Fetal Fibronectin Testing for Suspected Preterm Labour

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Fetal Fibronectin Testing for Suspected Preterm
Labour

• An emerging standard of care
• (Note Please feel free to use your own
  background design)

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Fetal Fibronectin Testing for Suspected Preterm
Labour

• Objectives
• Discuss incidence of preterm labour provincially
  and nationally
• Describe the benefits of fetal fibronectin
  testing
• Outline insert province approach to this emerging
  standard of care
• Provide detailed clinical decision making and
  procedures for fFN testing

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Preterm Labour (lt 37 weeks)

• 1 in 5 pregnant women exhibit signs and symptoms
  of preterm labour.
• 3-4 of births occur before 34 weeks
• Up to 70 of women identified as high-risk
  deliver at term.
• Maximum clinical judgment sensitivity for del
  lt1week from admission was lt50 with minimal
  cervical dilatation (lt 3 cm.).

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Preterm Birth

• Preterm birth rate is defined as the number of
  live births with a gestational age less than 37
  weeks completed weeks gestation
• gt7.6 (all Provinces) of all pregnancies result
  in preterm birth
• Sources ACOG Technical Bulletin,1995, No. 206
  National Vital Statistics Report 200048(3). St
  John EB et al. Am J Obstet Gynecol.
  2000182170-175. Macones, Am J ObGyn, Vol 181,
  12/99

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Rate of Preterm Delivery by Province/Territory
(excluding Ontario) 2000
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Add own provincial data
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The Challenge

• The preterm birth rate has not decreased in the
  last thirty years!!!

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20 percent increase
Source CPSS Report 2003 p. 74
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Preterm Birth
How do we identify who is at Risk?
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Prevention/Intervention Strategies
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Risk Assessment Markers

• Biophysical markers
• Measurement of cervical length
• Biochemical markers
• Fetal fibronectin (fFN)
• Salivary estriol (E3)
• Corticotropin-releasing hormone (CRH)
• Interleukin-6 (IL-6)

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Potential 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.

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Fetal Fibronectin (FN)

• Fetal Fibronectin (fFN) is not new in obstetrics
  practice
• 1st 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.
• gt200 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
  transports
• Canadian data is from level III hospitals, rural
  and remote hospitals.

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What is Fetal Fibronectin (FN)

• 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
  labour
• Fetal (FN) immunoassay detects concentrations of
  fetal fibronectin protein in cervicovaginal
  fluids.
• Presence of gt50 ng/mL considered positive.

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Fetal Fibronectin (FN)
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Normal FN Expression by Gestational Age
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Key Terminologyfor 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 identifies
• Specificity Percent of women who do NOT have
  preterm delivery whom the test correctly
  identifies

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Utility of FN for Predicting PTB in Symptomatic
Women

• PPV() NPV() Cx
  Dilatation(cm)
• Lockwood, 1991 (n117) 83 81
  None
• Morrison, 1993 (n28) 64 93
  ? 1
• Iams, 1995 (n192) 60 76 ? 3
• Burrus, 1995 (n37) 79 63 ? 3
• Bartnicki, 1996 (n112) 79 83
  ? 2
• Peaceman, 1997 (n725) 43 87 ? 3

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Women with Threatened Preterm Labour (1/25
deliver lt14 days)
FN - (80)
FN (20)
1/6 Deliver lt14 days
1/125 Deliver lt14 days
Peaceman, AJOG 1997 17713-8
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Nova Scotia Pilot Study April 2002-March 2004
(Armson Scott et. al.)

• Prospective cohort study
• Objectives
• To determine if introduction of rapid FN testing
  for suspected PTL will
• Reliably predict preterm birth
• Result in a reduction of
• PTL admissions/maternal transfer rates
• length of stay, tocolytic/corticosteroid use
• reproductive health care costs without
  compromising neonatal outcomes

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Conclusions from Nova Scotia Study

• A negative FN test for suspected PTL accurately
  identifies women not likely to deliver within 14
  days (98 -99 accurate)
• A positive FN test identifies women at high risk
  for preterm birth
• - 24 ? 7 days
• - 28 ? 14 days
• - 31 ? 34 weeks
• - 48 ? 37 weeks
• Diagnostic accuracy of FN superior to clinical
  criteria for women with suspected preterm labour

