Original Research

ajog.org

OBSTETRICS

A comparison of prevaginal and postvaginal

manipulation fetal fibronectin
Amy L. Turitz, MD; Christina M. Ackerman, MD; Denise L. Johnson, BA; Tracy C. Bank, BA;
Jimmy K. Duong, MPH; Shing M. Lee, PhD; Cynthia Gyam-Bannerman, MD, MSc

BACKGROUND: Fetal fibronectin (fFN) is used as a biomarker for

preterm delivery. Currently, its use is discouraged if there has been vaginal
manipulation in the previous 24 hours.
OBJECTIVE: Our objective is to determine if there are differences
between fFN results before and after vaginal manipulation in the form of
sterile vaginal exam or transvaginal ultrasound.
STUDY DESIGN: This was a prospective observational cohort study at
a single center of women between 22-33 6/7 weeks at risk for preterm
delivery due to: (1) a history of preterm delivery, short cervix, or multifetal
gestation; or (2) symptoms of preterm labor. We excluded women with
vaginal bleeding or infection, placenta previa, ruptured membranes,
cervical dilation >3 cm, or any form of vaginal manipulation in the previous 24 hours. Specimen A was collected prior to planned vaginal exam or
transvaginal ultrasound and specimen B was collected within 4 hours. The
agreement between specimens A and B was assessed using descriptive
statistics. Test characteristics of specimens A and B using the outcome of
preterm delivery (<37 weeks) were calculated.
RESULTS: In all, 310 specimen pairs from 237 women were collected.
Specimen A was positive in 37 (12%) instances and negative in 273 (88%)

Introduction
Fetal bronectin (fFN) is used as a
biomarker for preterm delivery. When
compared to clinical history, cervical
dilation, and contraction frequency,
previous studies have observed a superior ability of fFN to evaluate preterm
delivery.1-4 The strength of fFN testing
lies in its high negative predictive value,
such that a negative result is reassuring
against preterm delivery and thus
may lead to a decrease in antenatal interventions, resource utilization, health
care costs, and anxiety for women who
are destined to deliver at term.4
In many institutions, fFN has become
part of the standard evaluation of
women who present with concerns for

Cite this article as: Turitz AL, Ackerman CM, Johnson

DL, et al. A comparison of prevaginal and postvaginal
manipulation fetal fibronectin. Am J Obstet Gynecol
2016;214:646.e1-6.
0002-9378/$36.00
2016 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.ajog.2016.01.160

while specimen B was positive in 39 (13%) and negative in 271 (87%).

There were discordant results in 26 specimen pairs. Of these, 14 (5%)
negative specimen A results subsequently became positive for specimen
B, and 12 (32%) positive specimen A results became negative for specimen B. Overall, there was a 92% agreement between specimens A and B
(confidence interval, 88e94%). The specificity of specimens A and B for
preterm birth was 90% vs 89%, respectively, with a negative predictive
value of 87% for both. The false-negative rate was 12.8% for specimen
A and 13.3% for specimen B.
CONCLUSION: There is a moderately high degree of agreement
between prevaginal and postvaginal manipulation fFN results. Their test
characteristics for evaluating preterm birth are similar with strong specificity and negative predictive values, and their false-negative rates are not
clinically different. Consideration should be made to the utilization of
postvaginal manipulation fFN when a prevaginal manipulation specimen is
not available.
Key words: fetal fibronectin, preterm birth, sterile vaginal exam,

transvaginal ultrasound, vaginal manipulation

preterm labor. Its use, however, is

discouraged in several settings, such as
the presence of vaginal bleeding, rupture
of membranes, or within 24 hours
of vaginal manipulation, including
sterile vaginal examination (SVE) and
transvaginal ultrasound (TVUS). The
rationale for deferring testing in the
setting of bleeding or rupture of membranes has a physiologic basis, as both
maternal serum and amniotic uid have
been shown to contain fFN and may lead
to false-positive testing.5 In contrast,
there is no clear basis for deferring
testing after vaginal manipulation, and
the effect of SVE and TVUS on the
expression of fFN in cervicovaginal
secretions remains largely unknown.
These restrictions limit the utility of fFN
to exclude preterm labor in potentially
high-risk populations, as many patients
who could benet from this test have
undergone a digital examination or
TVUS in the previous 24 hours.
To that end, the objective of our study
is to determine if there are differences
between fFN results obtained before and

646.e1 American Journal of Obstetrics & Gynecology MAY 2016

after vaginal manipulation in the form of

SVE or TVUS, and to compare test
characteristics of prevaginal and postvaginal manipulation fFN tests in
predicting preterm delivery.

