Soft Markers SOGC

Disclaimer: This guideline was peer reviewed by the SOGCs Genetics Committee in
June 2013, and has been reaffirmed for continued use until further notice.
SOGC CLINICAL PRACTICE GUIDELINES

No 162, June 2005
Fetal Soft Markers in Obstetric Ultrasound

PRINCIPAL AUTHORS
Michiel C. Van den Hof, MD, Halifax NS
R. Douglas Wilson, MD, Philadelphia PA
CONTRIBUTING AUTHORS
DIAGNOSTIC IMAGING COMMITTEE
Stephen Bly, PhD, Health Canada Radiation Protection Bureau,
Ottawa ON
Robert Gagnon, MD, London ON
Ms. Barbara Lewthwaite, MN, Winnipeg MB
Ken Lim, MD,Vancouver BC
Lucie Morin, MD, Montreal QC
Shia Salem, MD, Toronto ON
GENETICS COMMITTEE
Victoria Allen, MD, Halifax NS
Claire Blight, BN, Halifax NS
Gregory Davies, MD, Kingston ON
Outcomes: The use of ultrasound in pregnancy has significant health

and economic outcomes for families and the health care system,
compared with no ultrasound use. The Society of Obstetricians and
Gynaecologists of Canada (SOGC) recommends a single routine
ultrasound evaluation at 16 to 20 weeks in all pregnancies.
Patients need to be counselled about the positive and negative
findings that ultrasound may reveal so they are prepared for
unexpected pregnancy knowledge and the possibility of further
testing options being offered.
Evidence: Committee members were asked to review specific soft
marker ultrasound topics after consensus was reached on the
most commonly published soft markers. Medline and PubMed
databases were searched for peer-reviewed English articles
published from 1985 to 2003. Reviews of each soft marker topic
were written by committee members with quality of evidence and
classification of recommendations. These reviews were then
circulated and discussed by the combined committee. Final format
for the guideline was completed by the committee chairpersons.
Values: The quality of evidence and classification of
recommendations followed discussion and consensus by the
combined committees of Diagnostic Imaging and Genetics of the
SOGC.
Phil Wyatt, MD, North York ON
Benefits, Harms, Costs: It is not possible at this time to determine

the benefits, harms, and costs of the guideline because this would
require health surveillance and research and health resources not
presently available; however, these factors need to be evaluated in
a prospective approach by provincial and tertiary initiatives.
Consideration of these issues is in the options and outcome
section of this abstract.
David C. Young, MD, Halifax NS
Recommendations:
Valerie Desilets, MD, Montreal QC

Alain Gagnon, MD, Vancouver BC
Gregory Reid, MD, Winnipeg MB
Anne Summers, MD, North York ON
Abstract
Objective: To evaluate ultrasound soft markers used in fetal genetic
screening.
Options: Ultrasound screening at 16 to 20 weeks is one of the most
common genetic screening and (or) diagnostic tests used during
pregnancy. The practical concern for ultrasound screening is
false-positive and false-negative (missed or not present) results.
The use and understanding of ultrasound soft markers and their
screening relative risks is an important option in the care of
pregnant women. Currently, the presence of a significant
ultrasound marker adds risk to the likelihood of fetal pathology, but
the absence of soft markers, except in controlled situations, should
not be used to reduce fetal risk.
Key Words: Ultrasound, soft marker, prenatal screening, fetus,

aneuploidy, trisomy, genetic
1. The screening ultrasound at 16 to 20 weeks should evaluate 8

markers, 5 of which (thickened nuchal fold, echogenic bowel, mild
ventriculomegaly, echogenic focus in the heart, and choroid plexus
cyst) are associated with an increased risk of fetal aneuploidy, and
in some cases with nonchromosomal problems, while 3 (single
umbilical artery, enlarged cisterna magna, and pyelectasis) are
only associated with an increased risk of nonchromosomal
abnormalities when seen in isolation (II-2 B).
2. Identification of soft markers for fetal aneuploidy requires
correlation with other risk factors, including history, maternal age,
and maternal serum testing results (II-1 A).
3. Soft markers identify a significant increase in fetal risk for genetic
disease. Timely referral for confirmation, counselling, and
investigation is required to maximize management options (III-B).
Validation: Peer-reviewed guideline development is part of the
committee process in addition to SOGC council and editorial
review.
Sponsors: SOGC.
J Obstet Gynaecol Can 2005;27(6):592612
These guidelines reflect emerging clinical and scientific advances as of the date issued and are subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
592
lJUNE JOGC JUIN 2005
INTRODUCTION
roviding an obstetric ultrasound at 16 to 20 weeks gestation has become standard practice in Canada.13
Although there are many potential benefits, the primary reason to routinely offer this scan is for the detection
of fetal abnormalities.46 Some obstetric ultrasound findings are considered variants of normal but are noteworthy
because they also increase the risk for underlying fetal
aneuploidy. These findings are known as soft markers
and should be considered distinct from fetal anatomic malformations and (or) growth restriction that also increase
perinatal and genetic risks.
The presence of soft markers increases the risk for fetal

