Prediction of Preeclampsia Using the Soluble fms-Like Tyrosine Kinase 1 to Placental Growth Factor Ratio: A Prospective Cohort Study of Unselected Nulliparous Women.
We sought to assess the ratio of sFlt-1 (soluble fms-like tyrosine kinase 1) to PlGF (placental growth factor) in maternal serum as a screening test for preeclampsia in unselected nulliparous women with a singleton pregnancy. We studied 4099 women recruited to the POP study (Pregnancy Outcome Prediction) (Cambridge, United Kingdom). The sFlt-1:PlGF ratio was measured using the Roche Cobas e411 platform at ≈20, ≈28, and ≈36 weeks of gestational age (wkGA). Screen positive was defined as an sFlt-1:PlGF ratio >38, but higher thresholds were also studied. At 28 wkGA, an sFlt-1:PlGF ratio >38 had a positive predictive value (PPV) of 32% for preeclampsia and preterm birth, and the PPV was similar comparing women with low and high prior risk of disease. At 36 wkGA, an sFlt-1:PlGF ratio >38 had a PPV for severe preeclampsia of 20% in high-risk women and 6.4% in low-risk women. At 36 wkGA, an sFlt-1:PlGF ratio >110 had a PPV of 30% for severe preeclampsia, and the PPV was similar comparing low- and high-risk women. Overall, at 36 wkGA, 195 (5.2%) women either had an sFlt-1:PlGF ratio of >110 or an sFlt-1:PlGF ratio >38 plus maternal risk factors: 43% of these women developed preeclampsia, about half with severe features. Among low-risk women at 36 wkGA, an sFlt-1:PlGF ratio ≤38 had a negative predictive value for severe preeclampsia of 99.2%. The sFlt-1:PlGF ratio provided clinically useful prediction of the risk of the most important manifestations of preeclampsia in a cohort of unselected nulliparous women.
From the Department of Obstetrics and Gynaecology, University of Cambridge, United Kingdom (U.S., F.G., E.C., D.S.C.-J., G.C.S.S.); NIHR (National Institute for Health Research) Cambridge Comprehensive Biomedical Research Centre, United Kingdom (U.S., F.G., E.C., D.S.C.-J., G.C.S.S.); and Roche Diagnostics International, Rotkreuz, Switzerland (M.H.). gcss2@cam.ac.uk.
Ulla
U
Sovio
From the Department of Obstetrics and Gynaecology, University of Cambridge, United Kingdom (U.S., F.G., E.C., D.S.C.-J., G.C.S.S.); NIHR (National Institute for Health Research) Cambridge Comprehensive Biomedical Research Centre, United Kingdom (U.S., F.G., E.C., D.S.C.-J., G.C.S.S.); and Roche Diagnostics International, Rotkreuz, Switzerland (M.H.).
Francesca
F
Gaccioli
From the Department of Obstetrics and Gynaecology, University of Cambridge, United Kingdom (U.S., F.G., E.C., D.S.C.-J., G.C.S.S.); NIHR (National Institute for Health Research) Cambridge Comprehensive Biomedical Research Centre, United Kingdom (U.S., F.G., E.C., D.S.C.-J., G.C.S.S.); and Roche Diagnostics International, Rotkreuz, Switzerland (M.H.).
Emma
E
Cook
From the Department of Obstetrics and Gynaecology, University of Cambridge, United Kingdom (U.S., F.G., E.C., D.S.C.-J., G.C.S.S.); NIHR (National Institute for Health Research) Cambridge Comprehensive Biomedical Research Centre, United Kingdom (U.S., F.G., E.C., D.S.C.-J., G.C.S.S.); and Roche Diagnostics International, Rotkreuz, Switzerland (M.H.).
Martin
M
Hund
From the Department of Obstetrics and Gynaecology, University of Cambridge, United Kingdom (U.S., F.G., E.C., D.S.C.-J., G.C.S.S.); NIHR (National Institute for Health Research) Cambridge Comprehensive Biomedical Research Centre, United Kingdom (U.S., F.G., E.C., D.S.C.-J., G.C.S.S.); and Roche Diagnostics International, Rotkreuz, Switzerland (M.H.).
D Stephen
DS
Charnock-Jones
From the Department of Obstetrics and Gynaecology, University of Cambridge, United Kingdom (U.S., F.G., E.C., D.S.C.-J., G.C.S.S.); NIHR (National Institute for Health Research) Cambridge Comprehensive Biomedical Research Centre, United Kingdom (U.S., F.G., E.C., D.S.C.-J., G.C.S.S.); and Roche Diagnostics International, Rotkreuz, Switzerland (M.H.).
Gordon C S
GC
Smith
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D005865:Gestational Age; D006801:Humans; D010298:Parity; D000072483:Placenta Growth Factor / Q000097:blood*; D011225:Pre-Eclampsia / Q000097:blood* / Q000175:diagnosis; D011237:Predictive Value of Tests; D011247:Pregnancy; D011256:Pregnancy Outcome; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D011446:Prospective Studies; D012372:ROC Curve; D012307:Risk Factors; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*; D055815:Young Adult
D015415:Biomarkers; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1
clinical markers; cohort studies; immunoassay; pregnancy; risk factors