Research Explorer | The University of Manchester
Full Title: Intra- and interexaminer variability in 3D fetal volume measurements during the second and third trimesters of pregnancy.Short Title: 3D fetal ultrasound reliabilityAuthors: Simcox LE1,2, Higgins LE1,2, Myers JE1,2, Johnstone ED1,2.1 Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester. 2 St. Mary’s Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL.Correspondence:Dr. Louise SimcoxClinical Research FellowMaternal and Fetal Health Research CentreUniversity of Manchester5th Floor ResearchSt. Mary’s HospitalOxford RoadManchesterM13 9WLLouise.simcox@postgrad.manchester.ac.ukTel: +44 (0) 777 607 7051Fax: +44 (0) 161 701 6971Keywords: Three-dimensional ultrasound, reliability, fractional thigh volume, total thigh volume, head volume, kidney volume, placental volume, VOCALAbstractObjective: To assess intra- and inter-examiner reliability of three dimensional fetal ultrasound measurements.Methods: Three dimensional (3D) fetal organ volumes (head, kidney, total thigh volume and fractional thigh volume (TVol)) were acquired during the second and third trimester, with the addition of placental volume in the second trimester, by 2 different experienced, blinded sonographers. 58 fetuses were examined from 21-39 weeks gestation. Intra and Inter-examiner reliability was assessed using Bland-Altman plots and their 95% limits of agreement, and intraclass correlation coefficients.Results: The most significant inter-examiner error was observed in second trimester kidney volume (95% limits of agreement ± 110%), and the best agreement was for third trimester TVol (95% limits of agreement ± 25%), and second trimester head volume (95% limits of agreement -7 to +25%). Second trimester and third trimester ICC results were all >0.75 apart from second trimester kidney volume intra (0.374) and inter-examiner (0.061) measurements, second trimester placenta inter-examiner measurements (0.390), and third trimester kidney inter-examiner measurements (0.647).Conclusions: 3D fetal ultrasound volumes of the head, kidney, total thigh and placenta have limited reproducibility and improvement in measurement techniques is needed before they can be used routinely to assess fetal growth. 3D TVol is reliably obtained in the late third trimester.IntroductionPrevious work has suggested that 3D sonography may facilitate more accurate assessment of fetal weight (either in addition to, or replacing, standard two-dimensional (2D) biometry), with measurements such as the inclusion of fractional limb volume in 2D fetal weight estimation formulas PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5ZYW5nPC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA (1-3). It is also proposed that the volume-rendering capabilities of 3D ultrasound will result in more accurate, precise and standardised measurements, which is particularly important in improving estimations of fetal weight in the late third trimester ADDIN EN.CITE <EndNote><Cite><Author>Platt</Author><Year>2000</Year><RecNum>137</RecNum><DisplayText>(4)</DisplayText><record><rec-number>137</rec-number><foreign-keys><key app="EN" db-id="2ptzwtrz3a5xaher5rtvttrv0vx299fatpzz">137</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Platt, L. D.</author></authors></contributors><titles><title>Three-dimensional ultrasound, 2000</title><secondary-title>Ultrasound Obstet Gynecol</secondary-title><alt-title>Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology</alt-title></titles><periodical><full-title>Ultrasound Obstet Gynecol</full-title><abbr-1>Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology</abbr-1></periodical><alt-periodical><full-title>Ultrasound Obstet Gynecol</full-title><abbr-1>Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology</abbr-1></alt-periodical><pages>295-8</pages><volume>16</volume><number>4</number><keywords><keyword>Gynecology/*trends</keyword><keyword>Humans</keyword><keyword>Medical Laboratory Science</keyword><keyword>Obstetrics/*trends</keyword><keyword>Ultrasonography/*methods/trends</keyword><keyword>Ultrasonography, Prenatal/methods/trends</keyword></keywords><dates><year>2000</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0960-7692 (Print)
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ADDIN EN.CITE.DATA (6, 7). Other studies, examining placental volumes in the first trimester, have demonstrated that 3D methods are superior when compared to 2D ultrasound ADDIN EN.CITE <EndNote><Cite><Author>Hata</Author><Year>2011</Year><RecNum>309</RecNum><DisplayText>(8)</DisplayText><record><rec-number>309</rec-number><foreign-keys><key app="EN" db-id="2ptzwtrz3a5xaher5rtvttrv0vx299fatpzz">309</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hata, T.</author><author>Tanaka, H.</author><author>Noguchi, J.</author><author>Hata, K.</author></authors></contributors><auth-address>Department of Perinatology and Gynecology, Kagawa University School of Medicine, Kagawa 761-0793, Japan. toshi28@med.kagawa-u.ac.jp</auth-address><titles><title>Three-dimensional ultrasound evaluation of the placenta</title><secondary-title>Placenta</secondary-title><alt-title>Placenta</alt-title></titles><periodical><full-title>Placenta</full-title><abbr-1>Placenta</abbr-1></periodical><alt-periodical><full-title>Placenta</full-title><abbr-1>Placenta</abbr-1></alt-periodical><pages>105-15</pages><volume>32</volume><number>2</number><keywords><keyword>Female</keyword><keyword>Fetal Growth Retardation/ultrasonography</keyword><keyword>Gestational Age</keyword><keyword>Hemangioma/ultrasonography</keyword><keyword>Humans</keyword><keyword>Hydrops Fetalis/ultrasonography</keyword><keyword>Imaging, Three-Dimensional/*methods</keyword><keyword>Placenta/blood supply/*ultrasonography</keyword><keyword>Placenta Diseases/ultrasonography</keyword><keyword>Pregnancy</keyword><keyword>Ultrasonography, Prenatal/*methods</keyword></keywords><dates><year>2011</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1532-3102 (Electronic)
