Progestogen maintenance therapy for prolongation of pregnancy after an episode of preterm labour: A systematic review and meta-analysis

Abstract

Background: Evidence for progestogen maintenance therapy after an episode of preterm labour (PTL) is contradictory.

Objectives: To assess effectiveness of progestogen maintenance therapy after an episode of PTL.

Search strategy: An electronic search in Central Cochrane, Ovid Embase, Ovid Medline and clinical trial databases was performed.

Selection criteria: Randomised controlled trials (RCT) investigating women between 16⁺⁰ and 37⁺⁰ weeks of gestation with an episode of PTL who were treated with progestogen maintenance therapy compared with a control group.

Data collection and analysis: Systematic review and meta-analysis were conducted. The primary outcome was latency time in days. Secondary neonatal and maternal outcomes are consistent with the core outcome set for preterm birth studies. Studies were extensively assessed for data trustworthiness (integrity) and risk of bias.

Main results: Thirteen RCT (1722 women) were included. Progestogen maintenance therapy demonstrated a longer latency time of 4.32 days compared with controls (mean difference [MD] 4.32, 95% CI 0.40-8.24) and neonates were born with a higher birthweight (MD 124.25 g, 95% CI 8.99-239.51). No differences were found for other perinatal outcomes. However, when analysing studies with low risk of bias only (five RCT, 591 women), a significantly longer latency time could not be shown (MD 2.44 days; 95% CI -4.55 to 9.42).

Conclusions: Progestogen maintenance therapy after PTL might have a modest effect on prolongation of latency time. When analysing low risk of bias studies only, this effect was not demonstrated. Validation through further research, preferably by an individual patient data meta-analysis is highly recommended.

Keywords: arrested preterm labour; meta-analysis; preterm birth; preterm labour; progesterone; progestogen; threatened preterm birth; threatened preterm labour; tocolysis.