Will she deliver preterm? Using Fetal Fibronectin to help you make clinical decisions

PROMOTIONAL FEATURE

Approximately 8 per cent of babies are born before 37 weeks’ gestation in the UK. Preterm birth is a significant cause of perinatal mortality and morbidity and the Department of Health is keen to reduce the UK preterm birth rate to 6 per cent by 2025. [1]

The mechanisms leading to late miscarriage, or spontaneous preterm birth, are multifactorial and only partially understood. While there are some known causes and risk factors, many women who do deliver preterm do not have identifiable risk factors. Meanwhile, many women with known risk factors do not deliver preterm, meaning that clinical decision making around preterm birth is challenging and confusing.

Symptomatic women

Most women presenting with symptoms of threatened preterm labour will not deliver in seven days, and more than 70 per cent of women will eventually deliver at term. [2,3,4] However, many women with symptoms of threatened preterm labour are admitted or transferred to another unit unnecessarily and given unnecessary interventions. I have cared for many women who are devastated at the thought of being transferred and admitted to another unit far away – especially if they have additional children to care for or other commitments. Overtreatment can lead to considerable risks to the mother and fetus, increased stress and anxiety for the woman and her family, and substantial financial costs to the NHS. Predictive testing can help to triage symptomatic women more effectively which can decrease inappropriate management and ward inefficiencies.

Asymptomatic women

Predictive testing can also be undertaken on asymptomatic high-risk women (i.e. women who currently have no symptoms of preterm labour but have a risk factor associated with preterm birth).

My colleagues and I find predictive testing useful from a clinical perspective as it can be used to help guide the antenatal appointment care plan for a woman, and determine which women require potential interventions (e.g. a cervical cerclage).

Predictive tests available

The current predictive tests available include transvaginal ultrasound measurement of the cervical length and biomarker swab tests. In the UK there are three biomarker swab tests available: Fetal Fibronectin (fFN), Actim® Partus and PartoSure™.

Current preterm birth guidance recommends that if a transvaginal cervical length scan is indicated but is not available or not acceptable, an fFN test could be undertaken to help diagnose preterm labour when a woman presents with symptoms of threatened preterm labour and intact membranes. [5] Where I have worked clinically in Central London, transvaginal ultrasound is often not available due to limited equipment and expertise – something which is common to lots of hospital units. [6] Meanwhile, an fFN test can be undertaken by anyone who is competent using a vaginal speculum. NICE has concluded that more research is required on the other two biomarker tests (Actim® Partus and PartoSure™). [6]

fFN testing and transvaginal cervical length scanning can also be used to triage women effectively who have risk factors for preterm birth but are asymptomatic. [7] This pathway can be delivered through a Preterm Birth Surveillance clinic. These specialist clinics are encouraged as the mechanism for reducing the preterm birth rate and are increasing. [1]

“Our high-risk preterm labour prevention clinic offered all women at least a second appointment with cervical length assessment following their initial review. We then introduced fFN quantification (in combination with cervical length measurement) for asymptomatic high-risk women between 22 and 24 weeks gestation. The high negative predictive value of low fFN allowed over 75 per cent of women to return to routine antenatal care without additional preterm birth review with none delivering prior to 34 weeks’ gestation.

“We use the QUIPP app to calculate an individualised risk of preterm birth by combining the fFN result and cervical length measurement. Feedback suggests that this information is particularly useful and in the vast majority, reassuring.

“Incorporating fFN testing within our service has resulted in reduced follow up without compromising outcome. This allows targeting of resources to those at greatest risk of preterm birth.”

Melanie Griffin, Consultant Obstetrician, University Hospitals Bristol NHS Foundation Trust

What is fetal fibronectin?

fFN is a glycoprotein (often described as a ‘biological glue’) found between the chorion and the decidua. Typically, fFN is absent from cervicovaginal secretions until around 36 weeks (around the onset of labour). High amounts detected in cervicovaginal secretions between 22 weeks and 36 weeks are associated with preterm labour.

fFN is a swab test which is taken with consent from the posterior fornix of the vagina using a vaginal speculum. The swab test is then processed through a bedside analyser machine, which gives a result within ten minutes.

