PlGF-123 for the diagnosis of Pre-eclampsia in the 3rd Trimester
Research type
Research Study
Full title
To determine the utility of Placental Growth Factor (PlGF)-123 testing for the Diagnosis of Pre-eclampsia in the Third Trimester of Pregnancy.
IRAS ID
281640
Contact name
D M Fullerton
Contact email
Sponsor organisation
Nottingham University Hospitals NHS Trust
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
Summary of Research
The ability to use PlGF-123 to rule-out pre-eclampsia will ensure that patients are not subjected to unnecessary hospital stays ensuring that NHS resources are appropriately targeted. PlGF testing will be performed on pregnant women between 20 weeks and 34 weeks plus 6 days of gestation, presenting to the Antenatal Baby Care (maternity surveillance unit) or labour ward, or who are in-patients on B26 with hypertension and/or proteinuria, with or without symptoms consistent with pre-eclampsia for a 12 month period.
PlGF will be measured on the same serum samples utilised for current pre-eclampsia investigations and so additional blood samples are not required.
The PlGF results will not be reported to the clinical team and will have no effect on clinical decisions.
Following completion of the pregnancy the hospital system Medway will be investigated to determine if the PlGF levels correlate with patient out-comes and if PlGF can be used as a rule-out test for pre-eclampsia. If PlGF is identified as a suitable rule-out marker, the suitability of the manufacturer defined cut-off will be determined.
Study aims:
1) To determine the clinical utility of PlGF as a rule-out test for pre-eclampsia in women presenting to the Antenatal Baby Care Unit at Nottingham University Hospitals NHS Trust between 20 weeks and 34 weeks plus 6 days gestation with clinical suspicion of pre-eclampsia.
2) To determine the potential cost-savings and release of hospital resources upon the introduction of PlGF as a rule-out for pre-eclampsia (Number of inappropriate hospital bed days due to inability to rule-out pre-eclampsia without an effective biochemical marker)
3) To determine the appropriate cut-off limit for the DELFIA Xpress PlGF-123 assay to rule out pre-eclampsia between 20 weeks and 34 weeks plus 6 days gestation.
4) To establish a PlGF assay in the Trisomy Screening laboratory in preparation for the introduction of Pre-eclampsia screening.Summary of Results
Pre-eclampsia is a major cause of maternal and foetal morbidity and mortality. It is a clinical diagnosis affecting 3% of pregnancies and is typically characterised by the onset of hypertension and proteinuria, maternal organ dysfunction or placental dysfunction after 20 weeks of gestation.
Placental growth factor (PlGF) was recommended by the National Institute of Clinical Excellence (NICE) as a test which could be used to both exclude and confirm pre-eclampsia in women with clinical symptoms. The use of this test would therefore identify cases of pre-eclampsia earlier, allowing early treatment and reduction of adverse events for both the pregnant woman and her baby. As pre-eclampsia could also be excluded in some cases, this would prevent unnecessary hospital stays, leading to cost savings.
All pregnant women in the third trimester of pregnancy (28 weeks and greater gestation) presenting to the Nottingham University Hospitals Antenatal Baby Care (Maternity Surveillance Unit) or labour wards with hypertension and/or proteinuria, with or without symptoms consistent with pre-eclampsia had a PLGF test requested when taking blood samples for pre-eclampsia studies. (Please note that additional blood samples were not taken for this study). PlGF was measured using the DELFIA® Xpress PlGF 1-2-3 assay assay in the Nottingham Clinical Pathology laboratory but the results were not released to the clinical teams. After completion of the pregnancy, the clinical notes were reviewed by the Nottingham clinical team to identify the outcome and this information was matched to the PlGF test results to determine if the test had correctly excluded or identified cases of pre-eclampsia.
109 samples were collected from women with suspected or confirmed pre-eclampsia. 40 of these samples were excluded as the women were not within the third trimester of their pregnancy. Of the remaining 69 samples, 43 patients did not develop pre-eclampsia, 12 patients developed pre-eclampsia after blood samples were collected and 14 patients developed pre-eclampsia before or on the day blood samples were collected.
The manufacturer guidelines for the use of PlGF-123 in the diagnosis of Pre-eclampsia suggests that PLGF levels greater than or equal to 50 pg/ml support a diagnosis of pre-eclampsia. 32 of the 69 women who did not develop pre-eclampsia also had a PlGF level below 50 pg/ml. The specificity of the test (the ability of PlGF to correctly identify women who do not have pre-eclampsia) was shown to be 74%. The positive predictive value of PlGF (the ability of PlGF to correctly identify women with pre-eclampsia) was 61%. This study therefore showed that PlGF could be used as a test to identify clinical cases of pre-eclampsia if a value of 50 pg/ml was used as the upper limit for identifying clinical cases.
The manufacturer guidelines for the use of PlGF-123 in the diagnosis of Pre-eclampsia also suggests that PLGF levels greater than or equal to 150 pg/ml excludes a diagnosis of pre-eclampsia. 25 of the 69 women who developed pre-eclampsia had a PlGF level below 150 pg/ml. The sensitivity of the test (the ability of PlGF to correctly identify women who have pre-eclampsia) was shown to be 96%. The negative predictive value of PlGF (the ability of PlGF to correctly identify women who do not have pre-eclampsia) was 94%. This study therefore showed that PlGF could be used as a test to exclude pre-eclampsia if a value of 150 pg/ml was used as the lower limit for identifying negative cases.
The results of this study are comparable with other reports in the literature as sensitivities of 72 and 88% have been reported for PlGF using a rule-out value of 150 pg/ml (Bremner et al 2022 and McCarthy et al 2019) and a specificity of 91% was identified using a rule-in value of 50 pg/ml (Bremner et al 2022).
PlGF is to be introduced into the Nottingham University Hospitals pre-eclampsia guideline “Guideline for Gestational Hypertension and Pre-eclampsia in the Community and Following Referral to Hospital”. The PlGF test results will be used in combination with clinical details to help decide management for women where pre-eclampsia is suspected.REC name
East Midlands - Nottingham 1 Research Ethics Committee
REC reference
21/EM/0060
Date of REC Opinion
15 Mar 2021
REC opinion
Favourable Opinion