Ioana Victoria Camen et al.

- Prediction of Preterm Birth with Serial Measurements of Ultrasound Markers

Original Paper
Prediction of Preterm Birth with Serial Measurements
of Ultrasound Markers
IOANA VICTORIA CAMEN1,7, MARIA MAGDALENA MANOLEA2,7,
SIDONIA CATALINA VRABIE2,7, MARIA SIDONIA SANDULESCU2,7,
MIRCEA SEBASTIAN SERBANESCU3, MIHAIL VIRGIL BOLDEANU4,
LILIANA NOVAC2,7, ANCA MARIA ISTRATE-OFITERU6,
SIMONA DANIELA NEAMTU5,8, ANDA LORENA DIJMARESCU2,7
1Ph.D. student, Doctoral School, University of Medicine and Pharmacology of Craiova, Romania
2Obstetrics
and Gynecology Department,
University of Medicine and Pharmacology of Craiova, Romania
3Medical Informatics Department, University of Medicine and Pharmacology of Craiova, Romania
4Immunology Department, University of Medicine and Pharmacy of Craiova, Romania
5Department of Hematology, Faculty of Pharmacy,

University of Medicine and Pharmacy of Craiova, Romania

6Department of Histology, Faculty of Medicine,

University of Medicine and Pharmacy of Craiova, Romania

7Department of Obstetrics and Gynecology, “Filantropia” Hospital from Craiova
8Department of Clinical Laboratory, “Filantropia” Hospital from Craiova

ABSTRACT: To compare the ability of cervical length (CL), anterior cervical angle (ACA), and cervical consistency
index (CCI) to predict premature birth. Methods. This prospective study involved 85 pregnant women who gave birth
prematurely and a control group of 31 pregnant women who gave birth at term. The study was performed in the
Obstetrics and Gynecology Clinic of the Municipal Clinical Hospital Filanthropia Craiova between January 1, 2019, and
January 1, 2022. Cases were examined using transvaginal ultrasonography (TVU) in the second and third trimesters
of pregnancy, and cervical length (CL), Anterior Cervical Angle (ACA), and Cervical Consistency Index (CCI) were
measured. Results. The mean value from the three measurements at all three parameters was statistically significant
with preterm birth (p<0.05). Cervical length <25mm, was highly significant in the prediction of preterm labor with a
sensitivity of 99%, specificity of 61%, positive predictive value (PPV) of 78%, negative predictive value (NPV) of 97 %,
and a positive likelihood ratio (LR+) of 2.54 and negative likelihood ratio (LR-) of 0.02. CCI also remains, despite low
specificity and PPV values, a potential predictive parameter in the prediction of preterm birth, with a sensitivity of 73%,
NPV of 92% and a LR+of 1.32 and LR- of 0.6 also correlated with CL, CCI being more difficult to interpret as an
independent predictive parameter. Conclusions. CL remains the standard parameter for predicting the preterm birth,
but in combination with other parameters, the prediction rate can increase significantly.

KEYWORDS: cervical length, anterior cervical angle, cervical consistency index, preterm birth.
interventions and of optimal decision
Introduction management [2].
It is estimated worldwide that 1 in 10 children It seems that a "short cervix" measured in the
are born prematurely, and approximately 1 second trimester of pregnancy by vaginal
million children are born prematurely each year ultrasound, may represent an increase in the
[1]. probability of premature birth if we refer to
Therefore, the prediction of premature birth is singleton pregnancies.
extremely important both for the impact that But the detection and monitoring of this
premature birth has on a personal level and in marker in the second trimester may allow the
terms of economic and health impact. administration of a specific treatment, thus
There is currently no single safe test to predict reducing this increased likelihood [3].
premature birth, but it has been found that a There are also situations in which in the
combination of tests can do this, or at least second trimester the cervix may have a normal
include the pregnant woman in a risk group, length or maybe at the lower limit, which has
benefiting from a series of prophylactic been recommended at 25mm [4,5].

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162 10.12865/CHSJ.48.02.04
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Current Health Sciences Journal Vol. 48, No. 2, 2022 April-June

