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The Journal of Maternal-Fetal & Neonatal Medicine

ISSN: 1476-7058 (Print) 1476-4954 (Online) Journal homepage: http://www.tandfonline.com/loi/ijmf20

Changes in ectocervical surface area in women


throughout pregnancy compared to non-pregnant
and postpartum states
Xueya Qian, Yanmin Jiang, Lei Liu, Shao-qing Shi, Robert E. Garfield & Huishu
Liu
To cite this article: Xueya Qian, Yanmin Jiang, Lei Liu, Shao-qing Shi, Robert E. Garfield &
Huishu Liu (2016): Changes in ectocervical surface area in women throughout pregnancy
compared to non-pregnant and postpartum states, The Journal of Maternal-Fetal & Neonatal
Medicine, DOI: 10.3109/14767058.2016.1140739
To link to this article: http://dx.doi.org/10.3109/14767058.2016.1140739

Published online: 10 Feb 2016.

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ISSN: 1476-7058 (print), 1476-4954 (electronic)
J Matern Fetal Neonatal Med, Early Online: 15
! 2016 Taylor & Francis. DOI: 10.3109/14767058.2016.1140739

ORIGINAL ARTICLE

Changes in ectocervical surface area in women throughout pregnancy


compared to non-pregnant and postpartum states
Xueya Qian1,2, Yanmin Jiang1, Lei Liu1, Shao-qing Shi1, Robert E. Garfield1, and Huishu Liu1
1

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Preterm Birth Prevention and Treatment Unit, Department of Obstetrics, Guangzhou Women and Childrens Medical Center, Guangzhou Medical
University, Guangzhou, China and 2Department of Obstetrics, First Affiliated Hospital of Jinan University, Guangzhou, China
Abstract

Keywords

Objective: The objective of this study is to estimate changes in the surface area of the ectocervix
(CA) in women during pregnancy and compare this to postpartum and non-pregnant states.
Methods: CA was evaluated in 210 normal nulliparous women divided into groups from early to
late gestation, 40 postpartum women, and 25 non-pregnant women. CA in cm2 was estimated
from analysis of images taken with an endoscope of the cervical face and an mm scale. An mm
scale was also used to determine fornix length and fornix area computed.
Results: The face, fornix, and total areas of the CA of non-pregnant and postpartum groups are
significantly smaller (p50.001) than these areas in groups during pregnancy. Generally, the CA
of the face, fornix, and total area are also less in early pregnancy compared with late gestation
(p50.01 to50.001). Total CA correlates with gestational age (r 0.196, p50.004).
Conclusions: (1) During pregnancy, CA slowly and progressively increases to475% area
compared with CA of non-pregnant patients and then reverts back to low CA postpartum.
(2) Increases in CA during pregnancy occur in both the face and fornix areas. (3) Increases in CA
reflect enlargement in cervical volume and remodeling during pregnancy.

Ectocervix, endoscope, fornix, postpartum,


pregnancy

Introduction
During pregnancy, the cervix remains closed and firm in
order to prevent passage of an immature infant through the
birth canal. Conversely, at term, the cervix is pliable and
opens sufficiently to allow delivery of a fetus [1]. The
transformation of the cervix from a closed rigid structure to
one that opens adequately for birth is an active dynamic
process that begins long before the onset of labor [25].
Cervical remodeling or ripening during pregnancy can be
loosely divided into three successive steps termed softening,
effacement, and dilation. Following birth remodeling continues with postpartum repair and return to the non-pregnant
rigid state. Changes leading to progressive softening in
pregnancy and ripening at term are related to microstructural
modifications mainly identified as an increased hydration and
loss of organization in connective tissue and extracellular
matrix [49]. Tissue hydration, collagen content, and tissue
elasticity all change progressively with cervical remodeling
during pregnancy and have been studied in many species.
These studies demonstrate that water content increases,
collagen disorganizes and decreases, glycosaminoglycans
decrease, hyaluronic acid increases, and proteoglycans
Address for correspondence: Professor Huishu Liu, Department of
Obstetrics and Gynecology, Guangzhou Women and Childrens Hospital,
9 Jinsui Road, Guangzhou, China. Tel: +86 139 2415 2738. E-mail:
huishuliu@hotmail.com

