OBSTETRICS
Abstract
Objective: To evaluate the contingent use of fetal fibronectin (fFN)
testing and cervical length (CL) measurement to predict preterm
delivery, and to validate the use of phosphorylated IGFBP-1 as a
predictor of preterm delivery.
Methods: We recruited 71 women with a clinical diagnosis of
preterm labour between 24 and 34 weeks, and tested for the
presence of fFN and IGFBP-1 in the cervicovaginal secretions of
all women immediately before CL measurement.
Results: Among the 66 women with complete outcome, four were
excluded from the final analysis as two had assessment for fFN
but no CL measurement, and another two had CL measured but
no screening for fFN. Among 62 women with complete results, the
mean gestational age at recruitment was 29.4 2.5 weeks. Six
women (9.6%) delivered within two weeks of assessment, and 14
(22.5%) delivered before 34 weeks. A positive fFN test resulted in
a sensitivity of 83%, a specificity of 84%, a positive predictive
value of 36%, and a negative predictive value of 98% for delivery
within two weeks; for CL < 25 mm, these figures were 50%, 52%,
10%, and 91%, respectively, and for a positive IGFBP-1, they were
17%, 93%, 20%, and 91%, respectively. A policy of contingent use
of fFN (in which the test was assumed to be positive if CL 15 mm,
and fFN was only measured if the CL was between 16 and 30 mm)
gave sensitivity, specificity, positive and negative predictive values
of 80%, 61%, 17%, and 97%, respectively for delivery within two
weeks. Using this contingent use protocol, only one third of
women needed fFN screening after CL measurement.
Conclusion: In this study, IGFBP-1 screening did not predict preterm
delivery and fFN screening provided the best predictive capacity.
A policy of contingent use of testing for fFN after CL measurement,
or contingent use of CL measurement after fFN screening
(depending on available resources) is a promising approach to
limit use of resources.
Rsum
Objectif : valuer lutilisation contingente du dpistage de la
fibronectine ftale (FNf) et de la mesure de la longueur cervicale
(LC) pour prdire laccouchement prterme, ainsi que valider
lutilisation de lIGFBP-1 phosphoryle titre de facteur prdictif
de laccouchement prterme.
Mthodes : Nous avons recrut 71 femmes ayant obtenu un
diagnostic clinique de travail prterme entre 24 et 34 semaines,
et nous avons cherch dterminer la prsence de FNf et
dIGFBP-1 dans les scrtions cervicovaginales de toutes les
femmes, immdiatement avant la mesure de la LC.
Rsultats : Parmi les 66 femmes ayant connu une issue complte,
quatre ont t exclues de lanalyse finale puisque deux dentre
elles avaient subi un dpistage de la FNf sans quune mesure de
la LC ne soit effectue, tandis que la LC des deux autres avait t
mesure sans quun dpistage de la FNf ne soit men. Chez les
62 femmes prsentant des rsultats complets, lge gestationnel
moyen au moment de ladmission ltude tait de 29,4
2,5 semaines. Six femmes (9,6 %) ont accouch dans les deux
semaines suivant lvaluation et 14 (22,5 %) ont accouch avant
e
la 34 semaine de gestation. Un rsultat positif au test FNf donnait
lieu une sensibilit de 83 %, une spcificit de 84 %, un
coefficient de prvision dun test positif de 36 % et un coefficient
de prvision dun test ngatif de 98 % pour ce qui est dun
accouchement dans les deux semaines; en ce qui concerne une
LC <25 mm, ces valeurs taient de 50 %, de 52 %, de 10 % et de
91 %, respectivement, tandis que dans le cas dun rsultat positif
au test IGFBP-1, elles taient de 17 %, de 93 %, de 20 % et de
91 %, respectivement. Une politique dutilisation contingente du
dpistage de la FNf (selon laquelle le test tait prsum positif
lorsque la LC 15 mm et la FNf ntait mesure que lorsque la LC
se situait entre 16 et 30 mm) a donn lieu une sensibilit, une
spcificit, un coefficient de prvision dun test positif et un
coefficient de prvision dun test ngatif de 80 %, de 61 %, de
17 % et de 97 %, respectivement, pour ce qui est dun
accouchement dans les deux semaines. En utilisant ce protocole
dutilisation contingente, seul le tiers des femmes ncessitait un
dpistage de la FNf la suite de la mesure de la LC.
307
OBSTETRICS
INTRODUCTION
reterm birth remains a major cause of perinatal morbidity and mortality,1 and its rate has not declined over the
last two decades despite the improvement in perinatal management.2 Assessing the probability of preterm delivery is
still a clinical challenge and is important because standard
clinical interventions (tocolysis, corticosteroid administration, and transfer to a tertiary care facility) are potentially
risky and expensive. Previous studies have shown that a
diagnosis of preterm labour based on digital examination
was less reliable than a diagnosis based on objective tests,
such as detection of fetal fibronectin in cervicovaginal
secretions and ultrasound measurement of cervical length.3
Fetal fibronectin, an extracellular matrix glycoprotein localized at the maternalfetal interface of the amniotic membranes between the chorion and the decidua, is found at
very low levels in cervicovaginal secretions under normal
conditions. Levels 50 ng/mL at or after 22 weeks gestation have been associated with an increased risk of spontaneous preterm birth.36 A recent meta-analysis has shown
that birth before 37 weeks was significantly decreased in
patients whose management was based on knowledge of
fFN results compared with controls whose fFN results
were not known.7
Transvaginal CL measurement is the other validated test to
predict preterm birth in women with threatened preterm
labour as well as in asymptomatic high-risk and low-risk
women.3,814 A CL measurement of 25 mm or less is generally considered an excellent indicator of an increased risk of
preterm delivery, particularly among women with preterm
labour.
