Ultrasound in Med. & Biol., Vol. 31, No. 7, pp. 883–887, 2005Copyright © 2005 World Federation for Ultrasound in Medicine & Biology

Printed in the USA. All rights reserved0301-5629/05/$–see front matter

doi:10.1016/j.ultrasmedbio.2005.04.006

● Original Contribution

THE EFFICACY ASSESSMENT OF THIGH VOLUME IN PREDICTINGINTRAUTERINE FETAL GROWTH RESTRICTION BY

THREE-DIMENSIONAL ULTRASOUND

CHIUNG-HSIN CHANG,* CHEN-HSIANG YU,* HUEI-CHEN KO,† CHU-LING CHEN,* andFONG-MING CHANG*

*Department of Obstetrics and Gynecology and †Research Institute of Behavior Medicine, National Cheng KungUniversity Medical College, Tainan, Taiwan

(Received 6 December 2004; revised 29 March 2005; in final form 7 April 2005)

Abstract—Intrauterine growth restriction (IUGR) is an important issue in perinatology. To assess the efficacy offetal thigh volume (ThVol) in predicting IUGR, we undertook a prospective cross-sectional study using quanti-tative 3-D ultrasound (US). During the study period, 30 fetuses with IUGR and 282 fetuses with non-IUGR wereincluded for the ThVol assessment in utero by 3-D US. All the fetuses were singletons and had follow-up to thedelivery to determine whether they were complicated with IUGR or not. Our results showed fetal ThVol assessedby 3-D US can differentiate fetuses with IUGR from fetuses with non-IUGR well. Using the 10th percentile as thescreening threshold, the sensitivity of fetal ThVol in predicting IUGR was 86.6%, with specificity 91.1%,predictive value of positive test 51.0%, predictive value of negative test 98.5% and accuracy 90.7%. In conclusion,fetal ThVol assessed by quantitative 3-D US can be used to predict fetuses with IUGR antenatally. We believefetal ThVol assessment by 3-D US would be a useful test in detecting fetuses with IUGR. (E-mail:fchang@mail.ncku.edu.tw) © 2005 World Federation for Ultrasound in Medicine & Biology.

Key Words: Thigh volume, IUGR, 3-D ultrasound.

INTRODUCTION

Fetuses with intrauterine growth restriction (IUGR) mayhave risks of perinatal morbidity and mortality (Lin andSantolaya-Forgas 1998, 1999). Previous studies had re-ported that IUGR fetuses have a six- to eightfold in-creased risk of perinatal mortality compared withcontrols (Garite et al. 2004; Harkness and Mari 2004;Lockwood and Weiner 1986; Regev and Reichman2004; Seeds 1984). Of those who survive, 50% havesignificant short- or long-term morbidity, including in-trapartum fetal distress, hypoglycemia, hypocalcemiaand meconium aspiration pneumonia (Dobson et al.1981; Garite et al. 2004; Harkness and Mari 2004; Lock-wood and Weiner 1986; Reed and Droegmueller 1983).They also have an increased frequency of abnormalneurologic development (Harvey et al. 1982). At least20% of stillborn fetuses are growth-restricted, a dispro-portionate fraction that indicates an elevated risk of in-

Address correspondence to: Dr. Fong-Ming Chang, Departmentof Obstetrics and Gynecology, National Cheng Kung University Med-

ical College and Hospital, 138 Victory Road, Tainan, Taiwan. E-mail:fchang@mail.ncku.edu.tw

883

trauterine demise (Manara 1980). Accurate antenatal di-agnosis may offer an opportunity to reduce the compli-cations associated with IUGR. When a diagnosis ofIUGR is made or suspected on the basis of sonographicfindings, the fetus should be closely monitored and,when indicated, promptly delivered. Previous reportsindicated that fetal thigh volume (ThVol) using 2-D USmay be a possible predictive factor of IUGR (Jeanty et al.1985). Yet, the efficacy of fetal ThVol assessment by2-D US in predicting IUGR remained to be enhanced.

