title: Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 19-24 weeks' gestation.
abstract: Preeclampsia (PE) affects 2-3% of all pregnancies and is a major cause of maternal and perinatal morbidity and mortality. The traditional approach to screening for PE is to use a risk-scoring system based on maternal demographic characteristics and medical history (maternal factors), but the performance of such an approach is very poor.
  
  
  
  To develop a model for PE based on a combination of maternal factors with second-trimester biomarkers.
  
  
  
  The data for this study were derived from prospective screening for adverse obstetric outcomes in women attending their routine hospital visit at 19-24 weeks' gestation in 3 maternity hospitals in England between January 2006 and July 2014. We had data from maternal factors, uterine artery pulsatility index (UTPI), mean arterial pressure (MAP), serum placental growth factor (PLGF), and serum soluble fms-like tyrosine kinase-1 (SFLT) from 123,406, 67,605, 31,120, 10,828, and 8079 pregnancies, respectively. Bayes' theorem was used to combine the a priori risk from maternal factors with various combinations of biomarker multiple of the median (MoM) values. The modeled performance of screening for PE requiring delivery at <32, <37, and ≥37 weeks' gestation was estimated. The modeled performance was compared to the empirical one, which was derived from 5-fold cross validation. We also examined the performance of screening based on risk factors from the medical history, as recommended by the American Congress of Obstetricians and Gynecologists (ACOG).
  
  
  
  In pregnancies that developed PE, the values of MAP, UTPI, and SFLT were increased and PLGF was decreased. For all biomarkers the deviation from normal was greater for early than for late PE, and therefore the performance of screening was inversely related to the gestational age at which delivery became necessary for maternal and/or fetal indications. Screening by maternal factors predicted 52%, 47%, and 37% of PE at <32, <37, and ≥37 weeks' gestation, respectively, at a false-positive rate of 10%. The respective values for combined screening with maternal factors and MAP, UTPI, and PLGF were 99%, 85%, and 46%; the performance was not improved by the addition of SFLT. In our population of 123,406 pregnancies, the DR of PE at <32, <37, and ≥37 weeks with the ACOG recommendations was 91%, 90%, and 91%, respectively, but at a screen positive rate of 67%.
  
  
  
  The performance of screening for PE by maternal factors and biomarkers in the middle trimester is superior to taking a medical history.
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College, London, United Kingdom.
authors.forename: Dahiana M
authors.initials: DM
authors.lastname: Gallo
authors.affiliation: Institute of Health Research, University of Exeter, Exeter, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Wright
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College, London, United Kingdom.
authors.forename: Cristina
authors.initials: C
authors.lastname: Casanova
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College, London, United Kingdom.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Campanero
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College, London, United Kingdom. Electronic address: kypros@fetalmedicine.com.
authors.forename: Kypros H
authors.initials: KH
authors.lastname: Nicolaides
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D004739:England; D005260:Female; D006801:Humans; D016013:Likelihood Functions; D000072483:Placenta Growth Factor / Q000097:blood; D011225:Pre-Eclampsia / Q000097:blood* / Q000175:diagnosis* / Q000517:prevention & control; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011673:Pulsatile Flow; D012372:ROC Curve; D018570:Risk Assessment; D018615:Ultrasonography, Doppler, Color; D055988:Uterine Artery / Q000000981:diagnostic imaging; 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; preeclampsia; pyramid of pregnancy care; second-trimester screening; soluble fms-like tyrosine kinase-1; survival model; uterine artery Doppler