title: Multicenter screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation: comparison with NICE guidelines and ACOG recommendations.
abstract: OBJECTIVE
  To compare the performance of screening for pre-eclampsia (PE) based on risk factors from medical history, as recommended by NICE and ACOG, with the method proposed by The Fetal Medicine Foundation (FMF), which uses Bayes' theorem to combine the a-priori risk from maternal factors, derived by a multivariable logistic model, with the results of various combinations of biophysical and biochemical measurements.
  
  
  METHODS
  This was a prospective multicenter study of screening for PE in 8775 singleton pregnancies at 11-13 weeks' gestation. A previously published FMF algorithm was used for the calculation of patient-specific risk of PE in each individual. The detection rates (DRs) and false-positive rates (FPRs) for delivery with PE < 32, < 37 and ≥ 37 weeks were estimated and compared with those derived from application of NICE guidelines and ACOG recommendations. According to NICE, all high-risk pregnancies should be offered low-dose aspirin. According to ACOG, use of aspirin should be reserved for women with a history of PE in at least two previous pregnancies or PE requiring delivery < 34 weeks' gestation.
  
  
  RESULTS
  In the study population, 239 (2.7%) cases developed PE, of which 17 (0.2%), 59 (0.7%) and 180 (2.1%) developed PE < 32, < 37 and ≥ 37 weeks, respectively. Screening with use of the FMF algorithm based on a combination of maternal factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF) detected 100% (95% CI, 80-100%) of PE < 32 weeks, 75% (95% CI, 62-85%) of PE < 37 weeks and 43% (95% CI, 35-50%) of PE ≥ 37 weeks, at a 10.0% FPR. Screening with use of NICE guidelines detected 41% (95% CI, 18-67%) of PE < 32 weeks, 39% (95% CI, 27-53%) of PE < 37 weeks and 34% (95% CI, 27-41%) of PE ≥ 37 weeks, at 10.2% FPR. Screening with use of ACOG recommendations detected 94% (95% CI, 71-100%) of PE < 32 weeks, 90% (95% CI, 79-96%) of PE < 37 weeks and 89% (95% CI, 84-94%) of PE ≥ 37 weeks, at 64.2% FPR. Screening based on the ACOG recommendations for use of aspirin detected 6% (95% CI, 1-27%) of PE < 32 weeks, 5% (95% CI, 2-14%) of PE < 37 weeks and 2% (95% CI, 0.3-5%) of PE ≥ 37 weeks, at 0.2% FPR.
  
  
  CONCLUSIONS
  Performance of screening for PE at 11-13 weeks' gestation by the FMF algorithm using a combination of maternal factors, MAP, UtA-PI and PlGF, is by far superior to the methods recommended by NICE and ACOG. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
authors.affiliation: Harris Birthright Center for Fetal Medicine, King's College Hospital, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: O'Gorman
authors.affiliation: Institute of Health Research, University of Exeter, Exeter, UK.
authors.forename: D
authors.initials: D
authors.lastname: Wright
authors.affiliation: Harris Birthright Center for Fetal Medicine, King's College Hospital, London, UK.|Chinese University of Hong Kong, Hong Kong, China.
authors.forename: L C
authors.identifier: http://orcid.org/0000-0002-3944-4130
authors.initials: LC
authors.lastname: Poon
authors.affiliation: Harris Birthright Center for Fetal Medicine, King's College Hospital, London, UK.
authors.forename: D L
authors.initials: DL
authors.lastname: Rolnik
authors.affiliation: Harris Birthright Center for Fetal Medicine, King's College Hospital, London, UK.
authors.forename: A
authors.identifier: http://orcid.org/0000-0001-5856-6072
authors.initials: A
authors.lastname: Syngelaki
authors.affiliation: Harris Birthright Center for Fetal Medicine, King's College Hospital, London, UK.|Homerton University Hospital, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: de Alvarado
authors.affiliation: Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: I F
authors.initials: IF
authors.lastname: Carbone
authors.affiliation: Centre Hospitalier Universitaire Brugmann, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: V
authors.initials: V
authors.lastname: Dutemeyer
authors.affiliation: Harris Birthright Center for Fetal Medicine, King's College Hospital, London, UK.|Medway Maritime Hospital, Gillingham, UK.
authors.forename: M
authors.initials: M
authors.lastname: Fiolna
authors.affiliation: Harris Birthright Center for Fetal Medicine, King's College Hospital, London, UK.|Lewisham University Hospital, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Frick
authors.affiliation: Harris Birthright Center for Fetal Medicine, King's College Hospital, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Karagiotis
authors.affiliation: Harris Birthright Center for Fetal Medicine, King's College Hospital, London, UK.|North Middlesex University Hospital, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Mastrodima
authors.affiliation: Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain.
authors.forename: C
authors.initials: C
authors.lastname: de Paco Matallana
authors.affiliation: Attikon University Hospital, Athens, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Papaioannou
authors.affiliation: Hospital Universitario San Cecilio, Granada, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Pazos
authors.affiliation: Hospiten Group, Tenerife, Canary Islands, Spain.
authors.forename: W
authors.initials: W
authors.lastname: Plasencia
authors.affiliation: Harris Birthright Center for Fetal Medicine, King's College Hospital, London, UK.
authors.forename: K H
authors.initials: KH
authors.lastname: Nicolaides
mesh_terms: D015415:Biomarkers / Q000097:blood*; D005260:Female; D005865:Gestational Age; D006801:Humans; D017410:Practice Guidelines as Topic; D011225:Pre-Eclampsia / Q000097:blood / Q000175:diagnosis*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011296:Prenatal Diagnosis; D011446:Prospective Studies; D012372:ROC Curve; D018570:Risk Assessment; D012955:Societies, Medical; D006113:United Kingdom; D014481:United States
chemical_list: D015415:Biomarkers
keywords: Bayes' theorem; first-trimester screening; mean arterial pressure; placental growth factor; pre-eclampsia; pregnancy-associated plasma protein-A; pyramid of pregnancy care; survival model; uterine artery Doppler