With the advancement of 3-D US, fetal ThVol canbe assessed more precisely by 3-D US than by 2-D US.In a previous study, we had reported the assessment ofnormal fetal thigh volume by 3-D US (Chang et al.2003a) and had constructed normal reference centiles offetal ThVol during normal gestation for further clinicalapplication (Chang et al. 2003a). Moreover, to the best ofour knowledge, no prenatal assessment of fetal ThVol inpredicting IUGR fetuses using 3-D US has been reportedto date. Therefore, in this study, we tried to use 3-D USto test the efficacy of ThVol measurement in predictingfetuses with IUGR. According to the Bayes’ theorem, we

compared the sensitivity, specificity, positive predictive

884 Ultrasound in Medicine and Biology Volume 31, Number 7, 2005

value (PPV) and negative predictive value (NPV) andefficacy of fetal ThVol assessed by 3-D US in detectingIUGR fetuses.

MATERIALS AND METHODS

PatientsWomen who attended the prenatal clinic and were

referred for an US examination for fetal biometry wereincluded. This study was undertaken by a prospectiveand cross-sectional design. The patients were examinedconsecutively without selection. All the fetuses includedin this study were singletons and the inclusion criteria ofthis study were as follows: 1. patients with defined lastmenstrual period and confirmed by a dating US exami-nation in early pregnancy, either by crown-rump lengthor biparietal diameter and 2. pregnancies with gestationalage (GA) ranging from 20 to 40 weeks of gestation. Thesetting was performed at the Ultrasound Unit of theDepartment of Obstetrics and Gynecology, NationalCheng Kung University Hospital. All the pregnantwomen gave their informed consent and this study wasalready approved by the Institutional Review Board ofNational Cheng Kung University Hospital.

Prenatal thigh volume assessment by 3-D ultrasoundAs in our previous reports (Chang et al. 2003a), the

calculation of ThVol using 3-D US was described asfollows. In brief, the 3-D US equipment (Voluson 530D,Kretz, Zipf, Austria), with a 3.0- to 5.0-MHz transab-dominal mechanical transducer (S-VAW 3 to 5), wasused for fetal thigh scanning in each fetus. The measure-ment of ThVol by 3-D US is demonstrated in Fig. 1.Stepwise measurements of fetal ThVol by 3-D US wereas described below. We initially used the traditional

Fig. 1. Stepwise measurements of the fetal ThV by 3-D US.

plane for measuring the femur length on the first screen

(upper left panel) and rotated this plane to make the thighand the femur in a horizontal position. Then we fixed thisplane as the basis and moved the cursor along the axis ofthe femur from one end of the diaphysis to the other end,slice by slice every 3 mm. The corresponding transaxialplane was simultaneously illustrated on the secondscreen (upper right panel) and the dot cursor was markedalong the outline of the thigh. The dotted area in theupper-right panel and the thickness of each slice wasmeasured by a built-in computer as we proceeded alongthe axis of the thigh. Meanwhile, reconstruction of theimage of the third plane was displayed (lower left panel)and the movement of the measured plane was displayedsimultaneously (lower right panel). The area enclosedwas calculated automatically by the 3-D US. The inte-gration of fetal ThVol was also calculated by the 3-D USautomatically when the cursor was moved forward andthe area was enclosed. The built-in 3-D-view softwareallows the 3-D volume to be displayed simultaneously inthree perpendicular orthogonal planes on the monitor.The data set was further saved into the built-in computeror on the laser disks for further retrieval and processing,such as volume determination or 3-D-image reconstruc-tion.

Outcome: IUGR or non-IUGRAll the fetuses in this study were scanned once only

and all had follow-up to delivery to determine whetherthey were born with or without IUGR. When their birthweights were below the 10th percentile for GA accordingto the Taiwanese standard (Hsieh et al. 1991), they wereclassified as IUGR; if their birth weights were above orequal to the 10th percentile for GA according to theTaiwanese standard, they were grouped as non-IUGR.

