Effectiveness of terbutaline pump for the prevention of preterm birth. A systematic review and meta-analysis

Abstract

Background: Subcutaneous terbutaline (SQ terbutaline) infusion by pump is used in pregnant women as a prolonged (beyond 48-72 h) maintenance tocolytic following acute treatment of preterm contractions. The effectiveness and safety of this maintenance tocolysis have not been clearly established. We aimed to systematically evaluate the effectiveness and safety of subcutaneous (SQ) terbutaline infusion by pump for maintenance tocolysis.

Methodology/principal findings: MEDLINE, EMBASE, CINAHL, the Cochrane Library, the Centre for Reviews and Dissemination databases, post-marketing surveillance data and grey literature were searched up to April 2011 for relevant experimental and observational studies. Two randomized trials, one nonrandomized trial, and 11 observational studies met inclusion criteria. Non-comparative studies were considered only for pump-related harms. We excluded case-reports but sought FDA summaries of post-marketing surveillance data. Non-English records without an English abstract were excluded. Evidence of low strength from observational studies with risk of bias favored SQ terbutaline pump for the outcomes of delivery at <32 and <37 weeks, mean days of pregnancy prolongation, and neonatal death. Observational studies of medium to high risk of bias also demonstrated benefit for other surrogate outcomes, such as birthweight and neonatal intensive care unit (NICU) admission. Several cases of maternal deaths and maternal cardiovascular events have been reported in patients receiving terbutaline tocolysis.

Conclusions/significance: Although evidence suggests that pump therapy may be beneficial as maintenance tocolysis, our confidence in its validity and reproducibility is low, suggesting that its use should be limited to the research setting. Concerns regarding safety of therapy persist.

Figure 1. Flow of retrieved records through screening and inclusion.

Figure 2. Mean gestational age at delivery (weeks).

Statistical heterogeneity for the RCT pooled estimate: I² = 0.0 percent, p-value>0.05. * There were discrepancies in the information presented in the text and table of this paper . Mean gestational age at delivery for SQ terbutaline pump was reported as 36.6 weeks in table (as reported above) and 37.2 weeks in text. The value 36.6 weeks was used to calculate difference in means. SQ = subcutaneous.

Figure 3. Mean birthweight (grams).

Statistical heterogeneity for the RCT pooled estimate: I² = 0.0 percent, p-value>0.05. * There were discrepancies in the information presented in the text and table of this paper . The numbers reported in the table were used to calculate the difference in means. However, the text reported group data with numbers switched for the groups (i.e. SQ terbutaline pump: 3229±584 and oral terbutaline: 3017±303). SQ = subcutaneous.