BJOG: an International Journal of Obstetrics and Gynaecology

March 2005, Vol. 112, Supplement 1, pp. 61 63

Controversies in diagnosis of preterm labour

Harald Leitich
Despite scientific advances, efforts to prevent preterm birth can be disappointing. Obstetric care must focus
on strategies to improve the outcome of preterm infants. The major goal is to delay preterm birth long enough
to allow the transfer of women about to deliver preterm to a facility with a neonatal intensive care unit and to
administer corticosteroids to enhance fetal lung maturation. A prerequisite for the success of this strategy is
the reliable identification of women who will give birth preterm. Although symptoms of preterm labour
strongly suggest preterm birth, contractions even if combined with cervical effacement and dilation do
not reliably predict preterm birth. The diagnosis of true preterm labour that will eventually lead to preterm
birth has been facilitated by the use of transvaginal cervical ultrasonography and by the detection of fetal
fibronectin (FFN) in cervicovaginal secretions. The main clinical value of these tests is that preterm birth is
very unlikely if the results of both tests are negative. This may help to avoid unnecessary transfer,
hospitalisation and treatment of women with false preterm labour. The detection of phosphorylated insulinlike growth factor binding protein-1 in cervicovaginal secretions, or elevated levels of inflammatory markers,
like interleukin-6, interleukin-8 and tumour necrosis factor-a (TNF-a), also predict preterm birth in
symptomatic women. These markers, however, are not routinely used to predict preterm birth in women with
symptoms of preterm labour.
INTRODUCTION
Even though efforts to prevent preterm birth have been
disappointing, modern obstetric care has been more successful in preparing the unborn child for a preterm birth.
The transfer of women about to give birth preterm to a
facility with a neonatal intensive care unit, the administration of corticosteroids to enhance fetal lung maturation and
tocolysis to delay birth long enough so that these preparations can be completed are interventions with proven
benefit to the preterm infant. A prerequisite for the success
of this strategy is the reliable identification of women who
will have a preterm birth. A test to identify women about to
give birth preterm should be both highly sensitive (i.e. all
preterm infants should be identified) and highly specific
(i.e. antenatal transfer, administration of corticosteroids and
tocolysis should be avoided in women who will ultimately
give birth at term).

THE DIAGNOSIS OF PRETERM LABOUR

If preterm birth is preceded by spontaneous preterm
labour, clinical signs and symptoms (such as contractions,
increased pressure or discharge) strongly suggest imminent delivery. These clinical signs and symptoms, in

Department of Obstetrics and Gynaecology, Medical

University of Vienna, Austria
Correspondence: Dr H. Leitich, Department of Obstetrics and
Gynaecology, Medical University of Vienna, Wahringer Gurtel 18 20,
1090 Vienna, Austria.
D RCOG 2005 BJOG: an International Journal of Obstetrics and Gynaecology

combination with the findings of a digital vaginal examination (such as changes in cervical consistency, effacement
or dilation) are often sufficient to make a diagnosis of
preterm labour.
In many cases, women with symptoms suggestive of
preterm labour even if combined with cervical effacement and dilation will not have a preterm birth, so that a
clinical diagnosis of preterm labour is often unreliable.
The problem in correctly identifying symptomatic women
who will ultimately give birth preterm can be exemplified
by the results of clinical studies in which women with
suspected preterm labour were included. Only 3% of the
women with suspected preterm labour who were included
in studies of fetal fibronectin (FFN) testing delivered within
7 10 days, and only 21% delivered before 37 weeks of
gestation.1
Fortunately, the diagnosis of true preterm labour that
will eventually lead to preterm birth has been facilitated
by the use of three tests that have been introduced into
routine obstetric care in the last two decades: the detection
of FFN or phosphorylated insulin-like growth factor binding protein-1 in cervicovaginal secretions, and transvaginal
cervical ultrasonography.
In a systematic review of symptomatic women, the
mean sensitivity and specificity of FFN testing to predict
a delivery within seven days after testing was 77% and
87%,2 with corresponding 95% confidence intervals (CIs)
of 67 88% and 84 91%, respectively. As in asymptomatic women, FFN was more predictive as a short term marker than as a long term marker for preterm birth. Mean
sensitivity rates for the outcomes of birth within 14 days,
21 days or before 34 weeks of gestation were 74%, 70%
and 63%, with corresponding mean specificity rates of
87%, 90% and 86%, respectively. The 95% CIs for these
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H. LEITICH

