Engineering, 2012, 5, 146-149
doi:10.4236/eng.2012.410B038 Published Online October 2012 (
Copyright © 2012 SciRes. ENG
Investigation of Bone Ratios for Prenatal Fetal Assessment in
Taiwanese Population
Feng-Yi Yang, Yi -Li Lin
Department of Biomedical Imaging an d Radiological Sciences , School of Bi om edical Science and Engineering,
Nati onal Yang-Ming University
Received 2012
The purpose of this study is to calculate the ratios of fetal limb bone to nasal bone length (NBL) obtained by transabdominal ultra-
sound between 19 and 28 weeks of gestation. Cross-section al data were obtained from 1408 women with singleton pregnancies who
underwent an advanced prenatal ultrasound examination from August 2006 to September 2008. The single measurement plane of
fetal limb bones was on the longest section of each structure with appropriate image magnification. To assess repeatability of the
intraob server, two r epeated measu rements wer e obt ained in 44 fetuses. The ratio of fetuses with bi parietal diameter (BP D)/N BL was
compared with those of fetal limb bones/NBL. The mean ratio was found between fetal NBL measurements and BPD (7.240), hu-
merus length (HL) (4.807), radius length (RL) (4.157), ulna length (UL) (4.502), femur length (FL) (5.131), tibia length (TL) (4.528),
and fibula length (FiL) (4.507). The reference ranges of fetal long bone length/NBL ratios for the second trimester was established by
transabdominal sonography. There were no significant increases in these ratios with gestational age, es pecially the HL/NBL ratio.
Keywords: Nasal Bone Length; Limb Bone; Ratio; Second Trimester; Ultrasound
1. Introduction
In aneuploid chromosomes, Down syndrome has a high inci-
dence rate in newborns [1]. The methods of screening for
chromosome anomalies, excluding amniocentesis, rely on ma-
ternal age and maternal serum biochemical markers. Recently,
fetal genetic ultrasound screening has been proposed as an ad-
ditional screening tool for aneuploidy [2]. Down syndrome
fetuses usually have facial abnormalities, with especially an
absent fetal nasal bone (NB) or NB hypoplasia due to delayed
NB ossification, which have been observed as a fetal sono-
graphic soft marker of Down syndrome [3].
Recent reports suggested that evaluation of the fetal NB
might help to identify fetuses at risk of Down syndrome. It has
been reported that about 65% of Down syndrome fetuses have
absent or short NB in fetal NB screening at the first and second
trimesters [4]. Only 1~2% of normal karyotype fetuses have
been ob served [5-7]. Down syndrome and absent or hypoplastic
fetal NB show similar evidence of high sensitivity, high speci-
ficity, and low false-positive rate for Down syndrome screening
by fetal NB examination [8-11].
Published data have shown that when comparing Down Syn-
drome fetuses with euploid fetuses, Down Syndrome fetuses
were more frequently associated with NB hypoplasia [12-15].
Reviewing several past studies, in addition to discussing the
relationship between nasal bone length (NBL) and gestational
age or biparietal diameter (BP D), the BPD/NB L ratio ≥ 10 and
≥ 11 were proposed for the definitions of nasal bone hypoplasia
in the second tri mester [ 13,15-19].
The fetal NB assessment is a very important part of prenatal
fetal examination. It is a useful diagnostic and screening tool
for Down syndrome. The purpose of this study was to investi-
gate the distributions of fetal limb bones length with respect to
NBL and to compare the differences of ratios between fetal
BPD/NBL an d fetal limb bone/NBL.
2. Methodology
2.1. Subjects
The cross-sectional fetal long bone measurements were carried
out with 1408 pregnancies as a part of advanced prenatal ultra-
sound examination from August 2006 to September 2008. The
gestational age of the fetuses was calculated from the accurate
estimated date of confinement obtained from patients. If the
estimated date of confinement was uncertain, the difference
between the ultrasonically estimated gestational age and deter-
mined gestational age was assumed t o be less than 10 days [20].