aneuploidy but is not diagnostic. Individual soft markers
will vary in the degree of association with fetal aneuploidy.
It has become practice to estimate the degree of association
as a likelihood ratio (LR) by which the a priori background
risk is altered. Detection of multiple soft markers will
increase the significance of the finding, compared with seeing the same marker in isolation.7,8 Nonsonographic factors, including maternal age, gestational age, past history,
and family history also influence the chance for aneuploidy
and should be considered to establish an accurate a priori
risk.912 In addition, maternal serum testing as an alternate
screening tool can complement and enhance the overall
screening process.1318 Providing an accurate assessment of
fetal genetic risk requires the ability to integrate known factors before patients can make an informed choice about
proceeding with invasive diagnostic testing.
The purpose of this guideline is to (1) evaluate the usefulness of each ultrasound soft marker, (2) assess whether a
specific soft marker should be looked for routinely on
screening ultrasound, (3) review potential nonkaryotypic
implications for soft markers, (4) suggest follow-up recommendations to deal with soft markers once detected, and (5)
provide assessment of the quality of information regarding
each marker. (See Table 1 for the quality of evidence and
classification of recommendation).19
REFERENCES
1. Periodic health examination, 1992 update: 2. Routine prenatal ultrasound
screening. Canadian Task Force on the Periodic Health Examination. Can
Med J 1992;147(5):62733.
2. Society of Obstetricians and Gynaecologists of Canada. Guidelines for the
performance of ultrasound examination in obstetrics and gynaecology. J
Soc Obstet Gynaecol Can 1995;17:2636.
3. Society of Obstetricians and Gynaecologists of Canada. Obstetric/gynaecologic ultrasound [policy statement]. J Soc Obstet Gynaecol Can
1997;65:8712.
4. Saari-Kemppainen A, Karjalainen O, Ylostalo P, Heinonen OP. Ultrasound
screening and perinatal mortality: controlled trial on systematic one-stage
screening in pregnancy. The Helsinki Ultrasound Trial. Lancet
1990;336(8712):38791.
5. Leivo T, Tuominen R, Saari-Kemppainen A, Ylostalo P, Karjalainen O,
Heinonen OP. Cost-effectiveness of one-stage ultrasound screening in
pregnancy: a report from the Helsinki ultrasound trial. Ultrasound Obstet
Gynecol 1996;7(5):30914.
6. Long G, Sprigg A. A comparative study of routine versus selective fetal
anomaly ultrasound scanning. J Med Screen 1998;5(1):610.
7. Nicolaides KH, Snijders RJ, Gosden CM, Berry C, Campbell S.
Ultrasonographically detectable markers of fetal aneuploidy. Lancet
1992;340:7047.
8. Bromley B, Lieberman E, Shipp TD, Benacerraf BR. The genetic
sonogram: a method of risk assessment for Down syndrome in the second
trimester. J Ultrasound Med 2002;21(10):108796; quiz 10978.
9. Stene J, Stene E, Mikkelsoen M. Risk for chromosome abnormality at
amniocentesis following a child with a non-inherited chromosome aberration. Prenatal Diagn 1984;4(special issue):8195.
10. Warburton D. Genetic Factors Influencing Aneuploidy Frequency. In:
Dellarco VL, Voytek PK, Hollaender A, editors. Aneuploidy: etiology and
mechanisms. New York: Plenum; 1985. p. 13348.
11. Society of Obstetricians and Gynaecologists of Canada. Guidelines for
health care providers involved in prenatal screening and diagnosis. SOGC
Clinical Practice Guidelines. No. 75; August 1998.
12. Dick PT. Periodic health examination, 1996 update: 1. Prenatal screening for
and diagnosis of Down syndrome. Canadian Task Force on the Periodic
Health Examination. Can Med J 1996;154(4):46579.
13. Vintzileos A, Guzman ER, Smulian JC, Yeo L, Scorza WE, Knuppel RA.
Second-trimester genetic sonography in patients with advanced maternal age
and normal triple screen. Obstet Gynecol 2002;99(6):9935.
14. DeVore GR, Romero R. Combined use of genetic sonography and maternal
serum triple marker screening: an effective method for increasing the detection of trisomy 21 in women younger than 35 years. J Ultrasound Med
2001;20(6):64554.
15. Benn PA, Kaminsky LM, Ying J, Borgida AF, Egan JF. Combined second-trimester biochemical and ultrasound screening for Down syndrome.
Obstet Gynecol 2002;100(6):116876.
16. Hobbins JC, Lezotte DC, Persutte WH, DeVore GR, Benacerraf BR,
Nyberg DA, et al. An 8-center study to evaluate the utility of mid-term
genetic sonograms among high-risk pregnancies. J Ultrasound Med
2003;22(1):338.
17. Verdin SM, Economides DL. The role of ultrasonographic markers for
trisomy 21 in women with positive serum biochemistry. Br J Obstet
Gynaecol 1998;105:637.
18. Drugan A, Reichler A, Bronstein M, Johnson MP, Sokol RJ, Evan MI.
Abnormal biochemical serum screening versus 2nd trimester ultrasound
detected minor anomalies as predictors of aneuploidy in low-risk patients.
Fetal Diagn Ther 1996;11:3015.
19. Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W. Canadian Task
Force on the Periodic Health Exam. Ottawa: Canadian Communication
Group; 1994. p. xxxvii.
JUNE JOGC JUIN 2005 l
593
Table 1. Criteria for quality of evidence assessment and classification of recommendations

Level of evidence*
Classification of recommendations
I:
A. There is good evidence to support the recommendation for

use of a diagnostic test, treatment, or intervention.
Evidence obtained from at least one properly designed

randomized controlled trial.
II-1: Evidence from well-designed controlled trials without

randomization.
B. There is fair evidence to support the recommendation for

use of a diagnostic test, treatment, or intervention.
C. There is insufficient evidence to support the recommenII-2: Evidence from well-designed cohort (prospective or
dation for use of a diagnostic test, treatment, or interretrospective) or case-control studies, preferably from more
vention.
than one centre or research group.
II-3: Evidence from comparisons between times or places with
or without the intervention. Dramatic results from
uncontrolled experiments (such as the results of treatment
with penicillin in the 1940s) could also be included in this
category.
D. There is fair evidence not to support the recommendation

for a diagnostic test, treatment, or intervention.
E. There is good evidence not to support the recommendation
for use of a diagnostic test, treatment, or intervention.
III: Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.
*The quality of evidence reported in these guidelines has been adapted from the Evaluation of Evidence criteria described in the Canadian Task
Force on the Periodic Health Exam.19
Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian
Task Force on the Periodic Health Exam.19
FETAL SOFT MARKERS USEFUL FOR SCREENING ULTRASOUND
ECHOGENIC INTRACARDIAC FOCUS (Figure 1)

