The clinical efficacy of oral tocolytic therapy. Progesterone for maintenance tocolytic therapy after threatened preterm labour: a randomised controlled trial. Randomized trial of antibiotics in addition to tocolytic therapy to treat preterm labor. [Tocolytic therapy with magnesium sulfate and terbutaline for inhibition of premature labor]. [The efficacy of prophylactic antibiotic and tocolytic therapy for premature rupture of the membranes--a prospective randomized study]. Single-centre randomised trial of ritodrine hydrochloride for preterm labour. [Treatment of preterm labor with ritodrine]. The effects of oral administration of progesterone for premature labor. Comparison of magnesium sulfate, terbutaline and a placebo for inhibition of preterm labor. A randomized study.
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. Women with preterm labour that is arrested with tocolytic therapy are at increased risk of recurrent preterm labour. The efficacy of maintenance tocolytic therapy after successful arrest of preterm labour remains controversial.
                The purpose of this study was to determine whether supplementation of vaginal progesterone after inhibition of preterm labour is associated with an increased latency period and a decreased recurrent of preterm labour.
                This trial was conducted in 70 women who presented with symptoms of threatened preterm labour, who after arrest of uterine activity were then randomised to progesterone therapy or no treatment. Treatment group received progesterone suppository (400 mg) daily until delivery and control group received no treatment.
                Longer mean latency until delivery (36/11 +/- 17/9 vs 24/52 +/- 27/2) (mean + standard deviation) days; respiratory distress syndrome 4 (10.8%) vs 12 (36.4%) P = 0.021; low birthweight 10 (27%) vs 17 (51.5%) P = 0.04; and birthweight (3101.54 +/- 587.9 g vs r 2609.39 +/- 662.9 g, P = 0.002), were significantly different between the two groups. No significant differences were found between recurrent preterm labour 13 (35.1%) vs 19 (57.6%), P = 0.092; admission to intensive care unit 9 (24.3%) vs 13 (39.4%), P= 0.205 ; and neonatal sepsis 2 (5.4%) vs 6 (18.2%) P = 0.136, for the progesterone and control groups, respectively.
                The use of vaginal progesterone suppository after successful parenteral tocolysis associated with a longer latency preceding delivery but failed to reduce the incidence of readmission for preterm labour. 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. 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. 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. 106 women between 24 and 33 weeks' gestation and in preterm labour, rigidly defined to include cervical dilatation plus regular uterine contractions, were randomly allocated to receive either intravenous ritodrine hydrochloride or no tocolytic treatment. Ritodrine treatment significantly delayed delivery for 24 hours or less but did not significantly modify the ultimate perinatal consequences of preterm labour. To investigate the treatment of preterm labor with the beta-adrenergic agonist ritodrine.
                126 women with preterm labor were randomly assigned to intravenous infusion of ritodrine or magnesium sulfate treatment. Using minimal effective dosage for inhibition of uterine activity, terminating therapy on time, and repeating the i.v. infusion if contraction restarted were the strategy for treatment.
                Ritodrine was significantly more effective both in the treating period for suppression of contraction (2.33 +/- 0.63 hr for initiation of inhibiting uterine activity, 9.38 +/- 3.88 days of accumulative treating period) and prolongation of gestation (4.81 +/- 2.83 wks) than that of the magnesium sulfate (P < 0.001, 0.005 and 0.01 respectively), and had a term labor of 73.44%. There was no serious cardiac and pulmonary complications in the ritodrine group.
                The present study has shown that ritodrine as a tocolytic agent is highly effective for the management of preterm labor and relative safe for mother and fetus. The potential tocolytic effect of natural progesterone administration on premature labor was investigated in a double-blind study. An oral progesterone formulation was used because its ability to increase both plasma and myometrial concentration of progesterone in pregnant women had been previously demonstrated. Furthermore, no commercial intravenous or intramuscular natural progesterone formulation is currently available in France. Fifty-seven patients in two obstetric clinics, admitted because of the risk of premature delivery, were included in the study, and uterine contractility and fetal cardiac rhythm were monitored in all of them. At random and after 30 minutes' rest, 29 women absorbed four capsules of 100 mg of progesterone each and 28 women absorbed four capsules of a placebo. Plasma progesterone levels were evaluated in all cases after 30 minutes' rest and 1 hour after absorption of the capsules. The results showed that bed rest and placebo administration decrease uterine activity in 42% of the cases and oral progesterone decreases activity in 75% to 88% of cases, depending on the initial severity of the menace of premature delivery. The difference between the effects of progesterone and of placebo is significant. The tocolytic effect of oral progesterone is not as intense or as rapid as the effect of intravenous beta-mimetics but is sufficient in 80% of cases, on the average, to stop the premature labor without any detectable side effects. This tocolytic effect of oral progesterone is related not just to an increase in plasma progesterone levels but probably to an increase in myometrial progesterone concentration. Magnesium sulfate has been recommended as a safe and effective agent for inhibiting preterm labor. Its reported adequacy as a tocolytic agent, however, has not been substantiated by randomized, controlled trials. To assess the efficacy of magnesium sulfate, we initiated a prospective, randomized study comparing the capabilities of magnesium sulfate, terbutaline and a placebo (5% dextrose in lactated Ringer's solution) for labor inhibition. The study population consisted of 54 patients between 26 and 34 weeks of gestation and in preterm labor. The diagnosis of labor was made if, following hydration, persistent uterine contractions occurred at a frequency of at least three in a ten-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 there were no significant differences between the three treatment groups with regard to capability of delaying delivery at least 48 hours. Also, there were no significant differences between the groups with regard to gestational age at delivery, birth weight and neonatal survival. The fact that delivery occurred in less than 48 hours of approximately one-half the patients under the best of circumstances emphasizes the need for more effective techniques for the inhibition of preterm labor and the need for a better understanding of the mechanisms involved in the initiation of preterm labor.
Currently, there is insufficient evidence to advocate progestational agents as a tocolytic agents for women presenting with preterm labour.