The importance of repeated measurements of the sFlt-1/PlGF ratio for the prediction of preeclampsia and intrauterine growth restriction.

AIMS: The sFlt-1/PlGF ratio has been evaluated as a diagnostic marker for preeclampsia (PE). The aim of this study was to explore the use of the sFlt-1/PlGF ratio as an aid in prediction for PE. METHODS: 150 patients with a high risk for PE were enrolled in this prospective study. Groups were compared according to the pregnancy outcome: controls (n=114), intrauterine growth restriction (IUGR) (n=14) and PE (n=22) with subclassification early PE<34 weeks (n=6). Measurements of sFlt-1 and PlGF were performed on the automated Elecsys system. Statistical comparison of the sFlt-1/PlGF ratio in different outcome groups and a mixed model analysis using random intercept models were performed. RESULTS: The sFlt-1/PlGF ratio was significantly higher in pregnancies complicated by PE up to 4 weeks before clinical diagnosis compared to controls (106.7 ± 47.7 vs. 21.0 ± 4.1; P=0.02). Levels of the sFlt-1/PlGF ratio were higher throughout pregnancy in women with IUGR compared to PE/control patients (intercept 1.57 vs. 1.30/0.67; P<0.05). The slope for the sFlt-1/PlGF ratio was significantly higher in PE and IUGR pregnancies compared to controls, indicating that a steep increase of the sFlt-1/PlGF ratio correlates with pathologic pregnancy outcomes. CONCLUSION: The sFlt-1/PlGF ratio can identify pathologic pregnancy outcomes such as IUGR and PE before clinical diagnosis. Repeated measurements are necessary to assess the dynamics in serum values. The time-dependent slope of the sFlt-1/PlGF ratio is predictive for future pregnancy outcome and risk of developing preeclampsia.

New gestational phase-specific cutoff values for the use of the soluble fms-like tyrosine kinase-1/placental growth factor ratio as a diagnostic test for preeclampsia.

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.

Automated measurement of sFlt1, PlGF and sFlt1/PlGF ratio in differential diagnosis of hypertensive pregnancy disorders.

OBJECTIVES: The utility of angiogenic and antiangiogenic biomarkers as diagnostic tools in preeclampsia (PE) has been shown in previous studies. Our study's aim was to evaluate the use of automated measurement of sFlt1, PlGF and their ratio (sFlt1/PlGF) in differential diagnosis of hypertensive pregnancy disorders. PATIENTS/METHODS: Sixty-four patients with PE/HELLP, 18 with pregnancy-induced hypertension (PIH), 22 with gestational proteinuria (GP) and 232 controls were investigated. The PE/HELLP group was divided into mild PE (mPE, n=31), severe PE (sevPE, n=20), superimposed PE (supPE, n=7) and HELLP syndrome (n=6). sFlt1 and PlGF were measured in serum samples on an automated platform. Statistical analysis was performed using parametric and non-parametric methods, ROC analysis and logistic regression method. RESULTS: PE patients showed higher sFlt1 and ratio and lower PlGF than controls (median ± SEM in pg/mL; 10888 ± 878 versus 2456 ± 116; 268 ± 39 versus 16 ± 2 and 68 ± 6 versus 439 ± 37, each p<0.001), subgroups showed similar differences in ratios (median ± SEM; supPE: 202 ± 110; mPE: 137 ± 27; sevPE: 497 ± 91; HELLP syndrome: 254 ± 72 versus controls 16 ± 2, each p<0.001). ROC analysis showed best performance for sFlt1/PlGF (AUC all PE: ratio 96.4%, sFlt1 92.8%, PlGF 92.4%, supPE: ratio 93.6%, mPE: ratio 94.8%, sevPE: ratio 99.4%, HELLP: ratio 98.6%, each versus controls). Patients with PIH and GP showed significant differences compared to controls (p ≤ 0.01, respectively), mPE (p ≤ 0.007), sevPE (p<0.001) and HELLP syndrome (p ≤ 0.003). CONCLUSION: The automated measurement of sFlt1/PlGF is a reliable diagnostic tool in differential diagnosis of hypertensive pregnancy disorders and gives additional valuable information for clinical management.