Insufficient evidence that progestogen maintenance prolongs pregnancy after preterm labor

Reference

Breuking SH, De Ruigh AA, Hermans FJR, et al. Progestogen maintenance therapy for prolongation of pregnancy after an episode of preterm labour: A systematic review. BJOG 2023;130(11):1306-1316.

Synopsis

These researchers conducted a meta-analysis of randomized controlled trials (1722 participants in 13 trials) that compared maintenance progestogen therapy after treatment for preterm labor (PTL) with a control treatment (placebo, no treatment, or standard care). Eligible studies included participants at gestational age between 16 0/7 weeks and 37 0/7 weeks who were diagnosed with PTL with intact membranes, and the researchers had no restriction on the type of progestogen or route of administration. They excluded studies that included participants with signs of intrauterine infection, indication for immediate delivery, or confirmed fetal anomaly. They also applied strict data integrity requirements for study inclusion. The most commonly used progestogen treatment was vaginal progesterone. Patients who received maintenance therapy had a mean latency of 39.4 days (vs 35.1 days for the control patients; mean difference 4.3 days; 95% CI 0.4 - 8.24), which was the primary outcome. However, when the analysis was restricted to the 5 studies with low risk of bias, the difference was 2.4 days (NS). The mean birthweight was modestly higher (mean 124 g) with maintenance therapy. Maintenance therapy did not reduce the incidence of preterm birth at less than 37 weeks' or 34 weeks' (secondary outcomes). The incidence of readmission for PTL was decreased in the maintenance therapy group but didn’t reach statistical significance. A sensitivity analysis of initiation of maintenance therapy within 48 hours showed a mean latency of 6.7 days (versus 3.35 days when therapy was started 48 hours after admission), which also did not reach statistical significance. If larger sample would find a statistically significant difference of 3 days, that would be clinically meaningful.