title: Vasoactive agents for the prediction of early- and late-onset preeclampsia in a high-risk cohort.
abstract: BACKGROUND
  To evaluate the soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and sFlt-1/PlGF ratio for the prediction of early- and late-onset preeclampsia in a high-risk cohort.
  
  
  METHODS
  We studied serial serum samples collected prospectively at 12+0-14+0, 18+0-20+0, and 26+0-28+0 weeks+days of gestation in 6 women who developed early-onset preeclampsia (before 34 weeks of gestation) and in 21 women who developed late-onset preeclampsia (after 34 weeks of gestation) with automated ElecSys 2010 immunoanalyzer (Roche Diagnostics, Germany). Twenty-six high-risk women and 53 women without risk factors with normal pregnancies served as controls.
  
  
  RESULTS
  Serum PlGF concentrations were lower at 18+0 to 20+0, and 26+0 to 28+0 weeks of gestation in women who developed early-onset preeclampsia compared to women who developed late-onset preeclampsia and to controls (p<0.05 for all comparisons). At 18+0 to 20+0 weeks of gestation area under the receiver-operating characteristic curve (AUC) for serum PlGF was 99.8% (p=0.0007, 95% CI 99.0-100.0). At 26+0 to 28+0 weeks of gestation serum sFlt-1/PlGF ratio explicitly detects those women who developed early-onset preeclampsia (AUC 100.0%, p=0.0007, 95% CI 100-100). Amongst women with late-onset preeclampsia, those who developed severe form of the disease (N=8) had significantly higher serum sFlt-1 concentrations at all three timepoints (p=0.004, p=0.006, and p=0.003, respectively) compared to women with non-severe form (N=13).
  
  
  CONCLUSIONS
  Low serum PlGF concentration predicts early-onset preeclampsia from the second trimester and elevated serum sFlt-1/PlGF ratio from 26 to 28 weeks of gestation. Elevated serum sFlt-1 concentration in the first trimester in women who later develop late-onset, severe preeclampsia may suggest different etiology compared to the late-onset non-severe form of the disease.
authors.affiliation: The Research Programs Unit, Women's Health, University of Helsinki, and Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Helsinki, Finland. pia.villa@helsinki.fi
authors.forename: Pia M
authors.initials: PM
authors.lastname: Villa
authors.forename: Esa
authors.initials: E
authors.lastname: Hämäläinen
authors.forename: Annukka
authors.initials: A
authors.lastname: Mäki
authors.forename: Katri
authors.initials: K
authors.lastname: Räikkönen
authors.forename: Anu-Katriina
authors.initials: AK
authors.lastname: Pesonen
authors.forename: Pekka
authors.initials: P
authors.lastname: Taipale
authors.forename: Eero
authors.initials: E
authors.lastname: Kajantie
authors.forename: Hannele
authors.initials: H
authors.lastname: Laivuori
mesh_terms: D000328:Adult; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005865:Gestational Age; D006801:Humans; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000097:blood* / Q000175:diagnosis*; D011237:Predictive Value of Tests; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood*; D012372:ROC Curve; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1