A Cochrane review included 38 studies with a total of 3 550 subjects. Nifedipine showed a significant reduction in birth less than 48 hours after trial entry compared with placebo or no treatment (RR 0.30, 95% CI 0.21 to 0.43; 2 trials, n=173) and an increase in maternal adverse effects (RR 49.89, 95% CI 3.13 to 795.02; 1 trial, n=89). Data for preterm birth (less than 37 weeks) were not combined; one placebo controlled trial showed no difference (RR 0.96, 95% CI 0.89 to 1.03) while the other (non-placebo controlled trial) reported a reduction (RR 0.44, 95% CI 0.31 to 0.62). No other outcomes were reported.
Comparing calcium channel blockers (CCBs, mainly nifedipine) with other tocolytics by type (including betamimetics, glyceryl trinitrate (GTN) patch, non-steriodal anti inflammatories (NSAID), magnesium sulphate and oxytocin receptor antagonists (e.g. atosiban), no significant reductions were shown in primary outcome measures of birth within 48 hours of treatment (CCB versus betamimetics RR 0.86, 95% CI 0.67 to 1.10; 19 trials, n=1505) or perinatal mortality.
Comparing CCBs with betamimetics, there were fewer maternal adverse effects (average RR 0.36, 95% CI 0.24 to 0.53; 15 trials, n=1305) and fewer maternal adverse effects requiring discontinuation of therapy (average RR 0.22, 95% CI 0.10 to 0.48; 16 trials, n=1217). Calcium channel blockers resulted in a non-significant increase in the interval between trial entry and birth (average MD 4.38 days, 95% CI 0.25 to 8.52; 10 trials, n=830), while decreasing preterm and very preterm birth (RR 0.89, 95% CI 0.80 to 0.98 and RR 0.78, 95% CI 0.66 to 0.93); respiratory distress syndrome (RR 0.64, 95% CI 0.48 to 0.86); necrotising enterocolitis (RR 0.21, 95% CI 0.05 to 0.96); intraventricular haemorrhage (RR 0.53, 95% CI 0.34 to 0.84); neonatal jaundice (RR 0.72, 95% CI 0.57 to 0.92); and admissions to neonatal intensive care unit (average RR 0.74, 95% CI 0.63 to 0.87).
Comparing CCBs with oxytocin receptor antagonist atosiban, data from one study (which did blind the intervention) showed an increase in gestational age at birth (MD 1.20 completed weeks, 95% CI 0.25 to 2.15) and reductions in preterm birth (RR 0.64, 95% CI 0.47 to 0.89); admissions to the neonatal intensive care unit (RR 0.59, 95% CI 0.41 to 0.85); and duration of stay in the neonatal intensive care unit (MD -5.40 days,95% CI -10.84 to 0.04). Maternal adverse effects were increased in the CCB group (average RR 2.61, 95% CI 1.43 to 4.74).
When compared with any other tocolytic agent (mainly betamimetics), calcium channel blockers (mainly nifedipine) reduced the number of women giving birth within 48 hours, RR 0.73 (95% CI 0.54 to 0.98) and within seven days, RR 0.76 (95% CI 0.59 to 0.99). Calcium channel blockers also reduced the requirement for women to have treatment ceased for adverse drug reaction, RR 0.15 (95% CI 0.06 to 0.43), the frequency of neonatal respiratory distress syndrome, RR 0.64 (95% CI 0.45 to0.91) and neonatal jaundice, RR 0.73 (95% CI 0.57 to 0.93).The following decision support rules contain links to this evidence summary: