Evidence for the Elecsys Immunoassay sFlt-1/PlGF ratio:
Rana and colleagues performed a prospective observational study investigating the association between the Elecsys sFlt-1/PlGF ratio and adverse outcomes in suspected pre-eclampsia.20 They found that in women presenting before 34 weeks’ gestation, sFlt-1/PlGF ratio out-performed current approaches (systolic blood pressure, alanine transaminase, creatinine, urate) at predicting adverse outcomes, with an AUC of 0.89. A cut-off point of 85 was identified, with sensitivity of 72.9% and specificity of 94.0% for adverse outcomes, in women presenting before 34 weeks’ gestation. sFlt-1/PlGF ratio was inversely correlated with time to delivery; delivery occurred within two weeks in 86.0% of women with a sFlt-1/PlGF ratio above 85. This was a single centre study, including 616 assessments of suspected pre-eclampsia, of which 81 were repeat evaluations.
The PROGNOSIS study was a multicentre observational study that analysed the predictive value of the Elecsys sFlt-1/PlGF ratio in 1050 women, with 500 women included in a development cohort to determine a ratio cut-off and 550 women as a validation cohort.21 This demonstrated that a ratio of ≤ 38 had a negative predictive value (NPV) of 99.3% (95% CI 97.9 – 99.9), with a sensitivity of 80.0 (95% CI 51.9 – 95.7) for ruling out pre-eclampsia in less than one week. The positive predictive value for a diagnosis of pre-eclampsia within four weeks was 36.7% (95% CI 28.4 – 45.8), with a 66.2% sensitivity (54.0 – 77.0). Predictive performance of sFlt-1 and PlGF analysed individually were not superior to the ratio, with AUC of 78.2% for PlGF alone, compared to 88.4% for sFlt-1/PlGF.21 They conclude that in clinical practice, high NPV is crucial in the evaluation of suspected pre-eclampsia, as failure to detect imminent disease could have important consequences for the woman or fetus. 199 women (19%) developed pre-eclamspia and this lower prevalence may explain the lower positive predictive value than the PELICAN study.12
The Elecsys sFlt-1/PlGF ratio has also been evaluated in the INSPIRE randomised controlled trial.22 370 women with suspected preterm pre-eclampsia were randomised on an individual level to revealed or non-revealed PlGF-based testing. Primary endpoint was hospitalisation within 24 hours of the test. The trial found no difference in the primary outcome but use of the test increased the proportion of high-risk patients admitted without influencing overall admission rate, which may reflect appropriate redistribution of resources. Overall, 85 women (23%) developed pre-eclampsia and all of those developing pre-eclampsia within seven days were admitted to hospital following the sFlt-1/PlGF test, demonstrating 100% sensitivity and 100% NPV for the defined primary endpoint. They concluded that larger trials are needed to assess whether the test could be used to mitigate adverse maternal and perinatal outcomes. The single centre nature of the trial, with 90% of participants of white ethnicity, limits its wider generalizability.