Prediction of Spontaneous Preterm Birth in Multiple Gestation by Cervical Elastogram
Conditions: Preterm Birth
Sponsor: Chinese University of Hong Kong

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Prediction of spontaneous preterm birth in multiple gestation by cervical elastogram 
 
 
Investigators: 
LEUNG Tak Yeung  
HUI Shuk Yi Annie 
POON Liona Chiu Yee 
LU Jing 
CHENG Yvonne Kwun Yue 
 
 
Affiliation:  
Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of 
Wales Hospital 
 
 
Compliance with the Declaration of Helsinki: Yes 
 
 
Protocol version: 1.3 (dated 18 Apr 2018) 
 
 
 
 
 
 
 
 
 
 

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Background 
 
Preterm birth is the leading cause of perinatal morbidity and mortality in multiple pregnancy, 
and the medical and educational expenditure and lost productivity associated with preterm 
birth is very high.  
 
The risk of preterm delivery in singleton pregnancy is 5-7%, and that in twin pregnancy is 7-8 
fold higher than singleton pregnancy. [1] Identification of pregnant women at risk of preterm 
birth could allow intervention to reduce their risk.  Treatment such as progesterone, cervical 
pessary, and surgical cerclage in selected cases have been shown to be effective measures to 
reduce the risk of preterm delivery in singletons. [2-4] Prevention of preterm birth in multiple 
pregnancy is more challenging.  A lot of preventive methods studied, including bed rest, 
tocolysis, nutritional adjustment, cerclage and cervical pessary, have not been shown to be 
effective. [5-10] Until very recently, a study have found that vaginal progesterone is effective 
in reducing preterm birth < 33 weeks in twin pregnancy with a risk reduction of 30%, and a 
significant reduction in neonatal death, respiratory distress syndrome, and composite 
morbidity and mortality was also demonstrated. [11] 
 
Premature dilatation and shortening of cervix have been demonstrated to be a very good 
predictor of preterm birth in singleton as well as twin pregnancies. [12-25] The ability to 
identify pregnant women with short cervix allows timely intervention to reduce their risk.  
Nevertheless, not all women who end up having preterm birth have a short cervix, prompting 
identification of other cervical signs to increase the prediction of preterm birth. 
 
Recently, a new ultrasound technology called sonoelastograhy has enabled the measurement 
of tissue stiffness. [26,27] It has been widely applied in assessment of breast lump and liver 
cirrhosis, as the tissue is stiffer in case of malignancy and cirrhosis. [28,29] Sonoelastography 
is potentially useful for the objective assessment of cervical consistency which could be 
related to risk of preterm birth.  A recent study has shown that strain in the internal cervical os 
has been shown to be associated with spontaneous preterm delivery in singleton pregnancies. 
[30] This study has shown some promising results in the use of elastography in prediction of 
preterm delivery, however, it is limited by the fact that the sonographic technique used is 
strain elastography, which could be affected by the pressure of the probe on the cervix.  On 
the other hand, shear wave elastography creates images based on moving waves and is 

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therefore a dynamic technique to assess energy loss when it travels through tissue.  The 
benefit being that the results are relatively independent of the operator, because strain 
elastography would not be affected by the pressure exerted on the cervix.  Furthermore, 
although strain elastography is good for measuring stiffness differences, such as stiff tumour 
inside softer liver tissue, it is not designed to measure overall variations in stiffness, as in 
cervical consistency. [31] 
 
The aim of this study is to assess the cervical consistency by shear wave elastography in 
prediction of preterm birth in multiple pregnancies. 
 
Hypothesis: 
We hypothesize that a ‘soft’ cervix as indicated by shear wave elastography is positively 
associated with the risk of preterm birth in twin pregnancies. 
 
 
Design of study 
This is a prospective non-interventional observational study. 
 
Methods 
 
Chinese women carrying multiple pregnancies attending antenatal visit at Prince of Wales 
Hospital are invited to join the study. The study details will be explained by the research 
assistant or one of the investigators and informed consent will be obtained. Demographic data, 
antenatal history will be obtained. Exclusion criteria include an age of less than 18 years, non-
Chinese, inability to provide consent and those who refuse to join.  
 
