Mid-Trimester
Endovaginal Sonography in Women at High Risk for Spontaneous Preterm Birth
JAMA. 2001;286:1340-1348
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
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 between March 1997 and November 1999 at 9 university-affiliated
medical centers in the United States in 183 women with singleton gestations who
previously had experienced a spontaneous birth before 32 weeks' gestation.
Observation Certified sonologists performed 590 endovaginal sonographic
examinations 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 cervical 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%; positive predictive value = 75%). After
controlling for cervical length, neither funneling (P = .24) nor dynamic shortening (P = .054) were significant independent predictors of
spontaneous preterm birth. However, using the shortest ever observed cervical
length on serial 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; sensitivity = 69%; specificity = 80%; positive predictive
value = 55%). Compared with a single cervical measurement at 16 weeks' to 18
weeks 6 days' gestation, serial measurements 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 spontaneous preterm birth before 35 weeks' gestation in high-risk
women.
JAMA. 2001;286:1340-1348
Preterm birth is the most important cause of
infant morbidity and mortality and complicates 11% of all pregnancies in the
United States.1 Most (80%) of
these births result from either spontaneous labor or membrane rupture.2 Since the development
of neonatal intensive care units, most neonatal deaths associated with
prematurity occur in infants born at less than 32 weeks' gestation, but
significant morbidities including sepsis, respiratory distress, and necrotizing
enterocolitis do not abate until 35 weeks' gestation, after which neonatal
outcomes are generally good.3, 4 To date, a prior
preterm birth is one of the strongest and most consistent predictors of
prematurity, and the risk of recurrence is inversely proportional to the
gestational age of the prior delivery.5, 6
Endovaginal ultrasound is a reliable technology
for imaging the cervix and lower uterine segment during pregnancy.7, 8 While there is ample
evidence that a shortened cervical length is associated with preterm birth,9-18 it is not known
when this risk factor becomes apparent in pregnancy or whether the adverse
cervical ultrasound findings develop over time. Moreover, most of the current
data linking cervical length to subsequent preterm birth have been collected
beyond 20 weeks' gestation.9-11, 14, 15 Importantly, most of
the available data have been collected either in unselected, low-risk
populations11, 13, 14, 18 or without physician
masking, which means interventions were applied on the basis of the sonographic
findings without a control group for comparison,14, 15, 17, 18 thus rendering the
predictive value of the cervical sonographic findings uncertain. The importance
of longitudinal observations and the natural history of cervical
characteristics in the mid-trimester have also not been well defined.12, 17-19
Our objective was to determine whether cervical
characteristics visualized 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 biological considerations, certain interventions (cerclage)
might be more effective if applied early in gestation (ie, before 24 weeks). We
hypothesized that endovaginal 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
university-affiliated centers, all members of the National Institute of Child
Health and Development, Maternal-Fetal Medicine Units Network, between March
1997 and November 1999. Women with singleton pregnancies who had experienced at
least 1 prior spontaneous preterm birth before 32 weeks' gestation 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 rupture) and a birth weight of less than 1500 g
were deemed satisfactory criteria. Women with chronic medical or obstetric
problems that might result in an indicated preterm birth (eg, hypertension, red
blood cell isoimmunization), a history of substance abuse, or uterine anomalies
were ineligible. Women who received a cerclage because of a clinical history of
cervical incompetence were also excluded. The institutional review board at
each center approved the study and potential participants 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 period (if available) with a sonographic evaluation at
or before 18 weeks' gestation. Concordance between the biometric parameters and
the menstrual date of 7 days or less confirmed the last menstrual period;
otherwise, the biometric data were used. After the initial endovaginal
sonographic evaluation, biweekly 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 physicians, ultrasound technologists, or
research 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
measurements and subjective assessments. The videotape was accompanied with a
detailed written description of each examination. Each sonologist independently
performed 10 endovaginal examinations on unselected patients in the
mid-trimester. The primary investigator critiqued the videotapes and
accompanying data sheets to identify deficiencies. When necessary, the sonologist
was asked to submit additional taped examinations and data sheets demonstrating
correction of any previously identified deficiencies. From the videotaped
examinations, the primary investigator also approved the ultrasound unit(s) at
each center.
