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ORIGINAL CONTRIBUTION
Mid-Trimester Endovaginal Sonography
in Women at High Risk
for Spontaneous Preterm Birth
John Owen, MD
Nicole Yost, MD
Vincenzo Berghella, MD
Elizabeth Thom, PhD
Melissa Swain, RN
Gary A. Dildy III, MD
Menachem Miodovnik, MD
Oded Langer, MD
Baha Sibai, MD
Donald McNellis, MD
for the National Institute of Child
Health and Human Development,
Maternal-Fetal Medicine
Units Network
P
RETERM BIRTH IS THE MOST IM-
portant cause of infant morbid-
ity and mortality and compli-
cates 11% of all pregnancies in
the United States.
1
Most (80%) of these
births result from either spontaneous la-
bor or membrane rupture.
2
Since the de-
velopment of neonatal intensive care
units, most neonatal deaths associated
with prematurity occur in infants born
at less than 32 weeks’ gestation, but sig-
nificant morbidities including sepsis,
respiratory distress, and necrotizing
enterocolitis do not abate until 35 weeks’
gestation, after which neonatal out-
comes are generally good.
3,4
To date, a
prior preterm birth is one of the stron-
gest and most consistent predictors of
prematurity, and the risk of recurrence
is inversely proportional to the gesta-
tional age of the prior delivery.
5,6
Endovaginal ultrasound is a reli-
able technology for imaging the cer-
vix and lower uterine segment during
pregnancy.
7,8
While there is ample evi-
dence that a shortened cervical length
is associated with preterm birth,
9-18
it
Author Affiliations are listed at the end of this article.
Members of the Maternal-Fetal Medicine Units Net-
work are listed at the end of this article.
Corresponding Author and Reprints: John Owen, MD,
Department of Obstetrics and Gynecology, Univer-
sity of Alabama at Birmingham, 61919th St S, OHB
458, Birmingham, AL 35249-7333 (e-mail: johnowen
@uab.edu).
Context Although shortened cervical length has been consistently associated with
spontaneous preterm birth, it is not known when in gestation this risk factor becomes
apparent.
Objective To determine whether sonographic cervical findings between 16 weeks’
and 18 weeks 6 days’ gestation predict spontaneous preterm birth and whether serial
evaluations up to 23 weeks 6 days’ gestation improve prediction in high-risk women.
Design, Setting, and Participants Blinded observational study performed be-
tween March 1997 and November 1999 at 9 university-affiliated medical centers in
the United States in 183 women with singleton gestations who previously had expe-
rienced a spontaneous birth before 32 weeks’ gestation.
Observation Certified sonologists performed 590 endovaginal sonographic exami-
nations at 2-week intervals. Cervical length was measured from the external os to the
functional internal os along a closed endocervical canal. Funneling and dynamic cer-
vical shortening were also recorded.
Main Outcome Measure Spontaneous preterm birth before 35 weeks’ gestation,
analyzed by selected cutoff values of cervical length.
Results Forty-eight women (26%) experienced spontaneous preterm birth before
35 weeks’ gestation. A cervical length of less than 25 mm at the initial sonographic
examination was associated with a relative risk (RR) for spontaneous preterm birth of
3.3 (95% confidence interval [CI], 2.1-5.0; sensitivity=19%; specificity=98%; posi-
tive predictive value=75%). After controlling for cervical length, neither funneling (P=.24)
nor dynamic shortening (P=.054) were significant independent predictors of sponta-
neous preterm birth. However, using the shortest ever observed cervical length on se-
rial evaluations, after any dynamic shortening, the RR of a cervical length of less than
25 mm for spontaneous preterm birth increased to 4.5 (95% CI, 2.7-7.6; sensitiv-
ity=69%; specificity=80%; positive predictive value=55%). Compared with a single
cervical measurement at 16 weeks’ to 18 weeks 6 days’ gestation, serial measure-
ments at up to 23 weeks 6 days significantly improved the prediction of spontaneous
preterm birth in a receiver operating characteristic curve analysis (P=.03).
Conclusions Cervical length assessed by endovaginal sonography between 16 weeks’
and 18 weeks 6 days’ gestation, augmented by serial evaluations, predicts spontane-
ous preterm birth before 35 weeks’ gestation in high-risk women.
JAMA. 2001;286:1340-1348 www.jama.com
1340 JAMA, September 19, 2001—Vol 286, No. 11 (Reprinted) ©2001 American Medical Association. All rights reserved.
at Medical Library of the PLA, on August 12, 2007 www.jama.comDownloaded from
is not known when this risk factor be-
comes apparent in pregnancy or
whether the adverse cervical ultra-
sound findings develop over time.
Moreover, most of the current data link-
ing cervical length to subsequent pre-
term birth have been collected beyond
20 weeks’ gestation.
9-11,14,15
Impor-
tantly, most of the available data have
been collected either in unselected, low-
risk populations
11,13,14,18
or without phy-
sician masking, which means interven-
tions were applied on the basis of the
sonographic findings without a con-
trol group for comparison,
14,15,17,18
thus
rendering the predictive value of the
cervical sonographic findings uncer-
tain. The importance of longitudinal
observations and the natural history of
cervical characteristics in the mid-
trimester have also not been well de-
fined.
12,17-19
Our objective was to determine
whether cervical characteristics visual-
ized with endovaginal sonography as
early as 16 weeks’ through 18 weeks 6
days’ gestation or longitudinally up to 23
weeks 6 days’ gestation would predict
spontaneous preterm birth in women
with a previous spontaneous preterm
birth before 32 weeks’ gestation. From
the standpoint of efficacy and other bio-
logical considerations, certain interven-
tions (cerclage) might be more effective
if applied early in gestation (ie, before 24
weeks). We hypothesized that endovagi-
nal sonography could identify women
whose cervical anatomy would make
them candidates for future mid-
trimester clinical intervention trials of
preterm birth prevention.
METHODS
This study was performed at 9 univer-
sity-affiliated centers, all members of the
National Institute of Child Health and
Development, Maternal-Fetal Medi-
cine Units Network, between March
1997 and November 1999. Women
with singleton pregnancies who had ex-
perienced at least 1 prior spontaneous
preterm birth before 32 weeks’ gesta-
tion were eligible; funding was not
available to study a concurrent, low-
risk control population. If obstetric
records were not available, a history
consistent with spontaneous preterm
birth (preterm labor or membrane rup-
ture) and a birth weight of less than
1500 g were deemed satisfactory crite-
ria. Women with chronic medical or ob-
stetric problems that might result in an
indicated preterm birth (eg, hyperten-
sion, red blood cell isoimmuniza-
tion), a history of substance abuse, or
uterine anomalies were ineligible.
