Authors' objectives: Predicting a diagnosis of pre-eclampsia is based on a combination of clinical assessment of blood pressure, presence of protein in the urine, symptoms and laboratory test abnormalities. Accurately detecting pre-eclampsia is important to avoid false-positive diagnoses which could lead to unnecessary antenatal admissions and/or preterm delivery. Four blood tests that measure the biomarkers of placental growth factor or the ratio of soluble fms-like tyrosine kinase-1 to placental growth factor are available (known as Triage, Elecsys, DELFIA Xpress, and BRAHMS Kryptor tests). Abnormal measurements of these biomarkers can be used as an aid to predict a diagnosis of pre-eclampsia and maternal and fetal outcomes. To evaluate the test accuracy, clinical effectiveness and cost-effectiveness of placental growth factor -based tests used in conjunction with standard clinical assessment for predicting pre-eclampsia and maternal and fetal outcomes in pregnant women who are referred to secondary care with suspected pre-eclampsia in weeks 20–37 of pregnancy. Pre-eclampsia affects approximately 6% of pregnant women, usually from around 20 weeks of gestation, with severe cases affecting 1–2% of pregnant women. If the condition is undetected or left untreated, it can result in serious, potentially fatal, maternal and neonatal complications, such as stroke, organ dysfunction, eclampsia, fetal growth restriction, or intrauterine death. The only cure for pre-eclampsia is to deliver the placenta (and therefore the baby); therefore, women are monitored until the optimum time for delivery. Pre-eclampsia can be asymptomatic, and it can be difficult to detect in women with pre-existing hypertension; therefore, assessment for pre-eclampsia is incorporated into routine antenatal assessments. Women are suspected of having pre-eclampsia if they have high blood pressure and/or proteinuria. If pre-eclampsia is suspected, current practice is to assess the patient for blood pressure, proteinuria, other symptoms such as oedema or neurological disturbances, and abnormal laboratory results. In addition, blood tests have been developed that measure levels of two proteins in the blood: placental growth factor (PLGF), which occurs in abnormally low levels in women with pre-eclampsia; and soluble fms-like tyrosine kinase-1 (sFlt-1), which occurs in abnormally high levels in women with pre-eclampsia. Two of these tests (Triage and Elecsys) have been recommended by the National Institute for Health and Care Excellence (NICE) for use as an aid in predicting a diagnosis of pre-eclampsia [NICE diagnostic guidance diagnostics guidance 23 (DG23)]. A further two tests which measure these proteins (BRAHMS Kryptor and DELFIA Xpress) are available but have not yet been evaluated for diagnostic or prognostic/predictive accuracy and cost-effectiveness for the NHS. This current report was commissioned to inform an update of NICE DG23. The four tests specified in the NICE scope for this update diagnostic assessment are: the Triage® PLGF test (QuidelOrtho, San Diego, CA, USA) San Diego; the DELFIA® Xpress PLGF 1-2-3 test™ (Revvity, Waltham, MA, USA); the Elecsys® sFlt-1 to PLGF ratio test (Roche Diagnostics Ltd, Rotkreuz, Switzerland) and the BRAHMS™ PLGF plus Kryptor™ test/BRAHMS sFlt-1 Kryptor test (ThermoFisher Scientific, Waltham, MA, USA). The aim of this study is to investigate the test accuracy, clinical effectiveness and cost-effectiveness of the four biomarker tests at predicting a diagnosis of pre-eclampsia in pregnant women presenting with suspected pre-eclampsia between 20 weeks and 37 weeks pregnancy, who have received standard clinical assessment (including blood pressure and/or proteinuria assessment). The objectives are to: assess any new evidence for the test accuracy and analytical validity of the BRAHMS Kryptor and DELFIA Xpress tests (NICE research recommendation 1.3) assess any new evidence for use of repeat testing for suspected pre-eclampsia: investigating test accuracy, intervals between tests, and scenarios when it might be used (NICE research recommendation 6.1) assess any new evidence for the accuracy of the Triage and Elecsys tests to rule in pre-eclampsia (NICE research recommendation 6.2) assess the impact of the tests on clinical decision-making (e.g. time to delivery or hospital admission), and on maternal and neonatal outcomes such as morbidity and mortality.

Authors' results and conclusions: Seventeen studies were included in the systematic review. Two large, randomised trials provided the best available evidence to inform the economic model: The PARROT trial (Triage test) and the INSPIRE trial (Elecsys test). When used as rule-out tests for pre-eclampsia (with neonatal outcomes included), all four tests produced higher quality-adjusted life-years and higher costs than both types of standard clinical assessment. The incremental cost per quality-adjusted life-year ranged from £637 (DELFIA test vs. standard clinical assessment from INSPIRE) to £47,393 (Triage test vs. standard clinical assessment from diagnostics guidance 23) per quality-adjusted life-year. Incremental costs and quality-adjusted life-years were always very small, with incremental costs always less than the cost of the test and incremental quality-adjusted life-years always

Authors' methods: A systematic review of the diagnostic/prognostic accuracy and clinical effectiveness of placental growth factor-based tests with standard clinical assessment. Database included MEDical Literature Analysis and Retrieval System, Excerpta Medica dataBASE and Cochrane Library. Other sources searched included relevant conference proceedings and websites, grey literature and research in progress. The most recent date of searching was 18 March 2021. An independent economic analysis was conducted using a decision tree model. The model includes short-term costs and quality-adjusted life-years for the management of women, maternal and neonatal outcomes and long-term outcomes for severe neonatal complications. The model compared the use of the test alongside standard clinical assessment to standard clinical assessment only. Two different estimates of standard clinical assessment were included, from the INSPIRE study and from National Institute of Health and Care Excellence Diagnostic Guidance 23. Although the evidence for placental growth factor-based tests is advancing, there remains uncertainty for key parameters, such as diagnostic sensitivity and specificity. This particularly affects the Elecsys test. Systematic review of test accuracy and clinical effectiveness A systematic review of diagnostic and prognostic accuracy and clinical effectiveness evidence was conducted according to a peer-reviewed protocol. Searches were based on a comprehensive search strategy. Bibliographic databases, including MEDical Literature Analysis and Retrieval System (MEDLINE), Excerpta Medica dataBASE (EMBASE), Web of Science, The Cochrane Library and the International Health Technology Assessment database, were searched for English-language references in November 2020, and these searches were updated in March 2021. Conferences, websites and confidential company submissions were also obtained, and reference lists of identified systematic reviews and meta-analyses were checked. Studies were eligible if they included women with suspected pre-eclampsia between 20 weeks and 37 weeks pregnancy and reported diagnostic accuracy of at least one of the specified tests for predicting pre-eclampsia when used alongside standard clinical practice. Risks of bias and generalisability of the included test accuracy studies were assessed using the quality assessment of diagnostic accuracy studies 2 instrument. Where included studies had outcomes additional to diagnostic and prognostic/predictive accuracy, they were appraised using the Cochrane Risk of Bias tool (if a randomised trial). Study selection, data extraction and critical appraisal were each performed by two reviewers, with any disagreements resolved through discussion and referred to a third reviewer for resolution as necessary. Data were synthesised narratively, the option of conducting a pre-planned meta-analysis was not pursued because the studies were too heterogeneous to allow for meaningful findings and conclusions.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hta/NIHR132386

Year Published: 2026

URL for published report: https://www.journalslibrary.nihr.ac.uk/hta/HDST9104

URL for additional information: English

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: England, United Kingdom

DOI: 10.3310/HDST9104

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk