The clinical efficacy of oral tocolytic therapy. Randomized trial of antibiotics in addition to tocolytic therapy to treat preterm labor. A randomized, blinded, placebo-controlled trial of antibiotics in idiopathic preterm labor. Tocolysis for repeat external cephalic version in breech presentation at term: a randomised, double-blinded, placebo-controlled trial. [Tocolytic therapy with magnesium sulfate and terbutaline for inhibition of premature labor]. Randomised trial of educational visits to enhance use of systematic reviews in 25 obstetric units. [The efficacy of prophylactic antibiotic and tocolytic therapy for premature rupture of the membranes--a prospective randomized study]. Antibiotic treatment of preterm labor with intact membranes: a multicenter, randomized, double-blinded, placebo-controlled trial. An oxytocin receptor antagonist (atosiban) in the treatment of preterm labor: a randomized, double-blind, placebo-controlled trial with tocolytic rescue.
Our purpose was to determine whether maintenance oral tocolytic therapy after preterm labor stabilization decreases uterine activity, reduces the rate of recurrent preterm labor and subsequent preterm birth, or improves neonatal outcome.
                Women with documented idiopathic preterm labor stabilized with acute tocolytic therapy were randomized to three groups: placebo, terbutaline 5 mg, or magnesium chloride 128 mg, all given orally every 4 hours. Patients and providers were blinded to group assignment. All subjects were enrolled in a comprehensive system of preterm birth prevention that included preterm labor education, weekly clinic visits, home uterine contraction assessment, daily phone contact, and 24-hour perinatal nurse access.
                Of the 248 patients who were randomized, 39 were delivered before discharge and 4 were lost to follow-up, leaving 205 for final analysis: 68 placebo, 72 terbutaline, and 65 magnesium. The terbutaline group had significantly more side effects than the placebo group did. All groups had otherwise similar perinatal outcomes when confounding variables were controlled for. Overall, the three groups had a preterm birth rate < 37 weeks of 55.6% delivery, < 34 weeks of 15.6%, a 20.4% rate of newborn intensive care unit admission, and a mean neonatal length of stay of 6.3 days.
                Maintenance oral tocolytic therapy did not decrease uterine activity, reduce the rate of recurrent preterm labor or preterm birth, or improve perinatal outcome. Overall improvement in perinatal outcome may be achieved with a comprehensive program of preterm birth prevention without the use of maintenance oral tocolytic therapy. The objective of this study was to assess whether antibiotic therapy plus tocolysis given to women in preterm labor would prolong pregnancy compared with tocolysis alone.
                A randomized, double-blind trial of intravenous mezlocillin and oral erythromycin therapy vs. placebo was used in addition to tocolysis among women in preterm labor < or =34 weeks gestation with intact membranes. Amniocentesis was performed, and chorioamnionic membranes were examined histologically and cultured for microorganisms after delivery.
                Clinical characteristics including gestational age at enrollment, frequency of contractions, cervical Bishop's score, and white blood cell count on admission were similar in the 2 groups. Antibiotic therapy was well tolerated. No significant differences in the interval to delivery, birth weight, and neonatal outcomes were observed between the 2 groups. Women in the antibiotic group had a significantly lower incidence of postpartum infections compared with women in the placebo group. Patients with evidence of upper genital tract infection in either group had a significantly shorter interval to delivery, lower gestational age at delivery, lower mean birth weight, and increased neonatal hospitalization time.
                Lack of an antibiotic effect on the gestational age at delivery may be due to the low prevalence of upper genital tract infection among unselected women in preterm labor, to advanced preterm labor unresponsive to antibiotic therapy, or to an inability of antibiotics given alone to inhibit the cytokine response. Further work is needed to identify markers of upper genital tract infection among women in preterm labor and to evaluate other potential therapeutic interventions. Because subclinical genital tract infection may play a major role in preterm birth, the efficacy of adjunctive antibiotic therapy in combination with standard parenteral tocolysis was examined in a randomized, blinded study of patients with idiopathic preterm labor. Labor was documented by three contractions in 20 minutes, cervical dilation of 1 cm or more, and the need for parenteral tocolysis. Enrollment was restricted to patients with intact membranes and without known causes for preterm labor. One hundred three patients at 24-34 weeks' gestation were randomized to intravenous ampicillin plus oral erythromycin or corresponding placebos. Compared with the placebo group, the adjunctive antibiotic group had a similar frequency of preterm birth (38 versus 44%), time to delivery (34 versus 34 days), birth weight (2847 versus 2855 g), and episodes of recurrent labor requiring parenteral tocolysis (0.43 versus 0.49). In our population, we found no benefit to the adjunctive use of ampicillin plus erythromycin. Significant differences in genital microflora between our patients and those of other studies may explain our results. External cephalic version (ECV) reduces the incidence of breech presentation at term and caesarean section for non-cephalic births. Tocolytics may improve success rates, but are time consuming, may cause side effects and have not been proven to alter caesarean section rates. The aim of this trial was to determine whether tocolysis should be used if ECV is being re-attempted after a failed attempt.
