A Cochrane review [Abstract] 1 included 37 studies with 3571 women and over 3 600 babies. In the magnesium sulphate versus control (all studies) no difference was seen for the risk of birth within 48 hours of treatment for women given magnesium sulphate compared with controls (whether placebo/no alternative tocolytic drug, betamimetics, calcium channel blockers, cox inhibitors, prostaglandin inhibitors, or human chorionic gonadotropin) in 19 trials. For different drugs, there was not enough power to detect significant differences, however there was a trend favouring betamimetics and calcium channel blockers: magnesium versus no drug (RR 0.56, 95% CI 0.27 to 1.14; 3 trials, n=182); vs betamimetics (RR 1.09; 95% CI 0.72 to 1.65; 7 trials, n= 503); vs calcium channel blockers (RR 1.19, 95% CI 0.86 to 1.65; 5 trials, n=588). No benefit was seen for magnesium sulphate on the risk of giving birth preterm (<37 weeks) or very preterm (<34 weeks). The risk of death (fetal and paediatric) was higher for infants exposed to magnesium sulphate (RR 2.82, 95% CI 1.20 to 6.62, 7 trials, 727 infants). The analysis did not show differences in neonatal/foetal deaths between magnesium sulphate and no magnesium sulphate, whether compared with placebo/no alternative tocolytic drug, or any specific class of tocolytic drug. However, there were only 3 fetal deaths
Another Cochrane review[Abstract] 2 included 4 studies with a total of 422 women to assess whether magnesium maintenance therapy is effective in preventing preterm birth after the initial threatened preterm labour is arrested. Three studies had high risk of bias and none included any long-term follow up of infants. No differences in the incidence of preterm birth or perinatal mortality were seen when magnesium maintenance therapy was compared with placebo or no treatment; or alternative therapies (ritodrine or terbutaline). The RR for preterm birth (less than 37 weeks) for magnesium compared with placebo or no treatment was 1.05 (95% CI 0.80 to 1.40; 2 studies, n=99); and 0.99 (95% CI 0.57 to 1.72; 2 studies, n=100) for magnesium compared with alternative therapies. The RR for perinatal mortality for magnesium compared with placebo or no treatment was 5.00 (95% CI 0.25 to 99.16; 1 study, 50 infants) and also compared with alternative treatments, was 5.00 (95% CI 0.25 to 99.16; 1 study, 50 infants). Women taking magnesium preparations were less likely to report palpitations or tachycardia than women receiving alternative therapies (RR 0.26, 95% CI 0.13 to 0.52; 3 studies, n= 237) but were much more likely to experience diarrhoea (RR 7.66, 95% CI 2.18 to 26.98, 3 studies, n=237).
A meta-analysis 3 197 studies (40 randomised trials, 138 non-randomised studies, and 19 case reports), of mixed quality. The 40 trials (randomising 19 265 women and their babies). In 9 trials the indication was tocolysis: There were no significant differences in perinatal death (RR 7.99, 95% CI 1.00 to 63.49; 2 trials, n=257), stillbirth (RR 5.70, 95% CI 0.28 to 116.8; 2 trials, n=257), or neonatal death (RR 0.78, 95% CI 0.11 to 5.67; 4 trials, n=445). Overall, there were no clear associations between antenatal magnesium sulphate for beneficial indications and adverse neonatal outcomes.
A Cochrane network meta-analysis [Abstract]4assessing 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) |
Primary/Secondary Keywords