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Ultrasound Obstet Gynecol. 2019 Mar;53(3):367-375. doi: 10.1002/uog.19178. Epub 2019 Feb 4.

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

Author information

1
Department of Obstetrics and Gynecology, Medical University Vienna, Vienna, Austria.
2
Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
3
University of Liège, CHR de la Citadelle, Liège, Belgium.
4
University of Oxford, Oxford, UK.
5
Oslo University Hospital and University of Oslo, Oslo, Norway.
6
Karolinska University Hospital, Stockholm, Sweden.
7
Uppsala University, Uppsala, Sweden.
8
Department of Obstetrics and Gynaecology, The University of Melbourne and Royal Women's Hospital, Melbourne, Australia.
9
Leipzig University, Leipzig, Germany.
10
Roche Diagnostics International Ltd, Rotkreuz, Switzerland.
11
Roche Diagnostics GmbH, Penzberg, Germany.
12
Charité -Universitätsmedizin, Berlin, Germany.

Abstract

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 1 week 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 + 6 weeks' 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® 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 1 week 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 3 weeks post-baseline with high negative predictive values (NPV) of 97.9% and 95.7%, respectively. The onset of pre-eclampsia within 4 weeks 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 2 weeks; ∆, 34.95 vs 2.30; P < 0.001 at 3 weeks).

CONCLUSION:

The Elecsys® immunoassay sFlt-1/PlGF ratio can help to rule out the onset of pre-eclampsia for 4 weeks in women with suspected pre-eclampsia. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

KEYWORDS:

PROGNOSIS; PlGF; angiogenic factors; pre-eclampsia; retesting; rule out; sFlt-1; sFlt-1/PlGF

PMID:
30014562
DOI:
10.1002/uog.19178
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