Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Oct 9:345:e6226.
doi: 10.1136/bmj.e6226.

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

David M Haas  1 , Deborah M Caldwell, Page Kirkpatrick, Jennifer J McIntosh, Nicky J Welton
Affiliations

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

David M Haas et al. BMJ. .

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.

PubMed Disclaimer

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work. DMC and NJW have taught for Pfizer and provided training on network meta-analysis to a research organization that undertakes systematic reviews and network meta-analysis for industry. None of these activities directly conflicts with the network meta-analysis presented.

Figures

None
Fig 1 Summary of steps for trial retrieval for network meta-analysis
None
Fig 2 Graphic representation of tocolytic trials retrieved for network meta-analysis. Lines represent trials comparing two classes of drug for treatment of preterm delivery. Numbers on lines represent number of trials and total number of participants in those trials
None
Fig 3 Results from network and pairwise meta-analyses for 48 hour delay in delivery. Direct meta-analysis refers to trials that compared two drug classes directly. In most cases analyses were undertaken using a random effects model. *Fixed effect meta-analyses. †Single trial. ‡Continuity correction used (0.5 added to each cell of 2×2 table)
None
Fig 4 Results from network and pairwise meta-analyses for neonatal mortality. Direct meta-analysis refers to trials that compared two drug classes directly. In most cases analyses were undertaken using a random effects model. *Fixed effect meta-analyses. †Single trial. ‡Continuity correction used (0.5 added to each cell of 2×2 table)
None
Fig 5 Results from network and pairwise meta-analyses for neonatal respiratory distress syndrome. Direct meta-analysis refers to trials that compared two drug classes directly. In most cases analyses were undertaken using a random effects model. *Fixed effect meta-analyses. †Single trial
None
Fig 6 Results from network and pairwise meta-analyses for maternal side effects. Direct meta-analysis refers to trials that compared two drug classes directly. In most cases analyses were undertaken using a random effects model. *Fixed effect meta-analyses. †Single trial
None
Fig 7 Rankings for efficacy of tocolytics and adverse events. Graph displays distribution of probabilities for each outcome. Ranking indicates probability that drug class is first “best,” second “best,” etc. Dot-dashed line represents 48 hour delay in delivery. Solid line indicates neonatal mortality. Dashed line indicates respiratory distress syndrome. Dotted line represents all cause maternal side effects
See this image and copyright information in PMC

Comment in

References

    1. Haas DM, Imperiale TF, Kirkpatrick PR, Klein RW, Zollinger TW, Golichowski AM. Tocolytic therapy: a meta-analysis and decision analysis. Obset Gynecol 2009;113:585-94. - PubMed
    1. Roberts D, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2006;(3):CD004454. - PubMed
    1. Hamilton BE, Martin JA, Ventura SJ. Births: preliminary data for 2008. Natl Vital Stat Rep 2010;58:1-17. - PubMed
    1. ACOG practice bulletin. Management of preterm labor. No 43, May 2003. Obstet Gynecol 2003;101:1039-47. - PubMed
    1. Goldenberg RL. The management of preterm labor. Obstet Gynecol 2002;100:1020-37. - PubMed

Publication types

MeSH terms

LinkOut - more resources