Soluble fms-like tyrosine kinase-1 to placental growth factor ratio: ruling out pre-eclampsia for up to 4weeks and value of retesting

• Published in: Ultrasound in obstetrics & gynecology 2019, Vol.53 (3), p.367
• Main Authors: Zeisler, H., Llurba, E., Chantraine, F. J., Vatish, M., Staff, A. C., Sennstrom, M., Olovsson, Matts, Brennecke, S. P., Stepan, H., Allegranza, D., Schoedl, M., Grill, S., Hund, M., Verlohren, S.
• Format: Article
• Language: English
• Subjects: angiogenic factors; PlGF; pre-eclampsia; PROGNOSIS; retesting; rule out; sFlt-1; sFlt-1/PlGF
• ISSN: 1469-0705; 0960-7692
• DOI: 10.1002/uog.19178

Objectives The soluble fms-like tyrosine kinase-1 ( sFlt-1) to placental growth factor ( PlGF) ratio is generally elevated some time before and at the clinical onset of pre-eclampsia. The PROGNOSIS study validated a sFlt-1/PlGF ratio cut-off of = 38 to rule out the onset of pre-eclampsia within 1week of testing in women with suspected disease. The aim of this study was to assess the predictive value of the sFlt-1/PlGF ratio to rule out the onset of pre-eclampsia for up to 4 weeks, and to assess the value of repeat measurements. Methods This was an exploratory post-hoc analysis of data from the PROGNOSIS study performed in pregnant women aged = 18 years with suspected pre-eclampsia, who were at 24+ 0 to 36+ 6weeks' gestation at their first clinic visit. Serum samples were collected at the first visit and weekly thereafter. sFlt-1 and PlGF levels were measured using Elecsys (R) sFlt-1 and PlGF immunoassays. Whether the sFlt-1/PlGF ratio cut-off of = 38 used to rule out the onset of pre-eclampsia within 1week could predict the absence of pre-eclampsia 2, 3, and 4 weeks post-baseline was assessed. The value of repeat sFlt-1/PlGF testing was assessed by examining the difference in sFlt-1/PlGF ratio 2 and 3 weeks after the first measurement in women with, and those without, pre-eclampsia or adverse fetal outcome. Results On analysis of 550 women, sFlt-1/PlGF ratio = 38 ruled out the onset of pre-eclampsia 2 and 3weeks post-baseline with high negative predictive values (NPV) of 97.9% and 95.7%, respectively. The onset of pre-eclampsia within 4weeks was ruled out with a high NPV (94.3%) and high sensitivity and specificity (66.2% and 83.1%, respectively). Compared with women who did not develop pre-eclampsia, those who developed pre-eclampsia had significantly larger median increases in sFlt-1/PlGF ratio at 2 weeks (., 31.22 vs 1.45; P< 0.001) and at 3 weeks (., 48.97 vs 2.39; P< 0.001) after their initial visit. Women who developed pre-eclampsia and/or adverse fetal outcome compared with those who did not had a significantly greater median increase in sFlt-1/PlGF ratio over the same period (., 21.22 vs 1.40; P< 0.001 at 2weeks;., 34.95 vs 2.30; P< 0.001 at 3weeks). Conclusion The Elecsys (R) immunoassay sFlt-1/PlGF ratio can help to rule out the onset of pre-eclampsia for 4 weeks in women with suspected pre-eclampsia.