Presentation on theme: "Fetal Fibronectin Testing for Suspected Preterm Labour"— Presentation transcript:
1Fetal Fibronectin Testing for Suspected Preterm Labour An emerging standard of care(Note: Please feel free to use your own background design)
2Fetal Fibronectin Testing for Suspected Preterm Labour ObjectivesDiscuss incidence of preterm labour provincially and nationallyDescribe the benefits of fetal fibronectin testingOutline insert province approach to this emerging standard of careProvide detailed clinical decision making and procedures for fFN testing
3Preterm Labour (< 37 weeks) 1 in 5 pregnant women exhibit signs and symptoms of preterm labour.3-4 % of births occur before 34 weeksUp to 70% of women identified as “high-risk” deliver at term.Maximum clinical judgment sensitivity for del <1week from admission was <50% with minimal cervical dilatation (< 3 cm.).
4Preterm BirthPreterm birth rate is defined as the number of live births with a gestational age less than 37 weeks completed weeks gestation>7.6% (all Provinces) of all pregnancies result in preterm birthSources: ACOG Technical Bulletin,1995, No. 206; National Vital Statistics Report 2000;48(3). St John EB et al. Am J Obstet Gynecol. 2000;182: Macones, Am J ObGyn, Vol 181, 12/99
5Rate of Preterm Delivery by Province/Territory (excluding Ontario) 2000
12Potential Benefits of An Evidence-Based, Risk Assessment Marker Identify women who are truly at risk.Identify and reassure women who are not at risk.Avoid separation of mother from her family.Avoid unnecessary expense of extended assessment time, admission time, transport to a tertiary centre.Avoid unnecessary tocolytic and steriod use.Improved resource utilization.Potential research benefits e.g. focus tocolytic trials on women who will potentially benefit.
13Fetal Fibronectin (ƒFN) Fetal Fibronectin (fFN) is not new in obstetrics practice1st literature appeared in 1985; as an oncogene marker.1st OB-specific literature appeared in 1991 in New England J. of Medicine by Lockwood, et al.>200 peer reviewed OB articles now published, 3 meta analyses, 9 Canada-specific abstracts presented at SOGC.Canada specific data documents reduced medication use, reduced hospital day stays, reduced transportsCanadian data is from level III hospitals, rural and remote hospitals.
14What is Fetal Fibronectin (ƒFN) Glycoprotein found in extracellular matrix of amniotic membranes.Binds chorion to decidua.Normally found in cervico-vaginal secretions until 22 weeks gestation and again near the time of labour.Released into cervical/vaginal fluid in response to inflammation or separation of amniotic membranes from decidua.Presence after 24 weeks is indicative of imminent labourFetal (ƒFN) immunoassay detects concentrations of fetal fibronectin protein in cervicovaginal fluids.Presence of >50 ng/mL considered positive.
17Key Terminology for Evaluating PTD Diagnostics Negative Predictive Value (NPV): Answers the question, “If a woman has a negative test, how likely is she NOT to deliver prematurely?”Positive Predictive Value (PPV): Answers the question, “If a woman has a positive test, how likely is she to deliver prematurely?”Sensitivity: Percent of women who have preterm delivery whom the test correctly identifiesSpecificity: Percent of women who do NOT have preterm delivery whom the test correctly identifies
18Utility of ƒFN for Predicting PTB in Symptomatic Women PPV(%) NPV(%) Cx Dilatation(cm)Lockwood, 1991 (n=117) NoneMorrison, 1993 (n=28) 1Iams, 1995 (n=192) 3Burrus, 1995 (n=37) 3Bartnicki, 1996 (n=112) 2Peaceman, 1997 (n=725) 3
19Threatened Preterm Labour Women withThreatened Preterm Labour(1/25 deliver <14 days)ƒFN -(80%)ƒFN +(20%)1/125Deliver <14 days1/6Deliver <14 daysPeaceman, AJOG 1997; 177:13-8
20Nova Scotia Pilot Study April 2002-March 2004 (Armson & Scott et. al.) Prospective cohort studyObjectivesTo determine if introduction of rapid ƒFN testing for suspected PTL will:Reliably predict preterm birthResult in a reduction of:PTL admissions/maternal transfer rateslength of stay, tocolytic/corticosteroid usereproductive health care costs without compromising neonatal outcomes