Women who received a cerclage be-
cause of a clinical history of cervical in-
competence were also excluded. The in-
stitutional review board at each center
approved the study and potential par-
ticipants who gave written, informed
consent could be enrolled as long as
their first endovaginal sonogram would
be performed between 16 weeks’ and
18 weeks 6 days’ gestation.
Gestational age was determined by
comparing a certain last menstrual pe-
riod (if available) with a sonographic
evaluation at or before 18 weeks’ ges-
tation. Concordance between the bio-
metric parameters and the menstrual
date of 7 days or less confirmed the last
menstrual period; otherwise, the bio-
metric data were used. After the initial
endovaginal sonographic evaluation, bi-
weekly visits were scheduled to end no
later than 23 weeks 6 days’ gestation
with a maximum of 4 sonograms per
patient.
Techniques
All sonograms were performed by phy-
sicians, ultrasound technologists, or re-
search nurses who received uniform
training and certification before patient
enrollment. Each sonologist reviewed a
training videotape of 8 complete mid-
trimester endovaginal sonograms that
demonstrated all the required measure-
ments and subjective assessments. The
videotape was accompanied with a de-
tailed written description of each exami-
nation. Each sonologist independently
performed 10 endovaginal examina-
tions on unselected patients in the mid-
trimester. The primary investigator cri-
tiqued the videotapes and accompanying
data sheets to identify deficiencies. When
necessary, the sonologist was asked to
submit additional taped examinations
and data sheets demonstrating correc-
tion of any previously identified defi-
ciencies. From the videotaped examina-
tions, the primary investigator also
approved the ultrasound unit(s) at each
center.
Each sonographic examination was
performed according to a defined pro-
tocol: patients were asked to empty their
bladder and then placed in a dorsal li-
thotomy position. The endovaginal probe
covered by a sterile, lubricated condom
was inserted and advanced along the
vaginal canal until an adequate sagittal
image of the cervix could be visualized.
The probe was withdrawn slowly until
the image blurred and then the inser-
tion pressure was increased only enough
to restore an adequate image.
11,20
An ad-
equate image for the measurement of cer-
vical length was defined as the visual-
ization of the internal os, external os, and
endocervical canal.
20
Cervical length was measured with
electronic calipers as the linear dis-
tance between the external os and the
functional internal os along a closed en-
docervical canal (F
IGURE 1). How-
ever, if the endocervical canal ap-
peared to be curved, cervical length was
also assessed as the sum of the lengths
of 2 contiguous linear segments, placed
Figure 1. Sagittal View of Anatomic
Landmarks for Endovaginal Sonography of
the Cervix
Functional
Internal Os
Bladder
Bladder
Reflection
SAGITTAL VIEW
Amniotic Cavity
Cervix
External Os
A
B
Transducer
Cervical length (A) is measured from the external os
to the internal os or to the functional internal os when
funneling (B) is present. The sweep of the ultrasound
transducer is indicated by the highlighted area.
MID-TRIMESTER ENDOVAGINAL SONOGRAPHY
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along the endocervical canal, connect-
ing the external os and functional in-
ternal os. If the maximum deflection of
canal curvature (defined as the dis-
tance between a line connecting the
internal os and external os and the
maximum excursion of the 2 linear
components) was at least 5 mm, the re-
corded cervical length measurement
was the sum of the 2 linear segments
(F
IGURE 2A); otherwise, the single lin-
ear distance measurement was re-
corded (Figure 2B).
Cervical length measurements were
performed 3 times. The sonologist as-
sessed the overall quality of the 3 im-
ages and recorded the cervical length
associated with the image that in his/
her opinion was associated with the
subjectively best image. However, if the
cervical length differed on images of
similar overall quality, the shortest ob-
served cervical length was recorded.
11
If a normal-appearing internal os could
not be recognized, the image was fur-
ther assessed for either funneling or a
poorly developed lower uterine seg-
ment. Funneling required prolapse of
the membranes through a dilated en-
docervical canal to the level of the func-
tional internal os. Funnel depth was
measured from the functional internal
os to its “shoulder,” visible more cepha-
lad toward the lower uterine segment
(Figures 1 and 2B). To be character-
ized as a funnel, the measured depth
had to be at least 5 mm.
A poorly developed lower uterine seg-
ment precluded a cervical length mea-
surement because the internal os could
not be visualized as a discrete struc-
ture. This subjective diagnosis was char-
acterized by the presence of an unusu-
ally long cervix (generally .50 mm),
an s-shaped endocervical canal, an in-
creased distance between the bladder
reflection and the amniotic cavity, 2 dif-
ferent echogenic areas in the cervix, and
an apparent internal os located appre-
ciably cephalad to the inferior edge of
the bladder reflection. For analyses of
cervical length as a continuous vari-
able, cases of poorly developed lower
segments were arbitrarily assigned a cer-
vical length of 62 mm, which was 1 mm
greater than the longest measured cer-
vical length (61 mm).
After baseline assessments were per-
formed, fundal pressure was applied for
15 seconds along the axis of the canal
by the sonologist
21
who maintained the
standard sagittal view of the cervix to de-
tect any fundal pressure–induced dy-
namic changes in the cervix. If the cer-
vix appeared to shorten, a funnel
developed (or increased in size), or if a
poorly developed lower uterine seg-
ment resolved as a result of the fundal
pressure, repeat measurements were ob-
tained. Sonograms lasted a minimum of
5 minutes to detect spontaneously oc-
curring dynamic changes, which also
prompted repeat measurements. Exami-
nations were videotaped for quality as-
surance.
According to the study protocol, the
results of each scan were not made
available to the patient’s managing phy-
sicians, except in cases of complete pla-
centa previa (placental tissue visual-
ized extending .1 cm on both sides of
the internal os) or fetal death. The rea-
son for any notification was recorded.
