Case study: Simple blood test gives pregnant women a fast and accurate diagnosis for pre-eclampsia
Pre-eclampsia is a common yet serious condition among pregnant women, affecting around 3% of pregnancies in the UK. NIHR-funded researchers have found that a blood test for placental growth factor (PlGF) can reduce the time to diagnose pre-eclampsia from 4 to 2 days. This quicker diagnosis reduces delays in arranging treatment for women most at risk of developing severe complications, and removes unnecessary monitoring for those who are not at risk.
A long wait to find a quick test for pre-eclampsia
Pre-eclampsia is a high blood pressure disorder that is more likely to develop in the second half of pregnancy. There is no cure, but diagnosing the condition early allows closer monitoring. In some cases, early delivery of the baby is necessary to reduce the risk of complications for both mother and baby.
Although most cases of pre-eclampsia improve soon after the baby is delivered, some women and babies are at risk of serious complications. The condition can cause low birth weight or premature birth. Women may suffer organ damage, and both mother and child are at long-term risk of health complications, such as heart disease.
The clinical signs of pre-eclampsia are high blood pressure and protein in the woman’s urine. These signs are often identified at routine antenatal appointments, but these methods of diagnosis are not completely reliable. If a doctor suspects pre-eclampsia, many women are admitted for further investigations and monitoring as a precaution.
Around 10% of pregnant women have such symptoms, while only around 3% actually have pre-eclampsia, so this uncertainty is worrying for the women and expensive for the NHS. This has highlighted the need for a quick, accurate and inexpensive test to reduce this uncertainty.
Putting PlGF to the test
Placental growth factor (PlGF) is a molecule made by the placenta. A low level of PlGF indicates a poorly functioning placenta and a higher risk of developing severe pre-eclampsia. Previous research has shown that measuring the concentration of PlGF in a woman’s blood is effective at diagnosing pre-eclampsia. It therefore helps identify women needing a greater level of care.
Professor Lucy Chappell, NIHR Research Professor in Obstetrics at King’s College London, is the first to investigate whether testing PlGF could help doctors decide how to treat women who are showing symptoms of pre-eclampsia in real clinical settings. The Placental growth factor to Assess and diagnose hypeRtensive pRegnant wOmen (PARROT) trial, funded by the NIHR Research for Patient Benefit Programme, sought to understand whether knowledge of PlGF concentration decreased the time for clinicians to make a diagnosis in women with suspected pre-eclampsia.
With the assistance of NIHR’s Clinical Research Network, the PARROT trial recruited more than 1,000 women with suspected pre-eclampsia from 11 UK maternity units. These women were randomly assigned to either receive a PlGF test alongside usual blood pressure and urine checks (intervention group) or blood pressure and urine checks alone (control group having standard care).
Use of the additional PlGF test (alongside blood pressure and urine checks) halved the time for doctors to diagnose pre-eclampsia from 4.1 days to 1.9 days, compared with the control group. The study, published in the Lancet, also showed that using a PIGF test reduced the number of serious complications for women before birth, such as eclampsia, stroke and death. There was no increase in the number of premature births.
“For many years, we have relied on imperfect ways to try and find which pregnant women are most likely to have pre-eclampsia and need urgent delivery within the next week or two,” said Professor Chappell. “This new blood test is a step change in maternity care, allowing us to flag women at higher risk for greater surveillance, whilst enabling lower risk women to return to usual antenatal care. This has become particularly important during the COVID-19 pandemic, in order to reduce unnecessary footfall in the maternity unit. It is really positive news that it will now be rolled out into clinical practice.”
Changing national practice for pre-eclampsia diagnosis
Approximately 7,000 women per year have symptoms of pre-eclampsia in the later stages of pregnancy, and the wait for a diagnosis is a worrying time. Halving the time to diagnosis from 4 to 2 days with a simple blood test that can be taken in any setting has improved patient care and safety in everyday practice.
Based on the impressive results of the study, in 2019 NHS England selected PlGF testing as one of the first ‘rapid uptake’ products to receive funding. Rapid uptake is an NHS Accelerated Access Collaborative initiative that makes new products quickly available to patients. This has given thousands more pregnant women the opportunity for a quicker diagnosis and, for those who need it, faster access to appropriate monitoring for pre-eclampsia. “It is really positive news that the test will now be rolled out into clinical practice,” said Professor Chappell.
Lauren is a mum who had pre-eclampsia when pregnant with all three of her children and who lost her first pregnancy at 26 weeks because of the condition.
Having access to the PlGF test is very important to families, especially if you’ve lost a baby or you’ve had a difficult pregnancy through pre-eclampsia. At least you know that you can go on to get an early diagnosis if it happens again so you get the best possible care.
Tommy’s is a charity that supports women like Lauren who have experienced miscarriage, stillbirth and premature birth, and also co-funded the PARROT study. Lizzie D’Angelo, Research and Policy Director at Tommy’s, said: "The results from the PARROT study have contributed to NHS England making the PlGF blood test more widely available. This will mean that doctors will be able to quickly identify the women at the greatest risk of developing severe pre-eclampsia.
“The test will ensure the right women receive the right care at the right time, and reduce stress for patients and providers by avoiding unnecessary hospital admissions and treatments - ultimately helping mothers get the care they need and improving the chances of a healthy birth for their baby."
To ensure that all patients receive the best care, the NICE guideline for treating suspected pre-eclampsia was updated in 2019 to recommend that PlGF testing is carried out to help rule out pre-eclampsia in women presenting with suspected pre-eclampsia after 20 weeks and before 35 weeks’ gestation. Commissioners and providers of antenatal care have welcomed PlGF testing being introduced into antenatal care.
Adopting PlGF testing into standard clinical practice saves the NHS £149 per woman who would previously have been admitted to hospital for precautionary monitoring. This translates to around £3 million savings for the NHS per year. Further savings may be made in the future if complications from pre-eclampsia can be avoided.
Professor Andrew Shennan, Professor of Obstetrics at King’s College London and a member of the PARROT team, said: “Very few diagnostic tests adopted by the NHS have actually had trials proving efficacy and cost effectiveness. We have achieved this with PlGF.”
A follow-on study, PARROT-2, is now underway to compare what happens to pregnant women who have repeat PlGF testing with those who don’t, and to see if this has any impact on complications for women or their babies.
There is growing international interest in adopting this model, with countries in Europe and Australasia pursuing adoption of PlGF-based testing. There is also interest from low-income settings in sub-Saharan Africa.
Read about the project on NIHR Funding and Awards.
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