The exclusion criteria included previous history of chromosome
abnormalities, fetal structural anomalies, and maternal compli-
2.2. Ultrasound
The fetal NBL was measured in the strict sagittal view of the
fetal head under appropriate image magnification (Figure 1)
[5,21]. independent document. Please do not revise any of the
current designations.
In order to avoid false finding that the NB was either absent
or shortened, the angle of the fetal nose was maintained be-
tween 45° and 135° [12,22]. The BPD was measured on the
transverse axial section of the fetal head which included the
midline falx and the thalami symmetrically positioned on either
side o f the falx from the outer edge of the nearer parietal bone
to the inner edge of the more distant parietal bone whilst visua-
F.-Y. YANG, Y. –L. LIN
Copyright © 2012 SciRes. ENG
lizing the septum pellucidum at one-third along the fron-
tal-occipit al dist ance. Th e single measu re ment pl ane of six li mb
bones (humerus, ulna, radius, femur, tibia, and fibula) was on
the longest section of each structure with appropriate image
magnificat ion (occup y three quarters of th e screen). In addition,
the transducer needed to be aligned to the long axis of the limb
bone to obtain a proper plane of the section. The ossified por-
tion of diaphysis and metaphysics were measured, while the
cartilagin ous ends o f the limb bones were excluded [23,24]. To
assess repeatability of the intraobserver, two repeated mea-
surements were obtained from 44 fetuses randomly chosen
during the process of ultrasound screening. The mean differ-
ences between the two measurements and the Cronbach's Alpha
value were calculated.
2.3. Statistics
In this study, statistical analysis was performed with the Statis-
tical Package for the Social Sciences (SPSS, Ver. 13.0 for
Windows; Chicago, IL, USA). A probability value of p < 0.05
was considered statistically significant. The mean, standard
deviation (SD), 95% confid ence in terval o f mean for BP D/NBL
and fetal long bones/NBL were calculated. Furthermore, the
correlation of gestational age and fetal long bones/NBL ratios
were analyzed by Pearson correlation.
3. Results
Table 1 represents the mean, standard deviation (SD), 95%
confidence interval of mean for the ratios of the BPD/NBL,
humerus length (HL)/NBL, ulna length (UL)/NBL, radius
length (RL)/NBL, femur length (FL)/NBL, tibia length (TL)/
NBL, and fibula length (FiL)/NBL
The linear regression examining the HL/NBL ratio versus
gestational age for our study population indicates that the ratio
did not change with gestational age. Although the regression
reveals that the BPD/NBL ratio decreases slightly with gesta-
tional age for fetuses, the change was not statistically signifi-
cant, which is similar to the previous literature.
Table 2 and Table 3 show the mean, SD, 95% confidence
interval of mean for the ratios of the BPD and HL to NBL with
advancing gestational age.
Figure 1. Mid-sagi ttal view showing detection and measurement of
the nasal bone.
In addition, the correlation coefficients between gestational
age and ratios of the fetal long bones to NBL were calculated
by Pearson correlation. Table 4 shows the correlation coeffi-
cients between gestational age and the ratios of the BPD and
HL to NBL.
Table 1. Distribution of the ratios of biparietal diameter (BPD) to
nasal bone le ngth (NBL ) and fetal long bone lengths to NBL.
Mean SD 95% Confidence Interval of Mean
Lower Bound Upper Bound
BPD/NBL 7.240 0.8487 7.194 7.285
HL/NBL 4.807 0.5782 4.768 4.846
RL/NBL 4.157 0.5023 4.123 4.191
UL/NBL 4.502 0.5494 4.465 4.539
FL/N B L 5.131 0.6336 5.088 5.174
TL/NBL 4.528 0.5609 4.490 4.565
FiL/NBL 4.507 0.5541 4.469 4.544
SD: standard deviation, SE: standard error, humerus length (HL), radius length
(RL), ulna length (UL), femur lengt h (FL) , t i bia length (TL) , f i bula length (FiL) .
Table 2. Distribution of the ratio of biparietal diameter (BPD) to
nasal bone length (NBL) against wee ks of gestation.