Cervical length measurement by transvaginal auspices of the University of Medicine and

ultrasound has been extensively studied for the Pharmacy of Craiova.
past 30 years, becoming the subject of over Eligibility criteria included singleton
600 publications [6]. pregnancies, ages over 18, and pregnancies with
Along with this ultrasound marker, others accurate gestational age.
have been used to improve the prediction of The exclusion criteria from the study were
premature birth. multiple pregnancies, major fetal structural
The measurement of the angle between the abnormalities, any vaginal bleeding, labor, or any
uterine wall and the cervical canal was initially medical or psychiatric condition that
used to successfully induce labor, but later it was compromises a woman's ability to participate.
found that an obtuse angle (≥95° and ≥105°) may A detailed interview was conducted at the first
be associated with an increased risk of premature monitoring visit to obtain demographic, clinical,
birth [7,8]. and medical history data.
Thus, this ACA parameter may be an Three ultrasound markers were serially
additional ultrasound marker for predicting monitored to predict premature birth: CL, ACA,
preterm birth. and CCI, in 3 periods of pregnancy: 18.0-22.6
Its detection rate can be improved if combined weeks, 28.0-31.6 weeks, and 32.0-35.6 weeks.
with other parameters, especially the length of the This monitoring was performed outside of
cervix and the presence of risk factors, standard obstetric care visits.
considering that this can predict about 40% of Cervical length was estimated as the distance
premature births, which is a significant between internal os and external os, measured by
percentage [9]. TVU.
Given that in recent years it has been found The anterior cervical angle was measured by
that measuring the length of the cervix for the angle created by two imaginary lines, one
low-risk populations has a low detection rate passing through the internal and external cervical
[10,11], other ultrasound parameters have been os and another following the anterior wall of the
found to show cervical changes that occur before uterus.
labor. CCI is the ratio between the thickness of the
Thus, another ultrasound parameter studied cervix after compression by the transvaginal
was the cervical consistency index, which transducer (AP’) and the thickness before
was defined and standardized by Parra-Saavedra compression (AP), expressed as a percentage,
et al. in 2011 [6]. measuring the degree of deformity of the cervix
A better detection rate of CCI than CL for low- during a standard vaginal ultrasound
risk populations was found in some studies [12]. examination.
As noted, there is currently no single or
combined test with high sensitivity that can Statistical Analysis
certainly identify women who will give birth For each group, we calculated the median
prematurely, so we could eliminate a several ACA, CL, and CCI. The differences between the
unnecessary interventions and expensive groups were tested with an ANOVA-test and a
treatment. Student-test for normal distribution and
But in the end, the most widely used homogeneity of variances.
ultrasound marker, CL, is a standard if not a A p-value of 0.05 was used as a significance
reliable predictor of preterm birth, at least in level.
selecting a risk group. Sensitivity, specificity, positive and negative
predictive values, and positive and negative
Materials and Methods likelihood ratios were calculated with their 95%
This prospective study included a group of Confidence Intervals.
85 pregnant women who had risk factors for
premature birth and who gave birth prematurely Ethical Consideration
and 31 pregnant women who gave birth at term, Patients were informed of the study design
which constituted the control group. and signed informed consent.
The study was performed in the Obstetrics Based on the Declaration of Helsinki, the
and Gynecology Clinic of the Municipal Clinical study received the approval of the Ethics
Hospital "Filantropia" Craiova, between Committee of the University of Medicine and
January 1, 2019, and January 1, 2022, under the Pharmacy of Craiova.

10.12865/CHSJ.48.02.04 163
Ioana Victoria Camen et al. - Prediction of Preterm Birth with Serial Measurements of Ultrasound Markers

Results compared to only 11 (9.48%) cases in the control

The average age of the group with premature group.
birth was 28.5 years±4.6 SD, the control As noted in Table 1, there are no statistically
group had an average age of 29.8 years±4.7 SD; significant differences in maternal age and BMI
37 (31.89%) patients who gave birth prematurely between groups.
were nulliparous, compared to 23 (19.82%) But because we could not differentiate
patients in the control group. between nulliparity and miscarriage as the only
History of premature births was present in risk factor in preterm birth, no other study has
21 (18.10%) patients who gave birth prematurely done this, we believe that nulliparity cannot be an
and only 2 (1.72%) patients in the control group; independent risk factor.
80 (68.96%) patients in the premature birth group This is because from the beginning, or during
had first or second-trimester miscarriage, pregnancy, other factors are added: obesity,
shortening of the cervix, pathology associated
with pregnancy, etc.
Table 1. Demographic maternal characteristics of study groups in correlation with premature birth.

