Prediction of Preterm Birth: Cervical Sonography

Maria Teresa Mella, MD, and Vincenzo Berghella, MD

The cervix has to open to allow vaginal birth. Ultrasound has now shown that this lower part
of the uterus begins to show changes weeks before eventual birth. Only transvaginal
ultrasound should be used to evaluate the cervix for prediction of preterm birth (PTB). The
shortest best cervical length (CL) is the most effective measurement for clinical use. Proper
technique is paramount for accurate results. The risk of PTB increases with ever shorter CL
(<25 mm). Other factors that must be carefully considered when using CL for prediction of
PTB are number of fetuses, risk factors for PTB, and gestational age at screening.
Semin Perinatol 33:317-324 2009 Elsevier Inc. All rights reserved.
KEYWORDS cervical length, prediction, preterm birth
Prediction Is the
Basis of Prevention
The aim of any healthcare worker assisting a patient is to
prevent disease. Often, the rst step in preventing disease is
early prediction. In the case of pretermbirth (PTB), one of the
best, if not the best, predictive test has been shown to be
cervical sonography. The cervix has to open to allow vaginal
birth. As we have known for decades, the process of parturi-
tion takes months of preparation, and early changes can be
detected in human beings.
With regard to the cervix, ultrasound has now shown that
this lower part of the uterus begins to show changes weeks
before eventual birth. Even for PTB, which often we had
characterized in the past as something happening suddenly
and unexpectantly, the changes are gradual and usually very
slow. In fact, in many high-risk women delivering preterm,
the cervix starts to shorten a fewmonths before pretermlabor
(PTL) or preterm premature rupture of membranes occurs.
Early detection of change is paramount in allowing inter-
ventions the chance to work before the pathology is so far in
its pathways as to thwart prevention. In this chapter, we will
review the evidence for cervical sonography as a screening
test for the prediction of PTB. There are nowmore than 1000
manuscripts published on this topic, and ample evidence to
support the efcacy of cervical sonography in the prevention
of PTB.
Evaluation of Cervical
LengthTechnical Aspects
Evaluation of cervical length (CL) may be done either sono-
graphically or through direct physical examination of the
cervix. Sonographic detection of CL may be approached
through transabdominal, translabial, or transvaginal routes,
with each method having its own benets and limitations.
Physical Examination
In the past, serial digital and speculum examinations have
been used to follow-up women with suspected cervical insuf-
ciency. The physical changes notable on examination, re-
vealing the likelihood of cervical insufciency, include bulg-
ing membranes, a pink or tan discharge, or appreciable
softening of the cervix and lower uterine segment. Of these
ndings, softening and development of the lower uterine
segment is most strongly correlated with early effacement.
However, these reported physical changes are often not evi-
dent until the cervix is signicantly effaced, as this process
begins at the internal os. Therefore, the absence of these
physical ndings cannot exclude cervical insufciency. In
addition, a digital examination has been found to be signi-
cantly less consistent than ultrasound in assessing CL. On
average, manual estimations of CL are shorter by 11 mmthan
sonographic measurements of CL.
1
Cervical funneling at the
internal os may also occur while the external os is fully
closed. Many multiparous women who deliver at term have
cervices that are already dilated 1-2 cm in the late second
trimester.
1
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gyne-
cology, Jefferson Medical College, Thomas Jefferson University, Phila-
delphia, PA.
Address reprint requests to Vincenzo Berghella, MD, Division of Maternal-
Fetal Medicine, Department of Obstetrics and Gynecology, Thomas Jef-
ferson University, 834 Chestnut St, Suite 400, Philadelphia, PA 19107.
E-mail: vincenzo.berghella@jefferson.edu
317 0146-0005/09/$-see front matter 2009 Elsevier Inc. All rights reserved.
doi:10.1053/j.semperi.2009.06.007
Transabdominal Ultrasound
In the 1970s, when ultrasonographic measures were rst
implemented to evaluate the cervix, transabdominal visual-
ization was the preferred approach. However, the limitations
of this technique are numerous and have made it fall out of
favor with perinatologists. Included among these shortcom-
ings are the following: (1) the increased distance from the
probe to the cervix, which results in poor image quality,
especially in obese populations; (2) the bladder needs to be
sufciently lled for a reliable image to be produced, leading
to elongation of the cervix and camouaging of any funneling
at the internal os; and (3) the likelihood that fetal parts will
obscure the cervix is higher, especially after 20 weeks of
gestation.
