Prediction of Preeclampsia Using the Soluble fms-Like Tyrosine Kinase 1 to Placental Growth Factor Ratio: A Prospective Cohort Study of Unselected Nulliparous Women.

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Gaccioli, Francesca  ORCID logo
Cook, E 
Hund, M 
Jones, David Stephen 

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.

clinical markers, cohort studies, immunoassay, pregnancy, risk factors
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American Heart Association
Medical Research Council (G1100221)
Medical Research Council (MR/K021133/1)
The work was supported by the National Institute for Health Research (NIHR) Cambridge Comprehensive Biomedical Research Centre (Women’s Health theme), and project grants from the Medical Research Council (United Kingdom; G1100221) and the Stillbirth and neonatal death society (Sands). The study was also supported by Roche Diagnostics (provision of equipment and reagents for analysis of sFlt-1 [soluble fms-like tyrosine kinase 1] and PlGF [placental growth factor]), by GE Healthcare (donation of 2 Voluson i ultrasound systems for this study), and by the NIHR Cambridge Clinical Research Facility, where all research visits took place.