title: sFlt-1/PlGF for prediction of early-onset pre-eclampsia: STEPS (Study of Early Pre-eclampsia in Spain).
abstract: OBJECTIVE
  A high ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) has been linked to pre-eclampsia (PE). We evaluated the sFlt-1/PlGF ratio as a predictive marker for early-onset PE in women at risk of PE.
  
  
  METHODS
  This prospective, Spanish, multicenter study included pregnant women with a risk factor for PE, including intrauterine growth restriction, PE, eclampsia or hemolysis, elevated liver enzymes and low platelet count syndrome in previous pregnancy, pregestational diabetes or abnormal uterine artery Doppler. The primary objective was to show that the sFlt-1/PlGF ratio at 20, 24 and 28 weeks' gestation was predictive of early-onset PE (< 34 + 0 weeks). Serum sFlt-1 and PlGF were measured at 20, 24 and 28 weeks. Multivariate logistic regression was used to develop a predictive model.
  
  
  RESULTS
  A total of 819 women were enrolled, of which 729 were suitable for analysis. Of these, 78 (10.7%) women developed PE (24 early onset and 54 late onset). Median sFlt-1/PlGF ratio at 20, 24 and 28 weeks was 6.3 (interquartile range (IQR), 4.1-9.3), 4.0 (IQR, 2.6-6.3) and 3.3 (IQR, 2.0-5.9), respectively, for women who did not develop PE (controls); 14.5 (IQR, 5.5-43.7), 18.4 (IQR, 8.2-57.9) and 51.9 (IQR, 11.5-145.6) for women with early-onset PE; and 6.7 (IQR, 4.6-9.9), 4.7 (IQR, 2.8-7.2) and 6.0 (IQR, 3.8-10.5) for women with late-onset PE. Compared with early-onset PE, the sFlt-1/PlGF ratio was significantly lower in controls (P < 0.001 at each timepoint) and in women with chronic hypertension (P < 0.001 at each timepoint), gestational hypertension (P < 0.001 at each timepoint) and late-onset PE (P < 0.001 at each timepoint). A prediction model for early-onset PE was developed, which included the sFlt-1/PlGF ratio plus mean arterial pressure, being parous and previous PE, with areas under the receiver-operating characteristics curves of 0.86 (95% CI, 0.77-0.95), 0.91 (95% CI, 0.85-0.97) and 0.93 (95% CI, 0.86-0.99) at 20, 24 and 28 weeks, respectively, and was superior to models using the sFlt-1/PlGF ratio alone or uterine artery mean pulsatility index.
  
  
  CONCLUSIONS
  The sFlt-1/PlGF ratio can improve prediction of early-onset PE for women at risk of this condition. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
authors.affiliation: Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Perales
authors.affiliation: Universidad de Murcia and IMIB-Arrixaca, Murcia, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Delgado
authors.affiliation: Hospital Universitario La Paz, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: de la Calle
authors.affiliation: Hospital Universitario Materno Infantil de Canarias, Gran Canaria, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: García-Hernández
authors.affiliation: Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: A I
authors.initials: AI
authors.lastname: Escudero
authors.affiliation: Hospital Universitario Miguel Servet, Zaragoza, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Campillos
authors.affiliation: Universidad de Murcia and IMIB-Arrixaca, Murcia, Spain.
authors.forename: M D
authors.initials: MD
authors.lastname: Sarabia
authors.affiliation: Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Laíz
authors.affiliation: Hospital Universitario La Paz, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Duque
authors.affiliation: Hospital Universitario Materno Infantil de Canarias, Gran Canaria, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Navarro
authors.affiliation: Hospital Universitario Miguel Servet, Zaragoza, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Calmarza
authors.affiliation: Roche Diagnostics International Ltd, Rotkreuz, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Hund
authors.affiliation: Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: F V
authors.initials: FV
authors.lastname: Álvarez
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000072483:Placenta Growth Factor / Q000097:blood*; D011225:Pre-Eclampsia / Q000097:blood / Q000175:diagnosis* / Q000000981:diagnostic imaging; D011237:Predictive Value of Tests; D011247:Pregnancy; D011256:Pregnancy Outcome; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis; D011446:Prospective Studies; D013030:Spain; D016216:Ultrasonography, Prenatal; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; C000608036:PGF protein, human; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: PlGF; biomarker; early-onset prediction; hypertension; pre-eclampsia; sFlt-1; sFlt-1/PlGF ratio