Mean SD 95% Confidence Interval of Mean
Lower Bound Upper Bound
19+019+6 7.500 0.9933 7.122 7.878
20+020+6 7.292 0.8878 7.153 7.430
21+021+6 7.212 0.8071 7.110 7.313
22+022+6 7.212 0.8492 7.118 7.306
23+023+6 7.333 0.8617 7.221 7.444
7.082 0.7409 6.952 7.212
25+025+6 7.236 0.9428 7.019 7.453
26+026+6 7.263 0.9209 7.020 7.505
27+027+6 7.228 0.7812 7.021 7.436
28+028+6 7.184 0.8161 6.894 7.473
SD: s tanda rd deviation, nas al bone length (NBL), biparie tal diamet er (BPD).
Table 3. Distribution of the ratio of humerus length (HL) to nasal
bone length (NBL ) against weeks of gestation.
Mean SD 95% Confidence Interval for Mean
Lower Bound Upper Bound
19+019+6 4.803 0.5607 4.590 5.017
20+020+6 4.711 0.5729 4.622 4.801
21+021+6 4.688 0.5637 4.617 4.759
22+022+6 4.712 0.5864 4.647 4.777
23+023+6 4.835 0.6163 4.756 4.915
24+024+6 4.662 0.5418 4.567 4.757
25+025+6 4.718 0.6419 4.570 4.866
26+026+6 4.683 0.5260 4.544 4.821
27+027+6 4.827 0.6241 4.661 4.993
28+028+6 4.631 0.6116 4.415 4.848
SD: s tanda rd deviation, nasal bone length ( NBL ) , h ume r us le ng t h ( H L ).
F.-Y. YANG, Y. –L. LIN
Copyright © 2012 SciRes. ENG
Table 4. Pearson correlation coefficients of gestational age with
ratios of the BPD/NBL and HL/ NBL .
GA 1 -.031 .001
gestational age (GA, ) na s al bo ne leng t h (NB L ), bipar iet al diame t er (BPD) ,
hume rus length (H L )
The study of intraobserver variability showed mean differ-
ences bet ween the two measurements ranging from 0.0591 to
0.1682 and Cronbach's Alpha value ranging from 0.997 to
4. Discussion
The present study provides the ratios of fetal limb bones to
NBL with reference range from 19 to 28 weeks of gestation in
normal Taiwanese fetuses. Each woman contributed one set of
measurements taken during advanced prenatal ultrasound ex-
amination and assessment. No significant change in the
BPD/NBL ratio, HL/NBL ratio, UL/NBL ratio, and RL/NBL
ratio with gestational age were demonstrated in our population
(Pearson correlation coefficient < 0.05).
According to previous published studies, the BPD/NBL ratio
was first described in 2005. A total of 136 fetuses were eva-
luated for the association between the BPD/NBL ratio and tri-
somy 21 in the second-trimester [19]. In many subsequent stu-
dies, assessments of the NBL/BPD ratio were done in the
second trimester. In recent studies, the optimal threshold values
for the BPD/NBL ratio were investigated for detection of tri-
somy 21.
The ultrasound measurements were done in 239 women with
a singleton pregnancy at 15-20 weeks of gestation at Massa-
chusetts General Hospital, USA. The receiver operating cha-
racteristic curve for the BPD/NBL ratio showed that using a
cutoff value of 9 or greater resulted in 100% of fetuses with
Down syndrome and 22% of euploid fetuses. If the cutoff value
were raised to 10 or greater, then 81% of fetuses with Down
syndrome and 11% of euploid fetuses would be identified. If
the cutoff value was 11 or greater, 69% of fetuses with Down
syndrome would be identified, compared with 5% of euploid
fetuses [17]. This was consistent with the others in the litera-
In this study, we calculated not only the fetal BPD/NBL ratio
but also ratios of the fetal limb bones to NBL between 19 and
28 weeks. Be sides, the fetal b iometry and limb bones length in
our study were compared with previously reported measure-
ments from other populations [25,26]. The biometry, limb
bones length, and fetal weight were all in the normal range.