2-4
Hassan
2
reports that the sensitivity of predicting
PTB is only 8%, a value signicantly lower than the other
methods; therefore, this method should be avoided and used
only when other techniques are not readily available.
Translabial (Transperineal) Ultrasound
Translabial (also known as transperineal) ultrasound was
originally used in France in the 1980s and proved to be more
fruitful than the transabdominal approach. This technique
involves having the woman lie on an examination table with
the knees and hips in a exed position, and placing a gloved
transducer on the perineumbetween the labia majora, ensur-
ing to keep the transducer in a sagittal orientation. A cushion
may be placed underneath the patient to elevate the hips and
enhance visualization of the cervix. Unlike transabdominal
ultrasound, this technique offers signicant improvements in
that the image is not obstructed by fetal parts, the bladder
does not have to be lled, and the transducer is closer to the
cervix, thus allowing for 100% visualization of the cervix.
Other advantages offered by this technique include the fact
that it does not require another transducer; it is noninvasive,
and it is therefore well accepted by most women. The biggest
downfalls to translabial ultrasound include the possibility
that gas in the rectummay impede the viewof the external os
and the technique is more challenging to master than other
ultrasonographic methods.
5
Transvaginal Ultrasound
Transvaginal ultrasonography (TVU) was rst described in
the late 1980s, around the same time as translabial ultra-
sound, as another method available to study the pregnant
cervix. It has become the gold standard for measuring CL
because it offers the same advantages as translabial ultra-
sound as well as improved visualization of the cervix without
the interference of bowel gas.
3
For transvaginal cervical
sonography to accurately measure CL, appropriate technique
is required to yield signicant prediction. Table 1 summa-
rizes the main aspects of this procedure.
3
Although TVU is the most sensitive and specic screening
test, it also has its limitations. Funneling of the cervix may be
masked if the bladder is not completely empty and if exces-
sive pressure is exerted on the cervix by the probe. In con-
trast, uterine contractions may mimic the appearance of cer-
vical funneling of the internal os (Table 2).
3,6
In such
instances the cervical canal may assume an S shape, and the
lower uterine segments (either anteriorly or posteriorly or
both) are thickened and asymmetric. Finally, before 14
weeks gestation, it is often difcult to distinguish the lower
uterine segment from the endocervical canal. This occurs
because the gestational sac has not reached a sufcient size to
completely expand the lower part of the uterus. Therefore,
CL should usually not be studied before 14 weeks.
3,4
Clearly, the cervix must be evaluated by TVU if accurate
prediction of PTB is desired. Unlike the other 2 sonographic
Table 1 Proper Technique of TVU Screening of The Cervix for
Prediction of PTB (Figs. 1-3)
1. Have the woman empty her bladder just before
ultrasound
2. Prepare the clean probe covered by a condom
3. Insert the probe (probe can be inserted by the woman
for her comfort)
4. Guide the probe in the anterior fornix of the vagina
5. Obtain a sagittal long-axis view of the entire
endocervical canal
6. Withdraw the probe until the image is blurred, and
reapply just enough pressure to restore the image (to
avoid excessive pressure on the cervix, which can
elongate it)
7. Enlarge the image so that the cervix occupies at least
2/3 of the screen, and both external and internal os
are seen
8. Measure the cervical length from the internal to the
external os along the endocervical canal
9. Obtain at least three measurements, and record the
shortest best measurement in millimeters
10. Apply transfundal pressure for 15 seconds, and record
cervical length again at least 3 times, recording best
measurement
11. Entire examination should last at least 5 minutes;
record only the shortest best cervical length obtained
for clinical management
Adapted from Berghella and Bega.