StatisticsAll the data of fetal ThVol measurements and rel-

evant clinical indices (such as gender, birth weight etc.)were put into an IBM-compatible personal computer forfinal analysis. We used our previous centile values offetal ThVol obtained from a normal population as dif-ferent screening thresholds (Chang et al. 2003a). Thestatistical efficacy of each threshold of ThVol was com-puted and a receiver-operating characteristic (ROC)curve was constructed to determine the optimal thresh-old. In addition, we compared the sensitivity, specificity,PPV, NPV and accuracy according to the Bayes’ theo-rem between the normal and IUGR fetuses. TheSPSS-PC statistical package (SPSS, Chicago, IL, USA)was used in this series to perform statistical calculation.

RESULTS

In total, 30 fetuses with IUGR and 282 fetuses with

non-IUGR were included in this study. The mean mater-

in tw

Predicting IUGR by thigh volume using 3-D ultrasound ● C.-H. CHANG et al. 885

nal age and SD was 30.2 � 4.9 y in the IUGR group vs.30.9 � 4.5 y in the non-IUGR group. The mean gravidityand SD was 1.8 � 0.9 in IUGR group vs. 2.2 � 1.1 innon-IUGR group. The mean parity and SD was 1.5 � 0.5in IUGR group vs. 1.8 � 0.7 in non-IUGR group. Themean gestational age and SD for 3-D US measurementwas 34.5 � 4.7 weeks in IUGR group vs. 32.0 � 6.0weeks in the non-IUGR group.

The mean gestational age and SD at delivery was37.8 � 2.5 weeks in IUGR group vs. 38.5 � 1.4 weeksin non-IUGR group. The mean lag-time and SD betweenmeasurement and delivery was 22.7 � 28.8 d in IUGRgroup vs. 46.1 � 39.5 d in non-IUGR group. The female-to-male ratio was 1.14 in IUGR group vs. 1.02 in non-IUGR group. The mean birthweight and SD was 2293 �565 g in IUGR group vs. 3050 � 471 g in non-IUGRgroup (p � 0.001). The mean birth length and SD was45.2 � 4.3 cm in IUGR group vs. 49.3 � 3.4 cm innon-IUGR group (p � 0.001). The mean 1-min Apgarscore and SD was 7.3 � 1.8 in IUGR group vs. 8.4 � 1.1in non-IUGR group (p � 0.001). The mean 5-min Apgarscore and SD was 8.9 � 1.2 in IUGR group vs. 9.7 � 0.7in non-IUGR group (p � 0.001). The incidence of pre-eclampsia in IUGR was 27% and of percentage of ges-tational diabetes in IUGR was 13%. The incidence ofsymmetrically-growth-retarded fetuses was 19% and ofasymmetrically-growth-retarded fetuses was 81%.

The scattergram of fetal ThVol vs. GA is demon-strated in Fig. 2. The fetal ThVol in IUGR fetuses wassignificantly smaller than that in non-IUGR fetuses (p �0.001). Using the different ThVol centiles values fromour previous report as screening thresholds (Chang et al.

Fig. 2. The scattergram of fetal ThV vs. GA

2003a), the efficacy of different thresholds of ThVol by

3-D US in predicting IUGR is shown in Table 1. Fromthe result of Table 1, we constructed a ROC curve (Fig.3). The optimal operating slope for the ROC curve cor-responded to a ThVol threshold of the 10th percentile,with sensitivity 86.6%, specificity 91.1%, PPV 51.0%,NPV 98.5% and accuracy 90.7%, respectively.

In this study, all the measurements of the fetalThVol were undertaken by one operator (CH. Chang)and no interobserver error needed to be considered. Thereproducibility data for determining the intraobservererror of the fetal ThVol were assessed by repeated mea-surements on 20 fetuses with 20 to 40 weeks of gestationby the same operator (CH. Chang). Our data showed avery high level of reproducibility (r2 � 0.99, p � 0.001).In addition, there was no statistical difference of intraob-server error, as examined by a paired t-test.

DISCUSSION

Precise assessment of fetal organ volumes by pre-natal US is very important in the evaluation of fetal

o groups; (�) IUGR, and (Œ) non-IUGR.

