Recommendations for NHSScotland
SHTG Council Considerations
Evidence Overview
Background
1. The following placental growth factor (PlGF)-based tests, used with standard clinical assessment, are recommended as an option to help clinicians rule in or rule out preterm (between 20 weeks and 36 weeks and 6 days of pregnancy) pre-eclampsia:
- DELFIA® Xpress PlGF 1‑2‑3
- DELFIA® Xpress sFlt‑1/PlGF 1‑2‑3 ratio
- Elecsys® immunoassay sFlt‑1/PlGF ratio
- Triage® PlGF Test
Not all manufacturers indicate their tests are suitable for use across the 20 weeks to 36 weeks and 6 days of pregnancy range. The tests should be used according to their indications for use.
2. Using PlGF-based testing may particularly benefit groups of people who have a higher risk of developing pre-eclampsia and having severe adverse pregnancy outcomes, such as people from African, Caribbean and Asian family backgrounds, or people from more deprived areas.
3. A positive PlGF-based test used alongside standard clinical assessment can help clinicians make a diagnosis of pre-eclampsia. The PlGF-based test does not indicate the severity of the condition. PlGF-based test results should not be used to make decisions about timing of birth in people with preterm pre-eclampsia. The NICE guideline on hypertension in pregnancy has recommendations on timing of birth.
4. The PIGF-based test should be used once per episode of suspected preterm pre-eclampsia. Further research is recommended on repeat testing. this should include:
- exploring the different scenarios in which repeat testing may be indicated
- the appropriate intervals between PIGF-based tests, and
- the diagnostic accuracy of repeat PIGF-based testing
5. BRAHMS sFlt‑1 Kryptor/BRAHMS PlGF plus Kryptor PE ratio is not recommended for routine use in the NHS. Further research is needed to show the accuracy of this test when using specified thresholds.
6. Further research is recommended into how the test will be used in people who are pregnant with more than one baby, and whether different test result thresholds are needed.
This Scottish Health Technology Group (SHTG) recommendation is based on guidance produced by the National Institute for Health and Care Excellence (NICE) in 2022. This guidance was considered and modified following an SHTG adaptation process.
NHSScotland is required to consider SHTG Recommendations.
In making recommendations for Scotland, the Council took into account the NICE guidance and the evidence review underpinning it, and the views of the Scottish topic experts.
1. The Council members discussed the potential benefits of PlGF-based testing in improving the care of pregnant people with suspected preterm pre-eclampsia and the appropriate targeting of treatment for patients. They noted that PlGF-based tests may particularly benefit groups of people who have a higher risk of developing pre-eclampsia and having severe adverse pregnancy outcomes, for example pregnant people from African, Asian or Caribbean backgrounds. People from more deprived areas may also have a greater risk of developing pre-eclampsia.
2. The Council highlighted the potential savings that could be realised through the use of PlGF based testing, via the avoidance of unnecessary hospital admissions when preterm pre-eclampsia can safely be ruled out, and the appropriate targeting of treatments for people with confirmed preterm pre-eclampsia.
3. PlGF-based testing is not used routinely anywhere in NHSScotland. The Council acknowledged that introducing PlGF-based tests would have implications for laboratory services, including taff workload and training.
4. The Council discussed whether some boards may be able to run the tests on behalf of other boards, and that this could help ensure equity of access to testing. The Council noted that out of area testing will affect the turnaround time from sample to a result, especially in remote and rural areas. Clinical experts advised that a test result within 4 hours is optimal, but that the test results will still be useful with a longer turnaround time.
5. The Council were mindful of the ongoing research around PlGF-based testing, particularly PARROT-2, which will provide information on the impact of testing on parent and fetal/neonatal outcomes, and data on the use of repeat testing within an episode of preterm
pre-eclampsia.
6. The Council agreed that PlGF-based tests should be equally accessible to people living in remote and rural areas across Scotland. The availability of PlGF-based testing as part of a laboratory platform or a point-of-care test may help to ensure that tests are available to suit local geographies.
NICE guidance on PlGF-based testing to help diagnose suspected preterm pre-eclampsia (published in July 2022) has been adapted for NHSScotland. The NICE guidance was appraised, and no barriers to use relating to relevance, reliability and transferability of the evidence were identified.
1. Based on a review of the evidence, in terms of clinical effectiveness, NICE concluded that the use of PlGF-based tests to rule in and rule out preterm pre-eclampsia have the potential to reduce time to diagnosis, reduce maternal adverse outcomes, and improve decisions about care.
2. The economic evaluation by NICE reported that PlGF-based tests are cost effective, providing more quality-adjusted life years (QALYs) at lower costs when compared with standard assessment. This is achieved through a reduction in the resource impact of false negative diagnoses, and by the avoidance of unnecessary hospital admissions in people who can be safely managed out of hospital. PlGF-based tests remained cost effective in all the modelled scenarios. The extent of cost savings and improvement to outcomes varied depending on the evidence used to model the effectiveness of standard assessment and how test results affect clinical decision making.
3. NICE recommends four PlGF-based tests. The decision on tests to use in NHSScotland should be made locally within each health board. This will depend on factors such as the existing analysers, geography and cost. NICE do not recommend any test over another.
4. The diagnosis of pre-eclampsia may be made based on the onset of new significant sustained hypertension and proteinuria alone. PlGF-based testing is likely to be most useful in pregnant people when the diagnosis of preterm pre-eclampsia is less clear.
What were we asked to look at
Diagnostics Guidance published by NICE in 2022 recommends four placental growth factor (PlGF)-based tests, intended for use alongside standard clinical assessment, to help decide on care for people with suspected preterm pre-eclampsia. SHTG was asked to adapt the NICE guidance for NHSScotland, to inform a Scotland-specific approach to the use of PlGF-based testing.
Why is this important?
Pre-eclampsia is a potentially serious complication in pregnancy, affecting up to 6% of pregnancies in the UK. Severe pre-eclampsia develops in around 1–2% of UK pregnancies. Approximately 10% of pregnant people will require further assessment and/or monitoring for suspected pre-eclampsia. In 2021, there were 52,584 pregnancies booked for maternity care in NHSScotland. Based on this, an estimated 5,260 pregnant people per year will present with suspected pre-eclampsia in Scotland.