History
Received 8 December 2015
Accepted 7 January 2016
Published online 8 February 2016

increase and, therefore, elasticity and extensibility (softness)


increases [1,4,612].
There is considerable interest in developing new techniques to observe and quantify cervical remodeling during
pregnancy. Better understanding of the process of cervical
remodeling is critical for the development of therapies to
treat cervical malfunction in term and preterm birth and
post-term pregnancy. Thus, various methods have been
used to evaluate changes in physical and mechanical
changes in the cervix during remodeling in vivo and in
vitro, including microscopy [1,13,14], electrical impedance
[15], extensibility tests [16], light-induced florescence
(LIF) [16,17], elastography [18], aspiration techniques
[19], ultrasound [20,21], Raman spectroscopy [22], and
other methods [23].
Recent studies have shown that the external cervical
surface area (CA) in a pregnant rat model using a small
endoscopic camera [24]. These studies demonstrated that (1)
the CA increases during gestation; (2) term birth and cervical
softening were partially prevented by progestin treatment
(progesterone, and 17ahydroxyprogesterone caproate)
[24,25]. Thus, studies of the CA might be used to evaluate
normal changes in the cervix during pregnancy and the effects
of various treatments. The primary aim of this study was to
examine CA in pregnant women at various times of
pregnancy and compare it with CA values obtained from
non-pregnant and postpartum patients.

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X. Qian et al.

J Matern Fetal Neonatal Med, Early Online: 15

Methods

Statistical analyses

Patients

The statistical significance of intergroup differences was


evaluated by analysis of variance (ANOVA) and Student
NewmanKeuls test. The Pearson correlation analysis was
used to study the association between CA and clinic data
(gestational age and BMI), r correlation coefficient. All
statistical tests were two-sided and the level of significance
was recognized as p50.05. Normality tests, sample size, and
power calculations were estimated for all data with an alpha
of 0.050 and a power of 0.80. All statistical analyses were
performed using the IBM SPSS 17.0 software (SPSS Inc.,
Chicago, IL).

Pregnant nulliparous women undergoing antenatal exams at


various stages of gestation before cervical dilation (n 210),
non-pregnant women of childbearing age at indeterminate
stages of menstrual cycle (n 25), and postpartum primiparous women (4060 days after delivery, n 40) were randomly
selected for this study during routine antenatal, postpartum, or
gynecological examinations. Written informed consent was
obtained from all the patients who were eligible for participation. The study protocol was approval by Medicine
Institutional Review Board of Guangzhou Women and
Childrens Medical Center (Protocol number 2014110533).
In the pregnant women, the completed gestational weeks
was determined by the date of the first day of the last
menstrual period and confirmed by ultrasound scan. Patients
were excluded from the study if they received any form of
therapy for the cervix or any treatment for complications that
would affect delivery patterns or if the whole cervical face
could not be visualized with the endoscopic camera. The
patients clinical records and information were obtained
regarding the following parameters: age and BMI (BMI at
time of CA measurements).
Measurement of ectocervix (CA)
Optical evaluation of the cervix was obtained from digital
photos taken with an endoscopic camera (Sunny Medical
Equipment Co., Shanghai, China). A speculum was inserted
into the vagina and opened to visualize the whole external
cervix and care was taken to not compress or distort the
cervix. CA in cm2 was estimated from measurements of face
of the cervix (face area) + fornix area to give the total area
(face area + fornix area). The face area was estimated from
morphometric analysis using ImageJ software (version 1.43,
download at rsb.info.nih.gov/ij) [26] of digital images taken
with the endoscope of the cervical face and an mm scale
together (used to correct for differences in distance of the
camera to the cervix and magnification of the photos) during
dilation of the vagina with a speculum. An mm scale was also
used to determine posterior cervical fornix length and fornix
area computed from the circumference of the face  the fornix
length. The accuracy of the mm scale for fornix measurements was estimated to be 1 mm. One investigator acquired
all digital data with the same camera for all data expressed in
this study. However, there were no significant differences
(p40.05) in measurements made by separate investigators at
the same time on some of the same patients.

