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Nifedipine best for tocolysis in preterm labor

Clinical Question:
What is the efficacy and safety of nifedipine as a tocolytic agent in women with preterm labor?

Bottom Line:
Nifedipine tocolysis for women in preterm labor is superior to beta2-adrenergic agonists for reducing the risk of delivery within 7 days. Nifedipine is as effective as magnesium sulfate, but with fewer adverse effects. There is insufficient evidence regarding comparisons with atosiban or nitric oxide donors. Nifedipine is not effective for maintenance tocolysis according to the results of 3 small studies. (LOE = 1a)

Reference:
Conde-Agudelo A, Romero R, Kusanovic JP. Nifedipine in the management of preterm labor: a systematic review and metaanalysis. Am J Obstet Gynecol 2011;204(2):134.e1-e20.  [PMID:21284967]

Study Design:
Meta-analysis (randomized controlled trials)

Funding:
Foundation + govt

Setting:
Various (meta-analysis)

Synopsis:
This methodologically rigorous meta-analysis of randomized controlled trials summarizes the evidence regarding the use of nifedipine tocolysis in the treatment of preterm labor compared with alternative tocolytics, placebo, or no treatment. The authors identified 26 trials including 2179 women who met inclusion criteria. More than 20 outcomes were assessed. Of the 23 trials evaluating acute tocolysis, 16 (n = 1278) compared nifedipine to beta2-adrenergics (ritrodrine = 11, terbutaline = 3, and isoxuprine = 2), 5 (n = 556) magnesium sulfate, and one each atosiban (n = 40) and nitric oxide donors (n = 50). The latter 2 comparisons were too small to draw conclusions. Nifedipine was superior to beta2-adrenergics to reduce the risk of delivery within 7 days (37% vs 45%; relative risk [RR] = 0.82; 95% CI, 0.7-0-0.97; number needed to treat [NNT] = 12), delivery before 34 weeks' gestation (48% vs 62%; RR = 0.77; 0.66-0.91; NNT=7), and maternal adverse events (20% vs 56%; RR = 0.31; 0.18-0.54; NNT=3). Mean birth weight was 179 g higher with terbutaline. Other neonatal outcomes likewise favored nifedipine, including significant reductions in respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, neonatal jaundice, admission to the neonatal intensive care unit (NICU), and NICU length of stay. Nifedipine compared with magnesium sulfate showed no differences for delivery within 48 hours, preterm birth, or time to delivery. However, nifedipine caused significantly fewer maternal adverse events (24% vs 36%; RR = 0.63; 0.48-0.86; NNT=8). There were no significant differences in the risk of major neonatal adverse events, but there were significant reductions with nifedipine for risk of admission to NICU and NICU length of stay. Three trials (n = 215) evaluated maintenance therapy (oral nifedipine 20 mg every 4 hours to 6 hours) versus placebo or no treatment. Nifedipine prolonged pregnancy by a mean of 6.3 days (1.2-11.4), but there were no significant differences between rates of preterm birth, recurrent preterm labor, or adverse neonatal outcomes.

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