Article

Prenatal Diagnosis of Trisomy 13

Analysis of 28 Cases

Csaba Papp, MD, Artur Beke, MD, Zoltan Ban, MD,

Zsanett Szigeti, MD, Erno Toth-Pal, MD, Zoltan Papp, MD

Objective. The purpose of this study was to investigate the role of second-trimester sonographic
examination in the prenatal diagnosis of trisomy 13. Methods. Of 22,150 fetal chromosome analy-
ses, 28 fetuses with trisomy 13 were found between 1990 and 2004. Sonographic findings of this
aneuploidy were analyzed in this study. Results. The average maternal age was 32.4 years; the aver-
age gestational age was 19.5 weeks. There was an 89.3% (n = 25) total prevalence of sonographic
abnormalities in fetuses with trisomy 13 in this series. Major (structural) malformations were seen in
23 cases (82.1%), whereas minor anomalies were detected on sonography in 16 cases (57.1%).
Although in 2 fetuses 1 minor anomaly was the only sonographic sign of trisomy 13, other cases with
minor anomalies (87.5% [n = 14]) were multiplex malformations, in which combinations of major and
minor anomalies were detected on sonography. The most frequently seen structural abnormalities
were central nervous system and facial anomalies (64.3% [n = 18]). Among central nervous system
anomalies, ventriculomegaly and holoprosencephaly were seen most frequently. Cardiovascular
anomalies were detected in 53.6% (n = 15) of the fetuses with trisomy 13. This high frequency under-
lines the importance of echocardiography in diagnosing this aneuploidy. Among minor anomalies,
increased nuchal translucency (21.4%) and echogenic bowel (17.9%) were the most common find-
ings. Conclusions. Second-trimester sonographic examination is capable of showing anomalies that
are characteristic of trisomy 13; thus, the scan can indicate whether fetal karyotyping is advisable.
Incorporation of careful assessment of the fetal cardiovascular system by sonography certainly increas-
es the detection rate of trisomy 13. Key words: echocardiography; prenatal sonography; trisomy 13.

T
Abbreviations
CNS, central nervous system; EIF, echogenic intracardiac
focus; IUGR, intrauterine growth restriction; NT, nuchal
translucency
Received January 5, 2006, from the First Department
of Obstetrics and Gynecology, Semmelweis University,
Faculty of Medicine, Budapest, Hungary. Revision
requested January 10, 2006. Revised manuscript
accepted for publication January 13, 2006.
Address correspondence to Csaba Papp, MD,
First Department of Obstetrics and Gynecology,
Semmelweis University, Faculty of Medicine, Baross ut
27, H-1088 Budapest, Hungary.
E-mail: papp@noi1.sote.hu
he multiplex malformation syndrome associat-
ed with trisomy 13 was first described by Patau
et al1 in 1960. Trisomy 13 is the third most com-
mon of the autosomal trisomies that give rise to
live-born neonates. The birth prevalence of this trisomy
is estimated at between 1 per 5000 and 1 per 20,000
births, resulting in neonates who die shortly after birth.2
It is characterized by multiple severe anomalies, which
include central nervous system (CNS) anomalies, facial
anomalies, heart defects, renal anomalies, and limb
anomalies.3 Although none of these anomalies are spe-
cific for trisomy 13, it has been accepted that it tends to
have more severe craniofacial and midline defects than
are found in trisomy 18 or 21.4
Because the prognosis of the syndrome is very poor,
early prenatal diagnosis is important. Because maternal
serum screening for trisomy 13 seems to be less promis-