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ADDIN EN.CITE.DATA (9-12).Sonographic volume calculations have now been described in a variety of fetal organs and structures PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Sb2VsZnNlbWE8L0F1dGhvcj48WWVhcj4yMDA0PC9ZZWFy
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ADDIN EN.CITE.DATA (13-20). In the majority of cases this is achieved by manual organ segmentation, using one of two methods: the multiple parallel plane method (multiplanar) or the rotational Virtual Organ Computer-aided Analysis (VOCAL; GE Medical Systems, Zipf, Austria) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Jb2Fubm91PC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48
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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Jb2Fubm91PC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48
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ADDIN EN.CITE.DATA (21). The VOCAL technique has the advantage of being quicker, and allowing the modification of the outline of the organ which is particularly useful for fetal organs with irregular shapes PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ub25uaTwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (18, 22-24), with good in-vitro reproducibility in some structures ADDIN EN.CITE <EndNote><Cite><Author>Barreto</Author><Year>2015</Year><RecNum>505</RecNum><DisplayText>(18)</DisplayText><record><rec-number>505</rec-number><foreign-keys><key app="EN" db-id="2ptzwtrz3a5xaher5rtvttrv0vx299fatpzz">505</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Barreto, E. Q.</author><author>Araujo Junior, E.</author><author>Martins, W. P.</author><author>Rolo, L. C.</author><author>Milani, H. J.</author><author>Nardozza, L. M.</author><author>Moron, A. F.</author></authors></contributors><auth-address>Department of Obstetrics, Paulista School of Medicine - Federal University of Sao Paulo (EPM-UNIFESP) , Sao Paulo - SP , Brazil and.</auth-address><titles><title>New technique for assessing fetal heart growth using three-dimensional ultrasonography: description of the technique and reference curves</title><secondary-title>J Matern Fetal Neonatal Med</secondary-title><alt-title>The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians</alt-title></titles><periodical><full-title>J Matern Fetal Neonatal Med</full-title><abbr-1>The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet</abbr-1></periodical><pages>1087-93</pages><volume>28</volume><number>9</number><dates><year>2015</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>1476-4954 (Electronic)
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ADDIN EN.CITE.DATA (24). Therefore, although this technique can be used interchangeably between some VOCAL and multiplanar techniques for regular volumes such as the fetal thigh PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BcmF1am8gSnVuaW9yPC9BdXRob3I+PFllYXI+MjAxMTwv
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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BcmF1am8gSnVuaW9yPC9BdXRob3I+PFllYXI+MjAxMTwv
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ADDIN EN.CITE.DATA (22), its results seem less valid when assessing irregular structures such as placental volumes PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaGVvbmc8L0F1dGhvcj48WWVhcj4yMDEwPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (23). Accurate 3D volume acquisition is dependent on the quality of the 2D image and as such is very operator dependent. This increases the likelihood for random measurement error and methodological inconsistencies between studies. A recent reliability study comparing biometry and fetal weight estimation using 2D and 3D ultrasound concluded that measurements performed with 3D ultrasound were less influenced by random errors ADDIN EN.CITE <EndNote><Cite><Author>Lima</Author><Year>2012</Year><RecNum>172</RecNum><DisplayText>(25)</DisplayText><record><rec-number>172</rec-number><foreign-keys><key app="EN" db-id="2ptzwtrz3a5xaher5rtvttrv0vx299fatpzz">172</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lima, J. C.</author><author>Miyague, A. H.</author><author>Filho, F. M.</author><author>Nastri, C. O.</author><author>Martins, W. P.</author></authors></contributors><auth-address>Departamento de Ginecologia e Obstetricia da Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo (FMRP-USP), Ribeirao Preto, Brazil.</auth-address><titles><title>Biometry and fetal weight estimation by two-dimensional and three-dimensional ultrasonography: an intraobserver and interobserver reliability and agreement study</title><secondary-title>Ultrasound Obstet Gynecol</secondary-title><alt-title>Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology</alt-title></titles><periodical><full-title>Ultrasound Obstet Gynecol</full-title><abbr-1>Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology</abbr-1></periodical><alt-periodical><full-title>Ultrasound Obstet Gynecol</full-title><abbr-1>Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology</abbr-1></alt-periodical><pages>186-93</pages><volume>40</volume><number>2</number><dates><year>2012</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1469-0705 (Electronic)