21Conclusions from Nova Scotia Study A negative ƒFN test for suspected PTL accurately identifies women not likely to deliver within 14 days (98% -99% accurate)A positive ƒFN test identifies women at high risk for preterm birth- 24% 7 days- 28% 14 days- 31% 34 weeks- 48% 37 weeksDiagnostic accuracy of ƒFN superior to clinical criteria for women with suspected preterm labour
22Conclusions from Nova Scotia Study Criteria for clinical use of ƒFN appear to be broad and inconsistentClinicians/patients somewhat reluctant to adhere to guidelines of non-intervention for negative ƒFN results, particularly in regional centres.Potential for reduction in maternal transfers, hospital admissions and associated health care costs
23Results from the Nova Scotia Study Implementation of province-wide Fetal Fibronectin testing currently ongoingSeed funding provided by NS Department of HealthGoalsTo reduce unnecessary maternal transfers and admissions for suspected preterm labourTo reduce psychosocial and financial burdens for families
24BC StudyFetal Fibronectin collected by speculum exam from admitted patients with symptomatic preterm labourAssays were performed in our laboratory. The results were revealed to the clinician within 1 – 8 hoursA retrospective chart review was undertaken to assess pregnancy outcomeAn estimate of the total hospital days saved was developed using the ALOS for patients admitted with a diagnosis of PTL prior to the utilization of the Fetal Fibronectin Assay
25Results Of 62 patients tested, outcomes were known for 47 patients. Delivered < 14 daysDelivered > 14 daysFFN +ve17138FFN –veSensitivity = 50% PPV = 12.5%Specificity = 84% NPV = 97%Farquharson, D., Lee, L.,Garg, A. Clinical utilization and cost saving analysis of fetal fibronectin assay in a tertiary care institution. Abstracted presented at 2003 SOGC meeting, Charlottetown.
26BC Study ResultsA total of 62 assays were conducted between May 2002 and March 2003Ages 18 – 39, mean 30GA on admission: 20 – 33 weeksLength of stay ranged 1 – 44 days, mean 4.7 daysNulliparas: 55 %Multiparas: 45 %
27BC Study ConclusionOur experience in which Fetal Fibronectin Assay (Adeza TLI) was used as an adjunct to diagnosis and management of preterm labour suggest reduced hospital utilization, and earlier reverse transfer of these patients to their referring institutions without adverse sequelae.
28Cost Savings (literature) Reduction in PTL admissions$486,000 saved(Joffe et al, AJOG 1999)Reduction in maternal transfers$30,297 saved(Giles et al, AJOG 2000)
29Resource Utilization - Canada Royal Victoria HospitalObservational cohort design20 week periods before and after ƒFNSingletons, weeks, suspected PTLAbenhaim JOGC 2005; 27:689-94
30Effect of ƒFN on Resource Utilization _________________________________________________________Baseline Period Study Period p value _________________________________________________________PatientsPreterm Births 9 (7.8%) (8.6%) NSPTL Admissions 28 (24.1%) (12.1%) 0.02Days HospitalizedMean LOSAdmission Costs $102, $26,169Mean Cost $3, $Abenhaim, JOGC 2005; 27:689-94
31Considerations Cost: Approximately $100+ per test Patient demand – not experienced by other centresPhysician overuseEstimate per years based on 2500 births/yrClose adherence to guidelineSavingsCost of admissionCost of transferOptimal use of tertiary bedsMaternal/family reassurance/satisfaction
32Patient <34 wks Gestation with Symptoms of Preterm Labour Network organizations will facilitate a supportive environment for adoption of CHN Practice Guidelines by incorporating the guidelines into their existing guideline process (order sets, intranet availability, etc).Network organizations will identify a “champion” to take the lead in ensuring implementation of the guideline at the organization.The CHN guideline will proceed through the organizational process for “approval” (MAC, Pharmacy, etc).Education sessions will be provided for staff. CHN will provide a Power Point Presentation for organizational use.CHN will monitor implementation through a variety of methods and report to members (surveys, chart audits, etc).Patient <34 wks Gestation with Symptoms of Preterm LabourSpeculum exam before VEfFN swab from posterior fornix(see Appendix A)CulturesManagement of PROMDiscard fFN swabEvidence of Ruptured MembranesIntact MembranesVaginal ExaminationCx ≥ 3 cm DilationRegular uterine activityDiagnosis