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.