Table 1. Efficacy of different percentiles of fetal thighvolumes in predicting IUGR

PercentileSen(%)

Spe(%)

PPV(%)

NPV(%)

Acc(%)

5th 13.4 94.3 20.0 91.1 86.510th 86.6 91.1 51.0 98.5 90.725th 100 80.1 34.9 100 82.050th 100 54.4 19.0 100 58.8

Sen � sensitivity; Spe � specificity; PPV � positive predictivevalue; NPV � negative predictive value; Acc � accuracy.

i.e., the

886 Ultrasound in Medicine and Biology Volume 31, Number 7, 2005

well-being and maturation (Chang et al. 1997a, 1997b,1997c; Chitty et al. 1994a, 1994b, 1994c). During thepast two decades, 2-D US has been the most commonlyused tool for the measurement of fetal organ dimensionsand volumes. Jeanty et al. (1985) had measured theThVol for assessing fetal growth and nutrition by 2-DUS. They concluded that fetal ThVol may be a possiblepredictive factor of IUGR. However, 2-D US cannotassess fetal ThVol accurately, because, when ThVol wasassessed by 2-D US, it was indirectly calculated using across-section area obtained from only one single cuttingsection plane, which is subject to a considerable error indetermining which plane should be the most appropriateplane (Favre et al. 1993, 1995; Vintzileos et al. 1987;Warda et al. 1986). In addition, when 2-D US wasapplied, fetal ThVol was calculated under the assumptionthat the thigh is a cylinder, yet this assumption is not true(Jeanty et al. 1985). Given these disadvantages, fetalThVol assessed by 2-D US had unsatisfactory results inpredicting fetal IUGR and fetal ThVol assessment using2-D US remained to be improved.

With the advent of 3-D US, it became an easy andnoninvasive approach to access any possible views andplanes whenever the targeted-scanned 3-D volume wasobtained (Kuo et al. 1992; Merz et al. 1995). Moreover,precise quantitative measurement of fetal organ dimen-sions becomes possible when the 3-D volume is retrieved(Chang et al. 1997a; Merz et al. 1995). Since our firstreport of primary application of 3-D US in obstetrics(Kuo et al. 1992), we have published a series of fetalorgan volume assessments using 3-D US, including fetalliver, heart, cerebellum, renal, adrenal gland, lung and

Fig. 3. ROC curve for the prediction of IUGR by diffthreshold cut-off (

brain volume from early second trimester to third trimes-

ter and obtained more accurate results (Chang et al.1997a, 1997b, 1997c; Chang et al. 2000a, 2000b, 2002a,2002b, 2003b, 2003c, 2003d; Liang et al. 1997; Yu et al.2000). From this prospective study of fetal ThVol as-sessment in detecting IUGR, as well as our previousstudy of ThVol centiles in normal gestation (Chang et al.2003a), we further proved that ThVol can be measuredby 3-D US with adequate precision and reproducibility.

In this study, we have tested various testing thresh-olds of ThVol obtained from normal fetuses in our pre-vious study (Chang et al. 2003a) in predicting fetal IUGRusing 3-D US. From Table 1 as well as Fig. 3, the bestscreening criterion of ThVol from the ROC curve inpredicting IUGR is the threshold of the 10th percentile.Using the 10th percentile of ThVol as the screeningcriterion, the results seem satisfactory, with sensitivity86.6%, specificity 91.1%, PPV 51.0%, NPV 98.5% andaccuracy 90.7%. These results imply that the efficacy ofThVol in detecting IUGR using 3-D US prenatally issuitable in clinical practice and that ThVol measurementby 3-D US can be a useful index to detect IUGR inclinical practice.

In conclusion, 3-D US-assessed fetal ThVol can beapplied in screening IUGR in utero. However, the sam-ple size of our study is relatively small. Further studywith a large-scale sample size of ThVol assessment by3-D US in predicting IUGR prenatally may be warranted,and it is now being undertaken in our Unit.

Acknowledgements—This study was supported in part by grants to FM.Chang and to CH. Chang from the National Science Council, ExecutiveYuan, Taipei, Taiwan. The authors are grateful to Ms. Yueh-Chin

hresholds of fetal ThV. Arrow corresponds to optimal10th percentile).

erent t

Cheng and Yi-Jen Wang for their assistance.

Predicting IUGR by thigh volume using 3-D ultrasound ● C.-H. CHANG et al. 887

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