Advice and recommendations for RANZCOG members in Australia who use fFN for preterm birth risk stratification in symptomatic women.

The use of adjunct tests for risk stratification for women/people presenting with signs and symptoms of preterm labour – consideration of alternatives to fetal fibronectin (fFN).

In early July 2024, Hologic announced that as of 30th September 2024, all sales of Rapid fFN® 10Q cassettes and Perilynx® analysers (Hologic) for fetal fibronectin (fFN) testing would cease globally and many Australian centres have already exhausted their stocks.

Risk stratification in the setting of threatened preterm labour allows the appropriate use of transfer, corticosteroids, magnesium sulfate, and tocolysis and the reassurance of women whose risk of preterm birth is low. fFN quantitative testing is one such method. Lack of access to fFN testing poses challenges for units where it has been used, with additional challenges for those in rural and remote settings. This has the potential to result in increased obstetric transfers and administration of antenatal corticosteroids, both of which have significant social, economic, and health burdens, notwithstanding their substantial benefits to the important minority who do go on to have a preterm birth.

This communiqué is intended to provide advice for RANZCOG members in Australia who use fFN as they transition to alternative strategies of preterm birth risk stratification in symptomatic women. Separate advice has already been prepared for members in Aotearoa New Zealand. Prediction of preterm birth in asymptomatic women is beyond the scope of this communiqué.

Alternative biomarkers to fetal fibronectin

Two products are commercially available: Partosure® (distributed in Australia by In Vitro Technologies) and Actim Partus® (Abbott Rapid Diagnostics). These test for placental alpha microglobulin-1 (PAMG-1) and phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1), respectively, and are qualitative tests in that they give only a “positive” or “negative” result.

Both have similar test performance characteristics in predicting preterm birth in symptomatic women, with their strength being in their negative predictive values around 95%, meaning that women who test negative have a 95% chance of not giving birth within seven days. There is no current evidence that either of these tests is importantly superior to the other.

Quantitative tests similar to Rapid fFN® 10Q are in commercial development but are not yet available.

Ultrasound cervical length assessment

Transvaginal ultrasound assessment of cervical length is clinically useful in the prediction of preterm birth in symptomatic women in the third trimester of pregnancy. This is a different application from routine cervical length screening of asymptomatic women in the second trimester.

Transvaginal ultrasound is relatively simple but requires specific training in order to maintain reliability as a screening test and most clinicians are not currently trained in performing this assessment. It requires special equipment and disinfection protocols and may not be available outside of business hours. These present limitations to the widespread use of cervical length assessment in women with threatened preterm labour but these may be overcome in some settings where facilities and expertise are available.

In symptomatic women, a shorter cervical length is associated with a higher chance of preterm birth. Various cut-off values are proposed as a standalone test, with 15mm being a reasonable compromise between negative predictive value and screen positive rates. Individual jurisdictions may prefer to use more conservative values depending on their capacity to provide care for the small proportion of women who will have false negative results.

QUiPP

QUiPP is a smartphone application designed to assess the risk of preterm birth in symptomatic women. The app incorporates other preterm birth risk factors to provide a more individualised prediction of preterm birth risk and has been thoroughly validated. It is designed to be used with a combination of cervical length and fFN but can be used with either of these clinical parameters alone. QUiPP does not currently have capacity to include other biomarkers.

Acknowledgement

This communiqué was prepared by Dr Scott White, RANZCOG Women’s Health Committee Chair, with the valuable input of Professor Katie Groom and Dr Lisa Dawes, Preterm Birth Service Leads, National Women’s Health, Te Toka Tumai, Auckland and Carosika Collaborative Steering Group members.

References

• National Institute for Health and Care Excellence (NICE), Biomarker tests to help diagnose preterm labour in women with intact membranes: Diagnostics guidance [DG33], published: 04 July 2018.
• Melchor, J. C., Khalil, A., Wing, D., Schleussner, E., & Surbek, D. (2018). Prediction of preterm delivery in symptomatic women using PAMG-1, fetal fibronectin and phIGFBP-1 tests: systematic review and meta-analysis. Ultrasound in obstetrics & gynaecology: the official journal of the International Society of Ultrasound in Obstetrics and Gynaecology, 52(4), 442–451.
• Sotiriadis, A., Papatheodorou, S., Kavvadias, A., & Makrydimas, G. (2010). Transvaginal cervical length measurement for prediction of preterm birth in women with threatened preterm labour: a meta-analysis. Ultrasound in obstetrics & gynaecology: the official journal of the International Society of Ultrasound in Obstetrics and Gynaecology, 35(1), 54–64.
• Conde-Agudelo, A., & Romero, R. (2016). Cervical phosphorylated insulin-like growth factor binding protein-1 test for the prediction of preterm birth: a systematic review and metaanalysis. American journal of obstetrics and gynaecology, 214(1), 57–73.
• Creswell, L., Rolnik, D. L., Burke, B., Daly, S., & O’Gorman, N. (2024). Performance of QUiPP App v.2 tool for prediction of preterm birth in asymptomatic high-risk women attending preterm specialist clinic: external validation study. Ultrasound in obstetrics & gynaecology: the official journal of the International Society of Ultrasound in Obstetrics and Gynaecology, 64(1), 71–78.
• Carosika Collaborative, Evidence summaries for alternative vaginal biomarkers and transvaginal cervical length in the prediction of spontaneous preterm birth in symptomatic wāhine/people.

Relevant RANZCOG clinical guidance statements

Measurement of cervical length for prediction of preterm birth (C-Obs 27)

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Image credit: Hologic