3 The diagnostic tests

3 The diagnostic tests

The interventions

Triage PlGF test

3.1 The Triage PlGF test (Alere International) is a CE‑marked, single‑use, fluorescence immunoassay device, which is used with the Triage MeterPro point-of-care analyser for the quantitative determination of placental growth factor (PlGF) in blood plasma samples. The test is intended for use with clinical judgement and other diagnostic tests, to help diagnose suspected pre‑eclampsia and the level of risk for delivery arising from pre‑eclampsia within 14 days of testing. It is recommended for use in pregnant women between 20 weeks and 34 weeks plus 6 days of gestation.

3.2 The test has a limit of detection of 9 picograms/ml and a measurable range of 12 to 3,000 picograms/ml. The test turnaround time is about 15 minutes. The test cut‑off values recommended by the company are shown in table 3.

Table 3 Recommended cut‑off values for the Triage PlGF test

Result

Classification

Interpretation

PlGF <12 pg/ml

Test positive – highly abnormal

Highly abnormal and suggestive of patients with severe placental dysfunction and at increased risk for preterm delivery

PlGF ≥12 pg/ml and <100 pg/ml

Test positive – abnormal

Abnormal and suggestive of patients with placental dysfunction and at increased risk for preterm delivery

PlGF ≥100 pg/ml

Test negative – normal

Normal and suggestive of patients without placental dysfunction and unlikely to progress to delivery within 14 days of the test

Abbreviations: PlGF, placental growth factor; pg/ml, picograms per millilitre.

Elecsys immunoassay sFlt‑1/PlGF ratio

3.3 The Elecsys immunoassay sFlt‑1/PlGF ratio (Roche Diagnostics) measures the amounts of PlGF relative to soluble FMS‑like tyrosine kinase‑1 (sFlt‑1; also known as VEGFR1) in serum samples from women with suspected pre‑eclampsia. The ratio is formed by combining the results from 2 CE‑marked sandwich electrochemiluminescence immunoassays (Elecsys PlGF and Elecsys sFlt‑1 assays), which are compatible with both the Roche Elecsys and the Cobas e automated analysers. The laboratory information system calculates and reports the sFlt‑1/PlGF ratio and the individual assay values. The Elecsys immunoassay sFlt‑1/PlGF ratio is intended to be used with clinical judgement and other diagnostic tests to diagnose pre‑eclampsia. The ratio may also be used to help predict pre‑eclampsia, eclampsia and HELLP syndrome in the short term. It may be used for testing pregnant women from 20 weeks' gestation up until the time of delivery.

3.4 The Elecsys sFlt‑1 assay has a limit of detection of 10 picograms/ml (measuring range 10 to 85,000 picograms/ml) and a limit of quantitation of 15 picograms/ml. The Elecsys PlGF assay has a limit of detection of 3 picograms/ml (measuring range 3 to 10,000 picograms/ml) and a limit of quantitation of 10 picograms/ml. The turnaround time of the Elecsys immunoassay sFlt‑1/PlGF ratio is about 18 minutes. The test cut‑off values recommended by the company are shown in table 4.

Table 4 Recommended cut‑off values for the Elecsys immunoassay sFlt‑1/PlGF ratio

sFlt‑1/PlGF ratio

Aid in diagnosis of pre‑eclampsia

20 weeks to 33 weeks plus 6 days

Rule‑out cut‑off

33

Rule‑in cut‑off

85

34 weeks to delivery

Rule‑out cut‑off

33

Rule‑in cut‑off

110

Short‑term prediction of pre‑eclampsia (24 weeks to 36 weeks plus 6 days)

Rule‑out*

<38

Rule‑in**

>38

* Rule‑out pre‑eclampsia for 1 week.

** Rule‑in pre‑eclampsia within 4 weeks.

DELFIA Xpress PlGF 1‑2‑3 test

3.5 The DELFIA Xpress PlGF 1‑2‑3 test (Perkin Elmer) is a CE‑marked solid-phase, 2‑site fluoroimmunometric sandwich assay for the quantitative determination of PlGF in serum samples. The assay is compatible with the 6000 DELFIA Xpress random access analyser. The test is intended to help diagnose pre‑eclampsia during the second and third trimesters of pregnancy, and is used with clinical assessment.

3.6 The assay has a limit of detection of 1.9 picograms/ml (measuring range 1.9 to 4,000 picograms/ml) and a limit of quantitation of 3.3 picograms/ml. The test has a turnaround time of about 30 minutes. The cut‑off values for PlGF measurements obtained during the second trimester are highly dependent on gestational day and the company suggests that cut‑off values should be established by individual laboratories. In the third trimester, in addition to laboratory-calculated cut‑off values based on gestational day, the company suggests that a fixed cut‑off value of 184 picograms/ml can be used. Levels of PlGF lower than 184 picograms/ml indicate an increased probability of pre‑eclampsia developing.

BRAHMS sFlt‑1 Kryptor/BRAHMS PlGF plus Kryptor PE ratio

3.7 The BRAHMS sFlt‑1 Kryptor/BRAHMS PlGF plus Kryptor PE ratio (Thermo Fisher Scientific) is formed by combining the results from 2 automated immunofluorescent sandwich assays, the BRAHMS sFlt‑1 Kryptor assay and the BRAHMS PlGF plus Kryptor assay. They are indicated for the quantitative determination of sFlt‑1 and PlGF in serum samples and are compatible with the BRAHMS Kryptor compact plus analyser. The assays are intended to be run at the same time, with the analyser reporting both the concentrations for each assay and the sFlt‑1/PlGF ratio. The BRAHMS sFlt‑1 Kryptor/BRAHMS PlGF plus KRYPTOR PE ratio is intended to be used with clinical assessment to help diagnose pre‑eclampsia.

3.8 The BRAHMS sFlt‑1 Kryptor assay has a limit of detection of 22 picograms/ml (measuring range 22 to 90,000 picograms/ml) and a limit of quantitation of 34 picograms/ml. The BRAHMS PlGF plus Kryptor assay has a limit of detection of 3.6 picograms/ml (measuring range 3.6 to 7,000 picograms/ml) and a limit of quantitation of 6.9 picograms/ml. Reference ranges for each of the assays and the sFlt‑1/PlGF ratio are given in the company instructions, and the company recommends that individual laboratories should validate these ranges or establish their own reference ranges before use. The turnaround time for the BRAHMS sFlt‑1 Kryptor assay is 9 minutes and the turnaround time for the BRAHMS PlGF plus Kryptor assay is 29 minutes.

The comparator

3.9 The comparator used in this assessment is standard clinical assessment to help diagnose suspected pre‑eclampsia, guided by a combination of the following clinical information:

  • maternal hypertension (categorised as mild, moderate or severe)

  • quantitative proteinuria test

  • clinical symptoms suggestive of pre‑eclampsia (for example, headache, oedema, visual disturbances)

  • fetal growth restriction.

  • National Institute for Health and Care Excellence (NICE)