To establish gestational phase adapted cutoffs for the use of the soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio as a diagnostic tool for preeclampsia in the clinical setting, a multicenter case–control study including a total of 1149 patients was performed. We report normal values of sFlt-1, PlGF, and the sFlt-1/PlGF ratio based on the analysis of a total of 877 patients with uneventful pregnancy outcome. A total of 234 patients with preeclampsia and a matched cohort consisting of 468 patients with normal pregnancy outcome were compared, and sFlt-1 and PlGF were measured on an automated platform. Separate cutoffs for the sFlt-1/PlGF ratio were determined for the early (20+0–33+6 weeks) and the late gestational phase (34+0 weeks–delivery). For each of the 2 gestational phases, 2 independent cutoffs framing an equivocal zone were determined: the first cutoff with focus on high sensitivity, and the second focusing on high specificity. Between 20+0 and 33+6 weeks, the cutoffs at ≤33 and ≥85 resulted in a sensitivity/specificity of 95%/94% and 88%/99.5%, respectively. An sFlt-1/PlGF ratio of ≤33 had the lowest likelihood of a negative test (0.05; 95% confidence interval, 0.02–0.13), whereas values ≥85 had the highest likelihood of a positive test (176; 95% confidence interval, 24.88–1245). After 34+0 weeks, the cutoffs at ≤33 and ≥110 yielded a sensitivity/specificity of 89.6%/73.1% and 58.2%/95.5%, respectively. The approach to use multiple cutoffs for the early and late gestational phase enhances the diagnostic accuracy of the sFlt-1/PlGF ratio as a diagnostic tool for preeclampsia.

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Objective: Preterm birth is the leading cause of perinatal morbidity and mortality worldwide. Treatment of preterm labor with tocolysis has not been successful in improving infant outcome. The administration of progesterone and related compounds has been proposed as a strategy to prevent preterm birth. The objective of this trial was to determine whether prophylactic administration of vaginal progesterone reduces the risk of preterm birth in women with a history of spontaneous preterm birth.Methods: This randomized, double‐blind, placebo‐ controlled, multinational trial enrolled and randomized 659 pregnant women with a history of spontaneous preterm birth. Between 18 + 0 and 22 + 6 weeks of gestation, patients were assigned randomly to once‐daily treatment with either progesterone vaginal gel or placebo until either delivery, 37 weeks' gestation or development of preterm rupture of membranes. The primary outcome was preterm birth at ≤ 32 weeks of gestation. The trial was analyzed using an intent‐to‐treat strategy.Results: Baseline characteristics were similar in the two treatment groups. Progesterone did not decrease the frequency of preterm birth at ≤ 32 weeks. There was no difference between the groups with respect to the mean gestational age at delivery, infant morbidity or mortality or other maternal or neonatal outcome measures. Adverse events during the course of treatment were similar for the two groups.Conclusion: Prophylactic treatment with vaginal progesterone did not reduce the frequency of recurrent preterm birth (≤ 32 weeks) in women with a history of spontaneous preterm birth. The effect of progesterone administration in patients at high risk for preterm delivery as determined by methods other than history alone (e.g. sonographic cervical length) requires further investigation. Copyright © 2007 ISUOG. Published by John Wiley & Sons, Ltd.