As part of continuing quality assur-
ance, a sample of the videotaped ex-
aminations was selected from each par-
ticipating center proportional to its
enrollment. The videotapes and data
sheets were reviewed by the primary in-
vestigator in conjunction with an-
other subcommittee member blinded to
the pregnancy outcome. If any mea-
surements or subjective assessments
were deemed incorrect, the respon-
sible sonologist and study coordina-
tor were notified and asked to reexam-
Figure 2. Sagittal Views of Endovaginal Sonograms of the Cervix at 18 Weeks’ Gestation
Bladder Reflection
Bladder Reflection
Amniotic
Fluid
Functional
Internal Os
Functional
Internal Os
External Os
Bladder Reflection
Amniotic
Fluid
Internal Os
External Os
Normal-Appearing Cervix Cervix With Funneling
B
Fetus
Fetus
A
A, Normal-appearing cervix, note cervical length of 40 mm (the sum of the 2 linear segments, 28 mm and 12 mm) as the maximum canal deflection is 6 mm. Inferior
extent of bladder reflection is approximately at the same level as the internal os. B, Cervix with funneling at the internal os, cervical length measured from external os
to functional internal os is approximately 23 mm. Note asymmetric anterior and posterior “shoulders” cephalad to the internal os. Electronic calipers mark the endo-
cervical canal. Tick marks visible along the top of both images represent a 1-cm scale.
MID-TRIMESTER ENDOVAGINAL SONOGRAPHY
1342 JAMA, September 19, 2001—Vol 286, No. 11 (Reprinted) ©2001 American Medical Association. All rights reserved.
at Medical Library of the PLA, on August 12, 2007 www.jama.comDownloaded from
ine the videotape and make appropriate
corrections. Initially, examinations were
chosen at random. However, with in-
creasing experience we also devel-
oped criteria for selected reviews that
included all cases of funneling, cervi-
cal lengths less than 20 mm or greater
than 50 mm, poorly developed lower
uterine segments, spontaneous or fun-
dal pressure–induced dynamic changes,
and cases in which the physician was
notified.
Data Analysis
The primary outcome criterion for this
study was a spontaneous preterm birth
before 35 weeks’ gestation, defined as a
birth that resulted directly from either
preterm labor or spontaneous mem-
brane rupture before the onset of la-
bor. Deliveries effected for maternal or
fetal reasons were coded as indicated. As
part of the study design, we performed
a sample size calculation based on the
following assumptions. Since appropri-
ate mid-trimester sonographic pilot data
were unavailable, sample size was based
on data from the Preterm Prediction
Study,
11
which collected endovaginal
sonographic data at both 24 weeks’ and
28 weeks’ gestation. We assumed the fol-
lowing: spontaneous preterm birth rate
before 35 weeks for high-risk women
with a cervical length of 25 mm or
greater would be 10%; a cervical length
less than 25 mm would occur in 20% of
women; and the incidence of spontane-
ous preterm birth before 35 weeks would
be 30%. Considering also a desired ef-
fect size of a relative risk (RR) of 3.0 for
spontaneous preterm birth before 35
weeks (based on the presence or ab-
sence of a cervical length of ,25 mm,
2-tailed a =.05, b =.20), 170 patients
would have to be studied.
Data were analyzed using SAS ver-
sion 7.0 (SAS Institute Inc, Cary, NC).
Categorical variables were compared
using x
2
or the Fisher exact test, and
continuous data were compared with
the Wilcoxon rank sum test. Logistic
regression was used to model the rela-
tionship between cervical length and
spontaneous preterm birth control-
ling for funneling, recognition of
dynamic shortening, and the slope of
cervical length over time on serial evalu-
ations (as derived from linear regres-
sion models). Receiver operating char-
acteristic curves were used to compare
the performance of varying cervical
length cutoffs for the prediction of spon-
taneous preterm birth before 35 weeks.
Statistical significance was repre-
sented at P,.05.
Since serial examinations were per-
formed, we also compared spontane-
ous preterm birth either with cervical
length at the initial examination or the
shortest cervical length observed at any
examination. Similarly, we analyzed
cervical length before and after any dy-
namic shortening occurred. Thus, for
any given patient, up to 4 different cer-
vical lengths could be analyzed: (1) the
length at the initial evaluation before
dynamic shortening; (2) the initial
length after dynamic shortening and
considering the serial evaluations; (3)
the shortest observed length before
dynamic changes; and (4) the shortest
observed length after dynamic short-
ening.
RESULTS
From all the participating centers, 236
women were initially thought to be eli-
gible for this study based on their stated
obstetric history. A total of 24 patients
were found to be ineligible on review
of their records. An additional 19 pa-
tients declined to participate, plus 6
more patients verbally agreed to par-
ticipate but did not keep their first sono-
gram appointment and therefore were
not enrolled. We did not collect out-
come data on these 25 women who
were eligible but not enrolled. From the
original enrollment of 187, 4 patients
were excluded because they were lost
to follow-up.
A total of 590 endovaginal sono-
graphic examinations were performed
on our study population of 183 women
between March 1997 and July 1999.
The median duration of the sono-
graphic examinations was 5.3 min-
utes (range, 4-18 minutes) and the me-
dian number of scans per patient was
3 (range, 1-4). Nine of the 183 women
underwent a single sonographic evalu-
ation. Of these 9, 3 delivered within 2
weeks of their first scan, before their
next scheduled study visit. Of the 590
sonographic evaluations, 576 (98%)
were videotaped according to proto-
col, and 466 (79%) of the taped exami-
nations were later reviewed. After study
inception, 4 women received a cer-
clage by their managing physicians. The
183 women in the study had a mean
maternal age of 26 years (SD, 5 years);
119 (65%) were African American, 26
(14%) were white, and 38 (21%) were
Hispanic. The earliest prior delivery oc-
curred at a mean of 24 weeks’ (SD, 4.8
weeks’) gestation; 135 had a single prior
preterm birth, 37 had 2 prior preterm
births, and 10 had more than 2 prior
preterm births. On review, we deter-
mined that 1 patient had not experi-
enced a prior spontaneous preterm birth
before 32 weeks but, rather, had expe-
rienced an indicated preterm birth.
The mean gestational age at deliv-
ery was 35.2 weeks (SD, 6.3 weeks). A
total of 48 (26%) women experienced
a spontaneous preterm birth before 35
weeks; 35 (19%) before 32 weeks; 29
(16%) before 28 weeks; and 20 (11%)
before 24 weeks. An additional 5
women underwent an indicated pre-
term delivery at 31 weeks’ to 34 weeks’
gestation for obstetric complications. Of
the 48 spontaneous births before 35
weeks, 34 (71%) were associated with
preterm labor and 14 (29%) were as-
sociated with preterm membrane
rupture.
Initial Sonographic Evaluation
A total of 29 women (16%) had a poorly
developed lower uterine segment
throughout their entire initial evalua-
tion. Since these women had been ar-
bitrarily assigned a cervical length of 62
mm, the median baseline cervical length
at the first scan was 37 mm (range, 0-62
mm); the 10th percentile was 26 mm
and the 5th percentile was 23 mm. The
relationship between cervical length at
the initial evaluation and spontaneous
preterm birth before 35 weeks was
modeled with logistic regression.