Several studies have reported that fFN screening and CL
measurement provided similar results in predicting the risk
of preterm delivery.1520 However, whether combined fFN
and CL measurement improves the prediction of preterm
delivery and how the tests should be combined remain
unclear.3 Availability of one of the two tests may be an issue
in some facilities because the ultrasound expertise for CL
measurement may not be always available in small centres.
On the other hand, the additional cost of fFN testing may
be difficult to justify in centres where CL measurement is
readily available. Therefore, the use of CL or fFN as the
first-line test might be a more rational option, limiting the
ABBREVIATIONS
CL
cervical length
fFN
fetal fibronectin
308
Contingent Use of Fetal Fibronectin Testing and Cervical Length Measurement in Women With Preterm Labour
RESULTS
309
OBSTETRICS
N = 62
27.6 6.2
Nulliparous, n (%)
29 (46.8)
37 (59.7)
29.4 2.5
36.5 3.2
44 (71.0)
6 (9.7)
14 (22.6)
23 (37.1)
49.9 22.8
26.5 (051)
16 (28.8)
30 (48.4)
Cervical length 30 mm
24 (38.7)
14 (22.6)
5 (8.1 )
DISCUSSION
Contingent Use of Fetal Fibronectin Testing and Cervical Length Measurement in Women With Preterm Labour
Table 2. Predictive values for preterm birth of cervical length, fFN, IGFBP-1, and contingent use of fFN and cervical
length
Delivery
Sensitivity
% (95% CI)
Specificity
% (95% CI)
LR+
(95% CI)
LR
(95% CI)
PPV
% (95% CI)
NPV
% (95% CI)
83 (36100)
84 (7292)
5.2 (2.610.4)
0.2 (0.01.2)
36 (1365)
98 (89100)
Within 2 weeks
(prev 9.7%)
fFN +
IGFBP-1
17 (064)
93 (8398)
2.3 (0.317.6)
0.9 (0.61.3)
20 (0.572)
91 (8197)
CL < 25 mm
50 (1288)
52 (3865)
1.0 (0.42.4)
1.0 (0.42.2)
10 (226)
91 (7598)
Contingent fFN
50 (1288)
64 (5077)
1.4 (0.63.3)
0.8 (0.31.8)
13 (334)
92 (7998)
Contingent CL
83 (36100)
62 (4875)
2.2 (1.43.6)
0.3 (0.01.6)
19 (639)
97 (85100)
fFN +
50 (2377)
85 (7294)
3.4 (1.48.1)
0.6 (0.31.0)
50 (2377)
85 (7294)
IGFBP-1
14 (243)
94 (8399)
2.3 (0.412.4)
0.9 (0.71.1)
40 (585)
79 (6689)
CL < 25 mm
71 (4292)
58 (4372)
1.7 (1.12.7)
0.5 (0.21.2)
33 (1753)
87 (7196)
Contingent fFN
64 (3587)
71 (5683)
2.2 (1.23.4)
0.5 (0.21.0)
39 (2061)
87 (7396)
Contingent CL
71 (4292)
67 (5280)
2.1 (1.33.6)
0.4 (0.21.0)
38 (2059)
89 (7497)
75 (6486)
< 34 weeks
(prev 22.6%)
< 37 weeks
(prev 37.1%)
fFN +
48 (3560)
92 (8699)
6.2 (1.920.0)
0.5 (0.40.8)
79 (6889)
IGFBP-1
13 (521)
95 (89100)
2.5 (0.514)
0.9 (0.81.1)
60 (4872)
65 (5377)
CL < 25 mm
74 (5290)
67 (5081)
2.2 (1.33.7)
0.4 (0.20.8)
57 (3774)
81 (6493)
Contingent fFN
56 (3477)
74 (5887)
2.2 (1.24.2)
0.6 (0.41.0)
56 (3477)
74 (5887)
Contingent CL
65 (4384)
72 (5585)
2.3 (1.34.1)
0.5 (0.30.9)
58 (3777)
78 (6190)
fFN+: positive fetal fibronectin test; CL: cervical length; contingent fFN: CL measured in all cases, and fFN only for CL between 16 and 30 mm; contingent CL: fFN
tested in all cases, and CL only for negative fFN; LR+: likelihood ratio for a positive result; LR:likelihood ratio for a negative result; PPV: positive predictive value;
NPV: negative predictive value; prev: prevalence;
P > 0.05 for all comparisons between sensitivities; P< 0.001 vs. CL.
these tests on preterm birth rates, the duration of hospitalization, and overall costs now must be evaluated in
prospective studies.
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