A Cochrane review [Abstract] 1 included 20 studies, of which 12 trials, involving a total fo 1 367 women, compared betamimetics with placebo. As compared with placebo, betamimetics decreased the number of women in preterm labour giving birth within 48 hours (relative risk (RR) 0.68; 95% CI 0.53-0.88; 10 trials, n=1209). There was a trend towards a decrease in the number of births within seven days (RR 0.80; 95% CI 0.65 to 0.98;5 trials, n=911). No benefit was demonstrated for betamimetics on perinatal death (RR 0.84; 95% CI 0.46-1.55, 11 trials, n = 1332), or neonatal death (RR 1.90; 95% CI 0.27-3.00, 6 trials, n = 1174). No significant effect was demonstrated for respiratory distress syndrome (RR 0.87; 95% CI 0.71-1.08, 8 trials, n = 1239). Betamimetics were significantly associated with the following: withdrawal from treatment due to adverse effects; chest pain; dyspnoea; tachycardia; palpitation; tremor; headaches; hypokalemia; hyperglycemia; nausea/vomiting; and nasal stuffiness; and fetal tachycardia. Nine trials compared different types of betamimetics. Other betamimetics were compared with ritodrine in five trials (n = 948). Other comparisons were examined in single trials: hexoprenaline compared with salbutamol (n = 140), slow versus moderate release salbutamol (n = 52) and salbutamol compared with terbutaline (n = 200). Trials were small, varied and of insufficient quality to delineate any consistent patterns of effect.
Another Cochrane review 2 (abstract , review [Abstract]) assessing oral betamimetic maintenance therapy after threatened preterm labour included 13 studies with a total of 1 551 subjects. No differences were seen for admission to the neonatal intensive care unit when betamimetics were compared with placebo (relative risk 1.28, 95% CI 0.68 to 2.41 ; 2 RCTs of terbutaline with 2 600 women) or with magnesium (RR 1.11, 95% CI 0.43 to 1.46; one RCT of 137 women). The rate of preterm birth (less than 37 weeks) showed no significant difference in 6 RCTs, 4 comparing ritodrine with placebo/no treatment and two comparing terbutaline with placebo/no treatment (RR 1.08, 95% CI 0.91 to 1.35, 644 women). No differences between betamimetics and placebo, no treatment or other tocolytics were seen for perinatal mortality and morbidity outcomes.
Another Cochrane review 4 (abstract , review [Abstract]) included one trial with 64 singleton pregnancies comparing oral betamimetic agent isoxuprine with placebo. No difference was seen for perinatal mortality rate (RR 4.74, 95% CI 0.50 to 45.00), for reduction of spontaneous onset of preterm labour (RR 1.07, 95% CI 0.14 to 8.09) or preterm birth, less than 37 weeks' gestation, or for birthweight less than 2500 grams (RR 1.74, 95% CI 0.44 to 6.87) or neonatal death (RR 4.74, 95% CI 0.50 to 45.00).
A Cochrane network meta-analysis [Abstract]5assessing different tocolytic drugs included 122 trials with a total of 13 697 women (table T1). Nitric oxide donors ranked highest for delaying preterm birth by 48 hours and 7 days followed by calcium channel blockers, oxytocin receptor antagonists and combinations of tocolytics.
Outcome | Network evidence | Anticipated absolute effects for network estimate | ||
---|---|---|---|---|
RR (95% CI) Certainty | Risk with placebo or no treatment | Risk with tocolytic agent | Risk difference with tocolytic agent | |
Betamimetics | 1.12(1.05 to 1.20) Low | 645 per 1000 | 722 per 1000 | 77 more per 1000(from 32 to 129 more) |
Calcium channel blockers | 1.16(1.07 to 1.24)Low | 645 per 1000 | 748 per 1000 | 103 per 1000(from 45 to 155 more) |
Magnesium sulphate | 1.12(1.02 to 1.23) Moderate | 645 per 1000 | 722 per 1000 | 77 more per 1000(from 13 to 148 more) |
Oxytocin receptor antagonists | 1.13(1.05 to 1.22) Moderate | 645 per 1000 | 729 per 1000 | 84 more per 1000(from 32 to 142 more) |
Nitric oxide donors | 1.17(1.05 to 1.31) Moderate | 645 per 1000 | 755 per 1000 | 110 per 1000(from 32 to 200 more) |
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Primary/Secondary Keywords