Romero R, et al. - This study was performed to assess if vaginal progesterone prevents preterm birth and improves perinatal outcomes in asymptomatic women with a singleton gestation and a midtrimester sonographic short cervix. In this study, vaginal progesterone decreased the risk of preterm birth and enhanced perinatal outcomes in singleton gestations with a midtrimester sonographic short cervix, with no ascertainable harmful effects on childhood neurodevelopment.

Methods

• Researchers searched MEDLINE, EMBASE, LILACS, and CINAHL (from their inception to September 2017), Cochrane databases, bibliographies, and conference proceedings.
• They included randomized controlled trials comparing vaginal progesterone with placebo/no treatment in women with a singleton gestation and a midtrimester sonographic cervical length ≤25 mm.
• Systematic review and meta-analysis of individual patient data was performed.
• Peterm birth <33 weeks of gestation was assessed as the primary outcome.
• Secondary outcomes determined were adverse perinatal outcomes and neurodevelopmental and health outcomes at 2 years of age.
• Using a two-stage approach, individual patient data was analyzed.
• Calculation of pooled relative risks (RRs) with 95% confidence intervals (CIs) was performed.
• The GRADE methodology was used to assess quality of evidence.

Results

• Researchers identified data from 974 women (498 assigned to vaginal progesterone, 476 assigned to placebo) with a cervical length ≤25 mm participating in five high-quality trials.
• They observed an association of vaginal progesterone with a significant reduction in the risk of preterm birth <33 weeks of gestation (RR 0.62, 95% CI 0.47-0.81, P=0.0006; high-quality evidence).
• In addition, vaginal progesterone seemed significantly reducing the risk of preterm birth <36, <35, <34, <32, <30 and <28 weeks of gestation, spontaneous preterm birth <33 and <34 weeks of gestation, respiratory distress syndrome, composite neonatal morbidity and mortality, birthweight <1500 and <2500 g, and admission to the neonatal intensive care unit (RRs from 0.47 to 0.82; high-quality evidence for all).
• In the vaginal progesterone group, 7 (1.4%) neonatal deaths and in the placebo group, 15 (3.2%) neonatal deaths were evident (RR 0.44, 95% CI 0.18-1.07, P=0.07; low-quality evidence).
• The groups were comparable regarding maternal adverse events, congenital anomalies, and adverse neurodevelopmental and health outcomes at 2 years of age.