Definition and Imaging Criteria
Echogenic intracardiac focus (EICF) is defined as a focus

of echogenicity comparable to bone, in the region of the
papillary muscle in either or both ventricles of the fetal
heart.16 Eighty-eight percent are only in the left ventricle,
5% are only in the right, and 7% are biventricular.7 A grading system has been proposed comparing the echogenicity
of the intracardiac focus with surrounding bone. Grade 2
suggests that echogenicity is equal to bone, and grade 3 suggests it is greater.8 Using an appropriate transducer frequency (# 5 MHz) and appropriate gain setting, an EICF
can be diagnosed on the standard 4-chamber view of the
fetal heart.
Association With Fetal Aneuploidy
The association between isolated EICF and fetal

aneuploidy has been described in both retrospective and
prospective studies. The evidence is best for left or
biventricular EICF, but this is likely due to the greater frequency that foci are found in these locations.111 A
meta-analysis has suggested a likelihood ratio of 2.8 (95%
confidence interval [CI] 1.55.5);12 however, most studies
were undertaken in high-risk women. When the low-risk
population is evaluated, the finding of an isolated EICF is
associated with lower LRs, from 01.8.1317 Consensus of
the SOGC Imaging and Genetics Committees suggests an
LR of 2.
594
l JUNE JOGC JUIN 2005
Although the numbers are small, studies suggest that the

less frequent right-sided, biventricular, multiple, or particularly conspicuous EICF appear to be associated with a
higher risk for fetal aneuploidy, compared with the more
common single, left ventricular EICF.8,11,1821
Association With Nonchromosomal Abnormalities
EICF has not been associated with congenital heart disease

or other chromosomal abnormalities.2225 There may be
some ethnic difference regarding the incidence (Asian more
often than Caucasian) of EICF.26
Summary
EICF is readily diagnosed on the 4-chamber view of the

heart, which is an established part of the screening ultrasound at 16 to 20 weeks gestation.27 EICF is associated
with an increased risk for fetal aneuploidy. A prevalence of
0.5% to 12% has been described in the prenatal population.2,17 If EICF is seen, it should be reported, but as an isolated finding, no further ultrasounds, including
echocardiography, are required. The presence of EICF warrants evaluation of other risk factors for fetal aneuploidy,
including other soft markers, maternal age, and maternal
serum screening results. Based on an LR of 2, if the
midtrimester risk of fetal aneuploidy is greater than 1/600
(maternal age 31 years), referral for consultation, validation,
and counselling should be considered. If the background
risk for fetal aneuploidy is equivalent or less than 1/600 and
the EICF is isolated, no further investigations are necessary.
Figure 1. Echogenic intracardiac focus in the left ventricle of the heart
Recommendations
1. EICF should be evaluated as part of the 4-chamber cardiac review during the 16- to 20- week ultrasound (III-B).
2. Isolated EICF with a fetal aneuploidy risk less than 1/600
by maternal age (31 years) or maternal serum screen
requires no further investigations (III-D).
3. Women with an isolated EICF and a fetal aneuploidy risk
greater than 1/600 by maternal age (31 years) or maternal
serum screening should be offered counselling regarding
fetal karyotyping (II-2 B).
4. Women with right-sided, biventricular, multiple, particularly conspicuous, or nonisolated EICF should be offered
referral for expert review and possible karyotyping (II-2 A).
References
1. Bromley B, Lieberman E, Laboda L, Benacerraf BR. Echogenic intracardiac
focus: a sonographic sign for fetal Down syndrome. Obstet Gynecol
1995;86(6):9981001.
2. Petrikovsky BM, Challenger M, Wyse LJ. Natural history of echogenic foci
within ventricles of the fetal heart. Ultrasound Obstet Gynecol
1995;5(2):924.
3. Lim KI, Austin S, Wilson RD. Echogenic intracardiac foci: incidence
laterality, and association with Down syndrome: a prospective study. J
Ultrasound Med 1998;17(3):S11.
6. Winter TC, Anderson AM, Cheng EY, Komarniski CA, Souter VL, Uhrich
SB, et al. Echogenic intracardiac focus in 2nd-trimester fetuses with trisomy
21: usefulness as a US marker. Radiology 2000;216(2):4506.
7. Wax JR, Mather J, Steinfeld JD, Ingardia CJ. Fetal intracardiac echogenic
foci: current understanding and clinical significance. Obstet Gynecol Survey
2000;55(3):30311.
8. Wax JR, Royer D, Mather J, Chen C, Aponte-Garcia A, Steinfeld JD, et al.
A preliminary study of sonographic grading of fetal intracardiac foci: feasibility, reliability, and association with aneuploidy. Ultrasound Obstet
Gynecol 2000;16(2):1237.
9. Sepulveda W, Cullen S, Nicolaidis P, Hollingsworth J, Fisk NM. Echogenic
foci in the fetal heart: a marker of aneuploidy. Br J Obstet Gynaecol
1995;102(6):4902.
10. Bronshtein M, Jakobi P, Ofir C. Multiple fetal intracardiac echogenic foci:
not always a benign sonographic finding. Prenat Diagn 1996;16(2):1315.
11. Vibhakar NI, Budorick NE, Scioscia AL, Harby LD, Mullen ML, Sklansky
MS. Prevalence of aneuploidy with a cardiac intraventricular echogenic focus
in an at-risk patient population. J Ultrasound Med 1999;18(4):2658.
12. Smith-Bindman R, Hosmer W, Feldstein VA, Deeks JJ, Goldberg JD.
Second-trimester ultrasound to detect fetuses with Down syndromea
meta-analysis. JAMA 2001;285(8):104455.
13. Anderson N, Jyoti R. Relationship of isolated fetal intracardiac echogenic
focus to trisomy 21 at the mid-trimester sonogram in women younger than
35 years. Ultrasound Obstet Gynecol 2003;21:3548.
14. Achiron R, Lipitz S, Gabbay U, Yagel S. Prenatal ultrasonographic diagnosis
of fetal heart echogenic foci: no correlation with Down syndrome. Obstet
Gynecol 1997;89:9458.
4. Manning JE, Ragavendra N, Sayre J, Laifer-Narin SL, Melany ML, Grant

