Terbutaline pump maintenance therapy for prevention of preterm delivery: a double-blind trial. A placebo-controlled randomized trial of the terbutaline pump for prevention of preterm delivery. Oral terbutaline after parenteral tocolysis: a randomized, double-blind, placebo-controlled trial. Global report on preterm birth and stillbirth (3 of 7): evidence for effectiveness of interventions. The clinical efficacy of oral tocolytic therapy. Efficacy and safety of nifedipine versus magnesium sulfate in the management of preterm labor: a randomized study. Oral terbutaline in the outpatient management of preterm labor. Randomized trial of antibiotics in addition to tocolytic therapy to treat preterm labor. Calcium supplementation in nulliparous women for the prevention of pregnancy-induced hypertension, preeclampsia and preterm birth: an Australian randomized trial. FRACOG and the ACT Study Group. Safety and efficacy of oral nifedipine versus terbutaline injection in preterm labor. Management options in women with preterm uterine contractions: a randomized clinical trial.
This study's aim was to determine whether maintenance therapy with terbutaline administered by pump prolongs gestation in women after treatment with intravenous magnesium sulfate tocolysis for suspected preterm labor.
                Consenting women with a singleton gestation and intact membranes who had uterine contractions and >1 cm cervical dilation, 80% effacement, or progressive cervical change and whose contractions were successfully arrested with intravenous magnesium were randomly assigned to receive either terbutaline or normal saline solution placebo by subcutaneous infusion pump. Pump therapy was administered with a standardized protocol. Pump therapy was discontinued and parenteral magnesium was resumed if recurrent preterm labor developed while women were on the therapeutic regimen at <34 weeks' gestation and no contraindication for tocolysis existed. If recurrent labor was arrested, pump therapy was restarted according to the original treatment group. A sample size of 48 women was required to detect a 2-week intergroup difference in mean time to delivery. Analyses were based on intent to treat.
                Fifty-two women received terbutaline (n = 24) or placebo (n = 28). At random assignment the groups were similar with respect to age, race, parity, previous preterm delivery, gestational age, and cervical examination. Overall there was a 1-day difference in mean time to delivery between the groups (terbutaline 29 +/- 22 days and placebo 28 +/- 23 days, P = .78). There were no differences in the rates of preterm delivery at <34 and <37 weeks' gestation. Neonatal outcomes were similar.
                Maintenance terbutaline therapy administered by pump does not prolong gestation in women successfully treated for suspected preterm labor. To determine the efficacy of the terbutaline pump for the prevention of preterm delivery, patients in preterm labor defined by progressive cervical change underwent intravenous magnesium sulfate tocolysis (with or without oral indomethacin, as necessary), and once labor was arrested, were randomized to one of three treatment arms: terbutaline by pump, saline by pump (blinded), or oral terbutaline. If recurrent preterm labor occurred despite maximization of therapy, the treatment arm was determined and therapy was changed; saline pump and oral terbutaline were switched to terbutaline pump, terbutaline pump was switched to oral terbutaline. Patients who continued to labor were readmitted for aggressive intravenous therapy. Women randomized to the terbutaline pump (n = 15), saline pump (n = 12), and oral terbutaline (n = 15) groups were similar in terms of gravidity, parity, days of tocolysis before study entry, gestational age at entry, and cervical dilatation at entry. The mean gestational age at delivery was the same in all three groups (35 weeks), as were neonatal outcomes. Terbutaline by pump, saline by pump, and oral terbutaline appear equivalent for the prevention of preterm delivery. The terbutaline pump should remain experimental. Our purpose was to determine whether oral terbutaline, used after successful intravenous tocolysis, will prolong pregnancy and prevent recurrent preterm labor.
                After successful intravenous tocolysis, 203 women with preterm labor at 24 weeks' to 34 weeks 6 days' gestation were randomized to terbutaline (5 mg orally, every 4 hours) or placebo until 37 weeks' gestation. Women with recurrent preterm labor were treated with intravenous magnesium sulfate; if tocolysis was successful, they continued with the initial study medication. The primary outcome was the percentage delivered of their infants within 1 week of beginning oral tocolytic therapy. Latency, recurrent preterm labor, and maternal and neonatal outcomes were also assessed.
