Award Title: Update of DG23 PlGF-based testing to help diagnose suspected pre-eclampsia
Funder: Department of Health and Social Care

Abstract: Pre-eclampsia is a serious condition that some people develop during pregnancy, usually in the second or third trimesters. It is important that it is timely and accurately diagnosed, as, without treatment, it can lead to significant health risks to mothers and foetuses. In routine antenatal care pregnant people are assessed for their level of risk for and signs of pre-eclampsia. People with suspected pre-eclampsia undergo further tests and if they are diagnosed with the condition they are closely monitored, and sometimes may be admitted to hospital. A type of test, known as the placental growth factor (PlGF) test, is available for use with or without soluble fms-like tyrosine kinase (sFlt), alongside standard assessments and clinical follow-up to help doctors to ‘rule in’ (i.e. to diagnose pre-eclampsia) or ‘rule out’ the condition (i.e. pre-eclampsia is not diagnosed). The PlGF test measures the amount of placental growth factor in a person’s blood. If levels are low, this may indicate pre-eclampsia. Use of this test may provide more accurate and timely diagnosis of preeclampsia and help identify people at lower risk of developing the condition, which could help avoid admission to hospital._x000D_
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In 2016 the National Institute for Health and Care Excellence (NICE) recommended two types of PlGF tests - the Triage PlGF test and the Elecsys immunoassay sFlt 1/PlGF ratio - for use in the NHS in England, for ruling out pre-eclampsia between 20 weeks and 34 weeks plus 6 days of gestation. NICE did not recommend two other available tests - The DELFIA Xpress PlGF 1-2-3 test and BRAHMS sFlt-1 Kryptor/BRAHMS PlGF plus Kryptor PE ratio - for routine use. Currently no test is recommended for ruling in pre-eclampsia. NICE’s guidance suggests that further research is done to find out if the DELFIA and BRAHMS tests are accurate in diagnosing pre-eclampsia. The guidance also recommends more research to find out if the Triage PIGF test and the Elecsys immunoassay sFlt-1/PIGF ratio test can accurately rule in pre-eclampsia. Since 2016 new research evidence has become available which potentially addresses NICE’s recommendations._x000D_
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We previously carried out a review of the available research evidence and constructed an economic model to determine the benefits and costs of these tests to patients and the NHS to inform the NICE guidance. In our current project, we will be updating the review and the economic model. We will search medical research databases to find new, relevant studies. We will then review the studies in detail, in an organised way using standard research methods. We will summarise and critically appraise the methods and results of the studies and judge whether any of them might be biased, and whether we can trust the results they give.

Lay Abstract: Pre-eclampsia is a serious condition that can occur during pregnancy, mostly in the second and third trimesters. Without timely and accurate diagnosis, monitoring and intervention it can lead to significant health risks to the mother and fetus. Pre-eclampsia is a heterogeneous and unpredictable condition, and the established method of diagnosis is assessment of standard key clinical signs and symptoms, including blood pressure measurement for hypertension, urinalysis to detect proteinuria and foetal monitoring for evidence of uteroplacental dysfunction with fetal growth restriction. People with suspected pre-eclampsia may be admitted to acute maternity units for initial evaluation and monitoring._x000D_
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Tests are available that measure the amount of placental growth factor (PlGF) in blood plasma or serum during pregnancy. PlGF is a protein involved in placental angiogenesis (the development of new blood vessels) and levels rise during the course of pregnancy, reaching a plateau at 26 to 30 weeks gestation. Abnormally low levels of PlGF during pregnancy may indicate placental dysfunction associated with pre-eclampsia. Some PlGF tests measure soluble FMS-like tyrosine kinase-1 (sFlt-1), an anti-angiogenic protein which disables proteins, such as PlGF, which are associated with blood vessel formation. In cases of pre-eclampsia levels of sFlt-1 are higher than normal._x000D_
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Use of PlGF-based tests (i.e. PlGF or sFlt-1/PlGF tests) to aid standard clinical assessments may provide an earlier and more accurate diagnosis in people who have signs and symptoms of possible pre-eclampsia. In turn, this can inform care decisions, such as avoiding hospital admission in people with low risk of developing pre-eclampsia.

Research Activity Codes: 6.3 MEDICAL DEVICES
Health Categories: REPRODUCTIVE HEALTH AND CHILDBIRTH