Results
Clinical characteristics of patients in study
Table 1 shows the age and body mass index (BMI) of
pregnant, non-pregnant, and postpartum patients used in this
study. There are no significant differences (p40.05) in ages
and BMI between the various groups.
Photos of cervix from pregnant, postpartum,
and non-pregnant women
Figure 1 shows representative photographs of the cervix of
women at early (A, 7 weeks) and late (B, 37 weeks) gestation,
and from women at non-pregnant (C) and postpartum (D)
stages. All photos were taken and printed at approximately the
same magnification.
Analysis of CA in non-pregnant, pregnant, and
postpartum patients
Table 2 shows the comparisons of mean areas (cm2 SEM) of
face, fornix, and total CA areas in each group of nonpregnant, pregnant (a range of 640 weeks gestation, divided
into various times) and postpartum. There are no differences
(p40.05) in mean areas of face, fornix, and total areas in nonpregnant versus postpartum CA values. However, the face,
fornix, and total areas of non-pregnant and postpartum mean
values are significantly smaller than the areas at all times of
pregnancy (p50.001). The total CA (cm2) in all pregnant
patients (n 210) significantly correlates (r 0.196,
p 0.004) with increasing of gestational age. Similarly, the
face and the fornix area of the cervix significantly correlate
with gestational age (face: r 0.176, p 0.011, and fornix:
r 0.173, p 0.012). In addition, the face area at514 and
1428 weeks versus 437 weeks is significantly smaller,
p50.01 as are the fornix and total areas at514 weeks versus
437 weeks, p50.001. Comparison of the face, fornix, and

Table 1. Clinical characteristics of patients.


Groups
Pregnant
Non-pregnant
Postpartum

Number of patients

Maternal age (years)

Gestational Age (weeks)

Body Mass Index (kg/m2)

210
25
40

28.97 (2142)
28.72 (2335)
28.87 (2136)

23.41 (4.441.1)
NA
NA

23.00 (16.4437.81)
21.63 (17.5028.13)
22.14 (17.8530.11)

Clinical characteristics of pregnant, non-pregnant, and postpartum patients in study including number of patients, maternal and
gestation ages, and body mass index (means with ranges in brackets) at times of measurements of CA. There are no significant
differences (p40.05) in maternal ages and body mass index between the groups.

Changes in ectocervix during perinatal stage

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DOI: 10.3109/14767058.2016.1140739

total areas of CA in the non-pregnant states versus late


gestation (437 weeks) demonstrate increases of about 50% in
face area, a 90% in fornix area, and a 75% in total area and
about the same decrease in CA postpartum (differences in
mean values at437 weeks gestation versus CA of nonpregnant and postpartum).

between face areas and BMI (r 0.022, p 0.753). In


addition, there are no significant differences (p40.05) in
face and total areas of CA versus BMI when patients with
different BMI values are divided into groups representing low
(BMI of518.5), mid (BMI of 18.524.99 and 2527.99) and
high BMI values (BMI of 2832), data not shown.

Analysis of BMI and CA

Discussion

The total CA does not correlate with the BMI of the patients
(r 0.120, p 0.056). Similarly, there is no correlation

In this study, the external cervical surface areas was examined


of the ectocervix (CA) of the face, fornix, and total CA of

Figure 1. Photographs of the cervix from


non-pregnant, pregnant, and postpartum
women. Representative photographs of the
face of the cervix from early (A, 7 weeks) and
late (B, 37 weeks) gestation, non-pregnant
(C), and postpartum (D). All photos are
printed at about the same magnification. Note
that areas of the areas of the face of the cervix
as measured in this study were calculated
from photos taken of the face of the cervix
and an mm scale in the same image to correct
for any differences in magnification (see
Methods section).

Table 2. Comparison of cervical areas in pregnant, non-pregnant and postpartum patients.


Areas (cm2, mean SEM)
Groups
Non-pregnant
Pregnant groups
514 wks
14528 wks
28537 wks
37 wks
Post-partum

Number of patients
25
34
103
54
19
40

Face

Fornix
a

Total (face + fornix)


a

4.59 0.24

12.05 0.64

16.94 0.71a

6.00 0.18bc
5.83 0.12b
6.28 0.16bc
6.85 0.39c
4.30 0.17a

18.52 0.74b
21.23 0.51c
20.64 0.63bc
23.25 1.26c
10.00 0.57a

24.52 0.81b
26.95 0.56bc
26.92 0.68bc
30.09 1.46c
14.45 0.71a

Cervical surface areas (mean areas, cm2 SEM) of face, fornix, and total areas in the number of patients in each group of
non-pregnant, pregnant (divided into various times of gestation in weeks, wks) and postpartum (4060 d after delivery).
Different superscript letters between mean values of each group of a column depict significant differences (p50.05) in
mean areas. Specific p values: There are no differences (p40.05) in mean areas of face, fornix, and total areas in nonpregnant versus postpartum values. Comparison of face, fornix, and total area of non-pregnant and postpartum mean
values versus all times of pregnancy p50.001; face area at 1428 weeks versus 437 weeks, p50.01; fornix and total
areas at 514 weeks versus. 437 weeks, p50.001.

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X. Qian et al.

women at different gestational ages and from non-pregnant


and postpartum women. We found that the CA of all areas
increase significantly with the gestational age but are
independent of BMI, except the fornix which enlarges
partially with elevated BMI. The CA of pregnant women
was significantly larger (about 75% greater in total CA area)
than the CA of non-pregnant and postpartum groups and the
CA increases gradually and progressively throughout gestation. This increase in size of the ectocervix during pregnancy
is probably related to and associated with increased tissue
hydration and remodeling of the connective tissue, changes in
the structure and composition of the cervix, during pregnancy
[16,11]. The postpartum reversal following pregnancy most
likely represents a return to the more rigid state of the cervix.
The consistent and precise identification of the changes
that occur in the cervix is one of the challenges that face
obstetricians today in order to determine normal cervical
function. Various new methods have been used to assess
cervical changes. Such as measurement by transvaginal
ultrasound scan [2022], by magnetic resonance imaging
[27], by second harmonic generation (SHG) microscopy [28],
by LIF [16], by Raman spectroscopy [22], and by electrical
impedance [18]. These methods are somewhat difficult to
operate, costly, and cumbersome compared with the endoscopic camera and morphometric analysis used in this study.
The external cervical surface face area was recently studied
in a pregnant rat model using a small endoscopic camera [24].
This study showed that the surface face area increased about
300% during gestation and an increase occurred during
preterm birth induced with RU486. One can assume that the
changes in CA observed in the present study accompany
changes in other dimensions of the cervix, as mentioned
above and that CA might be used to evaluate normal changes
in the cervix during pregnancy and the effects of various
treatments, including progestins.
The present study demonstrates that optical evaluation of
the ectocervix with an endoscopic camera can be useful for
the assessment of quantitative changes in cervical remodeling
in humans during pregnancy. The advantages of this technique are its non-invasiveness, ease of use, and possible cost
effectiveness. This optical evaluation method reveals changes
in the cervix earlier than many other techniques. This has
never been described in humans and may reveal a high
potential for the assessment of cervical changes in pregnancy
and this may offer an opportunity for early detection of
enhanced risk of premature delivery or for prediction of failed
induction of labor.
This optical evaluation is not without shortcomings and
limitations. These are: (1) It is limited to evaluation of only
the ectocervix. (2) There is considerable variability among
patients and knowledge of what constitutes normal cervical
changes throughout pregnancy could form the basis of
longitudinal studies of the cervix.
The optical evaluation of the cervix with an endoscopic
camera is not only helpful for the evaluation of the regular
cervical changes throughout pregnancy. It also could be of
value for the assessment of other obstetric problems and
diseases such as infections, cervical inflammation, dysplasias,
and cancers, especially in the context of follow-up examinations. The optical evaluation and the assessment of the

J Matern Fetal Neonatal Med, Early Online: 15

surface area of the cervix is a new, effective, non-invasive,


objective, low-cost method to assess cervical changes during
pregnancy and to evaluate the success of pharmacologic
interventions. It is clear that we still have much to learn about
the mechanisms and processes of cervical remodeling during
pregnancy.
We conclude that (1) total CA slowly and progressively
increases to about 75% during pregnancy and then reverts
back to lower CA postpartum. (2) The change in CA probably
reflects physiological changes in cervical volume and
remodeling. (3) CA might be used to estimate abnormal
function of the cervix in pregnant and non-pregnant women or
be predictive of successful vaginal delivery, induction or
cesarean section. (4) CA correlation with other data such as
collagen content, cervical length, or other measurements is
worthwhile to further examine the nature of cervical changes
in pregnancy and its correlation to clinical outcomes and
conditions.

Declaration of interest
The authors report that they have no conflicts of interest.

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