Women with shorter cervical lengths
MID-TRIMESTER ENDOVAGINAL SONOGRAPHY
©2001 American Medical Association. All rights reserved. (Reprinted) JAMA, September 19, 2001—Vol 286, No. 11 1343
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had correspondingly higher rates of
spontaneous preterm birth before 35
weeks (P,.001). From the regression
model, we determined that the odds of
spontaneous preterm birth before 35
weeks decreased by 24% for each 5-mm
increase in baseline cervical length. We
then examined various cervical length
cutoffs for their predictive accuracy
(T
ABLE 1).
Since we had arbitrarily assigned a
numeric cervical length value to women
with a poorly developed lower uterine
segment, we evaluated separately the
predictive value of this finding. Of the
29 women with a poorly developed
lower uterine segment throughout their
initial evaluation, only 3 (10%) expe-
rienced a spontaneous preterm birth be-
fore 35 weeks compared with a 29% rate
if the lower uterine segment was not
poorly developed (P =.03).
In 9 cases, the sonologist notified the
managing physicians after the sono-
gram had been performed. A total of 5
of these 9 cases were suspected pla-
centa previa and were reported accord-
ing to study protocol. However, in the
other 4 cases, the protocol was not fol-
lowed. Three were due to specific cer-
vical findings (cervical bending, fun-
neling, and internal os dilation) and in
1 case, the physician requested that the
cervical length measurement be un-
masked. Considering the potential for
bias associated with physician notifi-
cation and the 1 patient who had not
previously experienced a prior spon-
taneous preterm delivery, we deter-
mined the effect of omitting these 10
women from the analysis of the initial
sonographic evaluation. The RR for cer-
vical length less than 25 mm and spon-
taneous preterm birth before 35 weeks
increased slightly from 3.3 to 3.6.
Funneling
Funneling was noted in 16 patients (9%)
at their initial evaluation. These women
were significantly more likely to have
a spontaneous preterm birth before 35
weeks (56% vs 23%; P =.004). How-
ever, women with an observed funnel
also had a significantly shorter cervi-
cal length (median, 26 mm vs 38 mm
if no funnel was observed; P,.001).
Because cervical length was such a
strong predictor of spontaneous pre-
term birth before 35 weeks, we also
evaluated the finding of a funnel as a
potential independent predictor. The
presence of a funnel was not a signifi-
cant independent predictor, control-
ling for cervical length in a logistic
regression model (P =.24). We also
included either the presence of funnel-
ing or a cervical length cutoff of less than
25 mm in a contingency table with
spontaneous preterm birth before 35
weeks and observed a lower RR of 2.7
(95% confidence interval [CI], 1.7-
4.3) and a lower positive predictive
value of 59% than when we used an iso-
lated cervical length cutoff of less than
25 mm (Table 1).
Dynamic Changes
During their first sonographic evalua-
tion, 16 (9%) of 183 women had ob-
served dynamic changes. A total of 9 fol-
lowed fundal pressure and 7 were
spontaneous. The cervical lengths of
these 16 women shortened from a mean
of 49 mm (median, 62 mm) to a mean
of 30 mm (median, 25 mm); 2 of these
women also developed a funnel. In 6
cases, the initially observed, poorly de-
veloped lower uterine segment re-
solved. Similar to our analysis of fun-
neling, we included dynamic changes in
a logistic regression model with cervi-
cal length and observed a trend toward
dynamic changes as a significant inde-
pendent predictor of spontaneous pre-
term birth before 35 weeks (P =.054).
We also considered dynamic changes in
a contingency table with a cervical length
cutoff of less than 25 mm and sponta-
neous preterm birth before 35 weeks. As
with funneling, the inclusion of dy-
namic changes at the initial evaluation
did not improve the predictive accu-
racy of a cervical length cutoff of less
than 25 mm (RR, 2.4; 95% CI, 1.5-3.8;
positive predictive value, 52%).
Serial Evaluations
Serial evaluations demonstrated that
cervical length shortened from a me-
dian of 37 mm at the first scan to a me-
dian of 32 mm at the fourth scan. For
each of the 174 women with at least 2
sonographic evaluations, we com-
puted the rate of change of cervical
length by fitting a linear regression line
to their observed cervical length mea-
surements. The median rate of short-
ening in this group was 1.1 mm per
week. Removing the 41 women who
had a poorly developed lower uterine
segment and therefore an assigned cer-
vical length of 62 mm at any time dur-
ing their initial and serial evaluations,
we observed a median cervical length
shortening of 0.9 mm per week. The 44
women who experienced a spontane-
ous preterm birth before 35 weeks
shortened their cervixes at a median rate
of 2.5 mm per week compared with a
rate of 1.0 mm per week in the 130
women who did not (P =.03).
To determine the effect of serial ob-
servations on the predictive accuracy
of endovaginal sonography, we first in-
cluded the shortest observed cervical
length for each patient in a logistic re-
Table 1. Summary Predictive Values and Relative Risks (RRs) of Spontaneous Preterm Birth Before 35 Weeks by the Initial Cervical Length
at 16 Weeks’ to 18 Weeks 6 Days’ Gestation and Selected Cervical Length Cutoff Values
*
Cervical Length
Cutoff, mm
Below
Cutoff, No. Sensitivity, % Specificity, %
Positive
Predictive Value, %
Negative
Predictive Value, % RR (95% CI)
,15 5 10 100 100 76 4.1 (3.2-5.4)
,20 6 10 99 83 76 3.4 (2.2-5.3)
,25 12 19 98 75 77 3.3 (2.1-5.0)
,30 36 38 87 50 80 2.5 (1.6-3.9)
*
CI indicates confidence interval.
MID-TRIMESTER ENDOVAGINAL SONOGRAPHY
1344 JAMA, September 19, 2001—Vol 286, No. 11 (Reprinted) ©2001 American Medical Association. All rights reserved.
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gression model with spontaneous pre-
term birth before 35 weeks as the de-
pendent variable. In this analysis, the
shortest ever observed cervical length
before dynamic changes was a signifi-
cantly better predictor than the base-
line cervical length at the first scan. We
further analyzed the information from
serial evaluations by including the slope
of the derived regression line of cervi-
cal length over time before dynamic
changes in a logistic regression model,
alone, and also with the cervical length
at the first evaluation. The slope of
length over time was not a significant
predictor of spontaneous preterm birth
before 35 weeks (P=.07). However, af-
ter controlling for initial baseline length,
the slope became a statistically signifi-
cant predictor in the regression model
(P =.002).
