Methods

RCT. Randomisation by using a list from a random number table.
Blinding: not stated.
Losses to follow‐up: 6/71 (8.4%) women randomised were excluded after randomisation because of no follow‐up (3), multifetal gestation (1), and fetal anomaly (2), and their outcomes were not included in the analysis.

Participants

71 women with successful tocolysis (for at least 12 hours) after treatment with magnesium sulphate who met the following inclusion criteria: 26‐32 weeks' gestation; single, live uterine pregnancy; preterm labour (at least 4 contractions in 20 minutes and progressive cervical change OR single examination with cervix at least 2 cm dilated or at least 80% effaced); amniotic membranes intact.
Exclusion criteria: multifetal gestations, suspected chorioamnionitis, abruptio placentae, placenta praevia, fetal anomaly, premature rupture of membranes, pre‐eclampsia, intrauterine growth restriction, oligohydramnios, allergy to aspirin, diabetes.

Interventions

After successful tocolysis with IV magnesium sulphate women were randomised to receive either oral indomethacin 25 mg every 6 hours or terbutaline sulphate 5 mg every 4 hours.
Terbutaline = 30 mg/day.

Outcomes

Birth < 34 weeks, mean birthweight, mean length of stay in NICU, neonatal death, mean Apgar score at 5 min, baby requiring mechanical ventilation, intraventricular haemorrhage, side effects sufficient to cease medication, preterm birth within 48 hours, preterm birth within 1 week.

Notes

2 women in the terbutaline group stopped their medication, but their outcome data were included in the analysis.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random number table.

Allocation concealment (selection bias)

Unclear risk

Not stated.

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Not stated.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

8.4% losses to follow‐up.

Selective reporting (reporting bias)

Unclear risk

Unable to assess.

Other bias

Low risk

Methods

RCT. Randomisation was by the chief pharmacist 'randomly assigning' the participants to treatment groups.
Blinding: women and medical attendants were blinded.
Losses to follow‐up: 5 exclusions after randomisation (9.8% excluded); 2 in the terbutaline group and 3 in the placebo group due to uncontrolled labour.

Participants

51 women who met the following inclusion criteria: premature labour between 24 and 36 weeks of gestation, painful regular uterine contractions at intervals of < 5 min.
Exclusion criteria: abnormal fetal heart rate pattern; abruptio placentae; heavy vaginal bleeding from placenta praevia; maternal/fetal complications requiring immediate delivery; diabetes and chronic hypertensive disorders; IUGR; cervical dilatation; bulging or ruptured membranes.

Interventions

All women received ethanol IV for 12 hours and compazine. 2 hours before the ethanol dose ended, women were randomised to receive terbutaline sulphate 5 mg or placebo orally. Treatment was continued every 6 hours until the 38th week of gestation. Terbutaline = 20 mg/day.

Outcomes

Mean birthweight, respiratory distress syndrome, perinatal death, tachycardia, low blood pressure, nausea.

Notes

2 twin pregnancies in the terbutaline group and 3 twin pregnancies in the placebo group.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Pharmacist "Randomly assigning participants to treatment groups".

Allocation concealment (selection bias)

Low risk

Allocation through pharmacy.

Blinding (performance bias and detection bias)
All outcomes

Low risk

Women and medical attendants blinded.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

9.8% losses to follow‐up.

Selective reporting (reporting bias)

Unclear risk

Unable to assess.

Other bias

Low risk

Methods

RCT (method of randomisation unclear). Authors claim double blinding was present throughout the trial.
Losses to follow‐up: 1/70 left the hospital (from placebo group); 10 women gave birth within 24 hours. Of the remaining 59 women, 4 were continued on intramuscular treatment, leaving 55 (78.6%) who were placed on oral treatment.

Participants

55 women who had been successfully treated with IM ritodrine and met the inclusion criteria.
Inclusion criteria: gestation 20‐36 weeks, live fetus < 2500 g, intact membranes, 3‐4 contractions per 20 min, progressive cervical effacement or dilatation, informed consent.
Exclusion criteria: abnormal vaginal bleeding, ROM, cervical dilatation > 3‐4 cm, fever of unknown origin, erythroblastosis fetalis, cardiovascular or hypertensive disease, active thyroid disease, diabetes mellitus, known drug addiction.