Parameter Premature birth group Control group p-value

BMI (Median±SD) 24.2±3.34 24.5±3.03 0.955408
Maternal age in years (Median±SD) 28.5±4.62 29.8 ±4.71 0.17564
Nulliparous (n) 37 23
History of premature births (n) 21 2
First-trimester miscarriage (n) 57 8
Second-trimester miscarriage (n) 23 3
Note: BMI: body mass index
For preterm birth prediction we used CL, If we establish a cut-off of 65%, as established
ACA, and CCI, evaluated in Table 2. in the specialized research for the prediction of
Cervical shortening, assessed by measuring premature birth, the correlation with CL <25mm,
the length of the cervix, a parameter detected a shows that 11 cases had CCI <65%, compared to
few weeks before preterm birth, is one of the most only 4 cases with CL>25mm (Figure 1).
commonly used elements in predicting preterm 56 CCI<65%
45
birth. 60 Yes
The mean value from the three measurements 40 11 CCI<65%
4
20 No
showed that there was a significant difference 0
between CL and preterm birth, with the p-value Yes No
of the Student's test <0.05. CL<25 mm
In our study, the mean value of ACA showed
the same significant difference, the p-value of the Figure 1. Distribution of cases according to CCI,
Student's test <0.05. and CL.
Also, the average CCI is significantly lower in
the study group, compared to the control group The relationship between CL, ACA, CCI, and
(<0.05). preterm delivery are shown in Table 2.
Table 2. Correlation between CL, ACA, CCI, and preterm birth.

Parameter Premature birth group Term birth group p-value

Cervical length in mm (Media±SD) 21.10±3.60 31.96±2.90 0.00
Anterior uterocervical angle (Media±SD) in degree 101.43±3.95 92.73±2.48 0.00
Cervical consistency index in % (Media±SD) 77±8.31 79.23±6.72 0.00
Note: CL: cervical length; ACA: anterior cervical angle; CCI: cervical consistency index.
Making a correlation between the three visits In the case of CCI, only the measurement
at different gestational ages, we wanted to see performed at visit 3 (32.0-35.6 gestational week)
which is the most correct gestational age for did not show a statistically significant difference
predicting premature birth. in the risk of premature birth (Table 3).
In the case of CL and ACA we noticed a Prevalence of CL <25mm at the first visit was
statistically significant difference in the risk of 72.94% and was higher among women who gave
premature birth at all three gestational ages birth preterm compared to term pregnancies
studied. (3.22%).

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Current Health Sciences Journal Vol. 48, No. 2, 2022 April-June

During visits 2 and 3, the prevalence of CL 87.05% at visits 2 and 3, compared to 0% cases
<25mm was higher than in pregnancies that gave in pregnancies that gave birth at term.
birth at term (75.29% vs. 0% and 12.9%, Also, the percentage of cases that had a CCI
respectively). <65%, increased from the first visit, 8.23%, to
ACA>100° had increasing values, starting 67.05%, and 28.23% at visits 2 and 3, compared
from 8.23% at the first visit, at 67.05%, and to 0% cases in pregnancies that gave birth in term
(Table 3).
Table 3. Correlation between serial transvaginal CL, ACA, CCI measurements, and preterm birth.

Premature Premature
Term birth
birth birth Prevalence Prevalence
>37.0
32.0-33.6 34.0-35.6 of parameter of parameter ANOVA
Parameter gestational
p-value
gestational gestational in premature in term
week
week week birth (%) birth (%)
(Mean±SD)
(Mean±SD) (Mean±SD)
Cervical length (mm) <25mm
Visit 1 (18.0-22.6 gestational week) 20.85±5.04 22±4.16 34±3.47 72.94 3.22 0.00
Visit 2 (28.0-31.6 gestational week) 21±3.40 21.1±4.67 32.4±2.71 75.29 0 0.00
Visit 3 (32.0-35.6 gestational week) 21.45±3.78 20.7±3.76 29.2±5.28 75.29 12.90 0.00
Anterior cervical angle (degrees) >100° 0.00
Visit 1 (18.0-22.6 gestational week) 94±3.42 95.6±4.14 90.3±2.62 8.23 0 0.00
Visit 2 (28.0-31.6 gestational week) 101.3±3.56 101.5±4.84 92.4±2.64 67.05 0 0.00
Visit 3 (32.0-35.6 gestational week) 105.5±3.97 106.28±4.63 95.2±2.52 87.05 0 0.00
Cervical consistency index (%) <65% 0.00
Visit 1 (18.0-22.6 gestational week) 74.6±7.9 80.2±7.14 82.5±4.43 10.58 0 0.00
Visit 2 (28.0-31.6 gestational week) 72.7±8.58 79.5±7.34 81.2±9.05 16.47 0 0.00
Visit 3 (32.0-35.6 gestational week) 70.9±9.92 76.5±8.6 74.3±9.87 28.23 0 0.173

Sensitivity, specificity, predictive positive and birth before 37 gestational weeks, are given in
negative value, as well as positive and negative Table 4.
likelihood ratios for the prediction of preterm

Table 4. Predictive accuracy for preterm birth based on serial CL, ACA, and CCI measurements.