Moreover, the HL/NBL ratio did not change with gestational
age. The Pearson product-moment correlat ion co efficient o f the
HL/NBL with gestational age was lower than those of ratios
with gestational age.
The NB hypoplasia or absence is an important marker for
Down syndrome. The combination of other makers with the NB
assessment was associated with an improvement in detecting
the risk of Down syndrome [27]. Thu s, th ere is a need to est ab-
lish the specific evalu ated formulas by NBL with different me-
In this pilot study, our data have established the reference ra-
tio of the fetal limb bones to NBL in normal singleton Taiwa-
nese fetuses. To our knowledge, this is the first prospective
study to evaluate the ratios of the fetal limb bones to NBL in
the second trimester. Our data also show that the HL/NBL ratio
does not change with advancing gestational age. Comparing
with the lower limb, it is usually easier to visualize the upper
limb. The humerus is the easiest of the upper limb bones to
define with ultrasound, as it has less freedom of movement than
the forearm. We determined that the HL/NBL ratio was supe-
rior to that of BPD or other limb bones ratios. Additional veri-
fication for detecting the risk of chromosomal aneuploidy is
required before this approach can be applied in a clinical setting.
This study points out a better clinical approach for evaluating
fetuses with skeletal anomalies or risk of aneuploid chromo-
somes in the general population.
5. Acknowledgements
This study was supported by grants from the National Science
Council of Taiwan (no. NSC 100-2321-B-010-010 and NSC
99-2321-B-010-017), Cheng Hsin General Hospital Foundation
(no. 100F117CY25), Veterans General Hospitals University
System of Taiwan Joint Research Program (#VGHUST100-
G1-3 -3 and V100E6-007), Yen Tjing Ling Medical Foundation
(grant CI-100-17), Department of Health of Taiwan (DOH101-
[1] Bell, R., J. Rankin, and L.J. Donaldson, Down's syndrome: oc-
curren ce and out come in th e north of Engla nd, 1985 -99. P aedi atr
Perinat Epidemiol, 2003. 17(1): p. 33-9.
[2] Van den Hof, M.C. and R.D. Wilson, Fetal soft markers in ob-
stetric ultrasound. J Obstet Gynaecol Can, 2005. 27(6): p.
[3] Stempfle, N., et al., Skeletal abnormalities in fetuses with
Down's syndrome: a radiographic post-mortem study. Pediatr
Radio l, 19 9 9. 2 9( 9 ) : p. 682-8.
[4] Nicolaides, K.H., Nuchal translucency and other first-trimester
sonographic markers of chromosomal abnormalities. Am J Ob-
stet Gyne col, 2004. 191 ( 1) : p. 45 -67.
[5] Cicero, S., et al., Absence of nasal bone in fetuses with trisomy
21 at 11-14 weeks of gestation: an observational study. Lancet,
2001. 358(9294): p. 1665-7.
[6] Viora, E., et al., Ultrasound evaluation of fetal nasal bone at 11
to 14 weeks i n a c ons ecu t iv e seri es of 1 90 6 fet u s es. Pr enat Di a gn,
2003. 23(10): p . 784-7.
[7] Ramos-Corpas, D., J.C. Santiago, and F. Montoya, Ultrasono-
graphi c evaluation of fetal nasal bon e in a low-risk population at
11-13 + 6 gestational weeks. Prenat Diagn, 2006. 26(2): p.
[8] Monni, G., et al., Nuchal translucency and nasal bone for trisomy
21 sc r een in g: sin g le cen t er experience. Cr o at Med J, 2005. 4 6(5) :
p. 786-91.
[9] Bunduk i, V., et al., Fetal nasal bone length: reference ran ge and
clinical application in ultrasound screening for trisomy 21. Ul-
trasound Obstet Gynecol, 2003. 21(2): p. 156-60.
[10] Otano, L., et al., Association between first trimester absence of
fetal nasal bone on ultrasound and Down syndrome. Prenat Di-
agn, 2 002. 22(10) : p. 93 0-2.