preterm labourTreat for preterm labourSend fFN swabReassure motherCx < 3 cm dilatedOngoing uterine activityClinical suspicion of preterm labourCx Long + closedContractions subsidedNo clinical evidence of preterm labourPositiveTocolyticsCorticosteroidsAntibioticsConsider transfer to appropriate level of careNegativeF/U endovaginal ultrasound of the cervix (if available)Treatment of BVConsider repeat test in 7-14 days, if symptomaticRegular uterine contractions >6 per hourPelvic pressureLow abdominal pain and/or crampsLow backacheFetal FibronectinGuideline for Use in the Management of Preterm LabourPractice GuidelineJune 2006BackgroundA guideline addressing the use of the Fetal Fibronectin (fFN) test for women in preterm labour was recommended by members of the Child Health Network for the Greater Toronto Area during the operating plan consultation process. Members of the Maternal Newborn Task Force believed that the test had the potential to avert maternal transfers from regional and community hospitals and optimize the use of tertiary antenatal and neonatal beds. It was also expected that admissions to both community and regional hospitals could be also be reduced as physicians could be assured that mothers with a negative fFNtest would not deliver their babies within 14 days..The original draft was developed by an expert panel and will be distributed for comment and input. The final guideline will be developed after discussion of the comments from the membership of the Network.Implementation of the guideline will follow the approved process for guideline implementation as determined by the Board of Directors in December Briefly, the following steps will be followed during the implementation of the guideline throughout the Network:IntroductionFetal Fibronectin (fFN) is a glycoprotein produced by the chorionic membranes and is localized to the deciduas basalis adjacent to the intervillous space. Its primary purpose appears to be that of an adhesion molecule (tissue glue) which helps bind the chorionic membranes to the underlying maternal decidua. It is normally found in cervico-vaginal secretions until 22 weeks gestation but is virtually never found between 24 and 34 weeks gestation unless the cervix has undergone premature effacement and dilatation, usually in association with symptomatic uterine contractions. It can also be released in response to inflammation or separation of amniotic membranes from the deciduas. There is a strong association between the presence of Fetal Fibronectin in cervico-vaginal secretions and preterm labour after 24 weeks gestation.Expert Panel Discussion/Literature ReviewThe expert panel reviewed the literature provided in the package provided by the CHN. Trials have shown an association between the presence of fFN and preterm birth as well as a decrease in the risk of preterm birth when tests are negative for the presence of fFN. The literature was judged to be conclusive for the negative predictive value of the fFN test. A negative test confers a more than 95% likelihood of the woman remaining undelivered for the 14 days following a negative test result.The Expert Panel heard a presentation from Dr. Ford Luk, chief of obstetrics from York Central Hospital, who presented results on 35 women who had received the test at York Central and showed similar negative predictability reported in the literature as well as cost savings from the reduced admissions to the antenatal and birthing unit. This small sample of experience from the GTA was helpful for the Expert Panel to consider. Additional literature reflecting Canadian experience with the Fetal Fibronectin Test confirmed the utility and predictive value of the test.Agreement to proceed with the recommendation for use of fFN in Network Hospitals was reached. The following are the recommendations of the Panel:Purpose of the Fetal Fibronectin Test:The purpose of testing for Fetal Fibronectin in women with symptoms of premature labour is to:Prevent unnecessary admissions to community, regional and tertiary hospitalsPrevent unnecessary transfers of mothers with symptoms of preterm labour to tertiary or regional centresDecrease the numbers of out-of-region transfersDecrease costs associated with an admission to a