                To determine whether tocolysis should be used if ECV is being re-attempted after a failed attempt.
                Randomised, double-blinded, placebo-controlled trial.
                UK teaching hospital.
                One hundred and twenty-four women with a breech presentation at term who had undergone an unsuccessful attempt at ECV.
                Relative risks with 95% confidence intervals for categorical variables and a t test for continuous variables. Analysis was by intention to treat.
                Incidence of cephalic presentation at delivery. Secondary outcomes were caesarean section and measures of neonatal and maternal morbidity.
                The use of tocolysis for a repeat attempt at ECV significantly increases the incidence of cephalic presentation at delivery (RR 3.21; 95% CI 1.23-8.39) and reduces the incidence of caesarean section (RR 0.33; 95% CI 0.14-0.80). The effects were most marked in multiparous women (RR for cephalic presentation at delivery 9.38; 95% CI 1.64-53.62). Maternal and neonatal morbidity remain unchanged.
                The use of tocolysis increases the success rate of repeat ECV and reduces the incidence of caesarean section. A policy of only using tocolysis where an initial attempt has failed leads to a relatively high success rate with minimum usage of tocolysis. Magnesium sulfate has been recommended as a safe and effective tocolytic agent. However has not been substantiated by randomized, controlled trials. To assess the efficacy of magnesium sulfate, we initiated prospective randomized study competing the capabilities of magnesium sulfate and terbutaline for labor inhibition. The study population consisted of 30 patients (15 patients with terbutaline and 15 patients with magnesium sulfate) between 28 and 36 weeks of gestation and in preterm labor. One patient in terbutaline group was excluded of the study because we found a severe fetal distress. The diagnosis of labor was made if, persistent uterine contractions occurred at a frequency of at last three in a team-minute period and cervical examination suggested active labor. Success was defined as postponement of delivery for at least 48 hours after initiation of therapy. Despite a trend toward increased efficacy in the terbutaline group (tocolytic Bishop grade and its success) there were no significant differences between the two treatment groups with regard to capability of delaying delivery at least 48 hours. Although there were significant differences for terbutaline regard the tocolysis time. For all these reasons, the efficacy between both groups of treatment is similar, and in a future cases, will be necessary to choose the better agent for every case to study. To evaluate the effectiveness of an educational visit to help obstetricians and midwives select and use evidence from a Cochrane database containing 600 systematic reviews.
                Randomised single blind controlled trial with obstetric units allocated to an educational visit or control group.
                25 of the 26 district general obstetric units in two former NHS regions.
                The senior obstetrician and midwife from each intervention unit participated in educational visits. Clinical practices of all staff were assessed in 4508 pregnancies.
                Single informal educational visit by a respected obstetrician including discussion of evidence based obstetrics, guidance on implementation, and donation of Cochrane database and other materials.
                Rates of perineal suturing with polyglycolic acid, ventouse delivery, prophylactic antibiotics in caesarean section, and steroids in preterm delivery, before and 9 months after visits, and concordance of guidelines with review evidence for same marker practices before and after visits.
                Rates varied greatly, but the overall baseline mean of 43% (986/2312) increased to 54% (1189/2196) 9 months later. Rates of ventouse delivery increased significantly in intervention units but not in control units; there was no difference between the two types of units in uptake of other practices. Pooling rates from all 25 units, use of antibiotics in caesarean section and use of polyglycolic acid sutures increased significantly over the period, but use of steroids in preterm delivery was unchanged. Labour ward guidelines seldom agreed with evidence at baseline; this hardly improved after visits. Educational visits cost pound860 each (at 1995 prices).
