Tocolytic therapy: a meta-analysis and decision analysis

Abstract

Objective: To determine the optimal first-line tocolytic agent for treatment of premature labor.

Methods: We performed a quantitative analysis of randomized controlled trials of tocolysis, extracting data on maternal and neonatal outcomes, and pooling rates for each outcome across trials by treatment. Outcomes were delay of delivery for 48 hours, 7 days, and until 37 weeks; adverse effects causing discontinuation of therapy; absence of respiratory distress syndrome; and neonatal survival. We used weighted proportions from a random-effects meta-analysis in a decision model to determine the optimal first-line tocolytic therapy. Sensitivity analysis was performed using the standard errors of the weighted proportions.

Results: Fifty-eight studies satisfied the inclusion criteria. A random-effects meta-analysis showed that all tocolytic agents were superior to placebo or control groups at delaying delivery both for at least 48 hours (53% for placebo compared with 75-93% for tocolytics) and 7 days (39% for placebo compared with 61-78% for tocolytics). No statistically significant differences were found for the other outcomes, including the neonatal outcomes of respiratory distress and neonatal survival. The decision model demonstrated that prostaglandin inhibitors provided the best combination of tolerance and delayed delivery. In a hypothetical cohort of 1,000 women receiving prostaglandin inhibitors, only 80 would deliver within 48 hours, compared with 182 for the next-best treatment.

Conclusion: Although all current tocolytic agents were superior to no treatment at delaying delivery for both 48 hours and 7 days, prostaglandin inhibitors were superior to the other agents and may be considered the optimal first-line agent before 32 weeks of gestation to delay delivery.