Materials and Methods

We performed a prospective observational cohort study of women between
22 0/7 and 33 6/7 weeks at risk for
preterm birth who presented to our
institution from May 2014 through
August 2015. Women were eligible for
inclusion if they had: (1) risk factors for
preterm delivery, including a history of
spontaneous preterm delivery, sonographically identied short cervix in the
current pregnancy, or multifetal gestation; or (2) symptoms of preterm labor,
including abdominal and/or back pain,
cramping, pelvic and/or vaginal pressure, and contractions. No minimum
frequency of contractions or cervical
dilation was specied. Women were
excluded if they were <18 years of age
or had vaginal bleeding, rupture of
membranes, abnormal placentation, a

ajog.org
known vaginal or intrauterine infection,
or cervical dilation >3 cm. They were
also excluded if they had sexual
intercourse, used vaginal medication, or
had a TVUS or SVE within the previous
24 hours. Women with cervical cerclage
in situ were not excluded.
Women were recruited from 2 general
areas: obstetric ultrasound and the
labor and delivery triage unit. At our
institution, women with risk factors for
preterm delivery, including a history of
spontaneous preterm delivery, sonographically identied short cervix in the
current pregnancy, or multifetal gestation are offered cervical length screening
every 2 weeks between 16-28 weeks
gestation. Women with symptoms of
preterm labor are evaluated in the labor
and delivery triage unit. In these settings,
women who met the inclusion criteria
were approached by trained research
staff and offered enrollment in a
consecutive fashion when research staff
were available. A woman could be
enrolled >1 time in the study if they
presented on a different occasion during
the same pregnancy and continued to
meet inclusion criteria.
Once consent was obtained, fFN
sample was collected by an obstetric care
provider or research staff member prior
to vaginal manipulation, in the form of
SVE, TVUS, or both in some instances.
This was labeled specimen A and
considered to be the reference standard.
At the obstetrical providers discretion,
this specimen could be sent to the
inpatient laboratory and the result used
to guide clinical decision making. If the
obstetric provider did not think the
result would aid in clinical management,
specimen A was instead analyzed in the
research laboratory with the provider
blinded to results. A second fFNe
specimen Bewas collected within 4
hours following vaginal manipulation.
This specimen was considered to be the
index test and used solely for the purpose of this study.
The Rapid fFN Specimen Collection
Kit (Hologic, Sunnyvale, CA) was used
for all specimen collection. Specimens
were generally collected without the use
of a sterile speculum, as blind collections
have been shown to have excellent

OBSTETRICS

agreement with those collected with the

use of a sterile speculum in previous
studies.6,7 A sterile polyester-tipped
applicator was introduced into the posterior vagina for 10 seconds. The applicator was then returned to its tube,
which was then labeled with the patients
study number and specimen number.
Specimens sent to the inpatient hospital
laboratory were run upon receipt using a
solid-phase enzyme-linked immunosorbent assay in which cervicovaginal
samples are incubated in microtiter wells
coated with FDC-6, a monoclonal antibody specic for fFN. The resulting
antibody-antigen complex is washed to
remove nonspecically bound material
and then reacted with an enzyme-labeled
antibody directed against human bronectin. The microtiter well is then
washed again to remove unbound
labeled antibody and incubated with an
enzyme substrate. The presence or
absence of fFN is determined spectrophotometrically at a wavelength of 550
nm. The results are reported as negative
if the concentration of fFN is <0.050 mg/
mL and positive if the concentration is

