Transcript Fetal Fibronectin Testing for Suspected Preterm Labour in

Fetal Fibronectin Testing for
Suspected Preterm Labour
An emerging standard of care
(Note: Please feel free to use your
own background design)
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
Preterm Labour (< 37 weeks)
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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 “highrisk” deliver at term.
Maximum clinical judgment sensitivity for
del <1week from admission was <50%
with minimal cervical dilatation (< 3 cm.).
Preterm Birth
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Preterm 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 birth
Sources: ACOG Technical Bulletin,1995, No. 206; National Vital Statistics
Report 2000;48(3). St John EB et al. Am J Obstet Gynecol.
2000;182:170-175. Macones, Am J ObGyn, Vol 181, 12/99
Rate of Preterm Delivery by Province/Territory
(excluding Ontario) 2000
Add own provincial data
The Challenge…
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The preterm birth rate has not
decreased in the last thirty years!!!
Rate of preterm birth
Canada (excluding Ontario), 1991-2000
Preterm Births per 100 live births
8
7
6.6
6.7
6.6
6.8
7.0
7.1
7.1
7.2
7.4
7.6
6
20 percent increase
5
1991 1992 1993 1994 1995 1996 1997 1998 1999 2000
Source: CPSS Report 2003 p. 74
Calendar year
Preterm Birth
How do we identify who is at Risk?
Risk
Factors
Fetal
Fibronectin
Cervical
Length
Symptoms
of PTL
Prevention/Intervention
Strategies
Hydration
Tocolytics
Bedrest
Education Home
Frequent Targeting
Uterine
Digital
High Risk Monitoring
Exam
Women
Population
Based
strategies
Risk Assessment Markers
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Biophysical markers
 Measurement of cervical length
Biochemical markers
 Fetal fibronectin (fFN)
 Salivary estriol (E3)
 Corticotropin-releasing hormone (CRH)
 Interleukin-6 (IL-6)
Potential Benefits of An EvidenceBased, Risk Assessment Marker
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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.
Fetal Fibronectin (ƒFN)
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Fetal Fibronectin (fFN) is not new in obstetrics practice
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1st literature appeared in 1985; as an oncogene marker.
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1st OB-specific literature appeared in 1991 in New
England J. of Medicine by Lockwood, et al.
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>200 peer reviewed OB articles now published, 3 meta
analyses, 9 Canada-specific abstracts presented at
SOGC.
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Canada specific data documents reduced medication
use, reduced hospital day stays, reduced transports
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Canadian data is from level III hospitals, rural and
remote hospitals.
What is Fetal Fibronectin (ƒFN)
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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 Fibronectin (ƒFN)
Normal ƒFN Expression by
Gestational Age
Key Terminology
for Evaluating PTD Diagnostics
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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
Utility of ƒFN for Predicting PTB
in Symptomatic Women
PPV(%) NPV(%)
Cx
Dilatation(cm)
Lockwood, 1991 (n=117)
Morrison, 1993 (n=28)
Iams, 1995 (n=192)
Burrus, 1995 (n=37)
Bartnicki, 1996 (n=112)
Peaceman, 1997 (n=725)
83
64
60
79
79
43
81
93
76
63
83
87
None
1
3
3
2
3
Women with
Threatened Preterm Labour
(1/25 deliver <14 days)
ƒFN (80%)
ƒFN +
(20%)
1/125
Deliver <14 days
1/6
Deliver <14 days
Peaceman, AJOG 1997; 177:13-8
Nova Scotia Pilot Study April 2002-March
2004 (Armson & Scott et. al.)
Prospective cohort study
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Objectives
To determine if introduction of rapid ƒFN testing for suspected
PTL will:
1.
Reliably predict preterm birth
2.