Each sonographic examination was performed
according to a defined protocol: patients were asked to empty their bladder and
then placed in a dorsal lithotomy 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 insertion pressure
was increased only enough to restore an adequate image.11, 20 An adequate image for
the measurement of cervical length was defined as the visualization of the
internal os, external os, and endocervical canal.20
Cervical length was measured with electronic
calipers as the linear distance between the external os and the functional
internal os along a closed endocervical canal (Figure 1).
However, if the endocervical canal appeared to be curved, cervical length was
also assessed as the sum of the lengths of 2 contiguous linear segments, placed
along the endocervical canal, connecting the external os and functional
internal os. If the maximum deflection of canal curvature (defined as the
distance 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 recorded
cervical length measurement was the sum of the 2 linear segments (Figure 2A);
otherwise, the single linear distance measurement was recorded (Figure 2B).
Cervical length measurements were performed 3
times. The sonologist assessed the overall quality of the 3 images 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 observed cervical
length was recorded.11 If a normal-appearing
internal os could not be recognized, the image was further assessed for either
funneling or a poorly developed lower uterine segment. Funneling required
prolapse of the membranes through a dilated endocervical canal to the level of
the functional internal os. Funnel depth was measured from the functional
internal os to its "shoulder," visible more cephalad toward the lower
uterine segment (Figure 1
and Figure 2B).
To be characterized as a funnel, the measured depth had to be at least 5 mm.
A poorly developed lower uterine segment
precluded a cervical length measurement because the internal os could not be
visualized as a discrete structure. This subjective diagnosis was characterized
by the presence of an unusually long cervix (generally >50 mm), an s-shaped endocervical canal, an increased
distance between the bladder reflection and the amniotic cavity, 2 different
echogenic areas in the cervix, and an apparent internal os located appreciably
cephalad to the inferior edge of the bladder reflection. For analyses of
cervical length as a continuous variable, cases of poorly developed lower
segments were arbitrarily assigned a cervical length of 62 mm, which was 1 mm
greater than the longest measured cervical length (61 mm).
After baseline assessments were performed,
fundal pressure was applied for 15 seconds along the axis of the canal by the
sonologist21 who maintained
the standard sagittal view of the cervix to detect any fundal pressure–induced
dynamic changes in the cervix. If the cervix appeared to shorten, a funnel
developed (or increased in size), or if a poorly developed lower uterine
segment resolved as a result of the fundal pressure, repeat measurements were
obtained. Sonograms lasted a minimum of 5 minutes to detect spontaneously
occurring dynamic changes, which also prompted repeat measurements.
Examinations were videotaped for quality assurance.
According to the study protocol, the results of
each scan were not made available to the patient's managing physicians, except
in cases of complete placenta previa (placental tissue visualized extending
>1 cm on both sides of the internal os) or fetal death. The reason for any
notification was recorded. As part of continuing quality assurance, a sample of
the videotaped examinations was selected from each participating center
proportional to its enrollment. The videotapes and data sheets were reviewed by
the primary investigator in conjunction with another subcommittee member
blinded to the pregnancy outcome. If any measurements or subjective assessments
were deemed incorrect, the responsible sonologist and study coordinator were
notified and asked to reexamine the videotape and make appropriate corrections.
Initially, examinations were chosen at random. However, with increasing
experience we also developed criteria for selected reviews that included all
cases of funneling, cervical lengths less than 20 mm or greater than 50 mm,
poorly developed lower uterine segments, spontaneous or fundal 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 membrane rupture before the onset of labor.
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 appropriate 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 following: 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 spontaneous preterm birth before 35 weeks would be 30%.
Considering also a desired effect size of a relative risk (RR) of 3.0 for
spontaneous preterm birth before 35 weeks (based on the presence or absence of
a cervical length of <25 mm, 2-tailed 
= .05, 
= .20), 170
patients would have to be studied.
Data were analyzed using SAS version 7.0 (SAS
Institute Inc, Cary, NC). Categorical variables were compared using 
2 or
the Fisher exact test, and continuous data were compared with the Wilcoxon rank
sum test. Logistic regression was used to model the relationship between
cervical length and spontaneous preterm birth controlling for funneling,
recognition of dynamic shortening, and the slope of cervical length over time
on serial evaluations (as derived from linear regression models). Receiver
operating characteristic curves were used to compare the performance of varying
cervical length cutoffs for the prediction of spontaneous preterm birth before
35 weeks. Statistical significance was represented at P<.05.
Since serial examinations were performed, we
also compared spontaneous 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
dynamic shortening occurred. Thus, for any given patient, up to 4 different
cervical 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 shortening.
RESULTS
From all the participating centers, 236 women
were initially thought to be eligible 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 patients declined to participate, plus 6
more patients verbally agreed to participate but did not keep their first
sonogram appointment and therefore were not enrolled. We did not collect
outcome 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 sonographic
examinations were performed on our study population of 183 women between March
1997 and July 1999. The median duration of the sonographic examinations was 5.3
minutes (range, 4-18 minutes) and the median number of scans per patient was 3
(range, 1-4). Nine of the 183 women underwent a single sonographic evaluation.
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 protocol, and 466 (79%) of the taped examinations were
later reviewed. After study inception, 4 women received a cerclage 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 occurred 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 determined that 1 patient had not experienced a prior spontaneous preterm
birth before 32 weeks but, rather, had experienced an indicated preterm birth.
The mean gestational age at delivery 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 preterm 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 associated with preterm
membrane rupture.
Initial Sonographic Evaluation
A total of 29 women (16%) had a poorly developed lower uterine segment
throughout their entire initial evaluation. Since these women had been
arbitrarily 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 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 (Table 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%) experienced a spontaneous preterm birth before 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 sonogram had been performed. A total of 5 of these 9 cases
were suspected placenta previa and were reported according to study protocol.
However, in the other 4 cases, the protocol was not followed. Three were due to
specific cervical findings (cervical bending, funneling, and internal os
dilation) and in 1 case, the physician requested that the cervical length
measurement be unmasked. Considering the potential for bias associated with physician
notification and the 1 patient who had not previously experienced a prior
spontaneous preterm delivery, we determined the effect of omitting these 10
women from the analysis of the initial sonographic evaluation. The RR for
cervical length less than 25 mm and spontaneous 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).
However, women with an observed funnel also had a significantly shorter
cervical length (median, 26 mm vs 38 mm if no funnel was observed; P<.001). Because cervical length was
such a strong predictor of spontaneous preterm 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 significant independent predictor, controlling
for cervical length in a logistic regression model (P = .24). We also included either the presence of funneling
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 isolated cervical length cutoff of less than 25 mm (Table 1).
Dynamic Changes
During their first sonographic evaluation, 16 (9%) of 183 women had observed
dynamic changes. A total of 9 followed 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 developed lower uterine
segment resolved. Similar to our analysis of funneling, we included dynamic
changes in a logistic regression model with cervical length and observed a
trend toward dynamic changes as a significant independent predictor of
spontaneous preterm 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 spontaneous preterm birth before
35 weeks. As with funneling, the inclusion of dynamic changes at the initial
evaluation did not improve the predictive accuracy 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 median of
37 mm at the first scan to a median of 32 mm at the fourth scan. For each of
the 174 women with at least 2 sonographic evaluations, we computed the rate of
change of cervical length by fitting a linear regression line to their observed
cervical length measurements. The median rate of shortening 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 cervical length of 62 mm at any time during
their initial and serial evaluations, we observed a median cervical length
shortening of 0.9 mm per week. The 44 women who experienced a spontaneous
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 observations
on the predictive accuracy of endovaginal sonography, we first included the
shortest observed cervical length for each patient in a logistic regression
model with spontaneous preterm birth before 35 weeks as the dependent variable.
In this analysis, the shortest ever observed cervical length before dynamic
changes was a significantly better predictor than the baseline cervical length
at the first scan. We further analyzed the information from serial evaluations
by including the slope of the derived regression line of cervical 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, after controlling for
initial baseline length, the slope became a statistically significant predictor
in the regression model (P =
.002).
Since previous reports examined the relationship
between static cervical length measured beyond 20 weeks' gestation 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 undergone 2 studies during this gestational period,
the former was preferentially 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%, respectively.
Finally, we examined the clinical utility 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 spontaneous
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 observed on serial examinations. We included the
shortest observed cervical length after any dynamic changes occurred in a
logistic regression model with spontaneous preterm birth before 35 weeks as the
dependent variable and found that it was a significantly better predictor than
the shortest observed cervical length at any scan prior to dynamic changes.
From the regression model, we determined that the odds of spontaneous preterm
birth before 35 weeks decreased by 43% for each 5-mm increase in the shortest
observed cervical length after dynamic changes.
Considering these dynamic changes, the median
rate of shortening remained 1.1 mm per week and 0.9 mm per week after removing
the 41 women who had a poorly developed lower uterine segment. We also analyzed
cervical length over time after dynamic changes using logistic regression. In
this case, the slope was a significant predictor of spontaneous preterm birth
before 35 weeks by itself (P<.001)
and also after controlling for initial baseline cervical length (P<.001). These analyses confirmed that
the inclusion of dynamic changes (ie, shortening) observed on serial
evaluations significantly improved the predictive accuracy of endovaginal
sonography for a spontaneous preterm birth.
We then examined the summary predictive values
of postdynamic change–cervical length measurements at a cutoff 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 cervical length cutoff of less
than 25 mm at the baseline scan, the shortest observed cervical length on
serial scans before any dynamic changes, and the shortest observed cervical
length considering dynamic changes from the serial endovaginal sonographic
evaluations.
Figure 3
depicts the receiver operating characteristic curves of the baseline cervical
length at 16 to 18 weeks' gestation prior to dynamic changes and the shortest
observed cervical length observed on serial evaluations after dynamic changes.
The latter measurement represented a statistically significant improvement over
the former with regard to the use of cervical length as a screening test for
the prediction of spontaneous preterm birth before 35 weeks (P = .03).
COMMENT
We performed a prospective, blinded
observational study to determine if endovaginal sonography of the cervix at 16
weeks' to 23 weeks 6 days' gestation would predict spontaneous preterm birth
with sufficient accuracy to justify mid-trimester intervention trials in
high-risk women. As a single measurement, 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 serial
observations of cervical length improved the predictive values. We conclude
that the natural history of cervical anatomy during midpregnancy can contribute
significant information as to the risk of subsequent spontaneous preterm birth.
We had previously recognized that in
approximately 10% of mid-trimester endovaginal sonograms, the cervical anatomy
appeared atypical and, in particular, a normal-appearing internal os could not
be readily identified. This led to our characterization of a poorly developed
lower uterine segment, which in some cases resolved into a measurable cervix.
If resolution occurred during the sonogram, this represented a dynamic change.
We recognized that, in a few of these transient cases, the cervical length
measurement after dynamic change was actually shortened (<25 mm). In other
cases, the poorly developed lower uterine segment persisted throughout the
entire examination, but resolved before the patient's next visit. In no cases
did this finding persist during all scheduled evaluations. We observed that the
incidence of poorly developed lower uterine segments decreased from 16% at the
first scan to less than 2% by the fourth evaluation. The finding of a poorly
developed lower uterine segment throughout the entire scan appeared to be
protective and justified our decision to consider it as a "long"
cervix in the analyses. Although primarily a subjective diagnosis, we have
summarized diagnostic criteria and believe that it represents a reproducible
observation with biological significance.