NICE guidance currently recommends using fFN testing qualitatively in women who arrive with symptoms of threatened preterm labour with the result either being negative or positive. If the fFN concentration is 50ng/ml or more the result is considered positive. [8] If the fFN concentration is under 50ng/ml the result is considered negative. [8] A negative result means that preterm labour is unlikely – clinically you could send this woman home with reassurance. Meanwhile a positive test can ensure that the appropriate care pathway and treatment are offered to the woman. fFN can also be quantitative (measuring the absolute concentration of fFN from 0 to over 500ng/ml) and research is emerging demonstrating the benefits of using fFN in this way on both symptomatic and asymptomatic women. [9]

“Maternity services at the Women & Children’s Hospital in Hull started using fFN in 2008, which allowed a reduction in admissions for threatened preterm labour, as all ‘negative’ results were discharged home. In 2013, we upgraded to quantitative fFN. Following this introduction, an audit was conducted which led to a change in testing to an outpatient area. Of 75 sets of records audited, 15 results were >50ng/ml, of these only 9 were >200ng/ml and required admission. It was therefore deemed that the testing and subsequent treatment of lower risk results could be managed in the outpatient area. This has resulted in a marked reduction in women attending Labour & Delivery Suite in threatened preterm labour. This use of the quantitative measurement has also resulted in further reduction in overnight admissions for women and an overall cost savings in both medication and inpatient stay costs for the Trust. A robust treatment protocol means that we will now only admit women with a result of >200ng/ml (unless any other condition is also present requiring admission), whilst all other women are discharged home with follow up appropriate to their result. The staff are familiar with the fFN test, they like its ease of use and simplicity and are confident in the outcomes and in making subsequent clinical decisions for their patients.”

Julia Chambers, Labour Ward Practitioner, Women & Children’s Hospital, Hull

Clinically I have found the fFN test to be an easy to use bedside test that can help triage women more effectively. fFN testing can aid clinical decision making so that women are offered suitable antenatal management and appropriate intervention – ensuring increased ward efficiencies and improved patient care. The feedback we have received also highlights the positive effect of the fFN test from the patient’s perspective, as it can reassure them and help them feel more in control.

Find out more about the fFN test at www.ffntest.co.uk or contact Hologic at ffntest@hologic.com.

By Naomi Carlisle, Senior Research Midwife, King’s College London

Views and opinions expressed herein by third parties are theirs alone and do not necessarily reflect those of Hologic.

References
1. Department of Health. (2017). Safer Maternity Care The National Maternity Safety Strategy – Progress and Next Steps. Available from https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/662969/Safer_maternity_care_-_progress_and_next_steps.pdf

2. Iams, J.D. et al. The Preterm Prediction Study: Can Low-Risk Women Destined For Spontaneous Preterm Birth Be Identified? American Journal Of Obstetrics And Gynecology, vol 184, no. 4, 2001, pp. 652-655. Elsevier BV, doi:10.1067/mob.2001.111248.

3. Nageotte, Michael P. et al. “Fetal Fibronectin In Patients At Increased Risk For Premature Birth”. American Journal Of Obstetrics And Gynecology, vol 170, no. 1, 1994, pp. 20-25. Elsevier BV, doi:10.1016/s0002-9378(94)70376-0.

4. Phillips, Courtney et al. “Risk Of Recurrent Spontaneous Preterm Birth: A Systematic Review And Meta-Analysis”. BMJ Open, vol 7, no. 6, 2017, p. e015402. BMJ, doi:10.1136/bmjopen-2016-015402.

5. National Institute for Health and Care Excellence (NICE). (2015). Preterm labour and birth NICE guideline. Available from https://www.nice.org.uk/guidance/ng25/resources/preterm-labour-and-birth-pdf-1837333576645

6. National Institute for Health and Care Excellence (NICE). (2018). Biomarker tests to help diagnose preterm labour in women with intact membranes. Available from
https://www.nice.org.uk/guidance/dg33/resources/biomarker-tests-to-help-diagnose-preterm-labour-in-women-with-intact-membranes-pdf-1053749042629

7. Min, J. et al. “Ability Of A Preterm Surveillance Clinic To Triage Risk Of Preterm Birth: A Prospective Cohort Study” Ultrasound In Obstetrics & Gynecology, vol 48, no. 1, 2016, pp. 38-42. Wiley, doi:10.1002/uog.15925.

8. Rapid fFN 10Q Cassettes [product insert]. AW-09189-001, Rev. 004. Manchester, UK: Hologic, Inc.; 2016.

9. Hezelgrave, Natasha L, and Andrew H Shennan. “Quantitative Fetal Fibronectin To Predict Spontaneous Preterm Birth: A Review”. Women& Health, vol 12, no. 1, 2016, pp. 121-128. SAGE Publications, doi:10.2217/whe.15.74.

Staff Writer