Since previous reports examined the
relationship between static cervical
length measured beyond 20 weeks’ ges-
tation and spontaneous preterm birth,
we performed a secondary analysis of all
sonographic evaluations performed at or
beyond 21 weeks’ gestation prior to any
dynamic changes. If a patient had un-
dergone 2 studies during this gesta-
tional period, the former was preferen-
tially selected. In this subgroup of 142
women, the RR of a cervical length less
than 25 mm and spontaneous preterm
birth before 35 weeks was 3.5 (95% CI,
1.9-6.5). The associated sensitivity and
specificity were 46% and 87%, respec-
tively.
Finally, we examined the clinical util-
ity of the shortest observed cervical
length not considering dynamic changes
on serial scans, using a cutoff of less than
25 mm for the prediction of spontane-
ous preterm birth before 35 weeks
(TABLE 2). Since cervical lengths tended
to shorten over time, more than 4 times
as many women (n=53 vs n=12) were
found to have a cervical length of less
than 25 mm during the study.
Dynamic Changes
and Serial Evaluations
We considered the additional effect of
spontaneous or fundal pressure–
induced dynamic changes that were ob-
served on serial examinations. We in-
cluded the shortest observed cervical
length after any dynamic changes oc-
curred in a logistic regression model
with spontaneous preterm birth be-
fore 35 weeks as the dependent vari-
able and found that it was a signifi-
cantly better predictor than the shortest
observed cervical length at any scan
prior to dynamic changes. From the re-
gression model, we determined that the
odds of spontaneous preterm birth be-
fore 35 weeks decreased by 43% for
each 5-mm increase in the shortest ob-
served cervical length after dynamic
changes.
Considering these dynamic changes,
the median rate of shortening re-
mained 1.1 mm per week and 0.9 mm
per week after removing the 41 women
who had a poorly developed lower uter-
ine segment. We also analyzed cervi-
cal length over time after dynamic
changes using logistic regression. In this
case, the slope was a significant pre-
dictor of spontaneous preterm birth be-
fore 35 weeks by itself (P,.001) and
also after controlling for initial base-
line cervical length (P,.001). These
analyses confirmed that the inclusion
of dynamic changes (ie, shortening) ob-
served on serial evaluations signifi-
cantly improved the predictive accu-
racy of endovaginal sonography for a
spontaneous preterm birth.
We then examined the summary pre-
dictive values of postdynamic change–
cervical length measurements at a cut-
off of less than 25 mm (n=60) for the
prediction of spontaneous preterm birth
before 35 weeks. Table 2 contains the
summary predictive values for a cervi-
cal length cutoff of less than 25 mm at
the baseline scan, the shortest ob-
served cervical length on serial scans be-
fore any dynamic changes, and the short-
est observed cervical length considering
dynamic changes from the serial endo-
vaginal sonographic evaluations.
F
IGURE 3 depicts the receiver oper-
ating characteristic curves of the base-
line cervical length at 16 to 18 weeks’
gestation prior to dynamic changes and
the shortest observed cervical length ob-
served on serial evaluations after dy-
namic changes. The latter measure-
ment represented a statistically
significant improvement over the
former with regard to the use of cervi-
cal length as a screening test for the pre-
diction of spontaneous preterm birth
before 35 weeks (P =.03).
COMMENT
We performed a prospective, blinded
observational study to determine if en-
dovaginal sonography of the cervix at
16 weeks’ to 23 weeks 6 days’ gesta-
tion would predict spontaneous pre-
term birth with sufficient accuracy to
justify mid-trimester intervention tri-
als in high-risk women. As a single mea-
surement, cervical length of less than
25 mm at 16 to 18 weeks’ gestation was
a significant predictor of spontaneous
preterm birth before 35 weeks, and the
inclusion of dynamic shortening and se-
Table 2. Summary Predictive Values and Relative Risks (RRs) of Spontaneous Preterm Birth Before 35 Weeks by Cervical Length of Less Than
25 mm at 16 Weeks’ to 18 Weeks 6 Days’ Gestation and Also Considering the Effect of Serial Sonographic Evaluations and Dynamic Changes
Up to 23 Weeks 6 Days’ Gestation
*
Cervical Length ,25 mm Sensitivity, % Specificity, %
Positive
Predictive Value, %
Negative
Predictive Value, % RR (95% CI)
First sonogram before dynamic changes 19 98 75 77 3.3 (2.1-5.0)
Shortest observed up to 23 weeks 6 days’ gestation
before dynamic changes
58 81 53 85 3.4 (2.1-5.5)
Shortest observed up to 23 weeks 6 days’ gestation
after dynamic changes
69 80 55 88 4.5 (2.7-7.6)
*
CI indicates confidence interval.
MID-TRIMESTER ENDOVAGINAL SONOGRAPHY
©2001 American Medical Association. All rights reserved. (Reprinted) JAMA, September 19, 2001—Vol 286, No. 11 1345
at Medical Library of the PLA, on August 12, 2007 www.jama.comDownloaded from
rial observations of cervical length im-
proved the predictive values. We con-
clude that the natural history of cervical
anatomy during midpregnancy can con-
tribute significant information as to the
risk of subsequent spontaneous pre-
term birth.
We had previously recognized that in
approximately 10% of mid-trimester en-
dovaginal sonograms, the cervical
anatomy appeared atypical and, in par-
ticular, a normal-appearing internal os
could not be readily identified. This led
to our characterization of a poorly de-
veloped lower uterine segment, which
in some cases resolved into a measur-
able cervix. If resolution occurred dur-
ing the sonogram, this represented a dy-
namic change. We recognized that, in
a few of these transient cases, the cer-
vical length measurement after dy-
namic change was actually shortened
(,25 mm). In other cases, the poorly
developed lower uterine segment per-
sisted throughout the entire examina-
tion, but resolved before the patient’s
next visit. In no cases did this finding
persist during all scheduled evalua-
tions. We observed that the incidence
of poorly developed lower uterine seg-
ments decreased from 16% at the first
scan to less than 2% by the fourth evalu-
ation. The finding of a poorly devel-
oped lower uterine segment through-
out the entire scan appeared to be
protective and justified our decision to
consider it as a “long” cervix in the analy-
ses. Although primarily a subjective di-
agnosis, we have summarized diagnos-
tic criteria and believe that it represents
a reproducible observation with biologi-
cal significance.
Our findings challenge previous re-
ports that funneling at the internal cer-
vical os is a useful predictor of pre-
term birth.