                Pregnancy outcome data were available in 200 women. There were no differences seen between the two groups in the incidence of delivery at 1 week (18% vs 24%, 95% confidence interval 0.44 to 1.29). In addition, there were no differences regarding median latency, mean gestational age at delivery, or the incidence of recurrent preterm labor (20% vs 16%, 95% confidence interval 0.64 to 2.71). Post hoc evaluation of 96 women enrolled before 32 weeks' gestation suggested pregnancy prolongation with maintenance oral terbutaline (p < 0.01).
                Maintenance oral terbutaline therapy initiated at 24 weeks' to 34 weeks 6 days' gestation after successful parenteral tocolysis is not associated with pregnancy prolongation or a reduction in the incidence of recurrent preterm labor. Interventions directed toward mothers before and during pregnancy and childbirth may help reduce preterm births and stillbirths. Survival of preterm newborns may also be improved with interventions given during these times or soon after birth. This comprehensive review assesses existing interventions for low- and middle-income countries (LMICs).
                Approximately 2,000 intervention studies were systematically evaluated through December 31, 2008. They addressed preterm birth or low birth weight; stillbirth or perinatal mortality; and management of preterm newborns. Out of 82 identified interventions, 49 were relevant to LMICs and had reasonable amounts of evidence, and therefore selected for in-depth reviews. Each was classified and assessed by the quality of available evidence and its potential to treat or prevent preterm birth and stillbirth. Impacts on other maternal, fetal, newborn or child health outcomes were also considered. Assessments were based on an adaptation of the Grades of Recommendation Assessment, Development and Evaluation criteria.
                Most interventions require additional research to improve the quality of evidence. Others had little evidence of benefit and should be discontinued. The following are supported by moderate- to high-quality evidence and strongly recommended for LMICs: Two interventions prevent preterm births--smoking cessation and progesterone. Eight interventions prevent stillbirths--balanced protein energy supplementation, screening and treatment of syphilis, intermittant presumptive treatment for malaria during pregnancy, insecticide-treated mosquito nets, birth preparedness, emergency obstetric care, cesarean section for breech presentation, and elective induction for post-term delivery. Eleven interventions improve survival of preterm newborns--prophylactic steroids in preterm labor, antibiotics for PROM, vitamin K supplementation at delivery, case management of neonatal sepsis and pneumonia, delayed cord clamping, room air (vs. 100% oxygen) for resuscitation, hospital-based kangaroo mother care, early breastfeeding, thermal care, and surfactant therapy and application of continued distending pressure to the lungs for respiratory distress syndrome
                The research paradigm for discovery science and intervention development must be balanced to address prevention as well as improve morbidity and mortality in all settings. This review also reveals significant gaps in current knowledge of interventions spanning the continuum of maternal and fetal outcomes, and the critical need to generate further high-quality evidence for promising interventions. 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. Our purpose was to establish the efficacy and safety of nifedipine versus magnesium sulfate in arresting preterm labor and the efficacy of nifedipine versus terbutaline in preventing recurrent labor.
                Singleton pregnancies at < 34 weeks in preterm labor were randomized to either oral nifedipine or intravenous magnesium sulfate. In case of tocolysis failure ritodrine was added. After labor was arrested, the patients in the nifedipine group were maintained on oral nifedipine, and those in the magnesium sulfate group were treated with oral terbutaline until completing 34 weeks.
                Of 100 patients 80 were considered eligible, of whom 39 were randomized to the nifedipine group. Both groups were comparable in terms of a number of entry variables, including cervical examination, contraction frequency, and gestational age. Both drugs were equally effective in arresting labor and delaying delivery > 48 hours, 92% versus 93%. Both study groups had a similar incidence of side effects, although four (10%) of magnesium sulfate-treated patients required drug discontinuation because of severe symptoms. Nifedipine was as effective as terbutaline in preventing recurrent labor, 26% versus 24%, and in achieving a gestation > 34 weeks, 62% versus 68%.
