Population differences and the effect of vaginal progesterone on preterm birth in women with threatened preterm labor

Objective: Threatened preterm labor (tPTL) is a complication of pregnancy. Identification of women and clinical definition differs between countries. This study investigated differences in tPTL and effectiveness of vaginal progesterone to prevent preterm birth (PTB) between two countries. Methods: Secondary analysis of a randomized controlled trial (RCT) from Argentina and Switzerland comparing vaginal progesterone to placebo in women with tPTL (n = 379). Cox proportional hazards analysis was performed to compare placebo groups of both countries and to compare progesterone to placebo within each country. We adjusted for baseline differences. Iatrogenic onset of labor or pregnancy beyond gestational age of interest was censored. Results: Swiss and Argentinian women were different on baseline. Risks for delivery514 days and PTB534 and537 weeks were increased in Argentina compared to Switzerland, HR 3.3 (95% CI 0.62-18), 54 (95% CI 5.1-569) and 3.1 (95% CI 1.1-8.4). In Switzerland, progesterone increased the risk for delivery514 days [HR 4.4 (95% CI 1.3-15.7)] and PTB537 weeks [HR 2.5 (95% CI 1.4-4.8)], in Argentina there was no such effect. Conclusion: In women with tPTL, the effect of progesterone may vary due to population differences. Differences in populations should be considered in multicenter RCTs.