Interventions

All women received bedrest, monitoring and IM ritodrine. If uterine activity was then controlled, the women were given ritodrine tablets (10 to 20 mg every 3 to 4 hours) or placebo until 37 to 38 weeks' gestation. Ritodrine = 30‐80 mg/day.

Outcomes

Mean birthweight, mean Apgar score at 5 min, preterm birth within 24 hours, preterm birth within 1 week, palpitations and flushing, perinatal death.

Notes

1 twin gestation in the ritodrine group and 4 twin gestations in the placebo group.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not stated.

Allocation concealment (selection bias)

Unclear risk

Not stated.

Blinding (performance bias and detection bias)
All outcomes

Low risk

Stated to be "Double blinded".

Incomplete outcome data (attrition bias)
All outcomes

High risk

21.4% losses to follow‐up.

Selective reporting (reporting bias)

Unclear risk

Unable to assess.

Other bias

Low risk

Methods

RCT (multicentre).
Randomisation: capsules were distributed in pharmacy coded drug boxes.
Blinding: not stated but control consisted of placebo tablets.
Losses to follow‐up: 1 mother could not be traced after moving.

Participants

95 women who met the following inclusion criteria: participated in a randomised comparison of 2 schedules of intravenous ritodrine administration (described elsewhere) where the arrest of active preterm labour occurred.
Exclusion criteria: treatment with indomethacin, rupture of membranes, severe side‐effects during intravenous treatment, > 34 weeks' gestation.

Interventions

At the start of maintenance treatment, all women had been on an intravenous dose of 50 microg/min ritodrine for 12 to 24 hours following successful arrest of contractions. Maintenance therapy consisted of 2 40 mg ritodrine sustained released capsules or 2 identical placebo capsules 3 times per day for 7 days. Ritodrine = 240 mg/day.

Outcomes

Perinatal death, birth at < 37 weeks, side‐effects sufficient to stop medication, vomiting, preterm birth within 1 week.

Notes

7 twin pregnancies and 1 triplet pregnancy in the ritodrine group; no multiple pregnancies in the placebo group.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Medication was distributed in pharmacy coded drug boxes.

Allocation concealment (selection bias)

Low risk

Allocation through pharmacy.

Blinding (performance bias and detection bias)
All outcomes

Low risk

Women blinded to treatment (use of placebo capsule).

Incomplete outcome data (attrition bias)
All outcomes

Low risk

1% loss to follow‐up.

Selective reporting (reporting bias)

Unclear risk

Unable to assess.

Other bias

Low risk

Methods

RCT. Randomisation was by sealed envelopes, generated from a table of random numbers.
Blinding: not stated.
Losses to follow up: 28/212 women (13%) were excluded because of non‐compliance (15 in the terbutaline group and 13 in the bed rest group).

Participants

212 women who met the following inclusion criteria: between 24 and 35 completed weeks of gestation, with at least one of the following: persistent uterine contractions (at least 6 contractions per hour), progressive cervical dilatation and/or effacement, dilatation at least 2 cm and 50% effacement on the initial cervical examination in the presence of uterine contractions.
Exclusion criteria: premature rupture of membranes on initial examination, preterm termination for obstetric indications, inability to reliably assess cervical change.

Interventions

All women were treated with intramuscular betamethasone and intravenous magnesium sulphate until uterine quiescence was achieved for 12‐24 hours, then treated with oral terbutaline for 24‐48 hours. The women were randomised to either terbutaline or bed rest and then divided into 4 groups:
group 1: those with a Bishop score of at least 5 with oral terbutaline; group 2: those with a Bishop score at least 5 without oral terbutaline; group 3: those with a Bishop score < 5 with oral terbutaline;
group 4: those with a Bishop score < 5 without oral terbutaline. For the purpose of this review, the groups 1 and 3 have been combined, and groups 2 and 4 have been combined, so that treatment of terbutaline is compared with no treatment, regardless of the Bishop score. Terbutaline dose = 5‐10 mg every 4‐6 hours (20‐60 mg/day).

