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

Hypertension. 2017 Apr;69(4):731-738. doi: 10.1161/HYPERTENSIONAHA.116.08620. Epub 2017 Feb 6.

Abstract

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.

Keywords: clinical markers; cohort studies; immunoassay; pregnancy; risk factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / blood
  • Female
  • Follow-Up Studies
  • Gestational Age
  • Humans
  • Parity*
  • Placenta Growth Factor / blood*
  • Pre-Eclampsia / blood*
  • Pre-Eclampsia / diagnosis
  • Predictive Value of Tests
  • Pregnancy
  • Pregnancy Outcome
  • Pregnancy Trimester, Second
  • Pregnancy Trimester, Third
  • Prospective Studies
  • ROC Curve
  • Risk Factors
  • Vascular Endothelial Growth Factor Receptor-1 / blood*
  • Young Adult

Substances

  • Biomarkers
  • Placenta Growth Factor
  • Vascular Endothelial Growth Factor Receptor-1