title: Screening for pre-eclampsia early in pregnancy: performance of a multivariable model combining clinical characteristics and biochemical markers.
abstract: OBJECTIVE
  To investigate the performance of a multivariable model combining a priori clinical characteristics and biomarkers to detect, early in pregnancy, women at higher risk of developing pre-eclampsia (PE).
  
  
  METHODS
  Nested case-control study.
  
  
  METHODS
  University medical centre, Quebec, Canada (CHU de Québec).
  
  
  METHODS
  A total of 7929 pregnant women recruited between 10 and 18 weeks of gestation. In all, 350 developed hypertensive disorders of pregnancy (HDP)-of which 139 had PE, comprising 68 with severe PE and 47 with preterm PE-and were matched with two women with a normal pregnancy.
  
  
  METHODS
  We selected a priori clinical characteristics and promising markers to create multivariable logistic regression models: body mass index (BMI), mean arterial pressure (MAP), placental growth factor, soluble Fms-like tyrosine kinase-1, pregnancy-associated plasma protein A and inhibin A.
  
  
  METHODS
  PE, severe PE, preterm PE, HDP.
  
  
  RESULTS
  At false-positive rates of 5 and 10%, the estimated detection rates were between 15% (5-29%) and 32% (25-39%), and between 39% (19-59%) and 50% (34-66%), respectively. Considering the low prevalence of PE in this population, the positive predictive values were 7% (5-9%) to 10% (7-13%) for PE and 2% (1-4%) to 4% (3-6%) in the preterm and severe PE subgroups. The multivariable model yielded areas under the receiver operating characteristics curves (AUC) between 0.72 (0.61-0.81) and 0.78 (0.68-0.88). When only BMI and MAP were included in the model, the AUC were similar to those of the a priori model.
  
  
  CONCLUSIONS
  In a population with a low prevalence of preterm PE, a multivariable risk algorithm using an a priori combination of clinical characteristics and biochemical markers did not reach a performance justifying clinical implementation as screening test early in pregnancy.
authors.affiliation: Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine, Université Laval, Québec, QC, Canada; CHU de Québec Research Centre, Hôpital St-François d'Assise, Quebec City, QC, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Giguère
authors.forename: J
authors.initials: J
authors.lastname: Massé
authors.forename: S
authors.initials: S
authors.lastname: Thériault
authors.forename: E
authors.initials: E
authors.lastname: Bujold
authors.forename: J
authors.initials: J
authors.lastname: Lafond
authors.forename: F
authors.initials: F
authors.lastname: Rousseau
authors.forename: J-C
authors.initials: JC
authors.lastname: Forest
mesh_terms: D062186:Arterial Pressure; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D002170:Canada; D005260:Female; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000097:blood* / Q000517:prevention & control; D007265:Inhibins / Q000097:blood*; D008403:Mass Screening; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000097:blood* / Q000517:prevention & control; D011237:Predictive Value of Tests; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000097:blood* / Q000517:prevention & control; D011257:Pregnancy Proteins / Q000097:blood*; D011261:Pregnancy Trimester, First / Q000097:blood; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D011673:Pulsatile Flow; D018570:Risk Assessment; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; C000608036:PGF protein, human; D011257:Pregnancy Proteins; C422362:inhibin A; D000072483:Placenta Growth Factor; D007265:Inhibins; D040281:Vascular Endothelial Growth Factor Receptor-1; D011266:Pregnancy-Associated Plasma Protein-A
keywords: Biomarkers; early pregnancy; model; pre-eclampsia