Our findings challenge previous reports that
funneling at the internal cervical os is a useful predictor of preterm birth.11, 22, 23 We were impressed by
the wide range of biological variability associated with funneling, which might
limit the reproducibility of this finding. For example, some women did not have
a distinctly recognizable shoulder above the functional internal os, depicted
in schematic diagrams of funneling, and thus caliper placement was operator
dependent. Measurement of funnel width as the distance between shoulders would
also have been problematic 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 measurement. Based on these
observations, we included funneling as a categorical 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 related to cervical
length. We postulate that some cervixes shorten through the process of
funneling, but that the remaining functional length is more important 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 shortening during serial evaluations significantly
improved the prediction of preterm birth. Fundal pressure as a provocative
maneuver has been evaluated in women at risk for cervical incompetence.21 We purposely excluded
women from our study who had undergone cerclage for a clinical history of
cervical incompetence and also recorded unprovoked, spontaneous dynamic
shortening.23 Thus, patient
selection likely explains why fundal pressure–induced dynamic changes were not
commonly observed. Spontaneous dynamic changes were also uncommon and, as
independent findings, did not further improve the predictive value of shortened
cervical length for spontaneous preterm birth. We conclude that cervical length
is the single most important sonographic finding for preterm birth prediction
in high-risk women. Although the precise mechanisms by which the cervix
shortens and contributes to spontaneous preterm birth may ultimately be shown
to have a differential impact on specific interventions, our results support
the concept that for the prediction of spontaneous preterm birth, the means by
which the cervix shortens may not be as important as the fact that it does
shorten.
Gestational age at examination, obstetric
history, concurrent risk factors for preterm birth (eg, multiple gestation),
subsequent uncontrolled interventions, the gestational age used to define the
preterm outcome, and other aspects of study design likely explain the observed
variance among published reports 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
relevant 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 because it is one of the largest and most
readily identified groups at risk. Although women with multiple gestations also
comprise a sizable and homogeneous risk group, the mechanisms by which
spontaneous preterm birth occurs in multiple gestations may be different than
the pathways that lead to recurrent spontaneous preterm birth in singleton
gestations.
To be clinically useful, the measurement of
cervical length should be reproducible and associated with reasonable
thresholds for intervention. From our quality assurance reviews, we were
satisfied that our training and certification resulted in standardized
measurements of cervical length among participating sonologists. Since reports
of cervical length assessment with endovaginal sonography have become
increasingly common in recent years, it is likely that many centers have
developed their own training and certification protocols. Nevertheless, from
our sonologist certification process, we recognized a learning curve associated
with this technique and caution against the use of cervical length assessment
by sonologists who have not had appropriate supervised experience.
With regard to intervention thresholds, we
recognize that the relationship between cervical length and spontaneous preterm
birth functions along a continuum as depicted in a receiver operating
characteristic curve (Figure 3).
Therefore, no single cervical length cutoff can completely discriminate between
eventual term and preterm births. Depending on the risks, effectiveness, and
costs of a particular intervention, different thresholds may be appropriate. We
believe that a cervical length cutoff of less than 25 mm represents an optimum
threshold for inclusion in future mid-trimester intervention trials of
cerclage. However, our findings do not support the concept of a
"normal" vs "abnormal" 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 understood.28 Further
investigations combining endovaginal sonography and other markers of
spontaneous preterm birth may increase our understanding of these mechanisms
and permit a more individualized and biologically focused approach to preterm
birth prevention. Until 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 cervical length measurement in women with a prior spontaneous
preterm birth remain investigational.
Author/Article Information
Author Affiliations: Department of
Obstetrics and Gynecology, University of Alabama at Birmingham (Dr Owen);
Department of Obstetrics and Gynecology, University of Texas Southwestern
Medical Center, Dallas (Dr Yost); Department of Obstetrics and Gynecology,
Thomas Jefferson University, Philadelphia, Pa (Dr Berghella); George Washington
University Biostatistics Center, Bethesda, Md (Dr Thom); Department of
Obstetrics and Gynecology, Wake Forest University, Winston-Salem, NC (Ms
Swain); Department 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 Gynecology,
University of Texas, San Antonio (Dr Langer); Department of Obstetrics and
Gynecology, University of Tennessee, Memphis (Dr Sibai); and the National
Institute of Child Health and Human Development, Bethesda, Md (Dr McNellis). Dr
Dildy is now with the Louisiana State University, Baton Rouge; Drs Miodovnik
and Langer are now with Columbia University, New York City, NY; Dr Sibai is now
with the University of Cincinnati, Ohio; and Dr McNellis is retired.