Outcomes

Neonatal death, respiratory distress syndrome, intraventricular haemorrhage, maternal readmission to hospital.

Notes

166 singleton gestations and 18 multiple gestations (11 twin pregnancies in the terbutaline group and 6 twin and 1 triplet pregnancy in the bed rest group).

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random number table.

Allocation concealment (selection bias)

Low risk

Sealed envelopes.

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Not stated (although blinding of women randomised to bed rest not possible).

Incomplete outcome data (attrition bias)
All outcomes

Low risk

13% loss to follow‐up.

Selective reporting (reporting bias)

Unclear risk

Unable to assess.

Other bias

Low risk

Methods

RCT. Randomisation from a random number table via sealed envelopes.
Blinding: not stated.
Losses to follow‐up: 22 women out of 113 (19.4%) were excluded after randomisation; 6 of these were for non‐compliance.

Participants

113 women who met the following inclusion criteria: singleton pregnancy; gestational age 20‐35 weeks; irregular uterine contractions with clear evidence of cervical dilatation and effacement; persistent, regular uterine contractions (min frequency 8/hr) with or without cervical change.
Exclusion criteria: known lethal fetal anomalies, chorioamnionitis, advanced cervical effacement and dilation (completely effaced and > 5 cm dilated).

Interventions

Parenteral tocolysis was given to all women (subcutaneous terbutaline and intravenous ritodrine) then women were randomly assigned to maintenance therapy with oral terbutaline (begun at 2.5 mg every 2 hours for 24 hours, then adjusted to 5 mg every 4 hours) or ritodrine (begun at 10 mg every 2 hours for 24 hours then adjusted to 20 mg every 4 hours). Terbutaline = 30 mg/day, ritodrine = 120 mg/ day.

Outcomes

Mean birthweight, perinatal deaths, hyperbilirubinaemia, tachycardia, tachypnoea, nausea/vomiting, antenatal readmission.

Notes

1 woman in each group was switched to the alternate drug because of intolerable side effects. In addition, there were 6 noncompliant women ‐ 4 from the ritodrine group and 2 from the terbutaline group. 2 of the 6 women chose to give birth elsewhere and the remaining 4 elected not to continue their medication because of side effects.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random number table.

Allocation concealment (selection bias)

Low risk

Sealed envelopes.

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Not stated.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

19% loss to follow‐up.

Selective reporting (reporting bias)

Unclear risk

Unable to assess.

Other bias

Low risk

Methods

RCT. Randomisation was by a computer‐generated table of random numbers.
Blinding: women blinded to allocation through use of a placebo.
Losses to follow up: of the 203 women entered in the study, 3 were lost to follow‐up (1.5%).

Participants

203 women who met the following inclusion criteria: admitted to the labour and delivery suite between December 1990 and June 1995 with the diagnosis of preterm labour (regular uterine contractions and documented cervical change). Women had been successfully treated with parenteral tocolysis.
Exclusion criteria: chorioamnionitis; vaginal bleeding suggesting abruptio placentae; medical history contraindicating use of terbutaline; premature rupture of membranes; maternal or fetal indication for delivery.

Interventions

Following successful parenteral tocolysis, women were randomly assigned to terbutaline (5 mg 5 times per day) or placebo. Terbutaline = 25 mg/day.

Outcomes

Perinatal death, respiratory distress syndrome, intraventricular haemorrhage, mean birthweight, birth within 48 hours, birth within 1 week.

Notes

3 twin pregnancies in each of the terbutaline and placebo groups.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random number table.

Allocation concealment (selection bias)

Unclear risk

Not stated.

Blinding (performance bias and detection bias)
All outcomes

Low risk

Women were blinded through the use of a placebo.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

1.5% loss to follow‐up.

Selective reporting (reporting bias)

Unclear risk

Unable to assess.

Other bias

Low risk

Methods

Randomisation was by a computer‐generated table of random numbers.

Allocation concealment through sealed opaque envelopes.
Blinding: women blinded to allocation through use of a placebo.
Losses to follow up: none reported.