EG, et al. Significance of fetal intracardiac echogenic foci in relation to
trisomy 21: a prospective sonographic study of high-risk pregnant women.
AJR Am J Roentgenol 1998;170(4):10834.
1.5 Caughey AB, Lyell DJ, Filly RA, Washington AE, Norton ME. The impact
of the use of the isolated echogenic intracardiac focus as a screen for Down
syndrome in women under the age of 35 years. Am J Obstet Gynecol
2001;185:10217.
5. Sohl BD, Scioscia AL, Budorick NE, Moore TR. Utility of minor
ultrasonographic markers in the prediction of abnormal fetal karyotype at a
prenatal diagnostic center. Am J Obstet Gynecol 1999;181(4):898903.
16. Bromley B, Lieberman E, Shipp TD, Benacerraf BR. The genetic sonogram:
a method of risk assessment for Down syndrome in the second trimester. J
Ultrasound Med 2002;21:108796.
595
Figure 2. Bilateral renal pyelectasis with anterior/posterior measurement
17. Nyberg DA, Souter VL, El-Bastawissi A, Young S, Luthhardt F, Luthy DA.
Isolated sonographic markers for detection of fetal Down syndrome in the
second trimester of pregnancy. J Ultrasound Med 2001;20:105363.
18. Petrikovsky B, Challenger M, Gross B. Unusual appearances of echogenic
foci within the fetal heart: are they benign? Ultrasound Obstet Gynecol
1996;8:22931.
19. Wax JR, Philput C. Fetal intracardiac echogenic foci: does it matter which
ventricle? J Ultrasound Med 1998;17:1414.
20. Bettelheim D, Deutinger J, Bernashek G. The value of echogenic foci (golf
balls) in the fetal heart as a marker of chromosomal abnormalities. Ultrasound Obstet Gynecol 1999;14:98100.
21. Bromley B, Lieberman E, Shipp TD, Richardson M, Benacceraf BR. Significance of an echogenic intracardiac focus in fetuses at high and low risk for
aneuploidy. J Ultrasound Med 1998;17:12731.
22. Wolman I, Jaffa A, Geva E, Diamant S, Strauss S, Lessing JB, et al.
Intracardiac echogenic focus: no apparent association with structural cardiac
abnormality. Fetal Diagn Ther 2000;15(4):2168.
23. Barsoom MJ, Feldman DM, Borgida AF, Esters D, Diana D, Egan JF. Is an
isolated cardiac echogenic focus an indication for fetal echocardiography? J
Ultrasound Med 2001;20(10):10436.
24. Homola J. Are echogenic foci in fetal heart ventricles insignificant findings?
Ceska Gynekol 1997;62(5):2802.
25. Degani S, Leibovitz Z, Shapiro I, Gonen R, Ohel G. Cardiac function in
fetuses with intracardiac echogenic foci. Ultrasound Obstet Gynecol
2001;18(2):1314.
26. Shipp TD, Bromley B, Lieberman E, Benacerraf BR. The frequency of the
detection of fetal echogenic intracardiac foci with respect to maternal race.
Ultrasound Obstet Gynecol 2000;15(6):4602.
27. Van den Hof MC, Demianczuk NN. Contents of a complete ultrasound
report. J Soc Obstet Gynaecol Can 2001;23(5):8278.
596
MILD PYELECTASIS (Figure 2)

Mild pyelectasis is defined as a hypoechoic spherical or

elliptical space within the renal pelvis that measures $ 5 mm
and # 10 mm.13 The measurement is taken on a transverse
section through the fetal renal pelvis using the maximum
anterior-to-posterior measurement.4 Measurements < 5
mm are normal, should not be designated as pyelectasis, and
should not be reported. Pyelectasis may also be referred to
as mild renal pelvic dilatation or mild hydronephrosis.
Isolated pyelectasis is seen in 0.7% of fetuses at 16 to 26

weeks gestation.5 It is an isolated finding in fetal Down syndrome in approximately 2%.6 Although the likelihood ratio
for Down syndrome is approximately 1.9, the 95% CI does
cross 1 (0.75.1), indicating lack of significance.6 In the
absence of other risk factors, the chance of Down syndrome in the presence of isolated mild pyelectasis remains
small and does not justify an invasive diagnostic procedure.
Fetal pyelectasis is associated with congenital

hydronephrosis, which is a commonly encountered birth
defect.7 Renal pelvis measurements > 10 mm should be
considered equivalent to congenital hydronephrosis with
appropriate follow-up. All fetuses with renal pelvic measurements $ 5 mm should have a neonatal ultrasound, and
those having measurements > 10 mm should also have a

