Fetal Fibronectin Testing for Suspected Preterm Labour

1
Fetal Fibronectin Testing for Suspected Preterm
Labour

• An emerging standard of care

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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 Ontarios approach to this emerging
  standard of care
• Provide detailed clinical decision making and
  procedures for fFN testing
• Provide supporting literature and studies, if
  required (slide appendix)

3
Acknowledgements

• Report of the Provincial Maternal-Newborn Fetal
  Fibronectin Testing Work Group, Adapted with
  Revisions Approved by Ontarios Provincial
  Maternal-Newborn Advisory Committee (December,
  2008)
• The Reproductive Care Program of Nova Scotia
• Original Guideline produced by sub-committee of
  the Canadian Perinatal Partnerships Coalition,
  October 15, 2007 with adaptations from the
  Greater Toronto Area (CHN) and the British
  Columbia Reproductive Care Program (BCRCP).

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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
  delivery lt1week from admission was lt50 with
  minimal cervical dilatation (lt 3 cm.)

5
Preterm Birth

• Defined as the number of live births at a
  gestational age of less than 37 completed weeks
• Major cause of neonatal morbidity and mortality

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Rate of Preterm Delivery by Province/Territory
2006/07 (CIHI)
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Ontario Preterm Births 2006/07

• 8.5 of total births occurred at lt37 weeks
  gestation (note 0.2 difference between CIHI and
  Niday data)
• 7.2 were between 32 and 36 weeks
• 1.3 were born before 32 weeks
• At tertiary hospitals
• 15.4 of births occurred at lt37 weeks
• 5.1 of births occurred at lt32 weeks
• Source Niday Perinatal Database

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The Challenge

• The preterm birth rate has not decreased in the
  last thirty years or has risen!!!
• In 1972 it was stated as 7 (Source CPS and
  SOGC, Regional Services in Reproductive Medicine,
  1972)

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Preterm Birth
How do we identify who is at Risk?
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Prevention/Intervention Strategies
Education Targeting High Risk Women
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Risk Assessment Markers

• Biophysical markers
• Measurement of cervical length
• Biochemical markers
• Fetal fibronectin (fFN)

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Other Risk Assessment Markers

• Salivary estriol (E3)
• A surge in levels of salivary estriol typically
  occurs several weeks prior to the onset of
  spontaneous labor and may be a risk predictor
  for preterm labor. High percentage of false
  positive results
• Corticotropin-releasing hormone (CRH)
• CRH is a placenta marker that determines the
  length of gestation and the timing of parturition
  and delivery. A rapid increase in circulating
  levels of CRH occurs at the onset of parturition,
  suggesting that, CRH may act as a trigger.
• Interleukin-6 (IL-6)
• Most sensitive test to identify intraamniotic
  infection and has the advantage of predicting
  preterm delivery risk and neonatal complications
  compared to the other tests

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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 steroid use
• Improved resource utilization
• Potential research benefits e.g. focus tocolytic
  trials on women who will potentially benefit

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What is Fetal Fibronectin (FN)

• Glycoprotein found in extracellular matrix of
  amniotic membranes and 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 Terminology

• 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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Cost Savings (literature)

• Reduction in admissions for preterm labour
• 486,000 saved
• (Joffe et al, AJOG 1999)
• Reduction in maternal transfers
• 30,297 saved
• (Giles et al, AJOG 2000)

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Considerations for Ontario

• Cost
• Approximately 100 per test
• Patient demand not experienced by other centres
• Physician overuse
• Estimate 2-4 of births (may vary with level of
  care)
• Close adherence to guideline will limit
  unnecessary tests
• Savings
• Cost of admission
• Cost of transfer
• Optimal use of tertiary antenatal and NICU beds
• Maternal/family reassurance/satisfaction

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Ontario Experience

• 2006 Increase in maternal antenatal transfers
  out of region/province/country
• Many women transferred did not deliver and were
  sent back undelivered
• Many women delivered preterm babies outside
  tertiary care centres due to lack of capacity for
  maternal antenatal transfers in tertiary
  perinatal centres
• MoHLTC commissioned Agnew Peckham to study the
  issue through the Provincial Council for
  Childrens Health (PCCH)
• Expert Panel formed to assist with study
• Recommended that fFN be implemented throughout
  Ontario to better determine those mothers needing
  tertiary care