11,22,23
We were impressed by
the wide range of biological variability
associated with funneling, which might
limit the reproducibility of this find-
ing. For example, some women did not
have a distinctly recognizable shoul-
der above the functional internal os, de-
picted in schematic diagrams of fun-
neling, and thus caliper placement was
operator dependent. Measurement of
funnel width as the distance between
shoulders would also have been prob-
lematic since some women had only 1
recognizable shoulder. In other cases,
asymmetric shoulders occurred, so it
was the sonologist’s choice as to which
one was used for funnel depth mea-
surement. Based on these observa-
tions, we included funneling as a cat-
egorical variable in the analyses.
Although women with a funnel had
significantly shorter cervical lengths
than women with no observed funnel,
our analyses confirmed that most, if not
all, of the preterm birth risk was re-
lated to cervical length. We postulate
that some cervixes shorten through the
process of funneling, but that the re-
maining functional length is more im-
portant than the precise method of
shortening. However, because our
sonographic examination windows
were necessarily limited (nominally, 20
minutes of real-time observations over
6 weeks), it is plausible that some
women with a shortened cervical length
had previously experienced funneling
that was never observed.
Dynamic change, after controlling for
cervical length, was only a marginally
significant predictor of preterm birth;
however, dynamic cervical length short-
ening during serial evaluations signifi-
cantly improved the prediction of pre-
term birth. Fundal pressure as a
provocative maneuver has been evalu-
ated in women at risk for cervical in-
competence.
21
We purposely excluded
women from our study who had under-
gone cerclage for a clinical history of cer-
vical incompetence and also recorded
unprovoked, spontaneous dynamic
shortening.
23
Thus, patient selection
likely explains why fundal pressure–
induced dynamic changes were not com-
monly observed. Spontaneous dy-
namic changes were also uncommon
and, as independent findings, did not
further improve the predictive value of
shortened cervical length for spontane-
ous preterm birth. We conclude that cer-
vical length is the single most impor-
tant sonographic finding for preterm
birth prediction in high-risk women. Al-
though the precise mechanisms by
which the cervix shortens and contrib-
utes to spontaneous preterm birth may
ultimately be shown to have a differen-
tial impact on specific interventions, our
results support the concept that for the
prediction of spontaneous preterm birth,
the means by which the cervix short-
ens may not be as important as the fact
that it does shorten.
Gestational age at examination, ob-
stetric history, concurrent risk factors for
preterm birth (eg, multiple gestation),
subsequent uncontrolled interven-
tions, the gestational age used to define
the preterm outcome, and other as-
pects of study design likely explain the
observed variance among published re-
ports on the significance of cervical
length measurement for preterm birth
prediction.
9-14,16-18,23
For these reasons, we
defined prematurity as delivery before 35
weeks, which is more clinically rel-
evant than the traditional 37 week end
point; included only women with a prior
early spontaneous preterm birth; and
masked the sonographic results. We
chose this study population primarily be-
cause it is one of the largest and most
Figure 3. Receiver Operating Characteristic
Curves of Cervical Length Cutoffs for the
Prediction of Spontaneous Preterm Birth
Before 35 Weeks’ Gestation
1.0
0.3
0.6
0.5
0.4
0.7
0.8
0.9
0.2
0.1
0
0 0.1 0.4 0.6 0.8 1.00.2
0.50.3
False Positive Rate (1 – specificity)
Specificity
Sensitivity
0.7 0.9
00.10.40.60.81.0 0.20.5 0.30.70.9
P = .03
<25 mm Cervical Length Cutoff
Shortest Observed Cervical
Length (After Dynamic Shortening)
Cervical Length, First Sonogram
(Before Dynamic Shortening)
Solid line depicts the performance of cervical length
cutoffs at the initial 16 week to 18 week 6 day evalu-
ation before any dynamic shortening. Dashed line de-
picts the shortest observed cervical length from 16
weeks’ to 23 weeks 6 days’ gestation and also con-
siders any recognized dynamic shortening. For com-
parison, the solid dots on the curves represent a cut-
off of less than 25 mm.
MID-TRIMESTER ENDOVAGINAL SONOGRAPHY
1346 JAMA, September 19, 2001—Vol 286, No. 11 (Reprinted) ©2001 American Medical Association. All rights reserved.
at Medical Library of the PLA, on August 12, 2007 www.jama.comDownloaded from
readily identified groups at risk. Al-
though women with multiple gesta-
tions also comprise a sizable and homo-
geneous risk group, the mechanisms by
which spontaneous preterm birth oc-
curs in multiple gestations may be dif-
ferent than the pathways that lead to re-
current spontaneous preterm birth in
singleton gestations.
To be clinically useful, the measure-
ment of cervical length should be re-
producible and associated with reason-
able thresholds for intervention. From
our quality assurance reviews, we were
satisfied that our training and certifi-
cation resulted in standardized mea-
surements of cervical length among par-
ticipating sonologists. Since reports of
cervical length assessment with endo-
vaginal sonography have become in-
creasingly common in recent years, it
is likely that many centers have devel-
oped their own training and certifica-
tion protocols. Nevertheless, from our
sonologist certification process, we rec-
ognized a learning curve associated with
this technique and caution against the
use of cervical length assessment by
sonologists who have not had appro-
priate supervised experience.
With regard to intervention thresh-
olds, we recognize that the relation-
ship between cervical length and spon-
taneous preterm birth functions along
a continuum as depicted in a receiver op-
erating characteristic curve (Figure 3).
Therefore, no single cervical length cut-
off can completely discriminate be-
tween eventual term and preterm births.
Depending on the risks, effectiveness,
and costs of a particular intervention, dif-
ferent thresholds may be appropriate.
We believe that a cervical length cutoff
of less than 25 mm represents an opti-
mum threshold for inclusion in future
mid-trimester intervention trials of cer-
clage. However, our findings do not sup-
port the concept of a “normal” vs “ab-
normal” cervical length, which is
oversimplified. Our findings support the
concept that cervical “competence”
likely represents a continuum,
11,24-27
and
that the mechanisms that underlie the
syndrome of spontaneous preterm birth
are multifactorial and incompletely un-
derstood.
28
Further investigations com-
bining endovaginal sonography and
other markers of spontaneous preterm
birth may increase our understanding of
these mechanisms and permit a more in-
dividualized and biologically focused ap-
proach to preterm birth prevention. Un-
til properly designed trials of cerclage or
other interventions prove a benefit from
the finding of a “short” cervix in the mid-
trimester,
29-32
we recommend that cer-
vical length measurement in women
with a prior spontaneous preterm birth
remain investigational.
