3 The diagnostic tests

3 The diagnostic tests

Three interventions and 2 comparators were included in this assessment.

The interventions

Actim Partus

3.1 Actim Partus is a CE‑marked qualitative immunochromatographic point-of-care test designed to detect phosphorylated IGFBP‑1 (insulin-like growth factor binding protein‑1) in cervical secretions during pregnancy. Phosphorylated IGFBP‑1 is a protein made by the cells lining the uterus. When delivery is imminent, small amounts of phosphorylated IGFBP‑1 leak into the cervix.

3.2 The Actim Partus test kit contains a sterile polyester swab for specimen collection, a tube of specimen extraction buffer and a dipstick in a sealed foil pouch. No other instrumentation or consumables are needed. The sample is collected from the cervical os during a sterile speculum examination. The results are available in 5 minutes or less. Two lines indicate a positive result; 1 line is a negative result that indicates the woman will not deliver within 7 to 14 days; if no lines appear, the test is invalid.

3.3 The dipstick contains 2 monoclonal antibodies to human IGFBP‑1. One is bound to blue latex particles (the detecting label). The other is immobilised on a carrier membrane to catch the complex of antigen and latex-labelled antibody and indicate a positive result. If phosphorylated IGFBP‑1 is present in the sample, it binds to the antibody labelled with latex particles. The particles flow to the results area of the dipstick, and if phosphorylated IGFBP‑1 is bound to them, they bind to the catching antibody. A test line will appear if the concentration of phosphorylated IGFBP‑1 in the sample exceeds the detection limit of the test. A control line confirms correct performance of the test.

3.4 Actim Partus is for use in pregnant women with signs and symptoms of preterm labour and intact amniotic membranes, after 22 weeks plus 0 days of pregnancy. The test can be used if vaginal infections, vaginal medications and semen are present, but active vaginal bleeding may cause a false positive result. The test has a limit of detection of 10 nanograms/millilitre (ng/ml) and a measuring range of 10 to 8,000 ng/ml.

PartoSure

3.5 PartoSure is a CE‑marked qualitative lateral flow, immunochromatographic point-of-care test designed to detect placental alpha microglobulin‑1 (PAMG‑1) in vaginal secretions during pregnancy. PAMG‑1 is a protein released from the lining of the uterus into the amniotic cavity throughout pregnancy. It is found in very high concentrations in amniotic fluid and in very low concentrations in normal vaginal discharge. Studies have demonstrated a strong correlation between the presence of PAMG‑1 in cervicovaginal discharge and imminent delivery.

3.6 The PartoSure test kit contains a test strip, a vaginal swab and a plastic vial containing a solvent solution. No other instrumentation or consumables are needed. The sample may be collected with or without a speculum. The results are available in 5 minutes or less. Two lines indicate a positive result and a high risk of delivery within 7 days; 1 line indicates a negative result and a low risk of delivery within 7 to 14 days; no lines indicate an invalid result.

3.7 The test strip has a reactive area containing monoclonal anti-PAMG-1 antibodies bound to a gold particle (the detecting label). The sample flows through the reactive area and if PAMG‑1 is present, it binds to an anti-PAMG‑1 antibody, forming an antigen-antibody complex. This complex then flows to the test region of the strip where it is immobilised by a second anti-PAMG‑1 antibody. A test line appears if the concentration of PAMG‑1 in the sample exceeds the detection limit of the test. Unbound antigen-antibody complexes continue to flow along the test strip and are immobilised by another antibody, leading to the appearance of the internal control line.

3.8 PartoSure is for use in pregnant women with signs and symptoms of preterm labour, intact amniotic membranes and minimal cervical dilatation (3 cm or less), between 20 weeks plus 0 days and 36 weeks plus 6 days of pregnancy. The test can be used if vaginal infections, urine, semen and trace amounts of blood are present, but should not be used if there is significant discharge of blood. It can also be used shortly after a vaginal examination. The test has a limit of detection of 1 ng/ml and a measuring range of 1 to 40,000 ng/ml.

Rapid fetal fibronectin 10Q Cassette Kit

3.9 The Rapid fetal fibronectin (fFN) 10Q Cassette is a CE‑marked test for use in the PeriLynx System or the Rapid fFN 10Q System. It is designed for the quantitative detection of fetal fibronectin in cervicovaginal secretions to assess the risk of preterm delivery within 7 to 14 days. Fetal fibronectin is an adhesive glycoprotein that holds the membranes of the uterus to the fetal membranes. After 35 weeks of pregnancy, it begins to break down naturally, and is detectable in vaginal secretions. Fetal fibronectin detected between 22 and 35 weeks of pregnancy is an indicator of preterm birth risk.

3.10 NICE's guideline on preterm labour and birth recommends fetal fibronectin testing to determine the likelihood of birth within 48 hours for women who are 30 weeks plus 0 days pregnant or more, if transvaginal ultrasound measurement of cervical length is indicated but is not available or not acceptable. The guideline recommends a threshold of 50 ng/ml to interpret the test results. However, clinical experts have noted that a quantitative fetal fibronectin test would enable other thresholds to be used.

3.11 The Rapid fFN 10Q Cassette test can be done near the woman. In addition to the test kit, an analyser, printer, Rapid fFN Control Kit, QCette (quality control device) and pipette are needed. The sample is collected from the posterior fornix of the vagina during a speculum examination. It is incubated in the analyser for 7 minutes and then analysed, which takes 2 to 3 minutes. The analyser reports fetal fibronectin concentrations ranging from 0 to 500 ng/ml; concentrations greater than 500 ng/ml are displayed as 'greater than 500 ng/ml'. The instructions for use do not give any thresholds, therefore laboratories would need to set and validate their own thresholds. Internal controls are done automatically with every test.

3.12 The Rapid fFN 10Q Cassette is for use in pregnant women with signs and symptoms of early preterm labour, intact amniotic membranes and minimal cervical dilatation (less than 3 cm), between 22 weeks plus 0 days and 35 weeks plus 6 days of pregnancy. Assay interference from blood, bacteria, bilirubin and semen has not been ruled out. However, a negative test result (less than 10 ng/ml) in the presence of blood or semen is valid. Also, the fetal fibronectin concentration may be affected by cervical disruption caused by, but not limited to, sex, digital cervical examination or vaginal probe ultrasound.

The comparators

Fetal fibronectin

3.13 Fetal fibronectin testing, at a threshold of 50 ng/ml, is recommended in NICE's guideline on preterm labour and birth (see sections 2.16 to 2.19 of this document).

3.14 The fetal fibronectin test is available as a quantitative enzyme-linked immunosorbent assay (ELISA), and as a qualitative membrane immunosorbent assay. Examples include:

  • Fetal Fibronectin Enzyme Immunoassay; a quantitative assay with a recommended threshold of 50 ng/ml (Hologic)

  • Rapid fFN for the TLilQ System; a qualitative immunochromatographic assay with a limit of detection of 50 ng/ml (Hologic)

  • QuikCheck Fetal Fibronectin Test; a qualitative test with a limit of detection of 50 ng/ml (Hologic).

Clinical assessment

3.15 Clinical assessment is described in NICE's guideline on preterm labour and birth and in sections 2.11 to 2.13 of this document.

  • National Institute for Health and Care Excellence (NICE)