© 2006 by the American Institute of Ultrasound in Medicine • J Ultrasound Med 2006; 25:429–435 • 0278-4297/06/$3.50
Prenatal Diagnosis of Trisomy 13
ing than screening for trisomy 21, prenatal diag-
nosis of trisomy 13 is usually accomplished by
sonography. The database of our prenatal diag-
nosis unit was reviewed, and the data from the
years between 1990 and 2004 were analyzed.
During this period, we performed 22,150 fetal
invasive genetic tests. The total number of fetal
aneuploidy cases was 514 (2.3%). Among them,
28 fetuses with trisomy 13 fetuses were found.
The objectives of this study were to determine
the most frequent sonographic abnormalities
among fetuses with trisomy 13 and to evaluate
the possible role of second-trimester sono-
graphic examination in the prenatal diagnosis of
this aneuploidy on a large series of fetuses with
trisomy 13.
Materials and Methods
The genetic counseling database of the First
Department of Obstetrics and Gynecology,
Semmelweis University Medical School, was
reviewed during this study. Cytogenetic records
of fetuses were collected between 1990 and
2004, and karyotypically documented fetuses
with trisomy 13 were analyzed. During the study
period, 22,150 fetal chromosome analyses were
performed, and 514 chromosome abnormalities
(2.3%) were found. Among them, 28 fetuses with
trisomy 13 were identified prenatally. Singleton
fetuses who had prenatal sonography during the
second trimester in our institution made up the
study population. Mothers were referred to our
genetic counseling department for different rea-
sons, including advanced maternal age, family
history of genetic problems in previous preg-
nancies, questionable sonographic findings
found in other institutions, and abnormal triple
test results.
Cytogenetic evaluation of the fetuses was per-
formed either by amniocentesis (78.6% [n = 22])
or chorionic villous sampling (21.4% [n = 6]) fol-
lowed by amniotic cell culture (in cases of
amniocentesis) or a direct analysis method (in
cases of chorionic villous sampling) using stan-
dard techniques.
All sonographic examinations were performed
by 3 sonographers and were further evaluated by
2 obstetricians with great experience in mater-
nal-fetal medicine. Two sonography systems
were used for the examinations: an Ultramark 9
HDI 3000 system (Phillips Medical Systems,
Bothell, WA) and a Voluson 730 system (GE
430
Healthcare, Milwaukee, WI). The course of the
examinations followed the guidelines of the
Hungarian Society of Ultrasound in Obstetrics
and Gynecology and routinely targeted basically
all structures of the fetus: the head (brain and
face), neck, thoracic cavity (4-chamber view of
the heart and cardiac outflow tracts), abdominal
cavity, extremities (hands and feet), spine, long
bones, and genitalia. All the abnormalities of
each organ were recorded. If a patient underwent
more than 1 sonographic examination, only the
results of the first examination were included in
the analysis. The sonographic examinations were
done before knowledge of the cytogenetic results
of the fetuses to rule out any bias.
Each abnormality was classified as a “major”
structural anomaly, a “minor” (“soft”) sonographic
marker, or an “other” sonographic abnormality.
Major structural anomalies were defined as CNS
anomalies, cardiovascular anomalies, gastrointesti-
nal anomalies, genitourinary system anomalies,
limb anomalies, and facial anomalies. Among
minor anomalies, we paid special attention to
nuchal translucency (NT)/thickness greater than 6
mm, short femur or humerus (<10th percentile),
pyelectasias (>4 mm), echogenic bowel, echogenic
intracardiac focus (EIF), and choroid plexus cyst.
Other sonographic abnormalities were defined as
follows: intrauterine growth restriction (IUGR; esti-
mated fetal weight <10th percentile), hydrops and
pleural effusions, cystic hygroma, amniotic fluid
abnormalities (oligohydramnios or polyhydram-
nios), and umbilical cord abnormalities.
The sensitivity of the sonographic examina-
tion and of the different markers in detecting
trisomy 13 was determined by standard statisti-
cal methods.
Results
From our database, 28 fetuses with trisomy 13
were evaluated during the study period.
During the period between 1990 and 2004, we
performed 22,150 fetal karyotyping analyses
and we found 514 chromosome abnormalities
(2.3%). Among them, 28 fetuses with trisomy 13
were identified prenatally. All the fetal aneuploi-
dies were diagnosed by amniocentesis (78.6%) or
chorionic villous sampling (21.4%) after detailed
sonographic examinations.
The mean maternal age of the patients was 32.4
years (range, 17–44 years) at the time of the sono-
graphic examination. The median gestational
J Ultrasound Med 2006; 25:429–435
 Papp et al