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ADDIN EN.CITE.DATA (21).The aim of this study was to assess measurement reliability of 3D fetal volume measurements and placental volume measurements within and between examiners on the same occasion in the second and third trimester.Materials and MethodsStudy populationBetween January and June 2014, intra- and inter-examiner reliability of fetal and placental volume measurement was assessed in one tertiary referral unit (St Mary’s Hospital Manchester). This was part of a longitudinal prospective study of fetal and placental biometry using 2D and 3D ultrasound. Women with healthy uncomplicated pregnancies were invited to participate on the basis of strict inclusion and exclusion criteria. Exclusion criteria were; any fetus subsequently shown to have a serious congenital abnormality, pregnancies with multiple gestations, and maternal medical conditions that are known to affect growth such as maternal diabetes and chronic hypertension. Pregnancies were accurately dated using fetal crown-rump length (CRL) measurements prior to 14 weeks gestation. The study was approved by the Greater Manchester East National Research Committee (Ref 10/H1013/9), and all participants were enrolled following written informed consent. Ultrasonographic data collectionAll 3D ultrasonography was performed by two RCOG accredited sonographers (LS and LH), using a Voluson E6 (GE Healthcare) with 3D 4-8Hz curvilinear probe. 3D organ volumes (placenta, head, kidney, total thigh and TVol at 14-16 weeks, head, kidney total thigh and TVol at 20-22 weeks, 26-28 weeks and 34-36 weeks gestation) were acquired during each trimester. Intra and inter-operator reproducibility were assessed in 25 women in the second trimester and 33 women in the third trimester for the following ultrasound measures: 3D TVol, total thigh volume, head volume, kidney volume and placental volume using a VOCAL technique with manual delimitation. Excluding placental volume, which was only assessed in the second trimester, reliability was assessed at different gestational age time points in the second and third trimesters of pregnancy to evaluate previously reported increased inter-examiner percentage differences when measuring smaller fetal organ volumes ADDIN EN.CITE <EndNote><Cite><Author>Ioannou</Author><Year>2013</Year><RecNum>246</RecNum><DisplayText>(26)</DisplayText><record><rec-number>246</rec-number><foreign-keys><key app="EN" db-id="2ptzwtrz3a5xaher5rtvttrv0vx299fatpzz">246</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ioannou, C.</author><author>Sarris, I.</author><author>Napolitano, R.</author><author>Ohuma, E.</author><author>Javaid, M. K.</author><author>Papageorghiou, A. T.</author></authors></contributors><auth-address>Nuffield Department of Obstetrics & Gynaecology, University of Oxford, UK.</auth-address><titles><title>A longitudinal study of normal fetal femur volume</title><secondary-title>Prenat Diagn</secondary-title><alt-title>Prenatal diagnosis</alt-title></titles><periodical><full-title>Prenat Diagn</full-title><abbr-1>Prenatal diagnosis</abbr-1></periodical><alt-periodical><full-title>Prenat Diagn</full-title><abbr-1>Prenatal diagnosis</abbr-1></alt-periodical><pages>1088-94</pages><volume>33</volume><number>11</number><dates><year>2013</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1097-0223 (Electronic)
0197-3851 (Linking)</isbn><accession-num>23868615</accession-num><urls><related-urls><url>;(26). Automated volume measurements were obtained using the Voluson 4D view (GE Healthcare) tool. Each participant had a minimum of two volume calculations for each of the different measures, performed on separately acquired volumes. Examiner 1 (L.S.: 3 years of experience with 2D ultrasound and 1 year of experience with 3D ultrasound) performed growth measurements on the fetus using 2D ultrasound and acquired 3D volume datasets for later evaluation. Once all the data had been acquired, examiner 1 then left the examination room and examiner 2 (L.H.: 3 years of experience with 2D ultrasound and 1 year of experience with 3D ultrasound) entered to perform an examination to acquire the 3D volume datasets for determination of inter-examiner reliability and agreement. Afterwards, examiner 1 then re-entered the room and repeated the same examination to acquire the 3D volume datasets only for the evaluation of intra-examiner reliability and agreement. A series of three measurement sets were obtained (LS1, LH, LS2). The two examiners were not blinded to the clinical information or the name of each participant at the time of examination. However, volume measurements did not appear on the screen at the time of the ultrasound scan. The initial acquisition for examiner 1 took approximately 20 minutes; with the following further 2 examinations taking 15 minutes each, resulting in a total evaluation time of 50 minutes for each participant. Image data were archived on digital media for subsequent offline analysis and were analysed in a random order, blinded to patient identity, gestation and image pairing. Offline analysis time took approximately 2-5 minutes to estimate each fetal volume. Intra-examiner variation was assessed by comparison of LS1 and LS2 values, whilst inter-examiner reliability was assessed by comparison of LS1 and LH values ADDIN EN.CITE <EndNote><Cite><Author>Bland</Author><Year>2003</Year><RecNum>318</RecNum><DisplayText>(27)</DisplayText><record><rec-number>318</rec-number><foreign-keys><key app="EN" db-id="2ptzwtrz3a5xaher5rtvttrv0vx299fatpzz">318</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bland, J. M.</author><author>Altman, D. G.</author></authors></contributors><auth-address>St George's Hospital Medical School, London, UK.</auth-address><titles><title>Applying the right statistics: analyses of measurement studies</title><secondary-title>Ultrasound Obstet Gynecol</secondary-title><alt-title>Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology</alt-title></titles><periodical><full-title>Ultrasound Obstet Gynecol</full-title><abbr-1>Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology</abbr-1></periodical><alt-periodical><full-title>Ultrasound Obstet Gynecol</full-title><abbr-1>Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology</abbr-1></alt-periodical><pages>85-93</pages><volume>22</volume><number>1</number><keywords><keyword>Confidence Intervals</keyword><keyword>Data Interpretation, Statistical</keyword><keyword>Regression Analysis</keyword><keyword>*Research Design</keyword><keyword>Statistics as Topic</keyword><keyword>Statistics, Nonparametric</keyword></keywords><dates><year>2003</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0960-7692 (Print)