Corresponding Author and Reprints:
John Owen, MD, Department of Obstetrics and Gynecology, University of Alabama
at Birmingham, 619 19th St S, OHB 458, Birmingham, AL 35249-7333 (e-mail: [log in to unmask]).
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 intellectual 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 Development.
Previous Presentations: An abstract of this work was presented at the 2000 Annual Meeting
of the Society for Gynecologic Investigation, Chicago, Ill, March 24, 2000.
Other members of the
Maternal-Fetal Medicine Units Network and their contributions: University of Alabama at Birmingham:
Cherry Neely, RT, RDMS (study design, sonologist certification, and sonography),
Allison 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 Cincinnati, Ohio: Nancy Elder, MSN, RN (data
collection), Tammy Haskins (sonography), and Deni Schultz (sonography); George
Washington University Biostatistics Center, Washington, DC: Cora MacPherson,
PhD (study design, data analysis, and data quality assurance) and Sharon
Leindecker, MS (data quality assurance); Magee Women's Hospital, Pittsburgh,
Pa: Steve N. Caritis, MD (study design); University of Miami, Fla: Mary Jo
O'Sullivan, MD (study design); National Institute of Child Health and Human
Development, Bethesda, Md: Charlotte Catz, MD (funding), Sumner J. Yaffe, MD
(funding), and Cathy Spong, MD (manuscript editing); Ohio State University,
Columbus: Jay D. Iams, MD (study design and manuscript editing); University of
Tennessee, Memphis: Risa Ramsey, BSN, RN (data collection), Mary Peterson
(sonography), Joyce Fricke (sonography), and Jeff Livingston (sonography);
University of Texas at San Antonio: Susan Barker, RN (data collection), Connie
Leija (sonography); University of Texas, Southwestern Medical Center, 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
collection), 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 Dombrowski,
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 Prevention.
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
expectation?
Obstet Gynecol.
1991;77:343-347.
MEDLINE
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.
MEDLINE
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.
MEDLINE
5.
Goldenberg RL, Mayberry SK, Copper RL, DuBard MB, Hauth JC.
Pregnancy outcome following a second-trimester loss.
Obstet Gynecol.
1993;81:444-446.
MEDLINE
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 outcome.
Am J Obstet Gynecol.
1999;181:1216-1221.
MEDLINE
7.
Andersen HF.
Transvaginal and transabdominal ultrasonography of the uterine cervix during
pregnancy.
J Clin Ultrasound.
1991;19:77-83.
MEDLINE
8.
Iams JD.
Cervical ultrasonography.
Ultrasound Obstet Gynecol.
1997;10:156-160.
MEDLINE
9.
Andersen HF, Nugent CE, Wanty SD, Hayashi RH.
Prediction of risk for preterm delivery by ultrasonographic measurement of
cervical length.
Am J Obstet Gynecol.
1990;163:859-867.
MEDLINE
10.
Tongsong T, Kamprapanth P, Srisomboon J, et al.
Single transvaginal sonographic measurement of cervical length early in the
third trimester as a predictor of preterm delivery.
Obstet Gynecol.
1995;86:184-187.
MEDLINE
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.
MEDLINE
12.
Berghella V, Tolosa JE, Kuhlman K, Weiner S, Bolognese RJ, Wapner RJ.
Cervical ultrasonography compared with manual examination as a predictor of
preterm delivery.
Am J Obstet Gynecol.
1997;177:723-730.
MEDLINE
13.
Taipale P, Hiilesmaa V.
Sonographic measurement of uterine cervix at 18-22 weeks' gestation and the
risk of preterm delivery.