3
Table 2 Cautionary Notes for TVU of The Cervix
Bladder: must be completely empty, as uid in the bladder
can mask shortening and funneling
Excessive pressure: echogenicity of the cervix means that
there is extreme pressure from the probe. Ensure that
the thickness of the anterior and posterior lips are the
same
Contractions: a dynamic cervix, in which cervical length
and appearance change signicantly during the TVU
examination, is probably a sign of uterine and/or cervical
contractions. A contraction can also make the cervix
appear long and mask shortening and/or funneling. Be
patient, and allow >5 min of observation and
measurements and record the shortest cervical length
for clinical management
Cervix appears longer than 50 mm: in the rst trimester, as
the sac has not yet lled the uterine cavity, measurement
of the cervical length may appear too long as the lower
uterine segment is indistinguishable from the cervix
318 M.T. Mella and V. Berghella
techniques, transvaginal cervical imaging is highly reproduc-
ible, with low (10%) inter- and intraobserver variability.
7
In 95% of cases studied, the difference in CL between 2
measurements by the same observer and by 2 observers was
3.5 and 4.2 mm, respectively.
8
Clinical Application:
Prediction of Preterm
Birth by Transvaginal
Ultrasound of the Cervix
Screening Test
For the reasons mentioned earlier, transvaginal cervical sonog-
raphy, as opposed to any other method of investigation, is the
gold standard test for prediction of PTB, as it fulls all the re-
quirements for a good screening test at an acceptable cost.
First, transvaginal cervical ultrasonography can screen for
a clinically important and prevalent condition as PTB occurs
in almost 13% of births in the United States.
9
This technique
has been well described in published reports and can be
performed by trained sonographers. After a trained sonogra-
pher completes approximately 50 supervised transvaginal
examinations of CL, the inter- and intraobserver variability is
usually 10%.
7
There is high reproducibility of this method of
study when strict adherence to technique occurs (Table 1; Figs.
1-3).
3
Pitfalls must be avoided (Table 2).
Transvaginal sonography is a safe and acceptable method
of studying the cervix, as it is well accepted by 99% of
women, and pain is reportedly felt in 2% of the cases.
10
A
report by Carlan et al
11
showed that TVU of the cervix does
not result in inoculation of bacteria or increased risk of infec-
tion for the mother or fetus compared with women who do
not undergo transvaginal sonography.
Transvaginal cervical sonography is unlike any other
method used to evaluate the cervix because it can accurately
assess cervical insufciency at an early asymptomatic stage, at
a point where preventative measures may be used to thwart
PTB. Cervical changes visible on TVU include the initial
opening of the internal cervical os, progressive cervical wid-
ening and shortening of the endocervical canal from internal
to the external os, and dilation of the external os.
3
Optimal Timing and Frequency for Measuring
Cervical Length Via Transvaginal Ultrasound
Prior to 14 weeks gestation, almost all women, including
those at the highest risk of PTB, will have a normal CL. CL of
Figure 1 TVU of the cervix with normal CL (38 mm) at 23 wks.
Obtained using proper technique, as described in Table 1. (Color
version of gure is available online.)
Figure 2 U-shaped funnel with 29 mm closed (functional) CL at 21
wks. As the CL is between 25 and 29 mm, and there is a funnel, we
would suggest repeat TVU CL in 1-2 wks, especially in case of prior
PTB. (Color version of gure is available online.)
Figure 3 V-shaped funnel with 12-mm closed (functional) CL in a
woman at 16 wks, with history of spontaneous PTB at 17 wks. She
elected and received (ultrasound- and history-indicated) McDonald
cerclage the next day. (Color version of gure is available online.)
Prediction of preterm birth 319
25 mm at this gestation is seen only in women who have
had a previous second-trimester loss or those with a history
of a large cervical cone biopsy.
12
A CL of 25-50 mmis normal
at 14-24 weeks in all pregnant women (Fig. 1). In low-risk
women, mean CL at 14-30 weeks of gestation is 35-40 mm,
with the lower 10th percentile being 25 mm and the upper
10th percentile being 50 mm.