outcomes widened considerably, indicating larger heterogeneity within the results of the studies included in the
review.
The typical clinical performance of FFN testing in
symptomatic women has been calculated using pre- and
post-test probabilities.1 From a median pretest probability
of 3% for a delivery within 7 10 days after testing, the
positive and negative post-test probabilities were 14.4%
and 0.8%, respectively. In this way, positive and negative
post-test probabilities were neither high nor low enough to
rule in or out true preterm labour.
Phosphorylated insulin-like growth factor binding
protein-1 has been shown to predict preterm birth in symptomatic women.3 For the outcomes of birth within seven
days after testing or before 35 weeks of gestation, sensitivity rates were 94% and 100%, and specificity rates 85%
and 82%, respectively. These results are promising but need
to be reconfirmed by more studies in different populations.
Inflammatory markers that can be detected in cervicovaginal secretion and that have been shown to be significantly associated with preterm birth include interleukin
(IL)-6, IL-8 and tumour necrosis factor-a (TNF-a).4 6
These markers are not currently used in routine practice.
As in asymptomatic women, future clinical research using
inflammatory markers may deepen our understanding of
the role of infection in preterm labour.
In contrast to FFN testing, for which a common cutoff
value of 50 ng/mL was used in the great majority of diagnostic studies, the evaluation of cervical ultrasonography
in symptomatic women is complicated by the use of a variety of criteria to define abnormal results. Different cutoff values for cervical length were found to be optimal in
individual studies, and various criteria were used to define
dilatation of the internal cervical os.
Optimal cutoff values for cervical length in symptomatic women were found to range between 18 and 30 mm.7
Sensitivity and specificity rates at these optimal cutoff values ranged between 68% and 100% and between 44%
and 79%, respectively. The corresponding performance
rates for a dilated internal cervical os using various criteria ranged from 70% to 100% and from 54% to 75%,
respectively.
Because optimal test results were achieved at different
cutoffs, it is difficult to propose an overall optimal cutoff
value. In women in preterm labour, a high sensitivity rate
would be the primary target and a lower specificity rate
would be tolerated in most clinical settings, resulting in
more women being admitted to hospital. A cervical length
of 30 mm or less or a dilatation of the internal cervical os
would have detected 80 100% or 70 100% of women
who subsequently delivered preterm. Both parameters appear to be reasonably sensitive criteria for true preterm
labour, but suboptimal specificity must be expected.
Even though a series of studies of FFN testing and
cervical ultrasonography in both asymptomatic and symptomatic women have been published, only sparse data

Table 1. Combined FFN testing and cervical ultrasonography at 24 34

weeks of gestation and the rates of preterm delivery in symptomatic
patients.8
Delivery <37 weeks

FFN+

FFN

CL 26 mm
CL >26 mm
Pretest probability

52.4%
30.0%

44.4%
5.6%
26.3%

FFN = fetal fibronectin; CL = cervical length.

about the performance of a combination of FFN testing

and cervical ultrasonography in symptomatic women exist.
Preterm birth rates for all combinations of both tests
are available from one study, which included symptomatic
women at 24 34 weeks of gestation with singleton
pregnancies.8 The pretest probability of a delivery before
37 weeks of gestation in this study was 26.3%, which is
comparable to other studies that included women with
suspected preterm labour (Table 1). Positive tests of both
markers, either alone or in combination, raised the posttest probability for a delivery before 37 weeks of gestation
to 52.4%, which has only moderate clinical significance.
A negative result on both tests lowered the probability to
5.6%. This is less than the preterm delivery rate that would
be expected in the general population, suggesting that
symptomatic women with both a negative FFN test and a
normal result of cervical ultrasonography carry a risk of
preterm birth that is even lower than the average risk in the
general population.

CONCLUSION
The diagnosis of true preterm labour that will eventually
lead to preterm birth has been facilitated by the use of
transvaginal cervical ultrasonography and by the detection
of FFN in cervicovaginal secretions. Both tests do not
reliably rule in true preterm labour and a substantial
proportion of women will not give birth preterm even if
both tests are positive. The main clinical value of these
tests is that preterm birth is very unlikely if the results of
both tests are negative as the risk of preterm birth drops
below the baseline risk of preterm birth found in the
general population. This may help to avoid unnecessary
transfer, hospitalisation and treatment of women with false
preterm labour.

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D RCOG 2005 BJOG: an International Journal of Obstetrics and Gynaecology 112 (Suppl. 1), pp. 61 63

CONTROVERSIES IN DIAGNOSIS OF PRETERM LABOUR

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