title: Angiogenic factors combined with clinical risk factors to predict preterm pre-eclampsia in nulliparous women: a predictive test accuracy study.
abstract: OBJECTIVE
  To assess the performance of clinical risk factors, uterine artery Doppler and angiogenic markers to predict preterm pre-eclampsia in nulliparous women.
  
  
  METHODS
  Predictive test accuracy study.
  
  
  METHODS
  Prospective multicentre cohort study Screening for Pregnancy Endpoints (SCOPE).
  
  
  METHODS
  Low-risk nulliparous women with a singleton pregnancy were recruited. Clinical risk factor data were obtained and plasma placental growth factor (PlGF), soluble endoglin and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured at 14-16 weeks of gestation. Prediction models were developed using multivariable stepwise logistic regression.
  
  
  METHODS
  Preterm pre-eclampsia (delivered before 37(+0)  weeks of gestation).
  
  
  RESULTS
  Of the 3529 women recruited, 187 (5.3%) developed pre-eclampsia of whom 47 (1.3%) delivered preterm. Controls (n = 188) were randomly selected from women without preterm pre-eclampsia and included women who developed other pregnancy complications. An area under a receiver operating characteristic curve (AUC) of 0.76 (95% CI 0.67-0.84) was observed using previously reported clinical risk variables. The AUC improved following the addition of PlGF measured at 14-16 weeks (0.84; 95% CI 0.77-0.91), but no further improvement was observed with the addition of uterine artery Doppler or the other angiogenic markers. A sensitivity of 45% (95% CI 0.31-0.59) (5% false-positive rate) and post-test probability of 11% (95% CI 9-13) were observed using clinical risk variables and PlGF measurement.
  
  
  CONCLUSIONS
  Addition of plasma PlGF at 14-16 weeks of gestation to clinical risk assessment improved the identification of nulliparous women at increased risk of developing preterm pre-eclampsia, but the performance is not sufficient to warrant introduction as a clinical screening test. These findings are marker dependent, not assay dependent; additional markers are needed to achieve clinical utility.
authors.affiliation: Faculty of Medical and Human Sciences, Maternal & Fetal Heath Research Centre, Institute of Human Development, Manchester Academic Health Science Centre, Central Manchester University Hospitals NHS Foundation Trust, University of Manchester, UK. Jenny.myers@manchester.ac.uk
authors.forename: J E
authors.initials: JE
authors.lastname: Myers
authors.forename: L C
authors.initials: LC
authors.lastname: Kenny
authors.forename: L M E
authors.initials: LM
authors.lastname: McCowan
authors.forename: E H Y
authors.initials: EH
authors.lastname: Chan
authors.forename: G A
authors.initials: GA
authors.lastname: Dekker
authors.forename: L
authors.initials: L
authors.lastname: Poston
authors.forename: N A B
authors.initials: NA
authors.lastname: Simpson
authors.forename: R A
authors.initials: RA
authors.lastname: North
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000097:blood*; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D000071063:Endoglin; D005260:Female; D006801:Humans; D010298:Parity; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000097:blood* / Q000175:diagnosis* / Q000000981:diagnostic imaging; D011237:Predictive Value of Tests; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood*; D011261:Pregnancy Trimester, First / Q000097:blood; D011262:Pregnancy Trimester, Second / Q000097:blood; D047928:Premature Birth / Q000097:blood; D012372:ROC Curve; D011956:Receptors, Cell Surface / Q000097:blood*; D012307:Risk Factors; D018608:Ultrasonography, Doppler; D055988:Uterine Artery / Q000000981:diagnostic imaging; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; C064206:ENG protein, human; D000071063:Endoglin; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D011956:Receptors, Cell Surface; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: Angiogenic markers; placental growth factor; pre-eclampsia; sensitivity; specificity