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Provincial Maternal-Newborn fFN Testing Work Group

• Formed by PCMCH to advise strategy to implement
  fFN in Ontario
• Recommendations
• Promote fFN testing in all hospitals with
  birthing services
• Fund purchase of analyzers for those hospital not
  currently providing fFN
• Fund test kits for all hospital with birthing
  services including reimbursement for kits in
  fiscal 2008-09
• Support dissemination and implementation of
  revised CPPC Canadian National Fetal Fibronectin
  Guidelines (Oct 2008)
• Establish evaluation mechanism to determine the
  impact of fFN testing on resource utilization and
  patient outcomes

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Ontario Strategy

• Implementation of province-wide Fetal Fibronectin
  testing currently ongoing
• Seed funding provided by Ontario Ministry of
  Health for those already using the test and start
  up money for new users
• Goals
• To reduce unnecessary maternal transfers and
  admissions for suspected preterm labour
• To better determine and improve utilization of
  tertiary antenatal beds
• To reduce psychosocial and financial burdens for
  families
• To reduce out of region transfers through better
  utilization of beds
• To improve identification of women needing
  treatment for threatened preterm labour

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Ontario Guideline

• Based on national fFN Guideline developed by
  Canadian Perinatal Partnerships Coalition in 2007
• Recommendations
• Women with signs and symptoms of preterm labour
  between 24 and 34 weeks should be assessed with
  fFN test if they meet the criteria (see flowchart
  for contraindications)
• Swab is obtained by unlubricated speculum exam
  prior to vaginal exam or vaginal ultrasound
• Positive test gt50 ng/mL indicates possibility of
  preterm birth
• Negative test lt50 ng/mL indicates not in preterm
  labour

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(No Transcript)
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Contraindications

• Estimated gestational age lt24 weeks or gt34 weeks
• PROM (ruptured membranes)
• Vaginal bleeding
• Cervical dilatation 3cm (collect swab prior to
  vaginal exam)
• Cervical cerclage
• Vaginal exam or sexual intercourse within 24
  hours prior to testing
• DO NOT use lubricant for speculum exam

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FN Specimen Collection

• 3 Easy Steps
• During speculum examination, lightly rotate swab
  across posterior fornix of the vagina for 10
  seconds to absorb cervicovaginal secretions.
• Remove swab and immerse polyester tip in buffer.
  Break the shaft at the score even with the top of
  the tube.
• Align the shaft with the hole inside the tube cap
  and push down tightly over the shaft, sealing the
  tube. Ensure the shaft is aligned to avoid
  leakage.

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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 Ontario

• 5 Regional Coordinators to assist hospitals
  within 14 LHINs
• Web-Based learning tools including videos and
  oral presentation
• Ministry funding based on 4 birthing volumes for
  each hospital (higher for tertiary centres)
• Hologic support for implementation and ongoing
  support

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Conclusion

• Fetal Fibronectin is a useful adjunct to
  diagnosis and management of 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
• Better utilization of tertiary maternal antenatal
  beds and resources
• Improved percentage of preterm births (lt32 weeks)
  in tertiary centres

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Questions?
31
Thank you!
32
Supporting Research/Literature

• The next few slides contain summaries of various
  studies to support the use of Fetal Fibronectin
• These slides may be used as either part of or as
  an adjunct to the standard presentation on Fetal
  Fibronectin

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20 percent increase
Source CPSS Report 2003 p. 74 2006 added
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Fetal Fibronectin (FN)

• Fetal Fibronectin (fFN) 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, cost savings
• Canadian data is from level III hospitals, rural
  and remote hospitals.

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Utility of FN for Predicting Pre Term Birth in
Symptomatic Women

• PPV() NPV() Cx
  dil(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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Nova Scotia Study Conclusions

• 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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Nova Scotia Study Conclusions

• 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

40
BC Study

• Fetal Fibronectin collected from admitted
  patients with symptomatic preterm labour
• 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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BC Results

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

Delivered lt 14 days
Delivered gt 14 days
FFN ve
1
7
FFN ve
1
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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

• Experience in which Fetal Fibronectin Assay
  (Hologic TLI) was used as an adjunct to diagnosis
  and management of preterm labour suggest
• Reduced hospital utilization (admission, LOS)
• Earlier reverse transfer of these patients to
  their referring institutions without adverse
  sequelae.

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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