Vaginal progesterone decreases preterm birth ≤ 34 weeks of gestation in women with a singleton pregnancy and a short cervix: an updated meta-analysis including data from the OPPTIMUM study

Abstract

Objective: To evaluate the efficacy of vaginal progesterone administration for preventing preterm birth and perinatal morbidity and mortality in asymptomatic women with a singleton gestation and a mid-trimester sonographic cervical length (CL) ≤ 25 mm.

Methods: This was an updated systematic review and meta-analysis of randomized controlled trials comparing the use of vaginal progesterone to placebo/no treatment in women with a singleton gestation and a mid-trimester sonographic CL ≤ 25 mm. Electronic databases, from their inception to May 2016, bibliographies and conference proceedings were searched. The primary outcome measure was preterm birth ≤ 34 weeks of gestation or fetal death. Two reviewers independently selected studies, assessed the risk of bias and extracted the data. Pooled relative risks (RRs) with 95% confidence intervals (CI) were calculated.

Results: Five trials involving 974 women were included. A meta-analysis, including data from the OPPTIMUM study, showed that vaginal progesterone significantly decreased the risk of preterm birth ≤ 34 weeks of gestation or fetal death compared to placebo (18.1% vs 27.5%; RR, 0.66 (95% CI, 0.52-0.83); P = 0.0005; five studies; 974 women). Meta-analyses of data from four trials (723 women) showed that vaginal progesterone administration was associated with a statistically significant reduction in the risk of preterm birth occurring at < 28 to < 36 gestational weeks (RRs from 0.51 to 0.79), respiratory distress syndrome (RR, 0.47 (95% CI, 0.27-0.81)), composite neonatal morbidity and mortality (RR, 0.59 (95% CI, 0.38-0.91)), birth weight < 1500 g (RR, 0.52 (95% CI, 0.34-0.81)) and admission to the neonatal intensive care unit (RR, 0.67 (95% CI, 0.50-0.91)). There were no significant differences in neurodevelopmental outcomes at 2 years of age between the vaginal progesterone and placebo groups.

Conclusion: This updated systematic review and meta-analysis reaffirms that vaginal progesterone reduces the risk of preterm birth and neonatal morbidity and mortality in women with a singleton gestation and a mid-trimester CL ≤ 25 mm, without any deleterious effects on neurodevelopmental outcome. Clinicians should continue to perform universal transvaginal CL screening at 18-24 weeks of gestation in women with a singleton gestation and to offer vaginal progesterone to those with a CL ≤ 25 mm. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Keywords: cervical length; neonatal morbidity; neonatal mortality; prematurity; preterm delivery; progestins; progestogens; transvaginal ultrasound.

Figure 1

Study selection process.

Figure 2

Risk of bias of studies included in the systematic review. Risk of bias: , low; , unclear; , high.

Figure 3

Forest plot of the effect of vaginal progesterone on the risk of preterm birth ≤ 34 weeks of gestation or fetal death.