                Oral nifedipine is as effective as magnesium sulfate and terbutaline in arresting and preventing idiopathic preterm labor. Our purpose was to prove our hypothesis that once preterm uterine contractions and/or labor is controlled with intravenous tocolysis, oral terbutaline, as a maintenance drug, does not prolong pregnancy.
                Before discharge, 184 patients between 24 and 35 completed weeks' gestation were prospectively randomized to continued bed rest either with or without oral terbutaline. Assignment was made with stratification into four groups: group 1, those patients with a Bishop score > or = 5 with oral terbutaline (n = 50); group 2, those with a Bishop score > or = 5 without oral terbutaline (n = 53); group 3, those with a Bishop score < 5 with oral terbutaline (n = 41); group 4, those with a Bishop score < 5 without oral terbutaline (n = 40). Oral terbutaline was discontinued at 37 completed weeks.
                No statistically significant differences were found in the number of readmissions, the number of unscheduled hospital visits, and the neonatal outcomes among the four groups. The gestational age at delivery and percent of deliveries at > or = 37 weeks were not significantly different when group 1 was compared with group 2 and group 3 was compared with group 4.
                Oral terbutaline maintenance does not improve pregnancy outcome in patients who have had initial successful intravenous tocolysis. 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. A multicentre, randomized controlled double-blind trial in 5 maternity hospitals in Australia assessed the effect of a daily supplement of calcium (1.8g oral calcium or an oral placebo) taken daily until delivery, from less than 24 weeks' gestation, on the frequency of pregnancy-induced hypertension, preeclampsia and preterm birth (< 37 weeks' gestation) in 456 nulliparas with a singleton pregnancy. Treatment with calcium reduced the risk of preeclampsia (relative risk 0.44 [95% CI, 0.21-0.90], p = 0.02) and the risk of preterm birth (relative risk 0.44 [95% CI, 0.21-0.90], p = 0.02). No significant differences were seen between the 2 groups in the frequency of pregnancy-induced hypertension, although the study only had statistical power to detect large differences in this outcome. An updated systematic review of the 9 randomized trials of calcium supplementation in pregnancy shows a significant reduction in the risk of hypertension and preeclampsia although no effect on preterm birth. Calcium supplementation during pregnancy reduced the risk of preeclampsia and preterm birth in this nulliparous population. The available evidence for systematic review of all the randomized trials of calcium supplementation shows benefit in reducing the risk of hypertension and preeclampsia. 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. Our purpose was to evaluate three management strategies and to assess pregnancy outcomes in women with preterm uterine contractions.
                Consenting women seen in our hospital triage area with preterm uterine contractions were randomly assigned to observation alone, intravenous hydration, or one dose of subcutaneous terbutaline sulfate (0.25 mg). Eligible women had a singleton gestation between 20 and 34 weeks, intact membranes, more than three contractions in 30 minutes, and a cervical dilation < or = 1 cm and effacement < 80%. Women who had progressive cervical change at < 34 weeks were treated with intravenous tocolysis. Women with recurrent preterm uterine activity remained in their assigned group during subsequent triage visits.
                One hundred seventy-nine women were randomized: observation (56), hydration (62), and terbutaline (61). Women in these three groups were similar with respect to maternal age, race, parity, prior preterm births, gestational age at randomization, contraction frequency, and mean cervical dilatation. There were no intergroup differences in the mean days to delivery, the number of repeat triage visits, the incidence of preterm labor at < 34 weeks, or the frequency of preterm deliveries at < 34 weeks and < 37 weeks. Women assigned to terbutaline had contractions stopped and were discharged earlier (terbutaline 4.1 +/- 5.1 hours, observation 5.2 +/- 5.3 hours, hydration 6.0 +/- 5.7 hours; p = 0.006). No complications of therapy were observed.
                The use of intravenous hydration in the management of preterm contractions was of no benefit. The use of one dose of subcutaneous terbutaline resulted in the shortest length of triage stay but did not affect pregnancy outcome.
Terbutaline pump maintenance therapy has not been shown to decrease the risk of preterm birth by prolonging pregnancy. Furthermore, the lack of information on the safety of the therapy, as well as its substantial expense, argues against its role in the management of arrested preterm labor. Future use should only be in the context of well-conducted, adequately powered randomized controlled trials.
 [Note: The two citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]