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Tocolytic therapy for preterm delivery: systematic review and network meta-analysis. BMJ 2012 Oct 09;345:e6226

Date

10/11/2012

Pubmed ID

23048010

Pubmed Central ID

PMC4688428

DOI

10.1136/bmj.e6226

Scopus ID

2-s2.0-84867774233 (requires institutional sign-in at Scopus site)   272 Citations

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.

Author List

Haas DM, Caldwell DM, Kirkpatrick P, McIntosh JJ, Welton NJ

Author

Jennifer Jury Mcintosh DO Associate Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Calcium Channel Blockers
Female
Humans
Magnesium Sulfate
Obstetric Labor, Premature
Pregnancy
Pregnancy Complications
Pregnancy Outcome
Prostaglandin Antagonists
Randomized Controlled Trials as Topic
Time Factors
Tocolysis
Tocolytic Agents
Treatment Outcome
Vasotocin