age at the time of the sonogram was 19.5 weeks Table 2. Major Anomalies in Fetuses With Trisomy 13
(range, 13–25 weeks). The main indications for Anomaly n (%)
referral to our prenatal diagnostic unit includ-
CNS anomalies 18 (64.3)
ed advanced maternal age (66.3%), abnormal
Ventriculomegaly 11 (39.3)
maternal serum screening (8.4%), and abnor- Holoprosencephaly 5 (17.9)
mal sonographic findings in other institutions Posterior fossa cyst 2 (7.1)
(15.3%). Most of the examinations were per- Cardiovascular anomalies 15 (53.6)
formed before the 22nd week of pregnancy. Ventricular septal defects 4 (14.3)
Facial anomalies 18 (64.3)
The demographic characteristics of the study
Midline defects 12 (42.9)
population are shown in Table 1. Renal anomalies 12 (42.9)
All fetuses were sonographically examined Omphalocele 1 (3.6)
before karyotyping. Therapeutic termination of Postaxial polydactyly 2 (7.1)
pregnancy was performed in all cases after prop-
er genetic counseling.
Among major anomalies (Table 2), the most
common were CNS anomalies (64.3% [n = 18]) the cardiac defects were diagnosed after that
and facial anomalies (64.3% [n = 18]). As far as year. Of the cardiac defects, there were 5 cases in
CNS anomalies are concerned, we detected ven- which fetal heart defects were the only signs of
triculomegaly in 39.3%, holoprosencephaly in trisomy 13 on sonography. This represents 17.9%
17.9%, and posterior fossa cysts in 7.1% of tri- (5/28) of all the cases. Without diagnosis of these
somy 13 cases. Among facial anomalies, 12 mid- cases, the sensitivity of sonography in detecting
line clefts were found (42.9%). Other facial trisomy 13 would be 71.4% (20/28) instead of
abnormalities that were detected included 89.3% (25/28).
microphthalmos (n = 2), protrusio bulbi (n = 2), Renal anomalies were detected in 42.9% (n =
and hypotelorism (n = 2). In 11 cases, both CNS 12) of the cases. Among them, pyelectasis (66.6%
anomalies and facial anomalies were seen on the [n = 8]) and cystic renal dysplasia (33.3% [n = 4])
scan. These cases represented 61.1% (11/18) of were seen.
all facial anomalies. Two cases of polydactyly (7.1%) and 1 omphalo-
Cardiovascular anomalies were detected in cele were also diagnosed with sonography.
53.6% (n = 15) of fetuses with trisomy 13. As far as minor anomalies (soft markers) were
Ventricular septal defects and dilated right cham- concerned (Table 3), we found a relatively high
ber were the most common, both had a frequen- percentage (21.4%) of increased NT (>6 mm),
cy of 26.7% (4/15) among cardiac defects. The echogenic bowel (17.9%), and EIF (14.3%). In all
remaining 7 fetuses with trisomy 13 had the fol- cases but 1, we also detected some other anoma-
lowing cardiac lesions: 2 outflow tract abnormal- lies in addition to EIF. Altogether, there were 21
ities, 2 hypoplastic left ventricles, 1 coarctation of fetuses in whom minor anomalies were seen. Of
the aorta, 1 truncus arteriosus communis, and 1 them, there were 2 cases in which a minor
tricuspid regurgitation. We introduced fetal anomaly was the only sonographic sign of tri-
echocardiography in our institution in 1994. All somy 13 (EIF in 1 of the cases and echogenic
bowel in the other). Both cases were diagnosed
during the last years of the study period (in 2003
Table 1. Demographic Characteristics of the Study and 2004, respectively).
Population
Demographic Value

Mean maternal age, y 32.4

Maternal age range, y 17–44 Table 3. Minor Anomalies in Fetuses With Trisomy 13
Mean gestational age at sonography, wk 19.5 Anomaly n (%)
Indication for referral, %
Advanced maternal age 66.3 NT >6 mm 6 (21.4)
Abnormal serum screening results 8.4 Choroid plexus cyst 3 (10.7)
Previous affected child 4.7 Echogenic bowel 5 (17.9)
Questionable fetal anatomy 15.3 EIF 4 (14.3)
Other 5.3 Short femur or humerus 3 (10.7)