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Conclusions from Nova Scotia Study

• Criteria for clinical use of FN appear to be
  broad and inconsistent
• Clinicians/patients somewhat reluctant to adhere
  to guidelines of non-intervention for negative
  FN results, particularly in regional centres.
• Potential for reduction in maternal transfers,
  hospital admissions and associated health care
  costs

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Results from the Nova Scotia Study

• Implementation of province-wide Fetal Fibronectin
  testing currently ongoing
• Seed funding provided by NS Department of Health
• Goals
• To reduce unnecessary maternal transfers and
  admissions for suspected preterm labour
• To reduce psychosocial and financial burdens for
  families

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BC Study

• Fetal Fibronectin collected by speculum exam from
  admitted patients with symptomatic preterm labour
• Assays were performed in our laboratory. The
  results were revealed to the clinician within 1
  8 hours
• A retrospective chart review was undertaken to
  assess pregnancy outcome
• An 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

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Results

• Of 62 patients tested, outcomes were known for 47
  patients.

Delivered lt 14 days
Delivered gt 14 days
FFN ve
1
7
1
38
FFN ve
Sensitivity 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.
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BC Study Results

• A total of 62 assays were conducted between May
  2002 and March 2003
• Ages 18 39, mean 30
• GA on admission 20 33 weeks
• Length of stay ranged 1 44 days, mean 4.7 days
• Nulliparas 55
• Multiparas 45

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BC Study Conclusion

• Our 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.

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Cost 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)

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Resource Utilization - Canada

• Royal Victoria Hospital
• Observational cohort design
• 20 week periods before and after FN
• Singletons, 24-34 weeks, suspected PTL
• 
  
• Abenhaim JOGC 2005 27689-94

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Effect of FN on Resource Utilization
__________________________________________________
_______ Baseline
Period Study Period p value
__________________________________________________
_______ Patients 116
116 Preterm Births 9 (7.8) 10
(8.6) NS PTL Admissions 28 (24.1) 14
(12.1) 0.02 Days Hospitalized 145
28 Mean LOS 5.2 0.6 0.01 Admission
Costs 102,660 26,169 Mean Cost 3,666
581 0.01
Abenhaim, JOGC 2005
27689-94
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Considerations

• Cost
• Approximately 100 per test
• Patient demand not experienced by other centres
• Physician overuse
• Estimate 20 -25 per years based on 2500 births/yr
• Close adherence to guideline
• Savings
• Cost of admission
• Cost of transfer
• Optimal use of tertiary beds
• Maternal/family reassurance/satisfaction

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Fetal Fibronectin Decision-Making Algorithm
BCRCP (2005) Obstetric Guideline 2A Preterm
Labour, p. 11
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Guidelines for Use of fFN test
Specimen should not be obtained in presence of
Cervical dilatation gt3 cm PROM Soaps, gels,
lubricants, or disinfectants Cervical
cerclage Moderate or gross vaginal
bleeding Sexual intercourse within 24 hours
Obtain specimen prior to procedures that may
disrupt cervix Digital examination Vaginal
ultrasound Microbiologic culture Pap smear
Source Honest et.al. BMJ, Aug 2002
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Specimen Collection for FN Testing

• Lightly rotate swab across either the posterior
  fornix of the vagina or the ectocervical region
  of the external cerical os for 10 seconds.

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Specimen Collection for FN Testing

• Remove swab and immerse Dacron tip in buffer
• Break the shaft even with the top of the tube (at
  the score)

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Specimen Collection for FN Testing

• Align the shaft with the hole inside the tube cap
  and push down tightly over the shaft to seal the
  tube.

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Fetal Fibronectin (FN) Test Results

• Rapid fFN for the TLi System
• Analyzer produces results in23 minutes
• Around-the-clock availability
• Rapid fFN is run like a pregnancy test
• Several sites in Canada run the assay in LD

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Implementation of fFN in insert
province/territory or region
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Conclusion

• Fetal Fibronectin is a useful adjunct to
  diagnosis and manage preterm labour
• Reduced hospital admission and transfers of women
  with symptoms of preterm labour.
• Decreased costs associated with hospital
  admissions, transfers
• Improved identification of women who need
  corticosteroid and tocolytic therapy
• Provide reassurance to women and families

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Questions?
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Thank you!