Maintenance therapy with calcium channel blockers for preventing preterm birth after threatened preterm labour

Calcium channel blockers have not been shown to reduce preterm birth or improve the outcomes for babies when given to women after contractions of preterm labour have been stopped.

Babies born premature (before 37 weeks of pregnancy) may not survive, or may have serious long-term problems if they do survive. Women who have had their preterm labour stopped with tocolytic treatment (medication to reduce uterine contractions), remain at risk of giving birth preterm. After this initial tocolytic treatment has been given to stop early labour, a maintenance tocolytic treatment may be given to try to prevent further early contractions and early birth. Calcium channel blockers are one of the types of tocolytic therapy that have been used in an attempt to prevent the onset of further preterm contractions.

We identified six randomised controlled trials involving a total of 794 women and their babies for this review. The trials were of moderate risk of bias overall. The trials did not demonstrate differences between calcium channel blocker maintenance therapy and placebo or no treatment in the prevention of preterm birth or perinatal death (fetal or neonatal deaths). None of the trials included any follow-up of the infants to assess longer-term development. Calcium channel blocker maintenance therapy (with a drug called nifedipine) was more likely than placebo or no treatment to prolong pregnancy, however the infants of these mothers were more likely to have a longer hospital stay. Based on the current studies, we found no convincing evidence that calcium channel blocker maintenance therapy prevents preterm birth for women after threatened preterm labour, or that it improves outcomes for babies.

Authors' conclusions: 

Based on the current available evidence, maintenance treatment with a calcium channel blocker after threatened preterm labour does not prevent preterm birth or improve maternal or infant outcomes.

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Background: 

Calcium channel blocker maintenance therapy is one of the types of tocolytic therapy that may be used after an episode of threatened preterm labour (and usually an initial dose of tocolytic therapy) in an attempt to prevent the onset of further preterm contractions.

Objectives: 

To assess the effects of calcium channel blockers as maintenance therapy on preventing preterm birth after threatened preterm labour.

Search strategy: 

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2013) and reference lists of retrieved studies.

Selection criteria: 

Randomised controlled trials of calcium channel blockers used as maintenance therapy to prevent preterm birth after threatened preterm labour, compared with placebo or no treatment.

Data collection and analysis: 

Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies.

Main results: 

We included six trials that enrolled 794 women and their babies and all assessed nifedipine as calcium channel blocker maintenance therapy. The six trials were judged to be at a moderate risk of bias overall. No differences in the incidence of preterm birth (risk ratio (RR) 0.97; 95% confidence interval (CI) 0.87 to 1.09; five trials, 681 women), birth within 48 hours of treatment (RR 0.46; 95% CI 0.07 to 3.00; two trials, 128 women) or neonatal mortality (average RR 0.75; 95% CI 0.05 to 11.76; two trials, 133 infants) were seen when nifedipine maintenance therapy was compared with placebo or no treatment. No stillbirths were reported in the one trial that provided data for this outcome. No trials reported on longer-term follow-up of infants.

Women receiving nifedipine maintenance therapy were significantly more likely to have their pregnancy prolonged (mean difference (MD) 5.35 days; 95% CI 0.49 to 10.21; four trials, 275 women); however, no differences between groups were shown for birth at less than 34 weeks' gestation, birth at less than 28 weeks' gestation, birth within seven days of treatment, or gestational age at birth. No significant differences were shown between the nifedipine and control groups for any of the secondary neonatal morbidities reported. Similarly, no significant differences were seen for the outcomes relating to the use of health services, except for in one trial, where infants whose mothers received nifedipine were significantly more likely to have a longer length of hospital stay as compared with infants born to mothers who received a placebo (MD 14.00 days; 95% CI 4.21 to 23.79; 60 infants).