                There was considerable uptake of evidence into practice in both control and intervention units between 1994 and 1995. Our educational visits added little to this, despite the informal setting, targeting of senior staff from two disciplines, and donation of educational materials. Further work is needed to define cost effective methods to enhance the uptake of evidence from systematic reviews and to clarify leadership and roles of senior obstetric staff in implementing the evidence. A comparative study in patients with premature rupture of the membranes (PROM) from 25 to 34 weeks of gestation was carried out, prospectively. Group 1 (34 patients) was given aggressively intrauterine therapy including the administration of tocolytic agents (ritodrine and/or magnesium sulfate) and prophylactic antibiotics (AB-PC 2g/day). Group 2 (41 patients) was managed conservatively with bed rest only. At the time of admission to the study, there were no clinical signs of infection, fetal distress, or active labor in either group. All patients were delivered if the pregnancy had reached 35 weeks of gestation or later, had established labor, or developed evidence of chorioamnionitis or fetal distress. Prolongation for more than 72 hours was greater in group 1 than in group 2. There was no difference in the incidence of chorioamnionitis, postpartum endometritis, or placental infection in the groups. However, the incidence of a low Apgar score (7 < at 5 min), requiring artificial ventilation, and infection was more common in group 1. It is concluded that the use of antibiotics and tocolytics might make the management of PROM more complicated. Although an association between subclinical intrauterine infection and preterm birth is well established, there is conflicting evidence regarding the benefits of antibiotic administration to women in preterm labor with intact membranes. We attempted to determine the effect of ampicillin-amoxicillin and erythromycin treatment on prolongation of pregnancy, the rate of preterm birth, and neonatal morbidity in patients with preterm labor and intact membranes.
                A multicenter, randomized, double-blinded, placebo-controlled trial was designed and implemented by the Maternal-Fetal Medicine Units Network of the National Institute of Child Health and Human Development. Two hundred seventy-seven women with singleton pregnancies and preterm labor with intact membranes (24 to 34 weeks) were randomly allocated to receive either antibiotics or placebos.
                Of the 2373 patients screened for participation in this study in six medical centers, 277 women were enrolled (n = 133 for antibiotics group vs n = 144 for placebo group). In each study group, 60% of patients completed all the study medications. The overall prevalence of microbial invasion of the amniotic cavity was 5.8% (14/239). No significant difference between the antibiotic group and the placebo group was found in maternal outcomes, including duration of randomization-to-delivery interval, frequency of preterm delivery (< 37 weeks), frequency of preterm premature rupture of membranes, clinical chorioamnionitis, endometritis, and number of subsequent admissions for preterm labor. Similarly, no significant difference in neonatal outcomes could be detected between the two groups including respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, sepsis, and admission and duration of newborn intensive special care unit hospitalization.
                The results of this study do not support the routine use of antibiotic administration to women in preterm labor with intact membranes. This study was designed to evaluate the efficacy and safety of the oxytocin receptor antagonist atosiban in the treatment of preterm labor.
                A multicenter, double-blind, placebo-controlled trial with tocolytic rescue was designed. Five hundred thirty-one patients were randomized to receive, and 501 received, either intravenous atosiban (n = 246) or placebo (n = 255), followed by subcutaneous maintenance with the assigned agent. Standard tocolytics as rescue tocolysis were permitted after 1 hour of either placebo or atosiban if preterm labor continued. The primary end point was the time from the start of study drug to delivery or therapeutic failure. Secondary end points were the proportion of patients who remained undelivered and did not receive an alternate tocolytic at 24 hours, 48 hours, and 7 days.
                No significant difference was found in the time from start of treatment to delivery or therapeutic failure between atosiban and placebo (median, 25.6 days vs 21.0 days, respectively; P =.6). The percentages of patients remaining undelivered and not requiring an alternate tocolytic at 24 hours, 48 hours, and 7 days were significantly higher in the atosiban group than in the control group (all P < or =.008). A significant treatment-by-gestational age interaction existed for the 48-hour and 7-day end points. Atosiban was consistently superior to placebo at a gestational age of > or =28 weeks. Fourteen atosiban-treated patients and 5 placebo-treated patients were randomized at <24 weeks; the incidence of fetal-infant deaths was higher for the atosiban group at <24 weeks. Maternal-fetal adverse events were similar except for injection-site reactions, which occurred more often with atosiban.
                In this trial the treatment of patients in preterm labor with atosiban resulted in prolongation of pregnancy for up to 7 days for those at a gestational age > or =28 weeks, and this occurred with a low rate of maternal-fetal adverse effects. In addition, at a gestational age > or =28 weeks, the infant morbidity and mortality of atosiban-initiated standard care were similar to those with placebo-initiated standard care. Given that all patients in this study were eligible for tocolysis and that, in practice, nearly all patients who are eligible for a tocolytic receive one, the benefit of using atosiban is the placebo-like maternal-fetal side effect profile. These observations support the use of this oxytocin receptor antagonist in the treatment of patients in preterm labor with intact membranes. Efficacy and infant outcome data at <28 weeks are inconclusive.
There is currently insufficient information available from randomised trials to support or refute the routine or selective use of tocolytic agents to facilitate infant birth at the time of caesarean section.
[Note: The six citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]