Result in a reduction of:
-
PTL admissions/maternal transfer rates
-
length of stay, tocolytic/corticosteroid use
-
reproductive health care costs without compromising
neonatal outcomes
Conclusions from Nova Scotia Study
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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 weeks
Diagnostic accuracy of ƒFN superior to clinical
criteria for women with suspected preterm labour
Conclusions from Nova Scotia Study
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Criteria for clinical use of ƒFN appear to be
broad and inconsistent
Clinicians/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
Results from the Nova Scotia
Study
Implementation of province-wide Fetal Fibronectin
testing currently ongoing
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Seed funding provided by NS Department of Health
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Goals
To reduce unnecessary maternal transfers and
admissions for suspected preterm labour
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To reduce psychosocial and financial burdens for
families
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BC Study
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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
Results
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Of 62 patients tested, outcomes were
known for 47 patients.
Delivered < 14 days
Delivered > 14 days
FFN +ve
1
7
FFN –ve
1
38
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.
BC Study Results
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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 %
BC Study Conclusion
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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.
Cost Savings (literature)
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Reduction in PTL admissions
$486,000 saved
(Joffe et al, AJOG 1999)
Reduction in maternal transfers
$30,297 saved
(Giles et al, AJOG 2000)
Resource Utilization - Canada
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Royal Victoria Hospital
Observational cohort design
20 week periods before and after ƒFN
Singletons, 24-34 weeks, suspected PTL
Abenhaim JOGC 2005; 27:689-94
Effect of ƒFN on Resource Utilization
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Baseline Period Study Period
p value
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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; 27:689-94
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
Fetal Fibronectin Decision-Making Algorithm
Patient <34 wks Gestation with Symptoms of Preterm Labour
•
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Evidence of
Ruptured
Membranes
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Speculum exam before VE
fFN swab from posterior fornix
(see Appendix A)
Cultures
•
Management of
PROM
Discard fFN swab
Intact Membranes
Vaginal Examination
Cx ≥ 3 cm Dilation
Cx < 3 cm Dilated
Cx Long + Closed
• Regular uterine activity
• Diagnosis preterm labour
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Contractions subsided
No clinical evidence of
preterm labour
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Reassure mother
Discard fFN swab
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Ongoing uterine activity
Clinical suspicion of preterm
labour
Treat for preterm labour
Discard fFN swab
Send fFN swab
Positive
•
•
Treat for preterm labour
- Tocolytics
- Corticosteroids
- Antibiotics
Consider transfer to appropriate
level of care
BCRCP (2005) Obstetric Guideline 2A – Preterm Labour, p. 11
Negative
•
•
•
•
Reassure mother
F/U endovaginal ultrasound of the
cervix (if available)
Treatment of BV
Consider repeat test in 7-14 days, if
symptomatic
Guidelines for Use of fFN test
Obtain specimen prior
to procedures that may
disrupt cervix:
Digital examination
Vaginal ultrasound
Microbiologic culture
Pap smear
Source: Honest et.al. BMJ, Aug 2002
Specimen should not
be obtained in presence
of:
Cervical dilatation >3 cm
PROM
Soaps, gels, lubricants, or
disinfectants
Cervical cerclage
Moderate or gross vaginal
bleeding
Sexual intercourse within
24 hours
Specimen Collection for ƒFN Testing
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Lightly rotate swab across either the posterior
fornix of the vagina or the ectocervical region
of the external cerical os for 10 seconds.
Specimen Collection for ƒFN Testing
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Remove swab and immerse Dacron® tip in
buffer
Break the shaft even with the top of the tube
(at the score)
Specimen Collection for ƒFN Testing
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Align the shaft with the hole inside the
tube cap and push down tightly over
the shaft to seal the tube.
Fetal Fibronectin (ƒFN) Test Results
Rapid fFN for the TLi™ System
 Analyzer produces results in
23 minutes
 Around-the-clock availability
 Rapid fFN is run like a pregnancy test
 Several sites in Canada run the assay in L&D
Implementation of fFN in insert
province/territory or region
Conclusion
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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
Thank you!