0960-7692 (Linking)</isbn><accession-num>12858311</accession-num><urls><related-urls><url>;(27).Each volume was only measured once and the methods of image analysis are described below.Fractional thigh volume acquisitionThis technique has previously been described by Lee et al PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MZWU8L0F1dGhvcj48WWVhcj4yMDA5PC9ZZWFyPjxSZWNO
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ADDIN EN.CITE.DATA (16). Image depth and magnification were adjusted for the volume of interest so that it filled at least two-thirds of the display screen. Each fractional thigh volume acquisition was acquired from a sagittal sweep of the entire femoral diaphysis. The volume was opened in the multiplanar mode with the sagittal view displayed in plane A, the axial view in plane B and the coronal view in plane C. Volume measurements were based on 50% of the femoral diaphysis (TVol) length. The femur diaphysis length (FDL) was measured in the sagittal plane and each volume was automatically sub-divided into 5 equidistant slices that were centred along the mid-thigh. Soft tissue borders were enhanced by the use of a colour filter (sepia) with additional gamma curve adjustments for brightness and contrast. Fractional thigh volumes were calculated after each of the 5 slices were manually traced from a transverse view of the extremity (Figure 1 – Fractional Thigh Volume).Virtual Organ Computer-aided Analysis (VOCAL, GE Healthcare)For this technique, the fetal organ of interest (thigh, kidney head or placenta) was displayed on the screen in three orthogonal planes (Figure 2 – Vocal 30 Head Volume; Figure 3 – Vocal 30 Placenta Volume; Figure 4 – Vocal 30 Thigh Volume; Figure 5 – Vocal 30 Kidney Volume). Plane A (top left image) was selected in the multiplanar display and the fetal organ outline was highlighted manually in that plane and the volume estimates were computed utilising the VOCAL program with a manual trace at 30o of rotation. The outer aspects of the different fetal organs were drawn on every image displayed sequentially in this plane. At the end of the 180o rotation, the volume was automatically calculated by the custom software PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CZW5pbm5pPC9BdXRob3I+PFllYXI+MjAxMDwvWWVhcj48
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ADDIN EN.CITE.DATA (28). For placental volumes, the sweep angle of the ultrasound probe was adjusted to a maximum of 850 to ensure that the whole placenta could be captured in its entirety in a single 3D sweep PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Kb25lczwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (29). For kidney volume acquisition, a coronal section of the fetal kidney with the organ proximal to the transducer and distal to the fetal vertebral column (to avoid acoustic shadowing), was identified by 2D ultrasound and the volume box adjusted accordingly to scan the entire kidney PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Zb3NoaXpha2k8L0F1dGhvcj48WWVhcj4yMDEzPC9ZZWFy
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ADDIN EN.CITE.DATA (19). Sweep angles were adjusted from 300 to 600 for fetal kidneys, and from 650 to 850 for acquisition of fetal head and thigh images depending on gestation. The justification for using 30 degrees for VOCAL rotational slices is largely based on previous literature that has revolved around the use of this method with good reliability demonstrated PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BcmF1am8gSnVuaW9yPC9BdXRob3I+PFllYXI+MjAxNDwv
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ADDIN EN.CITE.DATA (32, 33). Systematic bias was defined as the mean percentage difference between two measurements, and limits of agreement were reflected by the 95% confidence intervals (CI) of the mean percentage difference. If 0 lay within the 95% confidence intervals for the mean difference, we concluded there was no systematic bias. Inter and intra-examiner reliability was also assessed using absolute agreement two-way mixed intraclass correlation coefficients (ICCs) ADDIN EN.CITE <EndNote><Cite><Author>Kottner</Author><Year>2008</Year><RecNum>531</RecNum><DisplayText>(34)</DisplayText><record><rec-number>531</rec-number><foreign-keys><key app="EN" db-id="2ptzwtrz3a5xaher5rtvttrv0vx299fatpzz">531</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kottner, J.</author><author>Dassen, T.</author></authors></contributors><auth-address>Department of Nursing Science, Centre for Humanities and Health Sciences, Charite Universitatsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany. jan.kottner@charite.de</auth-address><titles><title>Interpreting interrater reliability coefficients of the Braden scale: a discussion paper</title><secondary-title>Int J Nurs Stud</secondary-title><alt-title>International journal of nursing studies</alt-title></titles><periodical><full-title>Int J Nurs Stud</full-title><abbr-1>International journal of nursing studies</abbr-1></periodical><alt-periodical><full-title>Int J Nurs Stud</full-title><abbr-1>International journal of nursing studies</abbr-1></alt-periodical><pages>1238-46</pages><volume>45</volume><number>8</number><keywords><keyword>*Data Interpretation, Statistical</keyword><keyword>Humans</keyword><keyword>*Nursing Assessment/methods/standards</keyword><keyword>Nursing Evaluation Research/*methods</keyword><keyword>*Observer Variation</keyword><keyword>Peas</keyword><keyword>Predictive Value of Tests</keyword><keyword>Pressure Ulcer</keyword><keyword>Psychometrics</keyword><keyword>*Research Design</keyword><keyword>Risk Assessment</keyword></keywords><dates><year>2008</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0020-7489 (Print)
