Vaginal progesterone is associated with a decrease in risk for early preterm birth and improved neonatal outcome in women with a short cervix: a secondary analysis from a randomized, double-blind, placebo-controlled trial

Objective To investigate the efficacy of vaginal progesterone to prevent early preterm birth in women with sonographic evidence of a short cervical length in the midtrimester. Methods This was a planned, but modified, secondary analysis of our multinational, multicenter, randomized, placebo-controlled trial, in which women were randomized between 18 + 0 and 22 + 6 weeks of gestation to receive daily treatment with 90 mg of vaginal progesterone gel or placebo. Cervical length was measured with transvaginal ultrasound at enrollment and at 28 weeks of gestation. Treatment continued until either delivery, 37 weeks of gestation or development of preterm rupture of membranes. Maternal and neonatal outcomes were evaluated for the subset of all randomized women with cervical length < 28 mm at enrollment. The primary outcome was preterm birth at <= 32 weeks. Results A cervical length < 28 mm was identified in 46 randomized women: 19 of 313 who received progesterone and 27 of 307 who received the placebo. Baseline characteristics of the two groups were similar. In women with a cervical length < 28 mm, the rate of preterm birth at <= 32 weeks was significantly lower for those receiving progesterone than it was for those receiving the placebo (0% vs. 29.6%, P = 0.014). With progesterone, there were fewer admissions into the neonatal intensive care unit (NICU; 15.8% vs. 51.9%, P = 0.016) and shorter NICU stays (1.1 vs. 16.5 days, P = 0.013). There was also a trend toward a decreased rate of neonatal respiratory distress syndrome (5.3% vs. 29.6%, P = 0.060). Conclusion Vaginal progesterone may reduce the rate of early preterm birth and improve neonatal outcome in women with a short sonographic cervical length. Copyright (C) 2007 ISUOG. Published by John Wiley & Sons, Ltd.