Participants

120 women who met the following inclusion criteria: singleton pregnancy; gestational age 24‐34 weeks; > 5 contractions per hour for 2 hours; modified bishop score > 3.

Interventions

Following successful parenteral tocolysis, women were randomly assigned to ritodrine (80 mg 3 times per day) or placebo.

Outcomes

Preterm birth < 34 weeks; preterm birth < 37 weeks; preterm birth in 72 hours; infant birthweight; perinatal mortality; NICU admission; Apgar score < 7 at 5 minutes; mechanical ventilation; maternal side effects (pulmonary oedema, tremor, tachycardia, shortness of breath).

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random number table.

Allocation concealment (selection bias)

Low risk

Sealed opaque envelopes.

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Not stated.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No reported losses to follow‐up.

Selective reporting (reporting bias)

Unclear risk

Unable to assess.

Other bias

Low risk

Methods

RCT. Randomisation was based on a computer‐generated number table with use of opaque sealed envelopes.
Blinding: not stated.
Losses to follow‐up: not stated, but do not appear to have been any.

Participants

55 women who met the following inclusion criteria: admitted for preterm labour between 28 and 35 weeks' gestation with the following cervical changes: at least 1 cm decrease in length and 1 cm increase in dilation; at least 1 cm increase in dilation if the cervix is already completely effaced; at least 2 cm decrease in length without dilation; or at least 2 cm increase in dilation at the internal os without effacement. Labour was successfully arrested with magnesium sulphate.
Exclusion criteria: ruptured membranes, abnormal bleeding, suspected chorioamnionitis, pre‐eclampsia, severe IUGR, fetal anomalies incompatible with life, non reassuring fetal heart rate pattern and cervical dilatation > 4 cm.

Interventions

Intravenous magnesium sulphate was continued for 12 hours after the uterine contractions ceased. Women were then randomised to receive either no treatment or oral terbutaline (dose unspecified) (the first dose of which was given 30 minutes before the discontinuation of IV magnesium sulphate).

Outcomes

Mean birthweight, preterm birth (< 37 weeks).

Notes

5 twin pregnancies in the terbutaline group and 3 twin pregnancies in the no treatment group.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random number table.

Allocation concealment (selection bias)

Low risk

Sealed opaque envelopes.

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Not stated.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Not stated; do not appear to be any losses to follow‐up.

Selective reporting (reporting bias)

Unclear risk

Unable to assess.

Other bias

Low risk

Methods

RCT.
Women were randomised to 1 of 3 groups, using sealed envelopes.
Blinding: examining physician was blinded for some aspects of weekly assessments.
Losses to follow‐up: not stated.

Participants

75 women who met the following inclusion criteria: admitted with a diagnosis of preterm labour (initial pelvic exam of 2 cm dilatation in conjunction with 2 or more contractions per 10 minutes of at least 30 seconds' duration or a change in cervical examination detected by the same examiner over a 1‐hour period of at least 30 seconds' duration).
Exclusion criteria: cervical dilatation equal to or more than 4 cm; ruptured membranes; obstetric haemorrhage; chorioamnionitis; pre‐eclampsia; eclampsia; fetal death; lethal congenital anomaly.

Interventions

All women were given IV magnesium sulphate and randomised to 1 of 3 groups following a 12‐hour contraction‐free period.
Group 1: 10 mg oral ritodrine every 2 hours for 24 hours, then changed to 20 mg every 4 hours; ritodrine = 120 mg/day.
Group 2: 535 mg SLOW MAG (enteric‐coated magnesium chloride) every 4 hours.
Group 3: observation only.

Outcomes

Preterm birth (< 36 weeks), headache, tachycardia, nausea, vomiting, chest pain.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not stated.

Allocation concealment (selection bias)

Low risk

Sealed envelopes.

Blinding (performance bias and detection bias)
All outcomes

Low risk

Blinding of some physician visits.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Not stated.

Selective reporting (reporting bias)

Unclear risk

Unable to assess.

Other bias

Low risk

Methods

RCT.
Randomisation: method not described.
Blinding: not stated.
Losses to follow up: 10 women (16.7%) ‐ 4 in terbutaline group and 6 in the magnesium group.