third trimester ultrasound.2
7. Aviram R, Pomeran A, Sharony R, Beyth Y, Rathaus V, Tepper R. The

increase of renal pelvis dilatation in the fetus and its significance. Ultrasound Obstet Gynecol 2000; 16:602.
Summary
8. Van den Hof MC, Demianczuk NN. Content of a complete obstetrical

ultrasound report. J Soc Obstet Gynaecol Can 2001;23(5):4278.
Evaluation of fetal kidneys, which includes possible

pyelectasis, is considered part of the routine screening ultrasound at 16 to 20 weeks gestation and should be reported.8
The finding of isolated pyelectasis does not appear to significantly increase the risk of fetal aneuploidy in low-risk
women and does not justify invasive prenatal testing, but
noninvasive maternal serum screening may assist in risk
assessment. Owing to the increased risk of fetal
hydronephrosis, a neonatal follow-up scan should be
arranged in all cases of mild isolated pyelectasis. A third trimester follow-up ultrasound should only be considered if
pyelectasis is $ 10 mm. Referrals should be considered for
women aged over 35 years and for women who have additional ultrasound findings, renal pelvis measurements > 10
mm, or maternal serum screening results showing increased
chromosomal risks.
Recommendations
1. Evaluation of fetal kidneys is a part of the screening ultrasound at 16 to 20 weeks, and if pyelectasis is visualized, the
renal pelvis should be measured in the anterior/posterior
diameter (III-B).
2. All fetuses with renal pelvic measurements $ 5 mm
should have a neonatal ultrasound, and those having measurements > 10 mm should be considered for a third trimester scan (II-2 A).
3. Isolated mild pyelectasis does not require fetal
karyotyping (II-2 E).
4. Referral for pyelectasis should be considered with additional ultrasound findings and (or) in women at increased
risk for fetal aneuploidy owing to maternal age or maternal
serum screen results (II-2 A).
References
1. Arger PH, Coleman BH, Mintz MC, Snyder HP, Camardese T, Arensen RL,
et al. Radiology 1985;156:4859.
2. Langer B, Simeoni U, Montoya Y, Casanova R, Schlaeder G. Antenatal
diagnosis of upper urinary tract dilation by ultrasonography. Fetal Diagn
Ther 1996;11:1918.
3. Wilson RD, Lynch S, Lessoway VA. Fetal pyelectasis: comparison of
postnatal renal pathology with unilateral and bilateral pyelectasis. Prenat
Diagn 1997;17:4515.
4. Devore, GR. Trisomy 21: 91% detection rate using second-trimester ultrasound markers. Ultrasound Obstet Gynecol 2000;16:13341.
5. Chudleigh PM, Chitty LS, Pembrey M, Campbell S. The association of
aneuploidy and mild fetal pyelectasis in an unselected population: the result
of a multicenter study. Ultrasound Obstet Gynecol 2001;17:197202.
6. Smith-Bindman R, Hosmer W, Feldstein VA, Deeks JJ, Goldberg JD. Second-trimester ultrasound to detect fetuses with Down syndrome. A
meta-analysis. JAMA 2001;285:104455.
SINGLE UMBILICAL ARTERY (Figure 3)

Single umbilical artery (SUA) is the absence of one of the

arteries surrounding the fetal bladder and in the fetal umbilical cord. Assessment of the umbilical arteries can be made
from the cord itself in either transverse or longitudinal sections.13 The umbilical arteries can also be assessed at the
cord insertion site into the fetal abdomen and on either side
of the fetal bladder as the vessels originate from the iliac
arteries. If needed, the assessment can be enhanced with
colour flow Doppler.
Isolated SUA has not been found to be significantly associated with fetal aneuploidy.16
Isolated SUA has been associated with both underlying fetal

renal and cardiac abnormalities,1,79 as well as low birth
weight.2,3,5
Summary
Assessment of cord vessels is considered a part of the routine obstetric ultrasound at 16 to 20 weeks.10 The finding of
a single umbilical artery warrants a detailed review of fetal
anatomy, including kidneys and heart (fetal echo). Appropriate fetal growth should be confirmed through clinical
evaluation with follow-up ultrasound for clinical concerns.
An isolated SUA does not warrant invasive testing for fetal
aneuploidy.
Recommendations
1. Assessment of cord vessels is considered a part of the
routine obstetric ultrasound at 16 to 20 weeks (III-A).
2. The finding of a single umbilical artery requires a more
detailed review of fetal anatomy, including kidneys and
heart (fetal echo) (II-2 B).
3. An isolated single umbilical artery does not warrant invasive testing for fetal aneuploidy (II-2 A).
References
1. Budorick NE, Kelly TE, Dunn JA, Scioscia AL. The single umbilical artery
in a high-risk patient population. What should be offered? J Ultrasound
Med 2001;20:61927.
2. Farrell T, Leslie J, Owen P. Accuracy and significance of prenatal diagnosis
of single umbilical artery. Ultrasound Obstet Gynecol 2000;16:6678.
3. Geipel A, Germer U, Welp T, Schwinger E, Gembruch U. Prenatal diagnosis of single umbilical artery: determination of the absent side, associated
597
Figure 3. Single umbilical artery on cross-section of cord
anomalies, Doppler findings and perinatal outcome. Ultrasound Obstet