Other risk factors of preterm delivery will also be documented:  
 
known cervical insufficiency 
 
surgical cerclage or pessary in previous pregnancy 
 
history of preterm prelabour rupture of membranes (PPROM) or spontaneous preterm 
birth before 34 weeks 
 
history of cervical surgery including cone biopsy, loop electrosurgical excision 
procedure,  cervical tear repair, etc 

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 
short cervix <2.5cm cervical length 
 
painless cervical os dilatation 
 
A trained researcher or an obstetrician will perform transvaginal scan for the cervix on the 
same day of the antenatal visit, or on a separate study date, if necessary.  Measurements will 
be done at 5 visits: 11-15 weeks, 16-19 weeks, 20-23 weeks, 24-27 weeks, 28-32 weeks. The 
number of visits will be depended on when the subjects are initially recruited. 
 
The following will be measured: 
 
Cervical consistency by sonoelastogrpahy 
 
Cervical length by 2D ultrasonography 
 
Posterior cervical angle by 2D ultrasonography 
 
Fetal viability  
 
The TVS measurement of the cervical length, posterior angle and sonoelastography is 
elaborated as follow: 
 
An USG machine equipped with shear wave elastography (SWE) is used (scale set to 
0-100kPa) 
 
Participants are asked to empty the urinary bladder before TVS, and lie in lithotomy 
position  
 
A 12-3MHz transvaginal transducer (with double condom cover and lubricant) is 
inserted into the  vagina gently, with no pressure exerted on the cervix 
 
The mid-sagittal view of the cervix is obtained and magnified 
 
The cervical length and the posterior angle are then measured as described in our 
previous study [32, 33] 
 
SWE mode is then switched on and a color box showing the elastogram is 
demonstrated  
 
The color box will be placed at the central part of the anterior lip of the cervix (more 
proximal to the USG probe than the posterior lip) 
 
Once the color box is uniformly filled with color signals on the elastogram, the image 
is frozen and a region of interest (Q-box) of size 10mm is placed to measure the tissue 
elasticity (in term of kPa). 
 
Women will be asked to perform Valsalva maneuvers and mesurements of cervical 

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length, posterior angle and elastography will be obtained under such maneuver. 
 
The acquisition time is kept short within ten seconds to avoid erroneous data 
collection.   
 
Images will be saved for future analyses, if necessary. 
 
Women, including those who are found to have a short cervix, will be managed according to 
the departmental protocol and their obstetric management will not be affected by the study.  
The obstetrician will be blinded to the finding of the sonoelastography and the finding would 
not affect the obstetric management of the women. 
 
The delivery data and neonatal outcome will be collected from the medical notes and hospital 
electronic system before the women are discharged after their delivery. 
 
 
Main outcome measures: 
1. 
The association of cervical consistency in mid trimester with spontaneous preterm 
birth in women carrying multiple pregnancies. 
2. 
The change in cervical consistency during pregnancy in women carrying multiple 
pregnancies. 
 
Sample Size:  
The risk of preterm birth <34 weeks in twin pregnancies is approximately 20%.  A sample 
size of 120 was determined as being sufficient to test the diagnostic performance of cervical 
elasticity in mid trimester assuming that the risk of preterm delivery <34 weeks vs >34 weeks 
is 1:5 and that cervical elasticity area under curve (AUC) of the receiver operating 
characteristics (ROC) curve was 0.7, with 80% power and alpha of 5%. From the start of 
recruitment up to March 2018, only 15 (34.1%) out of 44 cases had completed all five serial 
cervix measurements. We aim to collect 120 completed set of measurements to allow our 
result to be statistically significant. Therefore, we increase the sample size to 200.    
 
Statistical Analysis: 
Changes in the cervical elastography will be compared using the Student paired two-tailed t 
test, and in the case of unequal standard deviation (SD), using a Wilcoxon signed-rank paired 

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two-tailed test. For comparison of frequencies, Chi-square test, or a two-sided Fisher exact 
test will be used where appropriate. Linear regression will be used to assess the correlations.  
Statistical analysis was performed using the Statistical Package for Social Science (SPSS) 
version 20.0 (SPSS, IL). The level of statistical significance is set at p<0.05 (two-sided).  
 
Purpose and Potential 
A significant improvement in the prediction of preterm delivery allows accurate 
differentiation of those women who would benefit from treatment for prevention of preterm 
birth in multiple pregnancy.  This would avoid unnecessary intervention, reduce maternal and 
fetal complications, and has a potential to save medical cost. 
 
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