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ADDIN EN.CITE.DATA (35).ResultsThe median (range) gestational age at ultrasound examination in the 25 pregnant women examined in the second trimester and the 33 women in the third trimester was 23 (21-23) weeks and 33 (28-39) weeks respectively. In the second trimester kidney volume measurements, nine volumes were excluded in the inter-examiner reliability analysis and four volumes were excluded in the intra-examiner reliability analysis due to sub-optimal image quality and inability to define the correct plane of measurement.Bland Altman plots of the second trimester and third trimester volume measurements are presented in Figures 6, 7 and 8, 9 respectively. Intra-examiner reliability is shown in Table 1 and inter-examiner reliability is shown in Table 2. For all measurements, intra-examiner variability was smaller than inter-examiner variability. A systematic bias was noted between the two examiners for the measurement of second trimester placental volume (as reflected by a 95% CI of a mean that does not cross 0), with one examiner systematically generating larger volumes. There was also a trend to bias in inter-examiner third trimester head volume measurements (mean bias -10.6). The measurement of random error, as reflected by the 95% limits of agreement of the mean intra and inter-examiner differences on the Bland Altman plots, was relatively large for all measurements apart from head volume and TVol measurements. Random measurement error was largest for the second trimester inter-examiner kidney volume measurements (95% limits of agreement ± 110%), and the best agreement was for third trimester intra-examiner TVol measurements (95% limits of agreement ± 10%). This random error appeared to decrease with advancing gestation when fetal volumes were larger in all fetal volume measurements apart from the head volume measurements, where it remained similar both in the second trimester and third trimester measurements. (See Tables 1 and 2)Second trimester ICC results were all >0.75 apart from kidney volume intra and inter-examiner measurements and placenta inter-examiner measurements which were 0.374, 0.061 and 0.390 respectively. Third trimester ICC results were higher for all volume measurements. The best values were observed for third trimester intra and inter-examiner TVol measurements (0.992, 95% CI 0.983-0.996 and 0.943, 95% CI 0.882-0.973).DiscussionPrevious studies of 3D ultrasound parameters have been criticised for the lack of robust methods to assess measurement variability PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Jb2Fubm91PC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48
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ADDIN EN.CITE.DATA (21, 33, 36). We sought to address this by performing a prospective study that examined both inter and intra-observer agreement of several different fetal volumes at varying gestational ages by two different sonographers blinded to each other’s measurements.Our findings indicate that fractional thigh volume would be the most reliable 3D measurement of fetal growth to be used either longitudinally to model individual growth trajectories or perhaps cross-sectionally as a one off measurement at 34-36 weeks to help identify those fetuses with late-onset FGR. The ability to analyse fractional thigh volume on only a limited number of ultrasound machines, and the requirement for offline image analysis would currently limit the more widespread application of this measurement. ICC values from our study in the third trimester of pregnancy are very similar to ICC values obtained in previous studies for 2D fetal measurements such as head and abdominal circumference, bi-parietal diameter and femur lengthPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QZXJuaTwvQXV0aG9yPjxZZWFyPjIwMDQ8L1llYXI+PFJl
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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QZXJuaTwvQXV0aG9yPjxZZWFyPjIwMDQ8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (37) (0.943-0.992). Similar measurement reliability for fractional thigh volume has been reported in studies by Lee et al and Yang et al PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MZWU8L0F1dGhvcj48WWVhcj4yMDA5PC9ZZWFyPjxSZWNO
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ADDIN EN.CITE.DATA (8, 23, 39). These differing results may relate to the early gestation (first or early second trimester) at which these studies were performed, as placental volumes are significantly smaller at these gestations. Other studies that have looked at 3D placental volumes after 20 weeks gestation have either not carried out reliability analysis ADDIN EN.CITE <EndNote><Cite><Author>Artunc Ulkumen</Author><Year>2014</Year><RecNum>317</RecNum><DisplayText>(10)</DisplayText><record><rec-number>317</rec-number><foreign-keys><key app="EN" db-id="2ptzwtrz3a5xaher5rtvttrv0vx299fatpzz">317</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Artunc Ulkumen, B.</author><author>Pala, H. G.</author><author>Uyar, Y.</author><author>Koyuncu, F. M.</author><author>Bulbul Baytur, Y.</author></authors></contributors><auth-address>Perinatology Division, Obstetrics and Gynecology Department, Celal Bayar University School of Medicine , Manisa , Turkey.</auth-address><titles><title>The assessment of placental volume and mean gray value in preeclamptic placentas by using three-dimensional ultrasonography</title><secondary-title>J Matern Fetal Neonatal Med</secondary-title><alt-title>The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians</alt-title></titles><periodical><full-title>J Matern Fetal Neonatal Med</full-title><abbr-1>The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet</abbr-1></periodical><pages>1-4</pages><dates><year>2014</year><pub-dates><date>Jul 31</date></pub-dates></dates><isbn>1476-4954 (Electronic)