0.050 mg/mL. Only qualitative results
were reported for these specimens. Study
specimens were stored in a freezer at
e80.0 C within 10 minutes of collection
until run in the research laboratory.
Prior to analysis, these specimens were
placed in a 37 C water bath for 20 minutes, mixed, and then equilibrated to
room temperature for 30 minutes before
testing was performed. These specimens
were then analyzed in the research laboratory on a RapidfFN10Q system
(Hologic, Sunnyvale, CA), which uses
the same solid-phase enzyme-linked
immunosorbent assay described above
but provides both qualitative and quantitative results.
Data abstraction included gestational
age at specimen collection; time and date
of specimen collection, storage, and
analysis; qualitative results of all specimens; quantitative results if available;
type of vaginal manipulation (SVE or
TVUS); indication for vaginal manipulation; and cervical dilation and/or cervical length as available. Maternal and
obstetric characteristics and delivery
information were also collected and

Original Research

entered into a deidentied secure data

entry system. The study was performed
in accordance with the Standards for
Reporting of Diagnostic Accuracy
(STARD) guidelines for the reporting of
studies of diagnostic accuracy.8
A priori sample size calculations were
performed. Using the Clopper-Pearson
method and an estimated agreement of
97.5%, a sample size of 290 would be
required to produce a 2-sided 95%
condence interval (CI). Descriptive
statistics, proportion agreement with
CI calculation, and kappa statistics
were used to assess the agreement
between specimens A and B. Test
characteristicseincluding
sensitivity,
specicity, and positive and negative
predictive valuesewere calculated to
evaluate specimen B using specimen A as
the gold standard. Test characteristics
were also calculated to evaluate specimens A and B compared to the outcomes
of preterm (<37 weeks gestation) and
spontaneous preterm delivery.9,10 Analyses were performed using the specimen
pairs as the unit of analysis based on the
assumption that specimens obtained
from the same patient at different time
points are independent. Other analyses
were performed using the patient as the
unit of analysis, taking only the rst
specimen pair into account for patients
who had multiple enrollment, for variables that are specic to the patient.
Statistical analyses were performed using
Stata 12.0 (StatCorp, College Station,
TX). This study received institutional
review board approval from Columbia
University Medical Center.

Results
During the study period of May 2014
through August 2015, 310 specimen pairs
were collected from 237 women who
were seen in the obstetric ultrasound and
labor and delivery triage units at our
institution. Of these specimen pairs, 222
were obtained in the setting of TVUS
only, 72 in the setting of SVE only, and 16
in the setting of both SVE and TVUS.
Maternal and obstetric characteristics,
as well as delivery information, for the
237 women comprising the cohort, are
presented in Table 1. In all, 185 women
had 1 specimen pair collected during the

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OBSTETRICS

study period, 43 had 2 specimen pairs, 5

had 3 specimen pairs, 3 had 4 specimen
pairs, and 1 had 5 specimen pairs.
Delivery information was available for
215 (90.7%) of these women with a
median gestational age at delivery of 38.0
weeks (interquartile range 36.0-39.1).
Characteristics specic to the 310 specimen pairs are included in Table 2. The
median gestational age at the time of
enrollment was 27.4 weeks (interquartile
range 25.0-29.9). Short cervix was the
most common indication for vaginal
manipulation (38%), followed by a
history of preterm delivery (30%),
symptoms of preterm labor (27%), and
multiple gestation (25%). The median
time between collection of specimens
A and B was 3.0 minutes (interquartile
range 2.0-5.0).
Specimen A was positive in 37
instances (12%) and negative in 273
(88%) while specimen B was positive in
39 (13%) and negative in 271 (87%)
(Figure). There were discordant results
in 26 specimen pairs. Of these, 14 (5%)
negative specimen A results subsequently became positive for specimen B,
and 12 (32%) positive specimen A
results subsequently became negative for
specimen B. Overall, there was a 91.6%
(CI, 88.0e94.4%) agreement with a
kappa of 0.6 between specimens A
and B. The proportion agreement was
similar when looking at the specimens
collected before and after TVUS only
(91.9% [CI, 87.5e95.1%], kappa 0.5)
and SVE only (90.3% [CI, 81.0e96.0%],
kappa 0.7), and higher when both TVUS
and SVE were performed (93.8% [CI,
70.0e99.8%], kappa 0.8). Test characteristics of specimen B using specimen A
as the reference standard are presented in
Table 3, displaying a high specicity
(95%) and negative predictive value
(96%) compared to sensitivity (68%)
and positive predictive value (64%).
Of the 215 (90.7%) women for whom
delivery information was available, the
overall rate of preterm delivery was
30.2%. The overall rate of spontaneous
preterm delivery was 15.3%. Of the
women with available delivery information who had a positive specimen A and
subsequent negative specimen B result,
2 of 7 (28.6%) proceeded to have a

