title: Protocol for the prospective validation study: 'Screening programme for pre-eclampsia' (SPREE).
abstract: Pre-eclampsia (PE), which affects about 2% of pregnancies, is a major cause of maternal and perinatal morbidity and mortality. Early detection of PE can improve pregnancy outcome by providing timely intervention and closer monitoring. The current guideline from the UK National Institute for Health and Care Excellence (NICE) recommends that, at the booking visit, women identified with one major risk factor or more than one moderate risk factor for PE should be advised to take low-dose aspirin daily from 12 weeks until delivery. However, performance of the current method of screening is poor and identifies only about 35% of PE. Extensive studies in the last decade have established that the best performance for early prediction of PE can be achieved by using a novel Bayes' theorem-based method that combines maternal characteristics and medical history together with measurements of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) at 11-13 weeks' gestation. This forms the 'combined test', which could be simplified to the 'mini combined test' when only maternal factors, MAP and PAPP-A are taken into consideration. We present the protocol (version 3.1, 14 November 2016) for the 'Screening programme for pre-eclampsia' (SPREE) study, a prospective multicenter cohort study that will be carried out in seven National Health Service maternity hospitals in England. Eligible pregnant women attending their routine scan at 11-13 weeks' gestation will be invited to participate in this study. Maternal characteristics and history and measurements of MAP, UtA-PI, serum PAPP-A and PlGF will be recorded according to standardized protocols. The patient-specific risk for PE will be calculated and data on pregnancy outcomes collected. We hypothesize that the first-trimester mini combined test and combined test for PE screening, using the Bayes' theorem-based method, are likely to be superior to the current method recommended by NICE that is based on maternal demographics and history alone. Enrollment for the study commenced in April 2016. The study is registered on the International Standard Randomised Controlled Trial Number (ISRCTN) registry. 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 Y
authors.identifier: http://orcid.org/0000-0002-8176-9449
authors.initials: MY
authors.lastname: Tan
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
authors.forename: L
authors.initials: L
authors.lastname: Koutoulas
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: K H
authors.initials: KH
authors.lastname: Nicolaides
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.|Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
authors.forename: L C Y
authors.identifier: http://orcid.org/0000-0002-3944-4130
authors.initials: LCY
authors.lastname: Poon
mesh_terms: D005260:Female; D006801:Humans; D011225:Pre-Eclampsia / Q000175:diagnosis*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011296:Prenatal Diagnosis; D011446:Prospective Studies; D012107:Research Design; D013222:State Medicine; D006113:United Kingdom; D054928:Validation Studies as Topic
keywords: Bayes' theorem; National Institute for Health and Care Excellence; first-trimester screening; mean arterial pressure; placental growth factor; pre-eclampsia; pregnancy-associated plasma protein-A; uterine artery Doppler