J Ultrasound Med 2006; 25:429–435 431

Prenatal Diagnosis of Trisomy 13
Among the so-called other abnormalities (Table
4), we found 4 cases of polyhydramnios (14.3%),
3 cases of IUGR (10.7%), and 2 cases each of sin-
gle umbilical artery and fetal hydrops (7.1%) on
the scan of fetuses with trisomy 13. Interestingly,
in all cases of IUGR, we also detected polyhy-
dramnios as well. There were no oligohydram-
nios cases in our series.
Discussion
Trisomy 13 (Patau syndrome) is the third most
common autosomal trisomy among neonates.
At the beginning of the second trimester, the
proportion of trisomy 21 to trisomy 13 is about 8
to 1.5 Fetal diagnosis of trisomy 13 is possible
with maternal serum screening and sonograph-
ic screening. Studies of small numbers of cases
have reported that trisomy 13 may be associated
with a decrease in maternal serum free β-human
chorionic gonadotropin and pregnancy-associ-
ated plasma protein A.6,7 Although there are
studies of first-trimester screening for trisomy
13,8 the most important way of diagnosing this
aneuploidy seems to be second-trimester ultra-
sonographic examination followed by fetal kary-
otyping. The importance of knowing the
potential fetal aneuploidy is underlined by the
fact that, although 90% of trisomy 13 cases are
the result of a free-standing chromosome 13,
10% of them are the result of unbalanced
translocation. Thus, chromosome analyses to
look for an unbalanced translocation is impor-
tant so that accurate recurrence risks can be pro-
vided for the couple.
Because second-trimester sonographic fea-
tures of trisomy 13 may overlap with those of
other syndromes, the precise knowledge of pos-
sible sonographic symptoms of trisomy 13 is
important. We conducted a rather large series of
this aneuploidy, containing 28 cases, using the
database of the prenatal diagnosis unit of the
First Department of Obstetrics and Gynecology
Table 4. Other Abnormalities in Fetuses With
Trisomy 13
Abnormality n (%)
Fetal hydrops 2 (7.1)
Polyhydramnios 4 (14.3)
Single umbilical artery 2 (7.1)
IUGR 3 (10.7)
432
at Semmelweis University. To our knowledge, no
other series this large coming from a single insti-
tution has been reported in the literature.
The total prevalence of sonographic abnormali-
ties in our series was 89.3% (n = 25). Major malfor-
mations were seen in 23 cases (82.1%), whereas
minor anomalies were detected in 16 cases
(57.1%). Of the latter, there were 2 fetuses with tri-
somy 13 who showed only a minor anomaly on
the sonographic scan: in 1 case EIF and in the
other echogenic bowel as the only sign of the ane-
uploidy. All the other cases of minor anomalies
(87.5% [n = 14]) were multiplex malformations in
which different combinations of minor and major
abnormalities could be detected on sonography.
Three cases of trisomy 13 were undetected on
sonography in our series. The indications for fetal
karyotyping were advanced maternal age in all of
these cases. Cardiac anomalies were diagnosed
in all neonates after birth. All 3 were missed
before 1994, when we did not have echocardiog-
raphy as part of our prenatal diagnostic services.
The most frequently seen structural abnormal-
ities were facial anomalies and CNS anomalies
(64.3% [n = 18] both). Among facial anomalies,
midline defects were the most common (42.9%
[n = 12] of all cases). The high frequency of mid-
line facial defects concurs with that reported by
others.9 Of the 18 cases, 11 facial defects were
part of a multiplex malformation syndrome, that
is, combined with CNS defects. The high fre-
quency of facial anomalies on scans shows their
important role in diagnosing trisomy 13. As a
consequence, we always do a thorough sono-
graphic examination of the fetus, regarding
other fetal organs, if we detect any of the facial
defects.
Interestingly, among CNS defects, we detected
ventriculomegaly more frequently than holo-
prosencephaly (39.3% and 17.9%, respectively).
Of the 11 cases of ventriculomegaly, 5 were iso-
lated findings. In 6 cases of severe ventricu-
lomegaly, other fetal abnormalities could be
detected on sonography. The later cases were
diagnosed during the first years of the study peri-
od (1990–1995), and misdiagnosing “lobar holo-
prosencephaly” for “severe ventriculomegaly”
with sonography cannot be ruled out. Thus, at
least some of these 6 ventriculomegaly cases
might have been holoprosencephaly cases
instead of ventriculomegaly cases. Nevertheless,
cytogenetic evaluation of the fetus is recom-
mended in both instances.10
J Ultrasound Med 2006; 25:429–435