Participants

60 women who met the following inclusion criteria: preterm labour successfully arrested with parenteral treatment. Preterm labour is defined as: gestational age between 25 and 35 weeks, 3 contractions in 20 minutes that persisted despite IV hydration, or any cervical change.

Interventions

Once there had been uterine quiescence for 12 to 24 hours, the women were allocated to 2 groups. Group 1: magnesium oxide 200 mg orally every 3‐4 hours. Group 2: 2.5‐5 mg of terbutaline sulphate orally every 3‐4 hours. Terbutaline = 15‐40 mg/ day.

Outcomes

Mean birthweight, birth at < 36 weeks, tachypnoea, nausea, vomiting.

Notes

One set of twins in each group.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not stated.

Allocation concealment (selection bias)

Unclear risk

Not stated.

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Not stated.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

16.7% loss to follow‐up.

Selective reporting (reporting bias)

Unclear risk

Unable to assess.

Other bias

Low risk

Methods

RCT.
Randomisation: computer‐generated table at the pharmacy. Only the medical professionals responsible for medication distribution had access to group assignment.
Blinding: women and care providers were blinded to treatment group for care and outcomes assessment.
Losses to follow‐up: of the 248 women randomised, 39 (17%) delivered prior to discharge and were thus not included as part of the results, and a further 4 were lost to follow‐up (17.3% in total).

Participants

248 women who met the following inclusion criteria: preterm labour (defined by gestational age 24‐34 weeks, regular contractions of > 4 per hour, documented cervical change on serial digital exams, intact membranes and absence of any medical or obstetric complications requiring delivery); arrest of preterm labour with parenteral tocolysis; uterine quiescence documented by tocodymometry; absence of further cervical change.

Interventions

Following arrest of preterm labour with parenteral tocolysis the women were randomised to 1 of 3 groups: oral magnesium chloride (128 mg every 4 hours) ‐ 65 women, 69 infants; oral terbutaline sulphate (5 mg every 4 h) ‐ 72 women, 82 infants; placebo‐68 women, 71 infants. Terbutaline = 30 mg/ day.

Outcomes

NICU, tachypnoea, nausea, vomiting, mean birthweight.

Notes

Some results reported as being adjusted to account for multiple gestation (but no further details provided).
Compliance: 55% magnesium, 64% terbutaline, 62% placebo.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random number table.

Allocation concealment (selection bias)

Low risk

Medication distributed through pharmacy.

Blinding (performance bias and detection bias)
All outcomes

Low risk

Women and caregivers blinded.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

17.3% loss to follow‐up.

Selective reporting (reporting bias)

Unclear risk

Unable to assess.

Other bias

Low risk

Methods

Randomisation: "allocation of drugs carried out at random by the controlled with 2 subjects from each group for a total of 6 subjects per 1 set".
Blinding: women and care providers were blinded to treatment group through the use of placebo.
Losses to follow‐up: 15 women were excluded and lost to follow‐up (7.7% in total).

Participants

291 women who met the following inclusion criteria: preterm labour (defined by gestational age 24‐37 weeks, diagnosis of labour, dilation cervix < 3.5 cm and < 80% effacement); arrest of preterm labour with parenteral tocolysis.

Interventions

Following arrest of preterm labour with parenteral tocolysis the women were randomised to 1 of 3 groups: oral ritodrine (15 mg daily) ‐ 98 women; oral medroxyprogesterone acetate (15 mg daily) ‐ 98 women (not included in this review); placebo ‐ 95 women.

Outcomes

Preterm birth < 37 weeks; infant birthweight < 2500 grams; respiratory distress syndrome; maternal tachycardia, nausea.

Notes

Comparison with medroxyprogesterone acetate not included in this review.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

"allocation of drugs carried out at random by the controlled with 2 subjects from each group for a total of 6 subjects per 1 set."

Allocation concealment (selection bias)

Low risk

Medication distributed by pharmacy.

Blinding (performance bias and detection bias)
All outcomes

Low risk

Women and caregivers through use of placebo.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

7.7% loss to follow‐up.

Selective reporting (reporting bias)

Unclear risk

Unable to assess.

Other bias

Low risk