs may possibly be harmful. In this review the evidence for efficacy and safety of the various commonly used tocolytic drugs will be scrutinized, in particular their effect on infant health and maternal safety. Data on newer agents will also be reviewed, and future directions for tocolytic therapy will be explored. Keywords: Hexoprenaline; Pregnancy; Preterm labour; Tocolysis

The aim of this study was retrospective evaluation of progesterone efficacy in pregnant patients with preterm uterine contractions.190 women hospitalized at 1st Department of Obstetrics and Gynecology, Medical University of Warsaw, in 2007-2010, with symptoms of threatened preterm labor were enrolled in the study. 94 women were treated with tocolytics and steroids (control group), while 96 women received additionally 200 mg of progesterone vaginally until delivery or 34th weeks of gestation (progesterone group).The mean gestational age at admission was 27 weeks in progesterone group and 28 weeks in control group. Cervical length was similar in both groups. There were no significant differences in week of delivery between groups, but the progesterone group had significant increase in prolongation of pregnancy (7.6 versus 6.3 weeks, p = 0.039). Vaginal progesterone was associated with reduction of delivery before 34 weeks (9.8% versus 35.3%; p = 0.002) and neonatal birth weight1500 g (3.2% versus 20.6%; p = 0.011) only in patients presenting with uterine contractions after 27 weeks.The administration of vaginal progesterone after tocolysis in threatened preterm labor is associated with prolongation of pregnancy. The reduction of deliveries before 34 weeks was observed in patients presenting with contractions after 27 weeks gestation.