The possible relationship of holoprosen-
cephaly and chromosomal abnormalities has
been studied by several authors.11,12 Although
the etiology of holoprosencephaly is not com-
pletely clear, it is well accepted that genetic fac-
tors are important in the process.9 Thus, in cases
of a diagnosis of holoprosencephaly by sonogra-
phy, fetal karyotyping is recommended.
In all our holoprosencephaly cases, facial mid-
line defects were also detected with sonography.
That is understandable if we consider the devel-
opment of the early embryo. The abnormalities
of the prosencephalon are related directly to the
mesenchymal tissue of the prechordal meso-
derm, which is normally responsible for both the
cleavage of the telencephalon and the develop-
ment of the median structures: the orbits, nose,
median upper lip, and palate.13 Thus, prenatal
sonographic detection of a midline facial abnor-
mality also will allow a more definitive diagnosis
of holoprosencephaly and vice versa.
Cardiovascular anomalies were detected in
53.6% (n = 15) of the fetuses with trisomy 13. This
rather high frequency concurs with the data of
DeVore.14 Although fetal echocardiography is not
part of the routine second-trimester sonographic
screening protocol, incorporation of careful
assessment of the cardiovascular system in the
sonographic examination of the fetus certainly
increases the detection rate of fetal chromoso-
mal aberrations. For this reason, we perform
echocardiography in all cases in which any fetal
abnormality can be seen on a second-trimester
screening scan. Once we diagnose congenital
heart disease, we offer fetal karyotyping, regard-
less of the gestational age. We also perform a
thorough sonographic examination of all fetal
organs to look for other sonographically
detectable anomalies.
Renal anomalies were also detected in a consid-
erable percentage (42.9% [n = 12]) of our series.
Enlarged echogenic kidneys were diagnosed in
most of these cases (n = 10). This result is similar
to those reported by other studies regarding
fetuses with trisomy 13.15,16 When enlarged cystic
kidneys are seen on sonography, it is important to
distinguish trisomy 13 from Meckel-Gruber
syndrome.17 This autosomal recessive disorder
shows similar renal findings, but, unlike trisomy
13, it has a 25% recurrence risk.
As far as the minor anomalies (soft markers)
were concerned, we detected them with sonog-
J Ultrasound Med 2006; 25:429–435
Papp et al
raphy in 16 fetuses (57.1%) with trisomy 13. Most
of the fetuses with minor anomalies also showed
signs of other malformations (14/16 [87.5%]). In
2 cases, 1 minor anomaly was the only detectable
sonographic sign of trisomy 13. Although sono-
graphic diagnosis of major malformations plays
a pivotal role in diagnosing trisomy 13, our data
underlines the importance of the sonographic
detection of minor anomalies in this respect.
We found echogenic bowel in 17.9% (n = 5) of
fetuses with trisomy 13. This rate was higher than
Lehman et al15 reported and certainly higher
than that found in fetuses without chromosomal
abnormalities (≈1%).18 Of the 5 cases with
echogenic bowel, 4 were part of multiple malfor-
mations (80%), and only 1 case was an isolated
finding. In all cases, echogenic bowel was diag-
nosed in the second trimester in our series. In
addition to the association between chromoso-
mal abnormalities and hyperechoic bowel,19 it is
known that in fetuses with cystic fibrosis, a simi-
lar sonographic image can be described in the