Author Affiliations: Department of Obstetrics and Gy-
necology, University of Alabama at Birmingham
(Dr Owen); Department of Obstetrics and Gynecol-
ogy, University of Texas Southwestern Medical Cen-
ter, Dallas (Dr Yost); Department of Obstetrics and
Gynecology, Thomas Jefferson University, Philadel-
phia, Pa (Dr Berghella); George Washington Univer-
sity Biostatistics Center, Bethesda, Md (Dr Thom); De-
partment of Obstetrics and Gynecology, Wake Forest
University, Winston-Salem, NC (Ms Swain); Depart-
ment of Obstetrics and Gynecology, University of Utah,
Salt Lake City (Dr Dildy); Department of Obstetrics
and Gynecology, University of Cincinnati, Ohio
(Dr Miodovnik); Department of Obstetrics and Gy-
necology, University of Texas, San Antonio (Dr Langer);
Department of Obstetrics and Gynecology, Univer-
sity of Tennessee, Memphis (Dr Sibai); and the Na-
tional Institute of Child Health and Human Develop-
ment, Bethesda, Md (Dr McNellis). Dr Dildy is now
with the Louisiana State University, Baton Rouge; Drs
Miodovnik and Langer are now with Columbia Uni-
versity, New York City, NY; Dr Sibai is now with the
University of Cincinnati, Ohio; and Dr McNellis is re-
tired.
Author Contributions: Study concept and design:
Owen, Thom, Swain, Miodovnik, Langer, Sibai,
McNellis.
Acquisition of data: Owen, Yost, Berghella, Thom,
Dildy, Sibai, McNellis.
Analysis and interpretation of data: Owen, Berghella,
Thom, Dildy.
Drafting of the manuscript: Owen, Thom.
Critical revision of the manuscript for important in-
tellectual content: Owen, Yost, Berghella, Thom,
Swain, Dildy, Miodovnik, Langer, Sibai, McNellis.
Statistical expertise: Owen, Thom.
Obtained funding: Sibai, McNellis.
Administrative, technical, or material support: Owen,
Yost, Berghella, Swain, Dildy, Miodovnik, Langer,
McNellis.
Study supervision: Owen, Berghella, McNellis.
Funding/Support: This study was supported by grants
HD27869, HD21414, HD27860, HD27905, HD36801,
HD34116, HD34201, HD34208, and HD34136 from
the National Institute of Child Health and Human De-
velopment.
Previous Presentations: An abstract of this work was
presented at the 2000 Annual Meeting of the Soci-
ety for Gynecologic Investigation, Chicago, Ill, March
24, 2000.
Other members of the Maternal-Fetal Medicine Units
Network and their contributions: University of Ala-
bama at Birmingham: Cherry Neely, RT, RDMS (study
design, sonologist certification, and sonography), Al-
lison Northen, RN (data collection), John C. Hauth,
MD (study design), and Debbie Thom, RT, RDMS
(sonography); University of Chicago, Ill: Atef H.
Moawad, MD (study design); University of Cincin-
nati, Ohio: Nancy Elder, MSN, RN (data collection),
Tammy Haskins (sonography), and Deni Schultz
(sonography); George Washington University Biosta-
tistics Center, Washington, DC: Cora MacPherson, PhD
(study design, data analysis, and data quality assur-
ance) and Sharon Leindecker, MS (data quality assur-
ance); Magee Women’s Hospital, Pittsburgh, Pa: Steve
N. Caritis, MD (study design); University of Miami, Fla:
Mary Jo O’Sullivan, MD (study design); National In-
stitute of Child Health and Human Development,
Bethesda, Md: Charlotte Catz, MD (funding), Sum-
ner J. Yaffe, MD (funding), and Cathy Spong, MD
(manuscript editing); Ohio State University, Colum-
bus: Jay D. Iams, MD (study design and manuscript
editing); University of Tennessee, Memphis: Risa Ram-
sey, BSN, RN (data collection), Mary Peterson (sonog-
raphy), Joyce Fricke (sonography), and Jeff Livings-
ton (sonography); University of Texas at San Antonio:
Susan Barker, RN (data collection), Connie Leija (sonog-
raphy); University of Texas, Southwestern Medical Cen-
ter, Dallas: Kenneth J. Leveno, MD (study design and
manuscript editing), Julia McCampbell, BSN, RN (data
collection), and Rebecca Benezue (sonography);
Thomas Jefferson University, Philadelphia, Pa: Michelle
DiVito RN, MSN (data collection), Ronald J. Wapner,
MD (study design), and George Bega (sonography);
University of Utah, Salt Lake City: Micheal W. Varner,
MD (study design), Elaine Taggart, RN (data collec-
tion), and Ruth Zollinger (sonography); Wake Forest
University, Winston-Salem, NC: Paul Meis, MD (study
design) and Allison Henshaw (sonography); and Wayne
State University, Detroit, Mich: Mitchell Dom-
browski, MD (study design).
REFERENCES
1. Ventura SJ, Martin JA, Curtin SC, Mathews TJ, and
the Division of Vital Statistics, National Center for
Health Statistics, Centers for Disease Control and Pre-
vention. Report of final mortality statistics, 1995. Mon
Vital Stat Rep. 1997;45(S):1-81.
2. Tucker JM, Goldenberg RL, Davis RO, Copper RL,
Winkler CL, Hauth JC. Etiologies of preterm birth in
an indigent population: is prevention a logical expec-
tation? Obstet Gynecol. 1991;77:343-347.
3. Robertson PA, Sniderman SH, Laros RK Jr, et al.
Neonatal morbidity according to gestational age and
birth weight from five tertiary care centers in the United
States, 1983 through 1986. Am J Obstet Gynecol.
1992;166:1629-1645.
4. Seubert DE, Stetzer BP, Wolfe HM, Treadwell MC.
Delivery of the marginally preterm infant: what are
the minor morbidities? Am J Obstet Gynecol. 1999;
181:1087-1091.
5. Goldenberg RL, Mayberry SK, Copper RL, DuBard
MB, Hauth JC. Pregnancy outcome following a second-
trimester loss. Obstet Gynecol. 1993;81:444-446.
6. Mercer BM, Goldenberg RL, Moawad AH, et al. The
Preterm Prediction Study: effect of gestational age and
cause of preterm birth on subsequent obstetric out-
come. Am J Obstet Gynecol. 1999;181:1216-1221.
7. Andersen HF. Transvaginal and transabdominal ul-
trasonography of the uterine cervix during preg-
nancy. J Clin Ultrasound. 1991;19:77-83.
8. Iams JD. Cervical ultrasonography. Ultrasound Ob-
stet Gynecol. 1997;10:156-160.