Obstet Gynecol.
1998;92:902-907.
MEDLINE
14.
Heath VCF, Southall TR, Souka AP, Elisseou A, Nicolaides KH.
Cervical length at 23 weeks' of gestation: prediction of spontaneous preterm
delivery.
Ultrasound Obstet Gynecol.
1998;12:312-317.
MEDLINE
15.
Watson WJ, Stevens D, Welter S, Day D.
Observation on the sonographic measurement of cervical length and the risk of premature
birth.
J Matern Fetal Med.
1999;8:17-19.
MEDLINE
16.
Andrews WW, Copper R, Hauth JC, Goldenberg RL, Neely C, DuBard M.
Second-trimester cervical ultrasound: association with increased risk for
recurrent early spontaneous delivery.
Obstet Gynecol.
2000;95:222-226.
MEDLINE
17.
Cook C-M, Ellwood DA.
The cervix as a predictor of preterm delivery in "at-risk" women.
Ultrasound Obstet Gynecol.
2000;15:109-113.
MEDLINE
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 delivery.
Am J Obstet Gynecol.
2000;182:1458-1467.
MEDLINE
19.
Guzman ER, Mellon C, Vintzileos AM, Ananth CV, Walters C, Gipson K.
Longitudinal assessment of endocervical canal length between 15 and 24 weeks'
gestation in women at risk for pregnancy loss or preterm birth.
Obstet Gynecol.
1998;92:31-37.
MEDLINE
20.
Burger M, Weber-Rossler T, Willmann M.
Measurement of the pregnant cervix by transvaginal sonography: an interobserver
study and new standards to improve the interobserver variability.
Ultrasound Obstet Gynecol.
1997;9:188-193.
MEDLINE
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.
MEDLINE
22.
Berghella V, Kuhlman K, Weiner S, Texeira L, Wapner RJ.
Cervical funneling: sonographic criteria predictive of preterm delivery.
Ultrasound Obstet Gynecol.
1997;10:161-166.
MEDLINE
23.
Okitsu O, Mimura T, Nakayama T, Aono T.
Early prediction of preterm delivery by transvaginal ultrasonography.
Ultrasound Obstet Gynecol.
1992;2:402-409.
24.
Buckingham JC, Buethe RA, Danforth DN.
Collagen-muscle ratio in clinically normal and clinically incompetent 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.
MEDLINE
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 obstetric performance.
Am J Obstet Gynecol.
1995;172:1097-1106.
MEDLINE
27.
Craigo SD.
Cervical incompetence and preterm delivery [editorial].
N Engl J Med.
1996;334:595-596.
MEDLINE
28.
Goldenberg RL, Rouse DJ.
Prevention of premature birth.
N Engl J Med.
1998;339:313-320.
MEDLINE
29.
Althusius SM, Dekker GA, Van Geijn HP, Bekedam DJ, Hummel P.
Cervical incompetence prevention randomized cerclage trial (CIPRACT): study
design and preliminary results.
Am J Obstet Gynecol.
2000;183:823-829.
MEDLINE
30.
Rust OA, Atlas RO, Jones KJ, Benham BN, Balducci J.
A randomized trial of cerclage versus no cerclage among patients with
ultrasonographically detected second-trimester preterm dilatation of the
internal os.
Am J Obstet Gynecol.
2000;183:830-835.
MEDLINE
31.
Berghella V, Daly SF, Tolosa JE, et al.
Prediction of preterm delivery with transvaginal ultrasonography of the cervix
in patients with high-risk pregnancies: does cerclage prevent prematurity?
Am J Obstet Gynecol.
1999;181:809-815.
MEDLINE
32.
Hassan SS, Romero R, Maymon E, et al.
Does cervical cerclage prevent preterm delivery in patients with a short
cervix?
Am J Obstet Gynecol.
2001;184:1325-1331.
MEDLINE
Edward E.
Rylander, M.D.
Diplomat American
Board of Family Practice.
Diplomat American
Board of Palliative Medicine.