title: Competing-risks model in screening for pre-eclampsia by maternal factors and biomarkers at 35-37 weeks' gestation.
abstract: OBJECTIVE
  To develop a model for prediction of term pre-eclampsia (PE) based on a combination of maternal factors and late third-trimester biomarkers.
  
  
  METHODS
  Data were derived from prospective screening for adverse obstetric outcomes in women attending their routine hospital visit at 35-37 weeks' gestation in two maternity hospitals in the UK. Uterine artery pulsatility index (UtA-PI) was measured in 5362 pregnancies, mean arterial pressure (MAP) in 5386 and serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1) in 3920. Bayes' theorem was used to combine the a-priori risk of PE from maternal factors with various combinations of biomarkers, expressed as multiples of the median (MoM). Five-fold cross-validation was used to estimate the performance of screening for PE, requiring delivery at some stage after assessment. The empirical performance of screening was compared to model predictions.
  
  
  RESULTS
  In pregnancies that developed PE, the values of MAP, UtA-PI and sFlt-1 were increased and PlGF was decreased compared to unaffected pregnancies. For all biomarkers evaluated, the deviation from normal was inversely related to the gestational age at which delivery became necessary for maternal or fetal indications. Screening by maternal factors and by a combination of maternal factors with all biomarkers predicted 35% and 84% of PE, respectively, at a 10% false-positive rate.
  
  
  CONCLUSIONS
  A combination of maternal factors and biomarkers at 35-37 weeks' gestation can provide effective screening for term PE. 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: S
authors.initials: S
authors.lastname: Andrietti
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Silva
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: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D001794:Blood Pressure; D005260:Female; D006801:Humans; D008962:Models, Theoretical; D000072483:Placenta Growth Factor / Q000097:blood; D011225:Pre-Eclampsia / Q000097:blood / Q000000981:diagnostic imaging / Q000517:prevention & control*; D011237:Predictive Value of Tests; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D011296:Prenatal Diagnosis; D011446:Prospective Studies; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
chemical_list: D015415:Biomarkers; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: Bayes' theorem; mean arterial pressure; placental growth factor; pre-eclampsia; pyramid of pregnancy care; soluble fms-like tyrosine kinase-1; survival model; third-trimester screening; uterine artery Doppler