tertiary (or community and regional hospital) especially those related to a stay in the birthing unitProvide reassurance to mothers and their families that birth of their baby prematurely is highly unlikely within fourteen days of the onset of symptoms when the test is negative.General Recommendations:All women presenting in the Emergency Department or Birthing Unit with one or more signs/symptoms of threatened preterm labour ( Figure 1) should have a mandatory consult with a obstetrician who will perform an assessment of the patient and may order the test.Figure 1 Signs of Threatened Preterm LabourNOTE: PRIOR TO ANY VAGINAL EXAMINATION, A SPECULUM EXAM SHOULD BE DONE AND THE SWAB FOR FETAL FIBRONECTIN OBTAINED. THE DECISION TO SEND THE SWAB FOR TESTING CAN BE MADE ONCE THE PATIENT PHYSICAL ASSESSMENT IS COMPLETE.Indications for TestingIntended transfer of women between 24 and 34 completed weeksto a tertiary unit or regional unit, for example,Threatened preterm labour (Figure 1)Intact amniotic membranesCervix <3 cm dilatationEstablished fetal well-beingIntended admission of women between 32 and 34 completed weeks to a community or regional hospital with the above symptoms of preterm labourIntended administration of antenatal corticosteroidsContraindications for TestingEstimated gestational age (EGA) <24 weeks or >34 completed weeksPreterm rupture of membranes (PROM)Cervix ≥3 cm dilatationCervical cerclageActive vaginal bleedingVaginal exam or sexual intercourse in the past 24 hoursSpecimen CollectionUse only the ADEZA Fetal Fibronectin KitEquipment required includes the swab, collection tube, tube cap, test cartridge and instrument based system to perform the fFN test.Collect specimen during a speculum exam with special fFN swab using an unlubricated speculumSpeculum exam must occur before vaginal ultrasound, before digital examination and without the use of lubricants (all can alter predictability of the test)If any of the above exams have taken place, wait 24 hours and then obtain the testIf test cannot be performed within 8 hours of collection, refrigerate specimen until test is performedPerform test within 3 days of specimen collectionNOTE: Once the swab has been obtained, if subsequent physical exam does not indicate that there are sufficient signs of preterm labour (or if other contraindications are present i.e., ruptured membranes, cervical dilatation > 3 cm, etc.), the swab should be discarded and the test NOT performedTest ResultsPositive ≥ 50 ng/mlNegative ≤ 50 ng/mlFactors Affecting Accuracy of the TestFalse positive tests may be caused by:Digital exam prior to the speculum collection of the sampleMore than a minimal amount of blood in the specimen (fFN is present in plasma)The presence of amniotic fluid in the specimen(amniotic fluid contains high levels of fFN)Intercourse within the previous 24 hours (fFN is present in seminal fluid)False negative tests may be caused by:Presence of a lubricant on the speculumPositive Test ResultIndicates a higher risk of preterm deliveryConsider:Admission or transfer of the woman to an appropriate facility for treatment of preterm labour and possible delivery of a preterm baby<32 weeks – Tertiary centre≥32 weeks – Level 2 or Level 2+ centreAdministration of tocolytics and/or corticosteroids as indicatedNegative Test ResultIndicates that delivery will not take place within 7-14 days (>95% accuracy)Discharge home with instructions to return if symptoms worsen and limit activities that aggravate her symptoms if geographical, weather and other medical circumstances permitClose follow up care may include a vaginal ultrasound to assess cervical length (If cervical length is >2.5 cm it provides further reassurance that delivery will not occur preterm) +/- a swab for bacterial vaginosis.Re-evaluate in 7-14 daysPatient EducationThe purpose and function of the test should be explained to each patient in order to decrease ‘patient demand” for the test in subsequent weeksEvaluation/AuditAn audit tool monitoring the following parameters will be submitted to the Maternal/Newborn Task Force of the CHN for a quarterly report on the use and reliability of the test as well as the impacts on the CHN perinatal system. The following indicators will be monitored:The