Prevention of preterm delivery in twin gestations (PREDICT): a multicenter, randomized, placebo-controlled trial on the effect of vaginal micronized progesterone.

OBJECTIVE Studies on high-risk singleton gestations have shown a preventive effect of progesterone treatment on preterm delivery. This study was conducted to investigate the preventive effect of vaginal micronized progesterone in a large population of twin gestations. METHODS This was a double-blind, placebo-controlled randomized trial performed in 17 centers in Denmark and Austria. Women with twin gestations were randomized to daily treatment with progesterone pessaries or apparently identical placebo pessaries, starting from 20-24 weeks until 34 weeks' gestation. Primary outcome was incidence of delivery before 34 weeks' gestation. Secondary outcomes were maternal and neonatal complications and long-term infant follow-up, by Ages and Stages Questionnaire (ASQ), 6 months and 18 months after the expected date of delivery. We also updated a published meta-analysis to include our data and those of another recently published twin trial. RESULTS A total of 677 women were randomized to the two treatments. Two women in the placebo group were lost to follow-up. Baseline characteristics for the groups were similar. Incidence of delivery before 34 weeks was 15.3% in the progesterone group vs 18.5% in the placebo group (odds ratio, 0.8 (95% CI, 0.5-1.2)). Risks of maternal and neonatal complications were comparable for the two groups. Mean ASQ scores at 6 months and 18 months were not significantly different between the two groups (215 for infants in the progesterone group and 218 for infants in the placebo group at 6 months (P = 0.45) and 193 and 194, respectively, at 18 months (P = 0.89)). The meta-analysis gave a pooled odds ratio of 1.06 (95% CI, 0.86-1.31). CONCLUSION Progesterone treatment did not prevent preterm delivery in twin gestations. There were no harmful effects to fetuses and infants of maternal progesterone treatment.