13
Optimal timing for measur-
ing CL must be established because if attempted too early, the
lower uterine segment may be too difcult to separate from
the true cervix. In addition, after 30 weeks, the cervix nor-
mally shortens progressively in preparation for termlabor, so
a CL 25 mm after 30 weeks is physiological and not indic-
ative of PTB in asymptomatic women.
7
In most women who will have a PTB, a short CL is rst
noted at approximately 18-22 weeks of gestation; there-
fore, initial screening should be started at this time.
13
The
earlier the short CL is detected, the higher the likelihood
of PTB. There also exists an inverse relationship between
CL and PTL, in that the shorter the cervix, the greater the
likelihood that PTB will occur. In the highest risk women,
a CL 25 mm has a positive predictive value of 70% for
PTB at 35 weeks when detected at 14-18 weeks, and of
40% when detected at 18-22 weeks.
7
This observation
indicates that it may be benecial to screen these high-risk
women earlier than 18 weeks to determine their need for
intervention (Fig. 3).
The benet of repeated transvaginal sonographic examina-
tions and the ideal interval for repeating scans have not been
clearly established in the published reports. Given the varia-
tion in CL based on risk of PTB, current research shows that
it may be best to break down transvaginal ultrasonographic
screening into 3 groups: those at lowrisk, high risk, and very
high risk for PTB. If a screening program were employed in
relatively low-risk women, 1 TVU at approximately 18-22
weeks would probably be sufcient, with no need to repeat
the scan in the future.
3
In high-risk women, it seems that 2
normal CLs, 1 at 14-18 weeks of gestation and another at
18-22 weeks is enough. Finally, in very high-risk women,
including those with a previous second-trimester loss or very
early spontaneous PTB, it is best to undergo serial transvag-
inal examinations every 2 weeks from 14 to 24 weeks of
gestation.
3,14
Appropriate timing of CL measurement is nec-
essary so that changes leading to PTB are detected early
enough in the process to allow for intervention.
Cervical Evaluation: What to
Measure and What Not to Measure
Cervical Length
Although multiple cervical parameters have been evaluated
as predictors of PTB, CL continues to be the most reproduc-
ible and reliable indicator. Accurate measurements of CL
begin at the internal os, follow the path along the endocervi-
cal canal, and end at the external os. If the cervical canal is
curved (a deviation of the canal 5 mm from a straight line
from the internal to external os), then the canal can either be
traced, or the sum of 2 straight lines that follow the curve of
the canal can be used.
15
If the endocervical canal takes on a
curvilinear appearance, this is a reassuring nding because a
curved cervix usually signies a CL 25 mm (Fig. 1). A
worrisome nding would be a short, straight endocervical
canal.
Funneling
Funneling of the cervix is dened as the opening of the in-
ternal cervical os on ultrasound. In about 10% of low-risk
women
12
and 25%-33% of high-risk women,
7,15
the internal
os is open in the second trimester (Figs. 2 and 3). The open
portion of the cervix is the funnel length and the internal
diameter is the funnel width. Percent funneling is dened as
funnel length divided by total CL, in which total CL is equal
to the sumof funnel length and functional length. Functional
CL is dened as the portion of endocervical canal that re-
mains closed. Functional CL is the measurement that is typ-
ically used for calculations and predictions of PTB (Figs. 2
and 3).
Funneling of the internal portion of the cervix occurs along
a continuum. A normal closed cervix takes on a T appear-
ance. As the cervix begins to showfunneling, the rst shape it
morphs into is that of a Y. AY shape represents a small funnel,
which if it includes 25% of the cervix, it is not a clinically
signicant nding.
16
Next, the cervical funneling takes the
shape of a V. This represents a more signicant funnel that
extends closer to the external cervical os. Finally, the most
ominous funnel shape is that of a U as this shape is the most
indicative of PTB.
17
Dr Iams has created the following pneu-
monic for the progression TYVU: Trust Your Vaginal Ultra-
sound!
Evaluation of cervical funneling should take place over the
course of at least 5 minutes to resolve any question of mor-
phology of the upper cervical canal. Not only may uterine
segment contractions mimic the appearance of funneling, but
the funneled portion of the cervix may also merge with the
lower uterine segment and distort the image. There is higher
interobserver variability among trained sonographers when
detecting cervical funneling as opposed to when studying
CL.
