Evidence for the Triage PlGF Test:
The PELICAN study was a prospective, multicentre, observational study investigating the diagnostic accuracy of PlGF in diagnosing pre-eclampsia.12 This study showed that low PlGF had high sensitivity (0.96; 95% CI 0.89 – 0.99) and high negative predictive value (NPV 0.98; 0.93 – 0.995) in diagnosing pre-eclampsia necessitating delivery within 14 days, in women with suspected pre-eclampsia before 35 weeks’ gestation.12 The area under the receiver operating characteristic curve (AUC) for PlGF was greater than all other commonly used tests (systolic blood pressure, diastolic blood pressure, alanine transaminase, urate, dipstick proteinuria) for making a diagnosis in women presenting with suspected pre-eclampsia. Low PlGF was classified as <5th centile according to predetermined normal ranges.9 However, for implementation in clinical practice a threshold of <100pg/ml was identified, independent of gestation, with test performance similar to the 5th centile and retaining the same high sensitivity and NPV. When multiples of median were used for analysis, this reduced the predictive power of low PlGF (unpublished data). The study was conducted across seven sites in the United Kingdom and recruited 625 women; 346 developed pre-eclampsia, of whom 176 developed pre-eclampsia prior to 35 weeks’ gestation. Therefore, this demonstrates high test performance across a broad range of clinical settings and population demographics.
PlGF testing has been investigated in the PETRA trial, a prospective observational study recruiting 1,112 women from 24 centres across North America.14 This demonstrated that low PlGF concentration was strongly correlated with time to delivery in women with suspected pre-eclampsia before 35 weeks’ gestation (753 women). The median time to delivery was 10 days for low PlGF (100pg/ml or lower) and 2 days for very low PlGF (less than 12pg/ml). The sensitivity for diagnosing pre-eclampsia and delivery within 14 days was 92.5% and the NPV was 90.3%. This lower NPV may reflect the higher prevalence of pre-eclampsia in the study population, with 71% of participants (538 women) diagnosed with preterm pre-eclampsia. A secondary analysis of this study has also been reported.15 This found a significant association between low and very low PlGF and composites of perinatal and maternal adverse outcomes. The sensitivity and NPV of low PlGF for adverse neonatal outcomes were 95.8% and 99.2%, and for adverse maternal outcomes 86.8% and 98.1%. They conclude that women with abnormal PlGF are significantly more likely to suffer adverse neonatal and maternal outcomes, and that PlGF is useful for risk stratification.
PlGF testing has been evaluated in the PARROT trial, a multi-centre stepped-wedge cluster-randomised controlled trial.16The trial design involved random and sequential transition of maternity units (representing clusters) from concealed to revealed PlGF testing, alongside a simple clinical management algorithm. 1023 women with suspected preterm pre-eclampsia were enrolled from 11 maternity units across the UK. The time to diagnosis was reduced from 4.1 to 1.9 days, with a significant reduction in a composite of severe maternal adverse outcomes from 5.4% to 3.8% (aOR 0.32, 95% CI 0.11 – 0.96). There was no difference in gestational age at delivery or perinatal adverse outcomes. The study strengths include its broad inclusion criteria and a population who were diverse from an ethnicity and sociodemographic perspective, from multiple sites, thereby enhancing generalisability of the findings to the real-world setting. Therefore, this study provided novel evidence that PlGF testing proves a valuable diagnostic adjunct in suspected pre-eclampsia, allowing targeted surveillance for those at highest risk of adverse outcomes.
Initial studies using economic modelling demonstrated that PlGF-based testing may afford a cost-saving of between £330 and £1032 per woman tested.17, 18 In a more recent study describing their cost-effectiveness analysis of the PARROT trial, Duhig and colleagues found a total cost-saving of £149 per woman, based on £70 per Triage PlGF test.19 Given that there were 646,794 births in England in 2017 and 10% of pregnant women have suspected pre-eclampsia, with 30% of these presenting prior to 37 weeks’ gestation, PlGF testing could be performed in approximately 38,800 women per year. This represents a potential cost saving of £2,891,196 each year in England. These cost-savings are driven by a reduction in outpatient attendances for those with a normal, low risk result. There was an increased cost seen associated with inpatient admissions in those at higher risk. Despite this, overall PlGF testing was found to be cost saving, but the cost-effectiveness will depend on the cost of the test being performed. The authors conclude that their more conservative cost-saving is due to improved clinical risk stratification leading to appropriate redistribution of resources, rather than an overall reduction of resource use anticipated by hypothetical analyses.19