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ADDIN EN.CITE.DATA (40). Our results agree with previous work ADDIN EN.CITE <EndNote><Cite><Author>Hata</Author><Year>2011</Year><RecNum>309</RecNum><DisplayText>(8)</DisplayText><record><rec-number>309</rec-number><foreign-keys><key app="EN" db-id="2ptzwtrz3a5xaher5rtvttrv0vx299fatpzz">309</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hata, T.</author><author>Tanaka, H.</author><author>Noguchi, J.</author><author>Hata, K.</author></authors></contributors><auth-address>Department of Perinatology and Gynecology, Kagawa University School of Medicine, Kagawa 761-0793, Japan. toshi28@med.kagawa-u.ac.jp</auth-address><titles><title>Three-dimensional ultrasound evaluation of the placenta</title><secondary-title>Placenta</secondary-title><alt-title>Placenta</alt-title></titles><periodical><full-title>Placenta</full-title><abbr-1>Placenta</abbr-1></periodical><alt-periodical><full-title>Placenta</full-title><abbr-1>Placenta</abbr-1></alt-periodical><pages>105-15</pages><volume>32</volume><number>2</number><keywords><keyword>Female</keyword><keyword>Fetal Growth Retardation/ultrasonography</keyword><keyword>Gestational Age</keyword><keyword>Hemangioma/ultrasonography</keyword><keyword>Humans</keyword><keyword>Hydrops Fetalis/ultrasonography</keyword><keyword>Imaging, Three-Dimensional/*methods</keyword><keyword>Placenta/blood supply/*ultrasonography</keyword><keyword>Placenta Diseases/ultrasonography</keyword><keyword>Pregnancy</keyword><keyword>Ultrasonography, Prenatal/*methods</keyword></keywords><dates><year>2011</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1532-3102 (Electronic)
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ADDIN EN.CITE.DATA (40), to use the multiplanar method for image analysis ADDIN EN.CITE <EndNote><Cite><Author>Hata</Author><Year>2011</Year><RecNum>309</RecNum><DisplayText>(8)</DisplayText><record><rec-number>309</rec-number><foreign-keys><key app="EN" db-id="2ptzwtrz3a5xaher5rtvttrv0vx299fatpzz">309</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hata, T.</author><author>Tanaka, H.</author><author>Noguchi, J.</author><author>Hata, K.</author></authors></contributors><auth-address>Department of Perinatology and Gynecology, Kagawa University School of Medicine, Kagawa 761-0793, Japan. toshi28@med.kagawa-u.ac.jp</auth-address><titles><title>Three-dimensional ultrasound evaluation of the placenta</title><secondary-title>Placenta</secondary-title><alt-title>Placenta</alt-title></titles><periodical><full-title>Placenta</full-title><abbr-1>Placenta</abbr-1></periodical><alt-periodical><full-title>Placenta</full-title><abbr-1>Placenta</abbr-1></alt-periodical><pages>105-15</pages><volume>32</volume><number>2</number><keywords><keyword>Female</keyword><keyword>Fetal Growth Retardation/ultrasonography</keyword><keyword>Gestational Age</keyword><keyword>Hemangioma/ultrasonography</keyword><keyword>Humans</keyword><keyword>Hydrops Fetalis/ultrasonography</keyword><keyword>Imaging, Three-Dimensional/*methods</keyword><keyword>Placenta/blood supply/*ultrasonography</keyword><keyword>Placenta Diseases/ultrasonography</keyword><keyword>Pregnancy</keyword><keyword>Ultrasonography, Prenatal/*methods</keyword></keywords><dates><year>2011</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1532-3102 (Electronic)
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ADDIN EN.CITE.DATA (41-43). Yu et al produced normal ranges for fetal kidney volumes at different gestations ranging from20 weeks to 40 weeks ADDIN EN.CITE <EndNote><Cite><Author>Yu</Author><Year>2000</Year><RecNum>127</RecNum><DisplayText>(44)</DisplayText><record><rec-number>127</rec-number><foreign-keys><key app="EN" db-id="2ptzwtrz3a5xaher5rtvttrv0vx299fatpzz">127</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yu, C.</author><author>Chang, C.</author><author>Chang, F.</author><author>Ko, H.</author><author>Chen, H.</author></authors></contributors><auth-address>Department of Obstetrics and Gynecology, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan.</auth-address><titles><title>Fetal renal volume in normal gestation: a three-dimensional ultrasound study</title><secondary-title>Ultrasound Med Biol</secondary-title><alt-title>Ultrasound in medicine & biology</alt-title></titles><periodical><full-title>Ultrasound Med Biol</full-title><abbr-1>Ultrasound in medicine & biology</abbr-1></periodical><alt-periodical><full-title>Ultrasound Med Biol</full-title><abbr-1>Ultrasound in medicine & biology</abbr-1></alt-periodical><pages>1253-6</pages><volume>26</volume><number>8</number><keywords><keyword>Cross-Sectional Studies</keyword><keyword>Female</keyword><keyword>*Gestational Age</keyword><keyword>Humans</keyword><keyword>*Imaging, Three-Dimensional</keyword><keyword>Kidney/*ultrasonography</keyword><keyword>Pregnancy</keyword><keyword>Prospective Studies</keyword><keyword>Reference Values</keyword><keyword>*Ultrasonography, Prenatal</keyword></keywords><dates><year>2000</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0301-5629 (Print)