Parameter Sn Sp PPV NPV LR+ LR-

(IC 95%) (IC 95%) (IC 95%) (IC 95%) (IC 95%) (IC 95%)
Cervical length 99% 61% 78% 97% 2.54 0.02
Anterior cervical angle 100% 29% 11% 100% 1.41 0.00
Cervical consistency index 73% 45% 16% 92% 1.32 0.6
Note: Sn: Sensitivity; Sp: Specificity; VPP: positive predictive value;
NPV: negative predictive value; LR+: positive likelihood ratio; LR-: negative likelihood ratio.
Cervical length <25mm, which is the cutoff more difficult to interpret as an independent
commonly used in clinical practice, is highly predictive parameter.
significant in the prediction of preterm labor with
a sensitivity of 99%, specificity of 61%, PPV
78%, NPV 97% and an LR+2.54,
and LR-of 0.02.
Anterior cervical angle, despite low
specificity and positive predictive value, may be
significant in predicting the preterm birth
with a sensitivity of 100%, NPV of 100%, an
LR+of 1.41, and LR-of 0.00, especially in
correlation with cervical length.
Cervical consistency index also remains,
despite low specificity and positive predictive
values, a potential predictive parameter Figure 2. Pregnancy at 29.1 gestational weeks.
in the prediction of preterm birth, with a CL=12.3mm, funneling.
sensitivity of 73%, NPV of 92% and an LR+1.32
and LR-of 0.6 also correlated with CL, CCI being

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Ioana Victoria Camen et al. - Prediction of Preterm Birth with Serial Measurements of Ultrasound Markers

Discussion
Premature birth is an important problem for
modern obstetrics because it is a major cause of
increased neonatal mortality and morbidity, and
the installation of long-term neurological and
systemic problems.
The etiology of preterm birth is not yet fully
clarified, so the identification of risk factors as
well as the establishment of the risk of premature
birth has great importance for establishing correct
obstetrical management [13].
Figure 3. Pregnancy at 30.6 gestational weeks.
CL=16.3mm, funneling.
The evaluation of the measurement of the
length of the cervix is used to identify pregnant
women at risk of premature birth, this
measurement being a tool for predicting it.
In clinical practice, a cervical length of 25mm
has been chosen as a "cut-off" for establishing a
normal cervix or a shortened cervix when the
value falls below 25mm [14,15].
A large study conducted by Thain et al. in
2020 showed that in the 2nd and 3rd trimesters of
pregnancy there is a shortening of the length of
the cervix in patients who gave birth prematurely
[16].
Figure 4. The anterior uterocervical angle at 27.6 In our study, in agreement with other studies
gestational weeks. [17-19], the average value resulting from the
three measurements showed that there is a
significant difference between CL and premature
birth, the p-value of the Student test <0.05.
Also, cervical length <25mm (Figure 2, 3), is
highly significant in prediction of preterm labor
with sensitivity 99%, specificity 61%, PPV 78%,
NPV 97% and a LR+of 2.54 and LR-of 0.02.
Along with cervical length, which is the
standard for women with threatened preterm
birth, anterior cervical angle measurement can be
considered as an additional predictor of
premature birth risk, as shown by Daskalakis et
Figure 5. Pregnancy at 28.3 gestational weeks. al. in their study [20].
AP’ 19.6mm; CCI=57.8%.
But there is a weak database on the use of this
parameter in the management of threatened
preterm labor [21,22].
In the study performed, the mean anterior
cervical angle (Figure 4) between the group with
premature birth and the one with term birth
showed the same significant difference, the p-
value of the Student test <0.05 (preterm lot
101.43°±3.95 vs. term lot 92.73°±2.48), mean
ACA at the three visits showing a significant
difference (p-Anova <0.05).
Anterior cervical angle, despite low
Figure 6. Pregnancy at 28.3 gestational weeks.
specificity and positive predictive value, may be
AP 33.9mm. significant in predicting preterm birth with a
sensitivity of 100%, NPV of 100%, a LR+of 1.41,
and LR-of 0.00, especially in correlation with
cervical length.

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Current Health Sciences Journal Vol. 48, No. 2, 2022 April-June

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Corresponding Authors: Simona Daniela Neamtu, Department of Hematology, Faculty of Pharmacy,

University of Medicine and Pharmacy of Craiova, 2 Petru Rareş Street, 200349 Craiova, Dolj, Romania,
e-mail: simona_0712@yahoo.com

Anca-Maria Istrate-Ofiţeru, Department of Histology, University of Medicine and Pharmacy of Craiova,

2 Petru Rareş Street, 200349 Craiova, Dolj, Romania,
e-mail: ancaofiteru92@yahoo.com

168 10.12865/CHSJ.48.02.04