title: Maternal serum soluble fms-like tyrosine kinase-1 at 12, 22, 32 and 36 weeks' gestation in screening for pre-eclampsia.
abstract: OBJECTIVE
  To examine the distribution of maternal serum soluble fms-like tyrosine kinase-1 (sFlt-1) at 12, 22, 32 and 36 weeks' gestation in singleton pregnancies that develop pre-eclampsia (PE) and examine the performance of this biomarker in screening for PE.
  
  
  METHODS
  Serum sFlt-1 was measured in 7066 cases at 11-13 weeks, 8079 cases at 19-24 weeks, 8472 at 30-34 weeks and 4043 at 35-37 weeks. Bayes' theorem was used to combine the a-priori risk from maternal characteristics and medical history with serum levels of sFlt-1. The performance of screening for PE in women requiring delivery < 32, between 32 + 0 and 36 + 6 and ≥ 37 weeks' gestation was estimated.
  
  
  RESULTS
  In pregnancies that developed PE, serum sFlt-1 was increased and the separation in multiples of the median (MoM) values from normal was greater with earlier, compared to later, gestational age at which delivery for PE became necessary. In pregnancies that developed PE, the slope of the regression lines of sFlt-1 MoM with gestational age at delivery increased with advancing gestational age at screening. Measurement of sFlt-1 at 11-13 weeks did not improve the prediction of PE achieved by maternal factors alone, sFlt-1 at 19-24 weeks improved the prediction of PE delivering < 37 weeks but not for PE delivering ≥ 37 weeks, sFlt-1 at 30-34 weeks improved the prediction of PE delivering < 37 and PE delivering ≥ 37 weeks and sFlt-1 at 35-37 weeks improved the prediction of PE delivering ≥ 37 weeks. The detection rates (DRs), at a false-positive rate (FPR) of 10%, of PE delivering < 32 weeks were 52% and 65% with screening at 12 and 22 weeks, respectively. The DRs for PE delivering between 32 + 0 and 36 + 6 weeks were 44%, 44% and 93% with screening at 12, 22 and 32 weeks. The DR for PE delivering ≥ 37 weeks were 37%, 37%, 52% and 69% with screening at 12, 22, 32 and 36 weeks, respectively.
  
  
  CONCLUSIONS
  The performance of combined screening with maternal factors, medical history and serum sFlt-1 is superior for detection of early, compared to late, PE and improves with advancing gestational age at screening. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Tsiakkas
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
authors.forename: O
authors.initials: O
authors.lastname: Mendez
authors.affiliation: Institute of Health Research, University of Exeter, Exeter, UK.
authors.forename: A
authors.initials: A
authors.lastname: Wright
authors.affiliation: Institute of Health Research, University of Exeter, Exeter, UK.
authors.forename: D
authors.initials: D
authors.lastname: Wright
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: D001499:Bayes Theorem; D015415:Biomarkers / Q000097:blood; D005260:Female; D005865:Gestational Age; D006801:Humans; D011225:Pre-Eclampsia / Q000097:blood / Q000175:diagnosis*; D011237:Predictive Value of Tests; D011247:Pregnancy; D011264:Pregnancy Trimesters / Q000097:blood*; D047928:Premature Birth / Q000097:blood / Q000209:etiology; D011296:Prenatal Diagnosis / Q000379:methods*; D011446:Prospective Studies; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: Bayes' theorem; impaired placentation; pre-eclampsia; pyramid of pregnancy care; sFlt-1; screening