Gynecol 2000;15:1147.
4. Pierce BT, Dance VD, Wagner RK, Apodaca CC, Nielsen PE, Calhoun BC.
J Matern Fetal Med 2001;10:5963.
5. Rinehart BK, Terrone DA, Taylor CW, Isler CM, Larmon JE, Roberts WE.
Single umbilical artery is associated with an increased incidence of structural
and chromosomal anomalies and growth restriction. Am J Perinatol
2000;17(5):22932.
6. Murphy-Kaulbeck L, Van den Hof M. Single umbilical artery (SUA) and
fetal aneuploidy. Ultrasound Obstet Gynecol 2002;20(Suppl1):67.
7. Abuhamad AZ, Shaffer W, Mari G, Copel J, Hobbins J, Evans A. Single
umbilical artery: does it matter which artery is missing? Am J Obstet
Gynecol 1995;173:72832.
8. Persutte W, Hobbins J. Single umbilical artery: a clinical enigma in modern
prenatal diagnosis. Ultrasound Obstet Gynecol 1995;6:21629.
echogenicity of fetal bowel and surrounding bone relative

to the ultrasound machine gain setting minimizes observer
variability and should be used. Grade 2 suggests that
echogenicity is equal to bone whereas grade 3 suggests that
it is greater.3 Whenever echogenic bowel is suspected, the
gain setting should be lowered to enable this comparison
and to ensure that bowel hyperechogenicity is real.3 This
should help to minimize a false-positive diagnosis of
hyperechogenicity.
ECHOGENIC BOWEL (Figure 4)
The presence of echogenic bowel is associated with an

increased risk for fetal aneuploidy, including trisomy 13, 18,
21, and the sex chromosomes. It has been detected in 0.6%
to 2.4% of all second trimester fetuses2,49 and as an isolated
finding in 9% of fetuses with aneuploidy (2.8% to 25%).219
As a result, it has been suggested that the likelihood ratio for
this marker is 6 (CI 2.76.8).6
Echogenic bowel is defined as fetal bowel with homogenous areas of echogenicity that are equal to or greater than
that of surrounding bone.1 The echogenicity has been classified as either focal or multifocal.2 There have been various
techniques used to define echogenic bowel, partially
because of concerns raised about intra- and interobserver
variability.3 A grading system based on comparison of the
The presence of echogenic bowel has been associated with

an increased risk for cystic fibrosis in the fetus, congenital
infection, intra-amniotic bleeding, congenital malformations of the bowel, and other perinatal complications,
including intrauterine growth restriction. The risk of cystic
fibrosis in the fetus with echogenic bowel is approximately
2% (0 to 13%).3,1013,1821 The a priori risk will change if the
9. Van den Hof M, Murphy-Kaulbeck L. Single umbilical artery (SUA) and

risk of congenital heart disease (CHD). Ultrasound Obstet Gynecol
2002;20(Suppl1):83.
10. Van den Hof MC, Demianczuk NN. Content of a complete obstetrical ultrasound report. J Soc Obstet Gynaecol Can 2001;23(5):4278.
598
Figure 4. Fetal bowel that is as echogenic as surrounding bone
parental carrier status is known. The association between

congenital infection and hyperechogenic bowel has been
noted for the most common pathogens known to cause
fetal infections (cytomegalovirus [CMV], herpes, parvovirus, rubella, varicella, and toxoplasmosis).3,4,6,11,12,14,18,19
Intra-amniotic bleeding has also been identified as an etiology of echogenic bowel. This can result from intra-amniotic
bleeding owing to placental abruptions or invasive procedures.18,19,2224 Congenital malformations of the fetal bowel
can lead to increased echogenicity. Studies have suggested
that this is more likely with upper gastrointestinal (GI)
lesions. Other ultrasound features, such as ascites and
dilated loops of bowel, will often be present in this circumstance.18,19,2527 Echogenic bowel has also been reported
with poor fetal growth, which is associated with an increase
in perinatal morbidity and mortality.46,1014,18,19,28
Summary
Evaluation of the fetal abdomen is an established component of the screening obstetric ultrasound at 16 to 20
weeks.29 This includes an evaluation of bowel echogenicity
using an appropriate transducer (5 MHZ or less) and ultrasound gain setting. Echogenic bowel is associated with a
significantly increased risk for both chromosomal and
nonchromosomal fetal abnormalities. Timely referral for
validation, consultation, and further investigation is
important.
Further evaluations may include a detailed review of fetal
anatomy, growth, and placental characteristics. Laboratory
investigations may include a fetal karyotype, DNA testing

for cystic fibrosis, and testing for congenital infections
(maternal serum titres, fetal amniotic culture, or polymerase
chain reaction [PCR] for viral DNA). A maternal serum
screen may be considered because elevations in alpha
fetoprotein and hCG in the presence of echogenic bowel
may further define a population at increased risk for
perinatal morbidity and mortality. Obstetric and ultrasound
follow-up may also be important.
Recommendations
1. Evaluation of the fetal bowel should be done routinely
during the 16- to 20-week obstetric ultrasound (III-B).
2. Echogenic bowel should be identified by comparison
with the echogenicity of surrounding bone using an appropriate transducer and gain setting. Bowel echogenicity equal
to or greater than bone is significant (grade 2 or 3) (II-2 A).
3. No further investigations are required for grade 1
echogenic bowel (II-2 D).
4. Grade 2 and 3 echogenic bowel is associated with both
chromosomal and nonchromosomal abnormalities. Expert
review is recommended to initiate the following: a. detailed
ultrasound evaluation looking for additional structural
anomalies or other soft markers of aneuploidy (II-2 A); b.
detailed evaluation of the fetal abdomen looking for signs
of bowel obstruction or perforation (II-2 B); and c. detailed
evaluation of placental characteristics (echogenicity, thickness, position, and placental cord insertion site) (II-2 B); d.
genetic counselling (II-2 A); e. laboratory investigations that
599
should be offered, including fetal karyotype, maternal