TABLE 1

Maternal, obstetric, and delivery characteristics at patient levela

Characteristics

Enrolled

Maternal and obstetric characteristics

n 237
31.7  7.0

Maternal age, y
Body mass index, kg/m

29.1  5.9

2b

Prenatal care
Generalist private practice

30 (12.7)

MFM private practice

73 (30.8)

Clinic

134 (56.5)

Multiparous

182 (76.8)

History of FTB, >37 0/7 wk

104 (43.9)

History of PTB, 20 0/7e31 6/7 wk

55 (23.2)

History of PTB, 32 0/7e36 6/7 wk

38 (16.0)

History of second-trimester loss, 16e19 6/7 wk

Cerclage in situ

31 (13.1)

Smoking

12 (5.1)

Urogenital infection in pregnancy

Admission for preterm labor

9 (3.8)

76 (32.1)

Betamethasone administration

40 (16.9)
d

Magnesium sulfate administration

Tocolysis administrationd
Delivery characteristics

69 (29.2)
d

15 (6.3)
16 (6.8)
n 215

Gestational age at delivery, wk

38.0, 36.0e39.1

Preterm delivery

65 (30.2)

Spontaneous preterm delivery

33 (15.3)

Mode of delivery
Spontaneous vaginal
Operative vaginal

102 (47.4)
2 (0.9)

Cesarean

110 (51.2)

Combined

1 (0.5)

No. delivered
Singleton
Twin gestations
Higher-order multiple gestation
Birthweighte
Apgar at 5-mine
NICU admission

157 (73.0)
52 (24.2)
6 (2.8)
2860.4  768.8
9.0, 9.0e9.0
49 (22.8)

FTB, full-term birth; PTB, preterm birth; MFM, maternal-fetal medicine; NICU, neonatal intensive care unit.
Categorical data presented as n (%). Continuous data presented as mean  SD or median, interquartile range. Calculated
using patient as unit of analysis. Delivery information available for 215 women; b Information available for 233 women;
c
Defined as gonorrhea, chlamydia, bacterial vaginosis, yeast, and urinary tract infectioneall were treated; d Information
available for 236 women; e Information available for 214 women.
Turitz et al. Prevaginal and postvaginal manipulation fFN. Am J Obstet Gynecol 2016.

646.e3 American Journal of Obstetrics & Gynecology MAY 2016

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OBSTETRICS

TABLE 2

TABLE 3

Maternal and obstetric characteristics at specimen pair levela

Test characteristics of specimen

B for predicting specimen A
(n [ 310)a

Enrolled
n 310

Characteristics
Gestational age at enrollment, wk

Original Research

27.4, 25.0e29.9

Type of vaginal manipulation

Test characteristic

Percent

Sensitivity

67.6

Specificity

94.9

TVUS only

222 (71.6)

SVE only

72 (23.2)

Positive predictive value

64.1

Both TVUS and SVE

16 (5.2)

Negative predictive value

95.6

Indication for vaginal manipulation

Symptoms of preterm labor

83 (26.8)

History of preterm delivery

93 (30.0)

Short cervix

117 (37.7)

Multiple gestation

76 (24.5)

SVE, sterile vaginal examination; TVUS, transvaginal ultrasound.

a

Categorical data presented as n (%). Continuous data presented as median, interquartile range. Calculated using specimen
pairs as unit of analysis.
Turitz et al. Prevaginal and postvaginal manipulation fFN. Am J Obstet Gynecol 2016.

spontaneous preterm delivery. Of the

women who had a negative specimen A
and subsequent positive specimen B, 1 of
8 (12.5%) proceeded to have a spontaneous preterm delivery.
The test characteristics of specimens A
and B to evaluate preterm and spontaneous preterm birth are compared in
Table 4. The negative predictive values
for both specimens are identical when
evaluating for the outcome of preterm
birth (71%) and spontaneous preterm
birth (87%). In all, 187 women with
available delivery information had
negative specimen B results, irrespective
of the specimen A results; 25 (13.3%) of
these women subsequently had a

Calculated using specimen pairs as unit of analysis.

