Oral ritodrine and preterm premature rupture of membranes. [The efficacy of prophylactic antibiotic and tocolytic therapy for premature rupture of the membranes--a prospective randomized study]. A randomized, double-masked trial of prophylactic indomethacin tocolysis versus placebo in women with premature rupture of membranes. Safety and efficacy of oral nifedipine versus terbutaline injection in preterm labor. The therapeutic efficacy and cost-effectiveness of aggressive tocolysis for premature labor associated with premature rupture of the membranes. A randomized trial of ritodrine tocolysis versus expectant management in patients with premature rupture of membranes at 25 to 30 weeks of gestation.
A prospective randomized study was performed to determine whether or not oral ritodrine therapy significantly prolonged the latent period in patients with prematurely ruptured membranes. Compared with a control group of similar patients, those treated had a significantly prolonged mean latent period. In addition, 47.6% of the treatment group versus 14.2% of the control group had a latent period of more than one week. 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. Preterm premature rupture of membranes (PPROM) complicates 3% of pregnancies and frequently results in preterm birth, often within 48 hours of membrane rupture. Our objective was to determine if subjects with PPROM between 24 and 31 (6)/ (7) weeks' gestation benefit from a 48-hour course of prophylactic indomethacin tocolysis. This was a double-masked randomized controlled trial. Subjects with PPROM between 24 and 31 (6)/ (7) weeks' gestation were randomized to receive indomethacin or placebo for 48 hours in addition to corticosteroids and latency antibiotics. The primary outcome of the study was delivery within 48 hours. Maternal and neonatal outcomes were also compared. This study was concluded prematurely due to slow accrual after a total of 50 subjects were enrolled. A total of 23/25 (92%) subjects in the indomethacin group remained pregnant beyond 48 hours compared with 20/22 (90.9%) in the placebo group (relative risk, 1.01; 95% confidence interval, 0.84 to 1.21). The latency period medians and interquartile ranges were similar between the two groups [indomethacin 193 (92 to 376.5) hours versus placebo 199 (77.5 to 459) hours, P = 0.91], and no differences were noted in any maternal or neonatal secondary outcomes. This limited study demonstrates no benefit with the use of prophylactic indomethacin tocolysis for women with PPROM.
                © Thieme Medical Publishers. To compare the safety and tocolytic efficacy of oral nifedipine with intravenous terbutaline for the management of threatened preterm labor.
                Pregnant women between 24 and 36 completed weeks of single gestation with preterm labor were randomized to either oral nifedipine (n=20) or intravenous terbutaline (n=20) treatment. Nifedipine (immediate released capsule) 10 mg was crushed and swallowed, 10 mg every 20 minutes was allowed if necessary with a maximum 40 mg in the first hour. After that 20 mg nifedipine every 4 hours was given, up to 72 hours. Terbutaline was initially infused with the rate 10 g/min with an increment 5 microg/min every 10 minutes if required, until 25 microg/min was reached. Once the contractions had stopped for 2-6 hours, the patients were switched to subcutaneous injection with 0.25 mg terbutaline every 4 hours for 24 hours. The main safety outcome was the changes in maternal diastolic blood pressure from baseline and 1 hour after starting the treatment (deltaDBP(1hr)). Secondary outcomes were the efficacy to delay delivery > or =48 hours and 7 days, the adverse events and the birth outcomes.
                deltaDBP(1hr) was greater in the terbutaline group than that in the nifedipine group with no statistically significant difference. Hypotension (defined as BP < or = 90/60 mmHg) was found in one patient of the nifedipine group and two patients of the terbutaline group. Seventeen and 14 patients in the nifedipine group and 15 and 12 patients in the terbutaline group had delayed delivery > or =48 hours and 7 days, respectively. Mothers in the nifedipine group experienced fewer side effects than those in the terbutaline group. Maternal heart rate, at I hour after starting the treatment, increased significantly higher in the terbutaline group than in the nifedipine group. Birth outcomes were measured in all nifedipine group patients, but in only 16 of the terbutaline group patients. Six mothers in each group delivered after 37 weeks. Intraventricular hemorrhage (IVH) occurred in three babies (gestational aged 25, 29 and 37 weeks) born to mothers treated with terbutaline. In one baby, IVH related to trauma resulted from the delivery procedure.
                The safety and efficacy of nifedipine compares with that of terbutaline for treatment of preterm labor. We conducted a randomized trial comparing bed rest with tocolysis to determine the therapeutic efficacy, safety, and cost-effectiveness of tocolysis for the treatment of preterm labor after membrane rupture. One hundred nine women participated over a 26-month interval. Treatment groups did not differ significantly in terms of gestational age at membrane rupture, gestational age at delivery, birth weight, maternal or fetal infectious morbidity, respiratory distress syndrome, necrotizing enterocolitis, or perinatal mortality. Prolongation of intrauterine time after the onset of uterine contractions was seen in women receiving tocolysis (105.2 +/- 157 hours versus 62.1 +/- 77 hours, p = 0.06). This prolongation was not associated with a significant reduction in the total cost per surviving infant (tocolysis, $38,593 +/- $40,887 versus bed rest, $43,158 +/- $37,116; p = 0.445). The cost difference was artifactual. The number of very premature infants born (less than 28 weeks' gestation) was unequal in the two groups (12 in the bed rest group and 5 in the tocolysis group) and skewed the results. Before 28 weeks' gestation tocolysis was associated with a significant increase in intrauterine time after the onset of regular contractions (p = 0.05). However, there was no identifiable perinatal benefit garnered from the additional 5 days. After 28 weeks there were no significant differences between treatment groups in terms of intrauterine time after the onset of regular contractions and total cost per surviving infant. Because tocolysis does not improve perinatal outcome and can itself be associated with major maternal morbidity, it should be avoided after 28 weeks' gestation. Before 28 weeks' gestation tocolysis may greatly increase intrauterine time, but the benefit of this prolongation is not clear. Expectant management was compared with similar management plus ritodrine tocolysis in a randomized controlled trial in patients with premature rupture of membranes at 25 to 30 weeks of gestation. In the tocolysis group intravenously administered ritodrine was instituted at the onset of labor and then changed to the oral form if successful. Tocolysis was discontinued or not instituted after 31 weeks of gestation. Seventy-nine patients were randomized over a 4-year period, 39 in the tocolysis group and 40 in the expectant group. Twenty-three patients in the tocolysis group actually received ritodrine. No difference between the two groups was demonstrated in the interval between premature rupture of membranes and delivery or in reaching 32 weeks of gestation. No statistical difference was seen in maternal morbidity. Birth weights and gestational ages at delivery were similar between the two groups as were the incidences of neonatal morbidities caused by prematurity and infection and in the duration of neonatal hospital stays. Despite being conducted in those gestational ages in which prolongation of pregnancy might be expected to be of most benefit, no difference could be demonstrated with the addition of tocolytic therapy over expectant management alone.
Our review suggests there is insufficient evidence to support tocolytic therapy for women with PPROM, as there was an increase in maternal chorioamnionitis without significant benefits to the infant. However, studies did not consistently administer latency antibiotics and corticosteroids, both of which are now considered standard of care.