title: Longitudinal changes in maternal serum placental growth factor and soluble fms-like tyrosine kinase-1 in women at increased risk of pre-eclampsia.
abstract: OBJECTIVE
  To investigate longitudinal changes in maternal serum levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) in pregnant women who develop pre-eclampsia (PE) or gestational hypertension (GH).
  
  
  METHODS
  This was a prospective longitudinal study in women with singleton pregnancies identified by screening at 11 + 0 to 13 + 6 weeks' gestation as being at high-risk of PE. Blood samples were taken every 4 weeks until delivery. Values were compared in women who developed preterm PE (requiring delivery before 37 weeks' gestation), term PE or GH and those who remained normotensive.
  
  
  RESULTS
  A total of 1069 samples were analyzed in 234 women, including 172 who remained normotensive, 18 who developed GH, 22 who developed preterm PE and 22 who developed term PE. In the preterm PE group, compared to the normotensive group, sFlt-1 levels were significantly higher from 15 weeks' gestation onward and the difference increased with gestational age (P < 0.001). In the preterm PE group, compared to the normotensive group, PlGF levels were significantly lower from 11 weeks' gestation onward and the difference increased significantly with gestational age (P < 0.001). Similarly, in the term PE and GH groups, PlGF levels were lower from 13 and 27 weeks onward, respectively, and the differences increased significantly with gestational age (P < 0.001 for both groups). In the preterm PE group, compared to the normotensive group, the sFlt-1/PlGF ratio was significantly higher from 11 weeks onward and the difference increased significantly with gestational age (P < 0.001). A random slope model provided a significantly better fit to the data than did a single-level model for sFlt-1 (likelihood ratio (LR) = 516; degrees of freedom (df) = 3; P < 0.001), PlGF (LR = 542; df = 3; P < 0.001) and the sFlt-1/PlGF ratio (LR = 468; df = 3; P < 0.001).
  
  
  CONCLUSIONS
  Repeat measurements of the biochemical markers used in this study are likely to be better predictors of PE than are measurements at a single time point during pregnancy, as the differences between normotensive and hypertensive pregnancies increase with gestational age. In screening for preterm PE, maternal serum level of PlGF is a useful marker from the first trimester onward, while the level of sFlt-1 is likely to have a predictive value from the second trimester onward. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.
authors.affiliation: Department of Fetal Medicine, St George's University of London, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Khalil
authors.affiliation: Fetal Medicine Unit, Obstetrics and Gynecology Service, BioCruces Health Research Institute, Hospital Universitario Cruces, University of the Basque Country (UPV/EHU), Barakaldo, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Maiz
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Garcia-Mandujano
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Penco
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
authors.forename: K H
authors.initials: KH
authors.lastname: Nicolaides
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D042241:Early Diagnosis; D005260:Female; D005865:Gestational Age; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000097:blood*; D008137:Longitudinal Studies; D000072483:Placenta Growth Factor / Q000097:blood*; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000097:blood; D011446:Prospective Studies; D012680:Sensitivity and Specificity; 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: blood pressure; gestational hypertension; placental growth factor; pre-eclampsia; pregnancy screening; soluble fms-like tyrosine kinase-1