fetal abdomen during the second trimester.20
Contrary to the general view of echogenic bowel
as mainly a marker of trisomy 21, the great fre-
quency of echogenic bowel in our series shows
that this minor anomaly can be the marker of tri-
somy 13 as well.
Echogenic intracardiac focus was detected in
14.3% (n = 4) of fetuses with trisomy 13. This
rather high frequency concurs with the findings
of Lehman et al,15 who also detected a high fre-
quency of EIF in their series of fetuses with tri-
somy 13. It is known that the prevalence of EIF is
2% to 3.5% during the second trimester in fetuses
without chromosomal abnormalities.21 Despite
this high rate of incidental findings of EIF among
fetuses without abnormalities, our data stress the
importance of this minor marker in diagnosing
aneuploid fetuses. Interestingly, all 4 cases of EIF
were grade 2; that is, EIFs were as bright as adja-
cent bones. All the EIFs were diagnosed before
the 20th week of pregnancy in our series.
Increased NT (>6 mm) was found in 21.4% of
fetuses with trisomy 13. This number is remark-
ably similar to the findings of Snijders et al,22 who
reported a 22% frequency of nuchal edema in
fetuses with trisomy 13 in the second trimester.
Although first-trimester NT screening plays a piv-
otal role in screening for trisomy 21 (detection
rate, 75%),23 trisomy 18 (detection rate, 80%),24
and trisomy 13 (detection rate, 76%),5 its role in
433
Prenatal Diagnosis of Trisomy 13
screening for trisomy 13 in the second trimester
is also important (detection rate, 22%). The dis-
crepancy of the 2 frequencies of increased NT in
the first (76%) and second (22%) trimesters may
due to the high intrauterine lethality rate for
fetuses with trisomy 13 between the 12th and
24th weeks of pregnancy.5
Among sonographically detectable other abnor-
malities of fetuses with trisomy 13, polyhydram-
nios and IUGR had considerable frequency in
our study (14.3% and 10.7%, respectively). Other
studies claim an even higher frequency of IUGR
among fetuses with trisomy 13,16,25 but in those
studies, IUGR was diagnosed after the second
trimester in most of the cases. We diagnosed
IUGR and polyhydramnios together in all IUGR
cases. This combination is unusual for fetuses
without abnormalities26 and is suggestive of an
underlying chromosome aberration. That was
the case in our series and has also been reported
by Lehman et al.15
Finally, we think that second-trimester sono-
graphic examination is capable of showing
anomalies that are characteristic of trisomy 13;
thus, the scan can indicate whether fetal kary-
otyping is advisable. Incorporation of careful
assessment of the fetal cardiovascular system by
sonography certainly increases the detection rate
of trisomy 13.
References
1. Patau K, Smith DW, Therman E, Inborn SL, Wagner HP.
Multiple congenital anomaly caused by an extra chromo-
some. Lancet 1960; 1:790–793.
2. Hill LM. The sonographic detection of trisomies 13, 18, and
21. Clin Obstet Gynecol 1996; 80:349–356.
3. Moerman P, Fryns J, van der Steen K, Kleczkowska A,
Lauweryns J. The pathology of trisomy 13 syndrome: a
study of 12 cases. Hum Genet 1988; 80:349–356.
4. Brewer CM, Holloway SH, Stone DH, Carothers AD,
Fitzpatrick DR. Survival in trisomy 13 and trisomy 18 cases
ascertained from population based registers. J Med Genet
2002; 39:54.
5. Snijders RJM, Sebire NJ, Nicolaides KH. Maternal age and
gestational age-specific risk for chromosomal defects. Fetal
Diagn Ther 1995; 10:356–367.