serum screening, DNA testing for cystic fibrosis (if appropriate), and testing for congenital infection (II-2 A).
References
1. Sepulveda W, Sebire NJ. Fetal echogenic bowel: a complex scenario. Ultrasound Obstet Gynecol 2000;16:5104.
2. Al-Kouatly HB, Chasen ST, Streltzoff J, Chervenak FA. The clinical significance of fetal echogenic bowel. Am J Obstet Gynecol 2001;185:10358.
3. Slotnick RN, Abuhamad AZ. Prognostic implications of fetal echogenic
bowel. Lancet 1996;347:857.
4. Nyberg DA, Dubinsky T, Resta RG, Mahony BS, Hickock D, Luthy DA.
Echogenic fetal bowel during the second trimester: clinical importance.
Radiology 1993;188:52731.
20. Sepulveda W, Leung KY, Robertson ME, Kay E, Mayall ES, Fisk NM. Prevalence of cystic fibrosis mutations in pregnancies with fetal echogenic
bowel. Obstet Gynecol 1996;87:1036.
21. Berlin BM, Norton ME, Sugarman EA, Tsipis JE, Allitto BA. Cystic fibrosis
and chromosome abnormalities associated with echogenic fetal bowel.
Obstet Gynecol 1999;94:1358.
22. Sepulveda W, Reid R, Nicolaidis P, Prendiville On, Chapman RS, Fisk N.
Second trimester echogenic bowel and intraamniotic bleeding: association
between fetal bowel echogenicity and amniotic fluid spectrophotometry at
410 nm. Am J Obstet Gynecol 1996;174:83942.
23. Sepulveda W. Harris Birthright Research Center, Kings College Hospital
School London. Fetal echogenic bowel. Lancet 1996;(34):1043.
24. Petrikovsky B, Smith-Levitin M, Hosten N. Intra-amniotic bleeding and fetal
echogenic bowel. Obstet Gynecol 1999;93:6846.
5. Bromley B, Doubilet P, Frigoletto F, Krauss C, Estroff J, Benacerraf B. Is

fetal hyperechoic bowel on second trimester sonogram an indication for
amniocentesis? Obstet Gyneacol 1994;83:64751.
25. Phelps S, Fisher R, Partington A, Dykes E. Prenatal ultrasound diagnosis of

gastrointestinal malformations. J Ped Surgery 1997;32:43840.
6. Hill LM, Fries J, Hecker J, Grzybek P. Second trimester echogenic small

bowel: an increased risk of adverse perinatal outcome. Prenat Diagn
1994;14:84550.
26. Font GE, Solari M. Prenatal diagnosis of bowel obstruction initially manifested as isolated hyperechoic bowel. J Ultrasound Med 1998;17:7213.
7. Shohl BD, Scioscia AL, Budorick NE, Moore TR. Utility of minor
prenatal diagnostic center. Am J Obstet Gynecol 1999;181:898903.
27. Shyu MK, Shih JC, Lee CN, Hwa HL, Chow SN, Hsieh FJ. Correlation of
prenatal ultrasound and postnatal outcome in meconium peritonitis. Fetal
Diagn Ther 2003;18:25561.
8. Nyberg DA, Souter VL, Bastawissi AE, Young S, Luthhardt F, Luthy D.

Isolated sonographic markers for detection of fetal down syndrome in the
28. Achiron R, Mazkereth R, Orvieto R, Kuint J, Lipitz S, Rotstein Z.

Echogenic bowel in intrauterine growth restriction fetuses: does this jeopardize the gut. Am Obstet Gynecol 2002;100:1205.

sonogram. A method of risk assessment for down syndrome in the second
trimester. J Ultrasound Med 2002;21:108796.
10. Dicke JM, Crane JP. Sonographically detected hyperechoic fetal bowel: significance and implications for pregnancy management. Obstet Gynecol
1992;80:77882.
11. Muller F, Dommergues M, Aubry MC, Simon-Bouy B, Gautier E, Oury JF,
et al. Hyperechogenic fetal bowel: an ultrasonographic marker for adverse
fetal and neonatal outcome. Am J Obstet Gynecol 1995;173:50813.
12. Yaron Y, Hassan S, Geva E, Kupferminc MJ, Yavetz H, Evans MI. Evaluation of fetal echogenic bowel in the second trimester. Fetal Diagn Ther
1999;14:17680.
13. Ghose I, Mason GC, Martinez D, Harrison KL, Evans JA, Ferriman EL, et
al. Hyperechogenic fetal bowel: a prospective analysis of sixty consecutive
cases. Br J Obstet Gynaecol 2000;107:4269.
14. Stocker AM, Snijders RJ, Carlson DE, Greene N, Gregory KD, Walla CA, et
al. Fetal echogenic bowel: parameters to be considered in differential diagnosis. Ultrasound Obstet Gynecol 2000;16:51923.
15. Rotmensch S, Liberati M, Bronshtein M, Schoenfeld-Dimaio M, Shalev J,
Ben-Rafael Z, et al. Pernatal sonographic findings in 187 fetuses with down
syndrome. Prenat Diagn 1997;17:10019.
16. Smith-Bindman R, Hosmer W, Feldstein VA, Deeks JJ, Goldberg JD. Second-trimester ultrasound to detect fetuses with down syndrome: a
meta-analysis. JAMA 2001;285:104455.
17. Shipp TD, Benacerraf BR. Second-trimester ultrasound screening for
aneuploidy. Prenat Diagn 2002;22:296307.
THICKENED NUCHAL FOLD (Figure 5)