number of fFN tests performed by organization, level of care and as a wholeThe number of negative/positive tests recordedThe number of transfers of others to network hospitals for the diagnosis of premature labourThe number of transfers avoided through negative test resultsEstimated cost of the test to the system (# of tests performed multiplied by the cost of the test)Estimated savings to the system days avoided by use of test)Patient days for admission for preterm labour and compare to retrospective patient days in previous year prior to implementation of the fFN testFlowchartFetal Fibronectin Testing for Suspected Preterm LabourReferences:Abenhaim HA, Morin L, Benjamin A. Does Availability of Fetal Fibronectin Testing in the Management of threatened Preterm Labour Affect the Utilization of Hospital Resources? J Obstet Gynaecol Can 2005;27(7):ACOG Practice Bulletin. Assessment of Risk Factors for Preterm Birth. October 2001Anderson HF. Use of Fetal fibronectin in Women at Risk For Preterm labor. Clinical obstetrics and Gynecology;43(4):Armson BA, Dodds L, Dooley K, Howlett A, McPhee A, Scott H. Fetal Fibronectin Testing for Suspected Preterm labour in Nova Scotia. Am J Obstet Gynecol 2004;191:S115British Columbia Reproductive Care Program. Obstetric Guideline – Preterm Labour. February 2005Colombo DF. Predicting spontaneous preterm birth. BMJ 2002;325:Farquharson, D, Skoll A. Fetal Fibronectin. BCRCP Perspectives, Winter 2004Garite TJ, Casal D, Garcia-Alonso A, Kreadon US, Jimenez G, Ayala JA, Reimbold T. Fetal fibronectin: A new tool for the prediction of successful induction of labor. Am J Obstet Gynecol 1996;175:Giles W, Bisits A, Knox M, Madsen G, Smith R. The effect of fetal fibronectin testing on admissions to a tertiary maternal-fetal medicine unit and cost savings. Am J Obstet Gynecol 2000;182:Goldenberg RL, Iams JD, Das A, Mercer BM, Meis PJ, Moawad Ah, Miodovnik M, VanDorsten JP, Caritis SN, Thurnau, Dombrowski MP, Roberts JM, McNellis D. The Preterm Predeiction Study: Sequential cervical length and fetal fibronectin testing for the prediction of spontaneous preterm birth. Am J Obstet Gynecol 2000;182:Goldenberg RL, Mercer BM, Iams JD, Moawad AH, Meis PJ, Das A, McNellis D, Miodovnik M, Menard MK, Caritis SN, Thurnau GR, Bottoms SF. The preterm prediction study: Patterns of cervicalvaginal fetal fibronectin as predictors of spontaneous preterm delivery. Am J Obstet Gynecol 1997; 177:8-12.Honest H, Bachmann LM, Gupta JK, Kleijen J, Khan KS. Accuracy of cervicvaginal fetal fibronectin test in predicting risk of spontaneous preterm birth: systematic review. BMJ 2002;325:Iams JD. Prediction and Early Detection of Preterm Labor. Obstet Gynecol 2003;101:Iams JD, Casal D, McGregor JA, Goodwin TM, Kreadon US, Lowensohn R, Lockitch G. Fetal fibronectin improves the accuracy of diagnosis of preterm labor. Am J Obstet Gynecol 1995;173:141-5.Joffe GM, Jacques D, Bemis-Heys R, Burton R, Skram B, Shelburne P. Impact of the fetal fibronectin assay on admissions for preterm labour. Am J Obstet Gynecol 1999;180:581-6.Lopez RL, Francis JA, Garite TJ, Dubyak JM. Fetal fibronectin detection as a predictor of preterm birth in actual clinical practice. Am J Obstet Gynecol 2000;182:Lowe MP, Zimmerman B, Hansen W. Prospective randomized controlled trial of fetal fibronectin on preterm labor management in a tertiary care center. Am J Obstet Gynecol 2004;190:Macones GA, Segal SY, Stamilio DM, Morgan MA. Prediction of delivery among women with early preterm labor by means of clinical characteristics alone. Am J Obstet Gynecol 1999;181:Meis PJ, Goldenberg RL, Mercer BM, Iams JD, Moawad AH, Miodovnik M, Menard K, Caritis SN, Thurneau GR, Bottoms SF, Das A, Roberts JM, McNellis D. The preterm prediction study: Risk factors fro indicated preterm births. Am J Obstet Gynecol 1998;178:562-7.Mozurkewich EL, Naglie G, Krahn MD, Hayashi RH. Predicting preterm birth: A cost-effective analysis. Am J Obstet Gynecol 2000;182:Peaseman AM, Andrews WW, Thorp JM, Cliver SP, Lukes A, Iams JD, Coultrip L, Erikson N, Holbrook H, Elliot J, Ingardia C, Pietrantoni M. Fetal fibronectin as a predictor of preterm birth in patients with symptoms: A multicenter trial. Am J Obstet Gyncol 1997;177:13-18.Plaut MM, Smith W, Kennedy K. Fetal