12
Despite the high interobserver variability, funneling has
been shown to have good predictive accuracy for PTB. In a
study of high-risk women, minimal funneling (25%) be-
tween 14 and 22 weeks was not associated with a signicant
increased risk of PTB. In contrast, moderate (25%-50%) and
severe (50%) funneling were both associated with a 50%
likelihood of PTB.
7
If funneling is present, the CL is typically
25 mm.
12
Compared with a CL of 25 mm alone, CL plus
the presence of funneling will increase the sensitivity of pre-
dicting PTB from 61% to 74%, without changing specicity
and positive and negative predictive values.
14
In addition, the
risk of PTB has been found to be higher in instances in which
both a short CL (25 mm) and funneling is detected, as
opposed to short CL alone.
18
In contrast, if a normal CL of
25 mm is present; the additional nding of funneling does
not increase the risk of PTB.
19
In general, it is most important
to report CL, and we prefer, in most cases, not to report
320 M.T. Mella and V. Berghella
percent funneling even if present, because it does not affect
clinical management. Interventions based on TVU have been
based on a short CL, and not solely on the presence of fun-
neling.
Sludge
Intra-amniotic sludge on ultrasonography appears as a clus-
ter of free-oating hyperechogenic material within the amni-
otic uid near the uterine cervix. Sludge is an independent
risk factor for histologic chorioamnionitis and microbial in-
vasion of the amniotic cavity in women with spontaneous
PTL and intact membranes.
20
Moreover, the presence of
sludge is an independent risk factor for preterm premature
rupture of membranes and spontaneous preterm delivery.
Espinoza et al
21
in a study showed that 71% of women who
were found to have intra-amniotic sludge went into PTL
within 7 days, compared to 16%of women without the pres-
ence of sludge. The combination of sludge and a short
cervix (25 mm) confers a higher risk for spontaneous pre-
term delivery at 28 and 32 weeks than that of a short
cervix alone.
21
However, although intra-amniotic sludge has
been shown to be predictive of PTB, there is insufcient
evidence to assess whether measuring the presence of sludge
alone improves the predictive accuracy that is already pro-
vided by CL.
Three-Dimensional Ultrasound
Three-dimensional ultrasound can be used to assess CL. The
true CL is more easily identied with all 3 planes available. At
times, funneling is only detectable on planes other that the
2-dimensional sagittal plane. Despite these advantages, 3-di-
mensional ultrasound is not necessary in clinical practice to
assess CL.
3
Other Measurements
Many other parameters have been studied in transvaginal
sonographic imaging as factors to predict PTB. Examples in-
clude funnel width, funnel length, endocervical canal dilata-
tion, anterior and posterior cervical width, cervical position
(horizontal vs vertical), lower uterine segment thickness, cer-
vical angle, visibility of chorion at internal os, cervical index
(funnel length 1/functional length), and vascularity.
Among those mentioned, none have proven to be more reli-
able or predictive of PTB than CL.
3,22
Factors Affecting Prediction
TVU CL has been shown to be predictive in all populations
studied (Table 3).
12,15,23-28
One of the most important fea-
tures of this screening test for PTB is its sensitivity. Sensi-
tivity represents the detection ratethe percent of women
who will deliver preterm that are detected during asymp-
tomatic weeks before the PTB by visualizing a short CL on
TVU in the second trimester. This prediction is highly
dependent on several factors:
1. Number of Fetuses. TVUCL is most effective as a predic-
tor of PTB in singleton gestations. In multiple gesta-
tions, most of the women who eventually deliver pre-
termdo not manifest a short CL in the second trimester.
The sensitivity of this test is 50% in multiple gesta-
tions (Table 3).
