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Evidence summaries

Betamimetics for Preterm Labour

Betamimetics are effective for inhibiting preterm labour compared with placebo or no treatment. Multiple adverse effects must be considered. Maintenance therapy with betamimetics after threatened preterm labour is of no benefit. Level of evidence: "A"

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.

Delay in birth by 48 hours with different tocolytics compared with placebo or no treatment

OutcomeNetwork evidenceAnticipated absolute effects for network estimate
RR (95% CI) CertaintyRisk with placebo or no treatmentRisk with tocolytic agentRisk difference with tocolytic agent
Betamimetics1.12(1.05 to 1.20) Low645 per 1000722 per 100077 more per 1000(from 32 to 129 more)
Calcium channel blockers1.16(1.07 to 1.24)Low645 per 1000748 per 1000103 per 1000(from 45 to 155 more)
Magnesium sulphate1.12(1.02 to 1.23) Moderate645 per 1000722 per 100077 more per 1000(from 13 to 148 more)
Oxytocin receptor antagonists1.13(1.05 to 1.22) Moderate645 per 1000729 per 100084 more per 1000(from 32 to 142 more)
Nitric oxide donors1.17(1.05 to 1.31) Moderate645 per 1000755 per 1000110 per 1000(from 32 to 200 more)

The following decision support rules contain links to this evidence summary:

References

  • Neilson JP, West HM, Dowswell T. Betamimetics for inhibiting preterm labour. Cochrane Database Syst Rev 2014;(2):CD004352. [PubMed]
  • Dodd JM, Crowther CA, Middleton P. Oral betamimetics for maintenance therapy after threatened preterm labour. Cochrane Database Syst Rev 2012;12():CD003927. [PubMed]
  • Whitworth M, Quenby S. Prophylactic oral betamimetics for preventing preterm labour in singleton pregnancies. Cochrane Database Syst Rev 2008 Jan 23;(1):CD006395 [Review content assessed as up-to-date: 1 1.14(1.02 to 1.28)Very lowe1.12(1.02 to 1.23)Moderatej645 per 1000722 per 100077 more per 1000(from 13 to 148 more)December 2010]. [PubMed]
  • Wilson A, Hodgetts-Morton VA, Marson EJ et al. Tocolytics for delaying preterm birth: a network meta-analysis (0924). Cochrane Database Syst Rev 2022;(8):CD014978. [PubMed]

Primary/Secondary Keywords