Turitz et al. Prevaginal and postvaginal manipulation fFN. Am J Obstet Gynecol 2016.

spontaneous preterm birth. In comparison, 24 of 188 (12.8%) women with

negative specimen A results, regardless
of the specimen B results, proceeded to
have a spontaneous preterm birth.
The test characteristics of specimens A
and B compared to the outcomes of
spontaneous preterm delivery by type of
vaginal manipulation are presented in
Table 5. Specicity and negative predictive values were high, regardless of
whether TVUS only, SVE only, or both
were performed. The negative predictive
value of both specimens A and B were
highest in the TVUS only group (88%),
followed by SVE only (84-85%), and
lastly by both TVUS and SVE (80%).

FIGURE

Specimen A (prevaginal manipulation) and specimen B

(postvaginal manipulation) test results

Turitz et al. Prevaginal and postvaginal manipulation fFN. Am J Obstet Gynecol 2016.

Comment
As currently used, time-based restrictions on fFN testing often complicate its use, either depriving at-risk
women from having the test performed
or hospitalizing them for 24 hours of
observation to perform it at the recommended interval from vaginal manipulation. If fFN testing could be performed
at time of presentation regardless of
prior vaginal examination or TVUS,
this could prevent unnecessary hospital
admissions, reduce the burden on
physician and nurse resources, decrease
health care costs, and moderate patient
inconvenience and anxiety.
We found that there is a moderately
high degree of agreement between
prevaginal and postvaginal manipulation fFN results. This nding persisted
whether the vaginal manipulation
employed was TVUS, SVE, or both,
although was highest when the 2 were
used in combination. However, it must
be highlighted that 32% of the positive
specimen A results subsequently became
negative after vaginal intervention.
Using specimen B in these cases would
therefore reclassify approximately one
third of fFN-positive patients as negative, potentially leading to withholding
of interventions that may be clinically
warranted and benecial.
The test characteristics of specimens
A and B compared to the outcomes of
preterm and spontaneous preterm birth
were similar, with negative predictive
values for preterm birth <37 weeks
consistent with those established in the

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Original Research

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OBSTETRICS

literature.3,4 This held true when evaluated by type of vaginal manipulation,

with the highest specicity and negative
predictive value in the TVUS only group.
For women at risk of preterm birth,
false-negative test results are arguably
the most concerning as they may lead to
withholding of interventions that may
improve outcomes. In our study, the
false-negative rates of specimens A and B
for evaluating spontaneous preterm
birth were not clinically different (12.8%
vs 13.3%, respectively).
While many studies have demonstrated the ability of fFN to predict preterm delivery, there remains a gap in our
understanding of the nonphysiologic
restrictions surrounding its collection.
McKenna et al11 looked at the individual
effect of digital cervical examination,
and Ben-Haroush et al12 of transvaginal
cervical length measurements, on the
expression of fFN in cervicovaginal
secretions in women presenting with
symptoms of preterm labor. This is in
contrast to our study, which included
both TVUS and SVE, as well as women
with clinical risk factors for preterm
delivery in addition to those presenting
with symptoms of preterm labor. In
comparison to our study, the studies by
McKenna et al11 and Ben-Haroush et al12
were relatively small. In the McKenna
et al11 sample of 50 patients between
22-34 weeks gestation with fFN swabs
collected immediately prior to digital
examination and then 1-3 hours after,
86% of repeat fFN results remained unchanged after digital examination. While
2 of 16 positive results became negative,
5 of 34 initially negative results became
positive. They did not nd a statistical
difference between the paired initial and
repeat fFN results, but the authors
concluded that there was a signicant
clinical difference due to the cross-over
between results. In contrast, in the
Ben-Haroush et al12 cohort of 28
patients enrolled between 24-34 weeks
gestation with fFN swabs collected
immediately before and after vaginal
ultrasonography, all positive tests
remained positive on repetition and all
negative results remained negative. The
authors therefore concluded that transvaginal sonography does not affect fFN

