Tocolytic therapy for preterm delivery: Systematic review and network meta-analysis

David M. Haas, Deborah M. Caldwell, Page Kirkpatrick, Jennifer J. McIntosh, Nicky J. Welton

Research output: Contribution to journalArticle

201 Citations (Scopus)

Abstract

Objective: To determine the most effective tocolytic agent at delaying delivery. Design: Systematic review and network meta-analysis. Data sources: Cochrane Central Register of Controlled Trials, Medline, Medline In-Process, Embase, and CINAHL up to 17 February 2012. Study selection: Randomised controlled trials of tocolytic therapy in women at risk of preterm delivery. Data extraction: At least two reviewers extracted data on study design, characteristics, number of participants, and outcomes reported (neonatal and maternal). A network meta-analysis was done using a random effects model with drug class effect. Two sensitivity analyses were carried out for the primary outcome; restricted to studies at low risk of bias and restricted to studies excluding women at high risk of preterm delivery (those with multiple gestation and ruptured membranes). Results: Of the 3263 titles initially identified, 95 randomized controlled trials of tocolytic therapy were reviewed. Compared with placebo, the probability of delivery being delayed by 48 hours was highest with prostaglandin inhibitors (odds ratio 5.39, 95% credible interval 2.14 to 12.34) followed by magnesium sulfate (2.76, 1.58 to 4.94), calcium channel blockers (2.71, 1.17 to 5.91), beta mimetics (2.41, 1.27 to 4.55), and the oxytocin receptor blocker atosiban (2.02, 1.10 to 3.80). No class of tocolytic was significantly superior to placebo in reducing neonatal respiratory distress syndrome. Compared with placebo, side effects requiring a change of medication were significantly higher for beta mimetics (22.68, 7.51 to 73.67), magnesium sulfate (8.15, 2.47 to 27.70), and calcium channel blockers (3.80, 1.02 to 16.92). Prostaglandin inhibitors and calcium channel blockers were the tocolytics with the best probability of being ranked in the top three medication classes for the outcomes of 48 hour delay in delivery, respiratory distress syndrome, neonatal mortality, and maternal side effects (all cause). Conclusions: Prostaglandin inhibitors and calcium channel blockers had the highest probability of delaying delivery and improving neonatal and maternal outcomes.

Original languageEnglish (US)
Article numbere6226
JournalBMJ (Online)
Volume345
Issue number7879
DOIs
StatePublished - Oct 20 2012

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Tocolysis
Calcium Channel Blockers
Tocolytic Agents
Prostaglandin Antagonists
Magnesium Sulfate
Randomized Controlled Trials
Placebos
Mothers
Oxytocin Receptors
Newborn Respiratory Distress Syndrome
Placebo Effect
Information Storage and Retrieval
Infant Mortality
Odds Ratio
Pregnancy
Membranes
Network Meta-Analysis
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Haas, D. M., Caldwell, D. M., Kirkpatrick, P., McIntosh, J. J., & Welton, N. J. (2012). Tocolytic therapy for preterm delivery: Systematic review and network meta-analysis. BMJ (Online), 345(7879), [e6226]. https://doi.org/10.1136/bmj.e6226

Tocolytic therapy for preterm delivery : Systematic review and network meta-analysis. / Haas, David M.; Caldwell, Deborah M.; Kirkpatrick, Page; McIntosh, Jennifer J.; Welton, Nicky J.

In: BMJ (Online), Vol. 345, No. 7879, e6226, 20.10.2012.

Research output: Contribution to journalArticle

Haas, DM, Caldwell, DM, Kirkpatrick, P, McIntosh, JJ & Welton, NJ 2012, 'Tocolytic therapy for preterm delivery: Systematic review and network meta-analysis', BMJ (Online), vol. 345, no. 7879, e6226. https://doi.org/10.1136/bmj.e6226
Haas, David M. ; Caldwell, Deborah M. ; Kirkpatrick, Page ; McIntosh, Jennifer J. ; Welton, Nicky J. / Tocolytic therapy for preterm delivery : Systematic review and network meta-analysis. In: BMJ (Online). 2012 ; Vol. 345, No. 7879.
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abstract = "Objective: To determine the most effective tocolytic agent at delaying delivery. Design: Systematic review and network meta-analysis. Data sources: Cochrane Central Register of Controlled Trials, Medline, Medline In-Process, Embase, and CINAHL up to 17 February 2012. Study selection: Randomised controlled trials of tocolytic therapy in women at risk of preterm delivery. Data extraction: At least two reviewers extracted data on study design, characteristics, number of participants, and outcomes reported (neonatal and maternal). A network meta-analysis was done using a random effects model with drug class effect. Two sensitivity analyses were carried out for the primary outcome; restricted to studies at low risk of bias and restricted to studies excluding women at high risk of preterm delivery (those with multiple gestation and ruptured membranes). Results: Of the 3263 titles initially identified, 95 randomized controlled trials of tocolytic therapy were reviewed. Compared with placebo, the probability of delivery being delayed by 48 hours was highest with prostaglandin inhibitors (odds ratio 5.39, 95{\%} credible interval 2.14 to 12.34) followed by magnesium sulfate (2.76, 1.58 to 4.94), calcium channel blockers (2.71, 1.17 to 5.91), beta mimetics (2.41, 1.27 to 4.55), and the oxytocin receptor blocker atosiban (2.02, 1.10 to 3.80). No class of tocolytic was significantly superior to placebo in reducing neonatal respiratory distress syndrome. Compared with placebo, side effects requiring a change of medication were significantly higher for beta mimetics (22.68, 7.51 to 73.67), magnesium sulfate (8.15, 2.47 to 27.70), and calcium channel blockers (3.80, 1.02 to 16.92). Prostaglandin inhibitors and calcium channel blockers were the tocolytics with the best probability of being ranked in the top three medication classes for the outcomes of 48 hour delay in delivery, respiratory distress syndrome, neonatal mortality, and maternal side effects (all cause). Conclusions: Prostaglandin inhibitors and calcium channel blockers had the highest probability of delaying delivery and improving neonatal and maternal outcomes.",
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