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ADDIN EN.CITE.DATA (19). They were able to demonstrate excellent intra and inter-examiner agreement using Bland-Altman analysis. However, all 3D sonographic examinations in this study for analysis were performed by the same examiner, and inter-examiner agreement was not assessed by each examiner acquiring their own individual image of the kidney volumes. Our results demonstrate poor intra and inter-observer reliability with very high random measurement error both in the second and third trimester, but worse in the second trimester. This is likely due to the difficulty in acquiring images with a clear organ border as a result of acoustic shadowing from other structures, lack of measurement technique standardisation and the relatively smaller size of the organ. Our results would suggest fetal kidney volume should not be used as a measure of fetal growth in pregnancy.Most studies looking at 3D fetal brain volume in the second and third trimesters have not assessed inter-examiner reliability. There are no studies in the literature that report reliability analysis for 3D fetal head volume measurements in pregnancy. In one study by Roelfsema et al which looked at 3D measurement of normal fetal brain volume from 18-34 weeks gestation, intra-examiner reliability was good with a coefficient of variation (CV) for 3D fetal brain volume measurement of 10.2% for repeated tests within women and 2.2% for analyses of the same recorded volume ADDIN EN.CITE <EndNote><Cite><Author>Roelfsema</Author><Year>2004</Year><RecNum>129</RecNum><DisplayText>(13)</DisplayText><record><rec-number>129</rec-number><foreign-keys><key app="EN" db-id="2ptzwtrz3a5xaher5rtvttrv0vx299fatpzz">129</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Roelfsema, N. M.</author><author>Hop, W. C.</author><author>Boito, S. M.</author><author>Wladimiroff, J. W.</author></authors></contributors><auth-address>Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. n.roelfsema@erasmusmc.nl</auth-address><titles><title>Three-dimensional sonographic measurement of normal fetal brain volume during the second half of pregnancy</title><secondary-title>Am J Obstet Gynecol</secondary-title><alt-title>American journal of obstetrics and gynecology</alt-title></titles><periodical><full-title>Am J Obstet Gynecol</full-title><abbr-1>American journal of obstetrics and gynecology</abbr-1></periodical><alt-periodical><full-title>Am J Obstet Gynecol</full-title><abbr-1>American journal of obstetrics and gynecology</abbr-1></alt-periodical><pages>275-80</pages><volume>190</volume><number>1</number><keywords><keyword>Adult</keyword><keyword>Brain/*embryology</keyword><keyword>Embryonic and Fetal Development</keyword><keyword>Female</keyword><keyword>Gestational Age</keyword><keyword>Humans</keyword><keyword>*Imaging, Three-Dimensional</keyword><keyword>Pregnancy</keyword><keyword>*Ultrasonography, Prenatal</keyword></keywords><dates><year>2004</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0002-9378 (Print)
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ADDIN EN.CITE.DATA (45). In the former study, they reported a 9% failure rate to obtain a technically successful head volume measurement due to limited size of the recorded volume and position of the fetal head ADDIN EN.CITE <EndNote><Cite><Author>Roelfsema</Author><Year>2004</Year><RecNum>129</RecNum><DisplayText>(13)</DisplayText><record><rec-number>129</rec-number><foreign-keys><key app="EN" db-id="2ptzwtrz3a5xaher5rtvttrv0vx299fatpzz">129</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Roelfsema, N. M.</author><author>Hop, W. C.</author><author>Boito, S. M.</author><author>Wladimiroff, J. W.</author></authors></contributors><auth-address>Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. n.roelfsema@erasmusmc.nl</auth-address><titles><title>Three-dimensional sonographic measurement of normal fetal brain volume during the second half of pregnancy</title><secondary-title>Am J Obstet Gynecol</secondary-title><alt-title>American journal of obstetrics and gynecology</alt-title></titles><periodical><full-title>Am J Obstet Gynecol</full-title><abbr-1>American journal of obstetrics and gynecology</abbr-1></periodical><alt-periodical><full-title>Am J Obstet Gynecol</full-title><abbr-1>American journal of obstetrics and gynecology</abbr-1></alt-periodical><pages>275-80</pages><volume>190</volume><number>1</number><keywords><keyword>Adult</keyword><keyword>Brain/*embryology</keyword><keyword>Embryonic and Fetal Development</keyword><keyword>Female</keyword><keyword>Gestational Age</keyword><keyword>Humans</keyword><keyword>*Imaging, Three-Dimensional</keyword><keyword>Pregnancy</keyword><keyword>*Ultrasonography, Prenatal</keyword></keywords><dates><year>2004</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0002-9378 (Print)
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ADDIN EN.CITE.DATA (28). However, another study using a different method to measure fetal thigh volume longitudinally found similar higher random measurement error with 95% limits of agreement ± 32% for intra-examiner measurements and ± 58% for inter-examiner measurements ADDIN EN.CITE <EndNote><Cite><Author>Ioannou</Author><Year>2013</Year><RecNum>246</RecNum><DisplayText>(26)</DisplayText><record><rec-number>246</rec-number><foreign-keys><key app="EN" db-id="2ptzwtrz3a5xaher5rtvttrv0vx299fatpzz">246</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ioannou, C.</author><author>Sarris, I.</author><author>Napolitano, R.</author><author>Ohuma, E.</author><author>Javaid, M. K.</author><author>Papageorghiou, A. T.</author></authors></contributors><auth-address>Nuffield Department of Obstetrics & Gynaecology, University of Oxford, UK.</auth-address><titles><title>A longitudinal study of normal fetal femur volume</title><secondary-title>Prenat Diagn</secondary-title><alt-title>Prenatal diagnosis</alt-title></titles><periodical><full-title>Prenat Diagn</full-title><abbr-1>Prenatal diagnosis</abbr-1></periodical><alt-periodical><full-title>Prenat Diagn</full-title><abbr-1>Prenatal diagnosis</abbr-1></alt-periodical><pages>1088-94</pages><volume>33</volume><number>11</number><dates><year>2013</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1097-0223 (Electronic)