TABLE 4

Test characteristics of specimens A and B for predicting preterm birth

and spontaneous preterm birth (n [ 237)a
Sensitivity

Specificity

PPV

NPV

Specimen A

16%

89%

41%

71%

Specimen B

17%

89%

39%

71%

Specimen A

27%

90%

33%

87%

Specimen B

24%

89%

29%

87%

Preterm birth

Spontaneous preterm birth

NPV, negative predictive value; PPV, positive predictive value.

a
Calculated using patient as unit of analysis.
Turitz et al. Prevaginal and postvaginal manipulation fFN. Am J Obstet Gynecol 2016.

results. In our study, the largest to date to

address this question, we found a proportion agreement that fell between
those found by McKenna et al11 and
Ben-Haroush et al12 and persisted
when differentiated by type of vaginal
manipulation.
Our study had several strengths,
including the prospective nature of our
design. We included women at high risk
of preterm birth due to clinical factors as
well as symptoms of preterm labor to
increase the quotient of positive test
results in our cohort. All data were
derived from women at a single institution over a brief time period allowing for
consistency in the medical care and

minimal variability in practice patterns

between patients, which may have
affected management and gestational age
of delivery. Delivery information was
available for approximately 91% of
patients enrolled; the remainder transferred care during their pregnancy,
received care outside of our system
but utilized our system for ultrasounds
or emergency visits, or delivered inadvertently at an outside institution. A
limitation of our study was that we
included both TVUS and SVE, and
there may be unrecognized differences between these types of vaginal
manipulation. To account for this, we
analyzed our results by type of vaginal

TABLE 5

Test characteristics of specimens A and B for spontaneous preterm

birth by type of vaginal manipulation (n [ 237)a
Sensitivity

Specificity

PPV

NPV

Specimen A

12%

92%

17%

88%

Specimen B

12%

90%

13%

88%

Specimen A

42%

85%

42%

85%

Specimen B

33%

88%

40%

84%

Specimen A

50%

89%

67%

80%

Specimen B

50%

89%

67%

80%

TVUS only

SVE only

Both TVUS and SVE

NPV, negative predictive value; PPV, positive predictive value; SVE, sterile vaginal examination; TVUS, transvaginal ultrasound.
a

Calculated using patient as unit of analysis.

Turitz et al. Prevaginal and postvaginal manipulation fFN. Am J Obstet Gynecol 2016.

646.e5 American Journal of Obstetrics & Gynecology MAY 2016

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manipulation and found similar proportion agreements and test characteristics for evaluating spontaneous
preterm birth. We did not, however,
include other forms of vaginal manipulation, including sexual intercourse or
the use of vaginal medication, which are
similarly prohibitive against fFN testing.
In addition, our collection of specimen B
was not performed at a uniform time
after vaginal manipulation, although
most were collected within 3 minutes of
TVUS or SVE. All of the specimens
collected from the ultrasound unit were
collected without the use of a sterile
speculum. Unless there was an additional patient symptom that required the
use of a sterile speculum examination for
evaluation, they also were not used in the
labor and delivery triage unit. However,
because our protocol did not specify this
point, it is possible that some of the
specimens were collected with a sterile
speculum. While this may be a potential
confounder, it is not expected to affect
our results as previous data indicate
excellent agreement of fFN results with
and without a speculum.6,7
The high-risk nature of the women
enrolled in our study, based on clinical
risk factors in addition to symptoms of
preterm labor, resulted in a higher preterm birth rate among our cohort
compared to the national baseline.13 At
our institution, women with clinical risk
factors routinely return every 2 weeks for
cervical length evaluation and were
approached at these visits for study
enrollment. While a woman could be
enrolled multiple times, specimen A
served as the reference standard for
specimen B in calculating proportion
agreement with CI. In calculating the test
characteristics of specimens A and B to
evaluate the outcomes of preterm and
spontaneous preterm birth, we included
only the rst specimen pair for each
woman to account for possible clustering.
fFN is a valuable tool in the
limited armament against preterm birth.
Restrictions limiting its use should be