F.-Y. YANG, Y. –L. LIN
Copyright © 2012 SciRes. ENG
[11] Cicero, S., et al., Integrated ultrasound and biochemical screen-
ing for trisomy 21 using fetal nuchal translucency, absent fetal
nasal b on e, f ree b et a-h C G a n d P AP P -A at 11 to 14 weeks. Prenat
Diagn, 2003. 23(4): p. 306 -10.
[12] Cusick, W., et al., Fetal nasal bone length in euploid and aneup-
loid fetuses between 11 and 20 weeks' gestation: a prospective
stud y. J Ultrasound Med, 2004. 23(10): p. 1327-33.
[13] Viora, E., et al., Fetal nasal bone and trisomy 21 in the second
trimester. Prenat Diagn, 2005. 25(6): p. 511-5.
[14] Vi ntzil eos, A., C. Walt ers, and L. Yeo, Abs ent nasa l bone in th e
prenatal detection of fetuses with trisomy 21 in a high-risk pop-
ulat ion. O bste t Gyneco l , 2003 . 1 0 1( 5 Pt 1): p. 9 05-8.
[15] Odibo, A.O., et al., The association between fetal nasal bone
hypoplasia and aneuploidy. Obstet Gynecol, 2004. 104(6): p.
[16] Kanagawa, T., et al., Mid-secon d trimester m easuremen t of fet al
nasal bone length in the Japanese population. J Obstet Gynaecol
Res, 2006. 32(4) : p. 403-7.
[17] Bromley, B., et al., Fetal nose bone length: a marker for Down
syndrome in the second trimester. J Ultrasound Med, 2002.
21(12 ) : p. 1 387-94.
[18] Naraphut, B., et al., Nasal bone hypoplas ia i n tri som y 21 a t 1 5 to
24 weeks' gestation in A high risk Thai population. J Med Assoc
Thai, 2006. 89(7): p. 911-7.
[19] Tran, L.T., et al., Second-trimester biparietal diameter/nasal bone
length ratio is an independent predictor of trisomy 21. J Ultra-
sound Med, 2005. 24(6): p. 805-10.
[20] Shohat, T. and O. Romano-Zelekha, Ultrasonographic measure-
ments of fetal femur length and biparietal diameter in an Israeli
popula tion. Isr Med Assoc J, 2001. 3(3) : p. 166-8.
[21] Cicero, S., et al., Fetal nasal bone length in ch romosomally nor-
mal and abnormal fetuses at 11-14 weeks of gestation. J Matern
Fet al Neonatal Me d , 20 02. 1 1( 6) : p. 4 00-2.
[22] Sonek, J.D. and K.H. Nicolaides, Prenatal ultrasonographic
diagnosis of nasal bone abnormalities in three fetuses with Down
syndrome. Am J Obstet Gynecol, 2002. 186(1): p. 139-41.
[23] Goldstein, R.B., R.A. Filly, and G. Simpson, Pitfalls in femur
length measurements. J Ultrasound Med, 1987. 6(4): p. 203-7.
[24] De Biasio, P., et al., Reference values for fetal limb biometry at
10-14 weeks of gestation. Ultrasound Obstet Gynecol, 2002.
19(6): p. 588-91.
[25] M erz, E. and S. Wellek , [N ormal fet al growth profi le--a uni form
model for calculating normal curves for current head and abdo-
men parameters and long limb bones]. Ultraschall Med, 1996.
17(4): p. 153-62.
[26] Salomon, L.J., J.P. Bernard, and Y. Ville, Estimation of fetal
weight: reference range at 20-36 weeks' gestation and compari-
son with actual birth-weight reference range. Ultrasound Obstet
Gyne col, 2007 . 29(5) : p. 55 0-5.
[27] Odibo, A.O., et al., Evaluating the efficiency of using
second-trimester nasal bone hypoplasia as a single or a combined
marker for fetal aneuploidy. J Ultrasound Med, 2006. 25(4): p.
437-41; quiz 443.