12,15,23-28
2. Ob-Gyn Risk Factors. TVU CL is most sensitive in sin-
gleton gestations with poor obstetrical history. The
population most studied has been singleton gestations
with previous PTB. In these women, screening with
TVU CL in the second trimester is associated with high
sensitivity, as over two-thirds of women destined to
deliver preterm can be detected early while asymptom-
Table 3 Prediction of PTB by TVU in Different Populations of Pregnant Women
Author N PTB (%)
PTB
Dened
(wks)
GA
Studied
(wks)
CL
Cut-off
(mm) % Abn Sens Spec PPV NPV RR
Asymptomatic
Singleton: low-risk (Cross-sectional)
Iams
13
2915 4.3 < 35 22-25 25 10 37 92 18 97 6.2*
Singleton: prior PTB
Owen
15
183 26 < 35 16-24 25 69 80 55 88 4.5
Singleton: prior cone biopsy
Berghella
23
109 13 < 35 16-24 < 25 28 64 78 30 94 4.7
Singleton: mullerian anomaly
Airoldi
24
64 11 < 35 14-24 < 25 16 71 91 50 96 13.5
Singleton: prior D&E
Visintine
25
131 30 < 35 14-24 < 25 51 53 75 48 78 2.2
Twins
Goldenberg
26
147 32 < 35 22-24 < 25 18 30 88 54 74 3.2
Triplets
Guzman
27
47 34 < 32 15-20 < 25 8.5 25 100 100 72 NA
Symptomatic
Singletons with preterm labor
Venditelli
28
200 41 < 37 19-36 < 30 64 83 88 54 80 2.8
Abbreviations: PTB%, incidence of preterm birth; GA, gestational age; CL, cervical length; % Abn, percent abnormal; Sens, sensitivity; Spec, specicity; PPV,
positive predictive value; NPV, negative predictive value; RR, relative risk compared to those with normal CL, except *(here, comparison is for values above the 75th
percentile); NA, Not Available.
Prediction of preterm birth 321
atic by this test
15
(Table 3; Fig. 3). Sensitivity remains
50% in women with singleton gestations and other
risk factors for PTB, such as previous cone biopsy, Mul-
lerian anomaly, or previous multiple dilation and evac-
uations (D&Es) (Table 3).
23-25
The sensitivity is also
high in singleton gestations with PTL (Table 3).
28
It is
not surprising that interventions aimed at preventing
PTB based on TVU CL screening seems to be most
effective in these populations of singleton gestations
with risk factors for PTB. On the contrary, as the sen-
sitivity is 30% in multiple gestations, TVU CL is an
ineffective screening test for PTB in these popula-
tions.
26,27
In women with singleton gestations, but no particu-
lar risk factors for PTB, the sensitivity of this test is only
37% (Table 3).
12
Therefore, most of these women, who
represent the biggest group of women delivering pre-
term, do not seemto develop TVUCL shortening in the
second trimester. This may be the possible reason for
the ineffectiveness of intervention based on TVU CL
screening so far in this population.
3. CL. The shorter is the CL, the higher is the risk of
delivering preterm (Table 4).
29
Therefore, CL and pre-
dicted gestational age at delivery are directly propor-
tional. A CL of 25 mm represents the 10th and 25th
percentiles of distribution of CL for the general (low-
risk) and prior PTB population of singleton gesta-
tions, respectively. For ease of clinical use, 25 mm has
been chosen as the cut-off at and above which a cervix
can be called normal, and below which it can be
called short. A CL of 25 mm at or before 28 weeks
is always abnormal and associated with a higher inci-
dence of PTB (Table 4).
29
Many women with a CL 16-24 mm, especially
without other risk factors, may not deliver preterm.
Only 1%-2% of the general population of women
carrying an uncomplicated singleton gestation de-
velop a CL 15 mm before 24 weeks.
30
Different
interventions may have different efcacies depend-
ing on the degree of cervical shortening.
4. Gestational Age at CL Measurement. The earlier the short
CL in gestation is detected, the higher is the risk of PTB
(Table 4).
29
A TVU CL 25 mm, especially 28
weeks, may be physiological, as the cervix starts to
prepare for term (37 weeks) many weeks before the
process of labor becomes symptomatic and recogniz-
able clinically. This may be the reason why TVU CL is
uncommon and not generally recommended after 28
weeks.
