title: Proposed clinical management of pregnancies after combined screening for pre-eclampsia at 19-24 weeks' gestation.
abstract: OBJECTIVE
  To estimate the patient-specific risk of pre-eclampsia (PE) at 19-24 weeks' gestation by a combination of maternal characteristics and medical history with multiples of the median (MoM) values of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1), and stratify women into high-, intermediate- and low-risk management groups.
  
  
  METHODS
  This was a prospective observational study in women attending a second-trimester ultrasound scan at 19-24 weeks as part of routine pregnancy care. Patient-specific risks of delivery with PE < 32 weeks and < 36 weeks' gestation were calculated using the competing-risks model to combine the prior risk from maternal characteristics and medical history with MoM values of MAP, UtA-PI, PlGF and sFlt-1. On the basis of these risks, the population was stratified into high-, intermediate- and low-risk groups. Different risk cut-offs were used to vary the proportion of the population stratified into each risk category and the performance of screening for delivery with PE at < 32 weeks' gestation, at 32-35 weeks and at ≥ 36 weeks was estimated. In addition to empirical performance, we also derived model-based performance because the number of cases of PE delivering < 32 weeks was low.
  
  
  RESULTS
  The study population of 7748 singleton pregnancies included 268 (3.5%) that subsequently developed PE. Using a risk cut-off of 1 in 100 for PE delivering < 32 weeks' gestation and a risk cut-off of 1 in 300 for PE delivering < 36 weeks, the proportion of the population stratified into high-, intermediate- and low-risk was 0.9%, 17.2% and 81.9%, respectively. The high-risk group contained 97% of pregnancies with PE < 32 weeks and 45% of those with PE at 32-35 weeks. The intermediate-risk group contained a further 46% of women with PE at 32-35 weeks. The low-risk group contained only 0.03% of pregnancies with PE < 32 weeks and 9% of those with PE at 32-35 weeks.
  
  
  CONCLUSIONS
  Risk stratification of PE by the combined test at 19-24 weeks' gestation can identify, first, a group which constitutes < 1% of the total population and contains > 95% of those that will develop PE < 32 weeks and are in need of intensive monitoring at 24-31 weeks and, second, a group which constitutes < 20% of the total and contains > 90% of those that will develop PE at 32-35 weeks and are in need of reassessment at 32 weeks. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Litwinska
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: T
authors.initials: T
authors.lastname: Efeturk
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
authors.forename: I
authors.initials: I
authors.lastname: Ceccacci
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; D062186:Arterial Pressure; D005260:Female; D006801:Humans; D000072483:Placenta Growth Factor / Q000097:blood; D011225:Pre-Eclampsia / Q000097:blood / Q000000981:diagnostic imaging* / Q000517:prevention & control; D011247:Pregnancy; D011256:Pregnancy Outcome; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D011446:Prospective Studies; D011673:Pulsatile Flow; D018570:Risk Assessment; D016216:Ultrasonography, Prenatal; D055988:Uterine Artery / Q000503:physiopathology*
chemical_list: C000608036:PGF protein, human; D000072483:Placenta Growth Factor
keywords: mean arterial pressure; placental growth factor; pre-eclampsia; pyramid of antenatal care; soluble fms-like tyrosine kinase-1; uterine artery pulsatility index