fibronectin: The impact of a rapid test on the treatment of women with preterm labor symptoms. Am J Obstet Gynecol 2003;188:Reis FM, Gervasi MT, Florio P, Bracalente G, Fadalti M, Severi FM, Petragalia F. Prediction of successful induction of labor at term: Role of clinical history, digital examination, ultrasound assessment of the cervix and fetal fibronectin assay. AmJ Obstet Gynecol 2003;189:1361-7Rozenberg P, Goffinet F, Hessabi M. Comparison of the Bishop score, ultrasonographically measured cervical length and fetal fibronectin assay in predicting time until delivery and type of delivery at term. Am J Obstet Gynecol 2000;182:APPENDIX 1Expert Panel on Fetal FibronectinMembersDr. Tony Addison Obstetrician William Osler Health CentreDr. Jon Barrett Obstetrician Sunnybrook & Women’sDr. Tatiana Friere-Lizamat Obstetrician St. Michael’s HospitalDr. Mathias Gysler Chief of Obstetrics Credit Valley HospitalMs. Kathryn Hayward Murray Nursing Director Credit Valley HospitalMs. Nazira Jaffer Director North York General HospitalMs. Moya Johnson Clinical Advisor Child Health NetworkDr. Terry Logaridis Chief of Obstetrics Rouge Valley Health SystemDr. Fork Luk Chief of Obstetrics York Central HospitalDr. Nan Okun Obstetrician Mount Sinai HospitalDr. Andrew Shennan VP Perinatal Services Sunnybrook & Women’sDr. Nick Shiletto Obstetrician North York General HospitalDr. Jonathan Tolkin Medical Advisor Child Health NetworkDr. Rory Windrim Obstetrician Mount Sinai HospitalDr. Suzanne Wong Deputy Chief of Obstetrics St. Joseph’s Health CentreTony Wong Laboratory York Central Hospital Appendix 1 – Members of CHN Expert Panel Fetal Fibronectin Test Guideline See References for a complete list of literature used by the Expert Panel. Based on BC Reproductive Care Guideline on Management of Preterm Labour see Reference # 5fFN swab from posterior fornix (see Appendix A)Cx < 3 cm DilatedCx Long + Closed- Tocolytics- Corticosteroids- AntibioticsFetal Fibronectin Decision-Making AlgorithmBCRCP (2005) Obstetric Guideline 2A – Preterm Labour, p. 11
33Guidelines for Use of fFN test Specimen should not be obtained in presence of:Cervical dilatation >3 cmPROMSoaps, gels, lubricants, or disinfectantsCervical cerclageModerate or gross vaginal bleedingSexual intercourse within 24 hoursObtain specimen prior to procedures that may disrupt cervix:Digital examinationVaginal ultrasoundMicrobiologic culturePap smearSource: Honest et.al. BMJ, Aug 2002
34Specimen Collection for ƒFN Testing Lightly rotate swab across either the posterior fornix of the vagina or the ectocervical region of the external cerical os for 10 seconds.
35Specimen Collection for ƒFN Testing Remove swab and immerse Dacron® tip in bufferBreak the shaft even with the top of the tube (at the score)
36Specimen Collection for ƒFN Testing Speaker Notes:If the specimen is being transported to a central laboratory for analysis, place the tube on ice or store in a refrigerator at 2 to 8 degrees C. Do not freeze or expose the specimen to elevated temperatures.Align the shaft with the hole inside the tube cap and push down tightly over the shaft to seal the tube.
37Fetal Fibronectin (ƒFN) Test Results Rapid fFN for the TLi™ SystemAnalyzer produces results in 23 minutesAround-the-clock availabilityRapid fFN is run like a pregnancy testSeveral sites in Canada run the assay in L&DSpeaker Notes:With the Rapid fFN for the TLi™ System:Rapid analyzer produces results in 20 to 30 minutes.Based upon a laboratory’s capabilities and specimen transport times, test results are usually available in 2 to 4 hours.If a Rapid fFN TLi™ System is not available in the area, tests may be analyzed in a central laboratory utilizing the fFN Enzyme Immunoassay.Samples must be packed in ice and express shipped overnight to the central laboratory.Results are typically available within 24 hours.
38Implementation of fFN in insert province/territory or region
39ConclusionFetal Fibronectin is a useful adjunct to diagnosis and manage preterm labourReduced hospital admission and transfers of women with symptoms of preterm labour.Decreased costs associated with hospital admissions, transfersImproved identification of women who need corticosteroid and tocolytic therapyProvide reassurance to women and families