Gestational age at screening with TVU CL is also de-
pendent on which intervention will be used. For cer-
clage, most trials have been done between 16 and 23
weeks, so that TVU CL should occur in this period if
detection of a short cervix is aimed at offering a
cerclage. In case of progesterone, instead, this inter-
vention may still have a benet if initiated later in the
second or even early in the third trimester. There-
fore, gestational age at TVU CL screening may be
extended until after 24 weeks in the future if, and
when, there will be an effective intervention in case
of a positive test.
Screening for PTB by TVU CL is not very effective
when performed before 14 weeks. CL is not correlated
with maternal height; hence, short women do not
have a shorter CL than tall women.
31
In the rst trimes-
ter, even women at highest risk for PTB usually main-
tain a seemingly closed and long (25 mm) cervix even
on TVU.
13
This is because the endocervical canal is
continuous with the lower uterine segment, which is
falsely counted in the CL.
5. FFN Status. There have been several reports on the
interaction of TVU CL and FFN.
32-34
Although their
prediction overlaps slightly, most studies do report
that having both tests yield positive result does in-
crease the risk of PTB over having only one positive
test result. Unfortunately, no interventions that pre-
Table 4 Predicted Probability of Preterm Delivery Before Week 35, by Cervical Length (mm) and Time of Measurement (Week
of Pregnancy)
29
Weeks of Pregnancy
15 16 17 18 19 20 21 22 23 24 25 26 27 28
Cervical length (mm)
0 69.8 68.7 67.5 66.3 65.2 64.0 62.7 61.5 60.2 59.0 57.7 56.4 55.1 53.8
5 62.5 61.3 60.0 58.7 57.5 56.2 54.9 53.6 52.2 50.9 49.6 48.3 47.0 45.7
10 54.6 53.3 52.0 50.7 49.4 48.1 46.7 45.4 44.1 42.8 41.6 40.3 39.0 37.8
15 46.5 45.2 43.9 42.6 41.3 40.1 38.8 37.6 36.3 35.1 33.9 32.8 31.6 30.5
20 38.6 37.3 36.1 34.9 33.7 32.5 31.4 30.3 29.2 28.1 27.0 26.0 25.0 24.0
25 31.2 30.1 29.0 27.9 26.9 25.8 24.8 23.9 22.9 22.0 21.1 20.3 19.4 18.6
30 24.7 23.7 22.8 21.8 21.0 20.1 19.3 18.5 17.7 16.9 16.2 15.5 14.8 14.2
35 19.1 18.3 17.5 16.8 16.1 15.4 14.7 14.1 13.4 12.8 12.2 11.7 11.2 10.6
40 14.6 13.9 13.3 12.7 12.1 11.6 11.1 10.6 10.1 9.6 9.2 8.7 8.3 7.9
45 11.0 10.5 10.0 9.6 9.1 8.7 8.3 7.9 7.5 7.2 6.8 6.5 6.2 5.9
50 8.2 7.8 7.4 7.1 6.7 6.4 6.1 5.8 5.5 5.2 5.0 4.7 4.5 4.3
55 6.0 5.7 5.5 5.2 4.9 4.7 4.5 4.3 4.0 3.8 3.7 3.5 3.3 3.1
60 4.4 4.2 4.0 3.8 3.6 3.4 3.3 3.1 3.0 2.8 2.7 2.5 2.4 2.3
322 M.T. Mella and V. Berghella
vent PTB just based on a positive FFN have been yet
discovered. Therefore, FFN is not currently recom-
mended for asymptomatic women. We predict that
quantitative FFN screening will improve the effective-
ness of this screening test, especially when done before
24 weeks.
The combination and TVU CL and FFN for the as-
sessment of risk of PTB of the symptomatic woman
with PTL has been well studied, and it seems clinically
benecial. In fact, the woman in PTL between 24 and
34 weeks with a CL 30 mm has a 2% incidence of
delivering within 7 days, and 10% chance of deliver-
ing 35 weeks, and can be managed without special
interventions. A similar woman but one with a CL 20
mm has a very high risk of PTB, and deserves admis-
sion, steroids for fetal maturity, and tocolysis for 48
hours to ensure that a full steroid course is adminis-
tered. It is less clear what to do with the woman with
PTL and a TVU CL 20-29 mm, or borderline. In these
cases, we suggest that the FFN previously collected
should be sent. Women with positive FFN should be
managed similar to those with a CL 20 mm, while
those with a negative FFN can probably be observed
without intervention.