OBSTETRICS

questioned to make it a more widely and

applicable test to appropriately treat
patients at the highest risk of preterm
birth and decrease intervention, health
care costs, and anxiety for those patients
at reduced risk. Our study observed a
moderately high agreement between
prevaginal and postvaginal manipulation fFN with similar test characteristics
for predicting spontaneous preterm
birth, and thus supports the validity of
postvaginal manipulation fFN specimens in instances where prevaginal
manipulation specimens are not available. Due to the high cross-over rate
noted between positive specimen A
results that subsequently became negative, consideration should be made to
repeating the test in 24 hours for patients
who remain at highest risk or symptomatic. Future directions include using
the quantitative fFN results to assess the
difference between prevaginal and postvaginal intervention specimens, correlating fFN results and preterm birth rates
by indication for vaginal manipulation,
correlating the risk of preterm birth with
quantitative results, examining the effect
of cervical cerclage on fFN results, and
evaluating potential risk modiers for
positive fFN results and the outcome of
preterm birth.
n
Acknowledgment
The authors thank the maternal-fetal medicine
fellows and research staff in the Department of
Obstetrics and Gynecology at Columbia University Medical Center for their assistance in
screening and enrolling patients in this study.

References
1. Feinberg RF, Kliman HJ, Lockwood CJ. Is
oncofetal bronectin a trophoblast glue for human implantation? Am J Pathol 1991;138:537.
2. Lockwood CJ, Senyei AE, Dische MR, et al.
Fetal bronectin in cervical and vaginal secretions as a predictor of preterm delivery. N Engl J
Med 1991;325:669-74.
3. Iams JD, Casal D, McGregor JA, et al. Fetal
bronectin improves the accuracy of diagnosis
of preterm labor. Am J Obstet Gynecol
1995;173:141-5.
4. Peaceman A, Andrews W, Thorp J, et al.
Fetal bronectin as a predictor of preterm

Original Research

birth in patients with symptoms: a multicenter trial. Am J Obstet Gynecol 1997;177:

13-8.
5. Iams JD. Prediction and early detection
of preterm labor. Obstet Gynecol 2003;101:
402.
6. Roman AS, Koklanaris N, Paidas MJ, et al.
Blind vaginal fetal bronectin as a predictor of
spontaneous preterm delivery. Obstet Gynecol
2005;105:285.
7. Stafford IP, Garite TJ, Dildy GA, et al.
A comparison of speculum and nonspeculum
collection of cervicovaginal specimens for fetal
bronectin testing. Am J Obstet Gynecol 2008;
199:131.e1-4.
8. Bossuyt PM, Reitsma JB, Bruns DE, et al. The
STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration.
Ann Intern Med 2003;138:W1-12.
9. Meis PJ, Klebanoff M, Thom E, et al.
Prevention of recurrent preterm delivery by 17
alpha-hydroxyprogesterone caproate. N Engl
J Med 2003;348:2379-85.
10. Owen J, Hankins G, Iams JD, et al. Multicenter randomized trial of cerclage for preterm
birth prevention in high-risk women with shortened midtrimester cervical length. Am J Obstet
Gynecol 2009;201:375.e1-8.
11. McKenna D, Chung K, Iams J. Effect of
digital cervical examination on the expression
of fetal bronectin. J Reprod Med 1994;44:
796-800.
12. Ben-Haroush A, Poran E, Yogev Y,
Glezerman M. Vaginal fetal bronectin evaluation
before and immediately after ultrasonographic
vaginal cervical length measurements in symptomatic women at risk of preterm birth: a pilot
study. J Materrn Fetal Neonatal Med 2010;23:
854-6.
13. Hamilton BE, Martin JA, Ventura SJ. Births:
preliminary data for 2012. Natl Vital Stat Rep
2013;62:1-20.

Author and article information

From the Division of Maternal Fetal Medicine, Department
of Obstetrics and Gynecology, Columbia University
Medical Center (Drs Turitz, Ackerman, Johnson, and
Gyamfi-Bannerman, and Ms Bank); and Department of
Biostatistics, Columbia University (Mr Duong and Dr Lee),
New York, NY.
Received Nov. 20, 2015; revised Jan. 8, 2016;
accepted Jan. 14, 2016.
Hologic donated the fetal fibronectin specimen
collection kits and analyzer used in this study.
The authors report no conflict of interest.
Presented orally at the 34th annual meeting of the
Society for Maternal-Fetal Medicine, Atlanta, GA, Feb.
1-6, 2016.
Corresponding author: Amy L. Turitz, MD. amy.turitz@
gmail.com

MAY 2016 American Journal of Obstetrics & Gynecology

646.e6