6. Brizot ML, Snijders RJM, Bersinger NA, Kuhn P, Nicolaides
KH. Maternal serum pregnancy-associated plasma protein-
A and fetal nuchal translucency thickness for the prediction
of fetal trisomies in early pregnancy. Obstet Gynecol 1994;
84:918–922.
434
7. Spencer K, Noble P, Snijders RJM, Nicolaides KH. First-
trimester urine free beta hCG, beta core, and total oestriol
in pregnancies affected by Down’s syndrome: implications
for first-trimester screening with nuchal translucency and
serum free beta hCG. Prenat Diagn 1997; 17:525–538.
8. Taipale P, Hilesmaa V, Salonen R, Ylöstalo P. Increased
nuchal translucency as a marker for fetal chromosomal
defects. N Engl J Med 1997; 337:1654–1658.
9. McGahan JP, Nyberg DA, Mack LA. Sonography of facial
features of alobar and semilobar holoprosencephaly. AJR
Am J Roentgenol 1990; 154:143–148.
10. Bromley B, Frigoletto FD, Benacerraf BR. Mild fetal lateral
cerebral ventriculomegaly: clinical course and outcome.
Am J Obstet Gynecol 1991; 164:863–867.
11. Berry SM, Gosden C, Snijders RJ, Nicolaides KH. Fetal holo-
prosencephaly: associated malformations and chromoso-
mal defects. Fetal Diagn Ther 1990; 5:92–99.
12. Blaas HGK, Eriksson AG, Salvesen KA, et al. Brains and
faces in holoprosencephaly: pre- and postnatal description
of 30 cases. Ultrasound Obstet Gynecol 2002; 19:24–38.
13. DeMyer W. Classification of cerebral malformations. Birth
Defects 1971; 7:78–93.
14. De Vore GR. The genetic sonogram: its use in the detection
of chromosomal abnormalities in fetuses of women of
advanced maternal age. Prenat Diagn 2001; 21:40–45.
15. Lehman CD, Nyberg DA, Winter TC III, Kapur RP, Resta RG,
Luthy DA. Trisomy 13 syndrome: prenatal US findings in a
review of 33 cases. Radiology 1995; 194:217–222.
16. Nicolaides KH, Snijders RJM, Gosden CM, Berry C,
Campbell S. Ultrasonographically detectable markers of
fetal chromosomal abnormalities. Lancet 1992; 340:
704–707.
17. Nyberg DA, Hallesy D, Mahony BS, Hirsh JH, Luthy DA,
Hickock DE. Meckel-Gruber syndrome: importance of pre-
natal diagnosis. J Ultrasound Med 1990; 9:691–693.
18. Nyberg DA, Dubinsky Mahony BS, Luthy DAA, Hickok DE.
Sorenson T. Echogenic fetal bowel: clinical importance.
Radiology 1993; 188:527–531.
19. Nyberg DA, Resta RG, Luthy DA, Hickok DE, Mahony BS,
Hirsh JH. Prenatal sonographic findings of Down syn-
drome: review of 94 cases. Obstet Gynecol 1990; 76:
370–377.
20. Muller F, Aubry MC, Gasser B, Duchatel F, Boue J, Boue A.
Prenatal diagnosis of cystic fibrosis, II: meconium ileus in
affected fetuses. Prenatal Diagn 1985; 5:109–117.
21. Schechter AG, Fakhry J, Shapiro LR, Gewitz HG. In utero
thickening of the chordae tendinae. J Ultrasound Med
1987; 6:691–695.
22. Snijders RJM, Sebire NJ, Nayar R, Souka A, Nicolaides KH.
Increased nuchal translucency in trisomy 13 fetuses at
10–14 weeks’ gestation. Am J Med Genet 1999; 86:205–
207.
J Ultrasound Med 2006; 25:429–435
 Papp et al

23. Nicolaides KH. Screening for chromosomal defects.

Ultrasound Obstet Gynecol 2003; 21:313–321.

24. Sherod C, Sebire NJ, Soares W, Snijders RJM, Nicolaides

KH. Fetal trisomy 18 at 10–14 weeks’ gestation.
Ultrasound Obstet Gynecol 1997; 10:387–390.

25. Dicke JM, Crane JP. Sonographic recognition of major mal-

formations and aberrant fetal growth in trisomic fetuses.
J Ultrasound Med 1991; 10:433–438.

26. Sohaey R, Nyberg DA, Sickler GK, Wlliams MA. Idiopathic

polyhydramnios: association with fetal macrosomia.
Radiology 1994; 190:393–396.

J Ultrasound Med 2006; 25:429–435 435