35
6. Presence of Contractions. Most asymptomatic women with
a short CL on TVU in the second trimester are having
uterine contractions that they are not aware of.
36
There-
fore, we recommend that anytime a short CL is detected
before 28 weeks, the woman is sent to labor and delivery
for tocomonitoring. Women with a CL 25 mm and
contractions have twice the incidence of PTB than similar
women with a CL 25 mm but no contractions on the
monitor.
37
These characteristics lend support to the pos-
sible use of a tocolytic agent to attempt to prevent PTB in
these women. Indomethacin has been proposed as such
an intervention.
38
7. Presence of Infection. Infection is indirectly correlated
with CL: the shorter is the CL, the higher is the inci-
dence of intra-amniotic infection. Amniocentesis of
women with singleton gestations, a poor obstetrical
history and a TVUCL 25 mmin the second trimester
has revealed that the incidence of intra-amniotic infec-
tion in these women is about 1%-2%.
18
Therefore, it is
probably not indicated to routinely perform an amnio-
centesis on asymptomatic women with a short cervix.
In women who have regular contractions, this inci-
dence may increase to 5%-10%. Incidence of intra-amni-
otic infection is much increased if there are cervical
changes that can be detected by physical examina-
tion. After detection of short CL, manual examination
of the cervix is closed and long in about three-quarters
of women. In women who instead have visual (by
speculum examination) or manually detected dilata-
tion of the cervix, the incidence of intra-amniotic infec-
tion is much higher, up to 50%if the cervix is dilated by
2 cm. Bulging of membranes past the external os is
also associated with a high rate of infection and of PTB.
The presence of bacterial vaginosis further increases
the risk of PTB in women with a short cervix. Unfortu-
nately, there are no studies that evaluate whether an
intervention (eg, antibiotics) does decrease PTB in this
scenario. There are also no studies on any association
between other infections that contribute to PTB (eg,
Chlamydia, gonorrhea, etc.) and TVU CL.
Causes of Short Cervical Length
It is unclear what exactly causes PTB, and so it is unclear
what causes a shortening of CL in the second trimester. As
we have seen, contractions can shorten the cervix. The con-
trary is probably also true, that is, a short CL can eventually
be associated with contractions. The 2 probably have a com-
mon etiology in most cases. A short CL is associated with
intrauterine infection. Once again, it is unclear whether rst
bacteria weaken and shorten the cervix, or it is cervical
shortening that allows the vaginal ora to invade and infect
the originally sterile uterus. Both these mechanisms can oc-
cur, and create a catch 22 phenomenon.
Women with multiple D&Es often develop a short cervix
in the second trimester. To us, these are the women in whom
a cervical-insufciency mechanismcausing the short cervix is
most evident. On the contrary, in twins the cervix shortens
only at the very end, just before clinical signs, and not be-
cause of an abnormal cervix, but because of excessive pres-
sure from the quickly enlarging uterus above.
We encourage further research in the many yet unknown
mechanisms responsible for the development of a short CL in
the second trimester.
Conclusions
CL measurement by TVUin the second trimester is one of the
most effective screening methods for the prediction of PTB.
To achieve adequate prediction, proper technique of TVUCL
measurement should be followed (Table 1),
3
with particular
precautions (Table 2). CL is the most predictive of the nd-
ings on the cervix at TVU. Prediction of PTB varies widely
depending on several factors, particularly the population
studied (Table 3).
12,15,23-28
Its sensitivity is highest in asymp-
tomatic singleton gestations with risk factors for PTB (previ-
ous PTB, cone biopsy, Mullerian anomalies, and greater than
or equal to D&Es), and in symptomatic singleton gestations
with PTL. In all populations, the shorter is the CL, and the
earlier it is detected in pregnancy, the higher is the incidence
of PTB (Table 4).
29
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