9. Andersen HF, Nugent CE, Wanty SD, Hayashi RH.
Prediction of risk for preterm delivery by ultrasono-
graphic measurement of cervical length. Am J Ob-
stet Gynecol. 1990;163:859-867.
10. Tongsong T, Kamprapanth P, Srisomboon J, et al.
Single transvaginal sonographic measurement of cer-
vical length early in the third trimester as a predictor
of preterm delivery. Obstet Gynecol. 1995;86:184-
187.
11. Iams JD, Goldenberg RL, Meis PJ, et al. The length
of the cervix and the risk of spontaneous premature
delivery. N Engl J Med. 1996;334:567-572.
MID-TRIMESTER ENDOVAGINAL SONOGRAPHY
©2001 American Medical Association. All rights reserved. (Reprinted) JAMA, September 19, 2001—Vol 286, No. 11 1347
at Medical Library of the PLA, on August 12, 2007 www.jama.comDownloaded from
12. Berghella V, Tolosa JE, Kuhlman K, Weiner S, Bo-
lognese RJ, Wapner RJ. Cervical ultrasonography com-
pared with manual examination as a predictor of pre-
term delivery. Am J Obstet Gynecol. 1997;177:723-
730.
13. Taipale P, Hiilesmaa V. Sonographic measure-
ment of uterine cervix at 18-22 weeks’ gestation and
the risk of preterm delivery. Obstet Gynecol. 1998;
92:902-907.
14. Heath VCF, Southall TR, Souka AP, Elisseou A,
Nicolaides KH. Cervical length at 23 weeks’ of ges-
tation: prediction of spontaneous preterm delivery. Ul-
trasound Obstet Gynecol. 1998;12:312-317.
15. Watson WJ, Stevens D, Welter S, Day D. Obser-
vation on the sonographic measurement of cervical
length and the risk of premature birth. J Matern Fe-
tal Med. 1999;8:17-19.
16. Andrews WW, Copper R, Hauth JC, Goldenberg
RL, Neely C, DuBard M. Second-trimester cervical ul-
trasound: association with increased risk for recur-
rent early spontaneous delivery. Obstet Gynecol. 2000;
95:222-226.
17. Cook C-M, Ellwood DA. The cervix as a predic-
tor of preterm delivery in “at-risk” women. Ultra-
sound Obstet Gynecol. 2000;15:109-113.
18. Hassan SS, Romero R, Berry SM, et al. Patients
with an ultrasonographic cervical length #15 mm have
nearly a 50% risk of early spontaneous preterm de-
livery. Am J Obstet Gynecol. 2000;182:1458-1467.
19. Guzman ER, Mellon C, Vintzileos AM, Ananth CV,
Walters C, Gipson K. Longitudinal assessment of en-
docervical canal length between 15 and 24 weeks’ ges-
tation in women at risk for pregnancy loss or preterm
birth. Obstet Gynecol. 1998;92:31-37.
20. Burger M, Weber-Rossler T, Willmann M. Mea-
surement of the pregnant cervix by transvaginal sonog-
raphy: an interobserver study and new standards to
improve the interobserver variability. Ultrasound Ob-
stet Gynecol. 1997;9:188-193.
21. Guzman ER, Rosenberg JC, Houlihan C, Ivan J,
Waldron R, Knuppel R. A new method using vaginal
ultrasound and transfundal pressure to evaluate the
asymptomatic incompetent cervix. Obstet Gynecol.
1994;83:248-252.
22. Berghella V, Kuhlman K, Weiner S, Texeira L, Wap-
ner RJ. Cervical funneling: sonographic criteria pre-
dictive of preterm delivery. Ultrasound Obstet Gyne-
col. 1997;10:161-166.
23. Okitsu O, Mimura T, Nakayama T, Aono T. Early
prediction of preterm delivery by transvaginal ultra-
sonography. Ultrasound Obstet Gynecol. 1992;2:
402-409.
24. Buckingham JC, Buethe RA, Danforth DN. Col-
lagen-muscle ratio in clinically normal and clinically in-
competent cervixes. Am J Obstet Gynecol. 1965;91:
232-237.
25. Ayers JWT, DeGrood RM, Compton AA, Barclay
M, Ansbacher R. Sonographic evaluation of cervical
length in pregnancy: diagnosis and management of
preterm cervical effacement in patients at risk for
premature delivery. Obstet Gynecol. 1988;71:939-
944.
26. Iams JD, Johnson FF, Sonek J, Sachs L, Gebauer
C, Samuels P. Cervical competence as a continuum:
a study of ultrasonographic cervical length and ob-
stetric performance. Am J Obstet Gynecol. 1995;172:
1097-1106.
27. Craigo SD. Cervical incompetence and preterm de-
livery [editorial]. N Engl J Med. 1996;334:595-596.
28. Goldenberg RL, Rouse DJ. Prevention of prema-
ture birth. N Engl J Med. 1998;339:313-320.
29. Althusius SM, Dekker GA, Van Geijn HP, Beke-
dam DJ, Hummel P. Cervical incompetence preven-
tion randomized cerclage trial (CIPRACT): study de-
sign and preliminary results. Am J Obstet Gynecol.
2000;183:823-829.
30. Rust OA, Atlas RO, Jones KJ, Benham BN, Bal-
ducci J. A randomized trial of cerclage versus no cer-
clage among patients with ultrasonographically de-
tected second-trimester preterm dilatation of the internal
os. Am J Obstet Gynecol. 2000;183:830-835.
31. Berghella V, Daly SF, Tolosa JE, et al. Prediction
of preterm delivery with transvaginal ultrasonogra-
phy of the cervix in patients with high-risk pregnan-
cies: does cerclage prevent prematurity? Am J Ob-
stet Gynecol. 1999;181:809-815.
32. Hassan SS, Romero R, Maymon E, et al. Does cer-
vical cerclage prevent preterm delivery in patients with
a short cervix? Am J Obstet Gynecol. 2001;184:1325-
1331.
Every good poem, in fact, is a bridge built from the
known, familiar side of life over into the unknown.
Science too is always making expeditions into the un-
known. But this does not mean that science can su-
persede poetry. For poetry enlightens us in a differ-
ent way from science; it speaks directly to our feelings
or imagination. The findings of poetry are no more
and no less true than science.
—C. Day-Lewis (1904-1972)
MID-TRIMESTER ENDOVAGINAL SONOGRAPHY
1348 JAMA, September 19, 2001—Vol 286, No. 11 (Reprinted) ©2001 American Medical Association. All rights reserved.
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