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ADDIN EN.CITE.DATA (22) has supported this theory by suggesting that planes of measurement obtained during the volume acquisition using the XI VOCAL method are much better delimitated and therefore more reproducible than the standard VOCAL technique.One of the key strengths of the study is that images were obtained in a busy clinic setting by adequately trained sonographers but non-experts in the field of 3D ultrasound and this is more representative of a real world clinical situation. A limitation of this study is measurement reliability was only assessed between two different operators. This does not accurately reflect current clinical practice whereby there are a number of different trained sonographers in most scanning departments. In conclusion, fractional thigh volume is a measurement that can be accurately and reliably measured throughout pregnancy and may be a means of monitoring and detecting fetal growth problems especially in the case of late-onset fetal growth restriction. Other fetal volumes such as placenta, head, kidney and thigh measured using a VOCAL technique showed unacceptable measurement reliability and this must be considered when interpreting studies of fetal growth. Further work could concentrate on comparing reliability of 2D biometry measures with 3D biometry measures and estimated fetal weight (EFW) calculations in the late third trimester within a busy clinic setting, with several different examiners.AcknowledgementsThe authors would like to than the women who participated in the study, and the midwives at St Mary’s Hospital, Manchester, for their participation in recruitment.Conflicts of InterestThe authors declare no conflict of interest in the work presented here.TablesTable 1: Intra-examiner Differences between 1st and 2nd Measurements made by the Same ObserverMeasurementMean Bias (cm3)SD95% Limits of AgreementICC (95% CI)Second TrimesterPlacenta-6.9116.20-38.66 - 24.840.905 (0.780-0.959)Head0.529.77-18.63 - 19.680.931 (0.848-0.969)Kidney9.8953.69-95.34 - 115.100.374 (-0.533-0.746)Thigh-6.3317.54-40.70 - 28.040.917 (0.815-0.963)TVol-1.6912.58-26.36 - 22.970.960 (0.910-0.982)Third TrimesterHead0.376.83-13.01 - 13.760.972 (0.945-0.985)Kidney-0.2238.13-74.95 - 74.520.783 (0.559-0.893)Thigh-9.6216.51-41.98 - 22.750.879 (0.685-0.946)TVol2.915.55-7.96 - 13.780.992 (0.983-0.996)ICC – Intraclass Correlation Coefficient; CI – Confidence Interval; SD – Standard DeviationTable 2: Interobserver Differences between the 1st Measurement made by 2 different ObserversMeasurementMean Bias (cm3)SD95% Limits of AgreementICC (95% CI)Second TrimesterPlacenta44.2621.172.78 - 85.750.390 (-0.189-0.758)Head8.918.30-7.35 - 25.170.874 (0.262-0.961)Kidney2.3658.57-112.40 - 117.200.061 (-1.902-0.680)Thigh11.7923.41-34.09 - 57.680.811 (0.515-0.920)TVol0.2021.49-41.93 - 42.370.867 (0.703-0.940)Third TrimesterHead-10.629.75-29.74 - 8.490.882 (0.285-0.962)Kidney-18.8157.14-130.80 - 93.190.647 (0.281-0.828)Thigh10.6123.43-35.32 - 56.530.781 (0.505-0.899)TVol3.6413.21-22.24 - 29.530.943 (0.882-0.973)ICC – Intraclass Correlation Coefficient; CI – Confidence Interval; SD – Standard DeviationFiguresFigure 1: Measurement of fractional thigh volume. By placing two electronic cursors (arrowheads, upper left window), one at each end of the femoral diaphysis, the software defines a partial volume that is based on 50% of the bone length. Five equidistant axial limb slices are used to display soft tissue borders that are traced manually for each image slice (green dots) and the TVol measurement is calculated automatically (bottom right window).Figure 2: Measurement of fetal head volume using the VOCAL technique. Manual drawing of the contour of the head was performed in plane A.Figure 3: Measurement of placental volume using the VOCAL technique. Manual drawing of the contour of the placenta was performed in plane A.Figure 4: Measurement of fetal thigh volume using the VOCAL technique. Manual drawing of the contour of the thigh was performed in plane A.Figure 5: Measurement of fetal kidney volume using the VOCAL technique. Manual drawing of the contour of the kidney was performed in plane A.Figure 6: Inter-observer reliability of second trimester volume measurements using Bland-Altman plots. The average of both observer’s readings is shown on the x-axis and the between observer difference (expressed as a percentage of the average of both readings) on the y-axis. The mean bias between observations is depicted by a solid grey line and the 95% confidence intervals of the mean are indicated by the dotted lines. Plots are presented for Kidney (A), Thigh (B), Head (C), Placenta (D), TVol (E).Figure 7: Intra-observer reliability of second trimester volume measurements using Bland-Altman plots. The average of both readings from one observer is shown on the x-axis and the between reading difference (expressed as a percentage of the average of both readings) on the y-axis. The mean bias between observations is depicted by a solid grey line and the 95% confidence intervals of the mean are indicated by the dotted lines. Plots are presented for Kidney (A), Thigh (B), Head (C), Placenta (D), TVol (E).Figure 8: Inter-observer reliability of third trimester volume measurements using Bland-Altman plots. The average of both observer’s readings is shown on the x-axis and the between observer difference (expressed as a percentage of the average of both readings) on the y-axis. The mean bias between observations is depicted by a solid grey line and the 95% confidence intervals of the mean are indicated by the dotted lines. Plots are presented for Head (A), Kidney (B), TVol (C), Thigh (D).Figure 9: Intra-observer reliability of third trimester volume measurements using Bland-Altman plots. The average of both readings from one observer is shown on the x-axis and the between reading difference (expressed as a percentage of the average of both readings) on the y-axis. 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