The nuchal fold is the skin thickness in the posterior aspect

of the fetal neck. A nuchal fold measurement is obtained in
a transverse section of the fetal head at the level of the
cavum septum pellucidum and thalami, angled posteriorly
to include the cerebellum. The measurement is taken from
the outer edge of the occiput bone to the outer skin limit
directly in the midline.1 The definition of a thickened nuchal
fold has varied,1,2 although many researchers and centres
now use gestational-age specific criteria.3,4 Consensus for
this document is that a measurement $6 mm be considered
significant between 18 and 24 weeks and a measurement of
$ 5 mm be considered significant at 16 to 18 weeks.15 A
thickened nuchal fold should be distinguished from cystic
hygroma, in which the skin in this area has fluid-filled
loculations. A thickened nuchal fold should not be confused with nuchal translucency, which is a specific measurement of fluid in the posterior aspect of the neck at 11 to 14
weeks gestation.
18. Kesrouani AK, Guibourdenche J, Muller F, Denamur E, Vuillard E, Garel

C, et al. Etiology and outcome of fetal echogenic bowel. Fetal Diagn Ther
2003;18:2406.
19. Simon-Bouy B, Satre V, Ferec C, Malinge MC, Girodon E, Denamur E, et

al. Management of prenatally diagnosed hyperechogenic bowel. Am J Med
Genet 121A:209,2003.
A meta-analysis reviewed the performance of a thick nuchal

fold at 6 mm or greater and showed that the risk for Down
syndrome increased by approximately 17-fold (CI 835).6
600
Figure 5. Increased nuchal fold
A thickened nuchal fold can be associated with single gene

abnormalities, such as Noonan syndrome, multiple
pterygium syndrome, and skeletal dysplasias.7,8 Thickened
nuchal fold has also been associated with congenital cardiac
defects.7,9,10
Summary
Evaluation of the nuchal fold should be considered during

the screening ultrasound at 16 to 22 weeks gestation. A
nuchal fold of 6 mm or greater at 18 to 24 weeks or of 5 mm
or greater at 16 to 18 weeks should be considered significant
and should prompt referral for validation and consultation.
The finding of an isolated thickened nuchal fold significantly increases the risk for fetal aneuploidy, and fetal
karyotyping should be offered. Centres may use alternate
definitions, taking into account gestational age and other
risk factors. Nuchal index has been described as an effective
method to deal with the normal increase in nuchal fold measurement that accompanies advancing gestational age.
Nuchal index is the mean nuchal fold/mean biparietal
diameter (BPD) 100. A value of 11 or greater has a sensitivity of 50% and a specificity of 96%.11
The suggested association of nuchal fold thickening and
congenital heart defect is based on small studies. Careful
detailed ultrasound examination, including the 4-chamber
view and outflow tracts, should be performed. The rare
occurrence of an underlying syndromic etiology for the
increased nuchal fold justifies a directed, detailed anatomic

survey of the fetus and a careful newborn examination.12
Recommendations
1. Nuchal fold measurement should be a part of the screening obstetric ultrasound at 16 to 20 weeks (III-B).
2. A thickened nuchal fold significantly increases the risk of
fetal aneuploidy. Expert review is recommended, and
karyotyping should be offered (II-1 A).
3. A thickened nuchal fold is associated with congenital
heart disease and rarely with other genetic syndromes.
Expert review is recommended (II-2 B).
References
1. Benacerraf BR, Frigoletto FD. Soft tissue nuchal fold in the second trimester fetus: standards for normal measurements compared with those with
Down syndrome. Am J Obstet Gynecol 1987;157(5):11469.
2. Nyberg DA, Souter VL, El-Bastawissi A, Young S, Luthhardt F, Luthy DA.
Isolated sonographic markers for detection of fetal Down syndrome in the
3. Locatelli A, Piccoli MG, Vergani P, Mariani E, Ghidini A, Mariana S, et al.
Critical appraisal of the use of nuchal fold thickness measurements for the
prediction of Down syndrome. Am J Obstet Gynecol 2000;82(1)1928.
4. Bahado-Singh RO, Oz UA, Kovanci E, Deren O, Feather M, Hsu CD, et
al. Gestational age standardized nuchal thickness values for estimating
mid-trimester Down syndrome risk. J Matern Fetal Med 1999;8(2):3743.
5. Gray DL, Crane JP. Optimal nuchal skin-fold thresholds based on gestational age for prenatal detection of Down syndrome. Am J Obstet Gynecol
1994;171:12826.
6. Smith-Blindman R, Hosmer W, Feldstein VA, Deeks JJ, Goldberg JD. Second trimester ultrasound to detect fetuses with Down syndrome: a
meta-analysis. JAMA 2001;285(8):104455.
601
Figure 6. Slightly enlarged posterior horn of the lateral ventricle
7. Souter VL, Nyberg DA, El-Bastawissi A, Zebelman A, Luthhardt F, Luthy

DA. Correlation of ultrasound findings and biochemical markers in the second trimester of pregnancy in fetuses with trisomy 21. Prenat Diagn
2002;22(3):17582.
8. Shipp TD, Benacerraf BR. Second trimester ultrasound screening for
aneuploidy. Prenat Diagn 2002;22:296307.
9. DeVore GR, Alfi O. The association between an abnormal nuchal skin fold,
trisomy 21, and ultrasound abnormalities identified during the second trimester of pregnancy. Ultrasound Obstet Gynecol 1993;3:38794.
10. Dahlgren LS, Sandor GS, Lim KI. Is the nuchal index increased in fetuses
with congenital structural heart defects? Am J Obs Gynecol 2002;(Suppl
187);(6):5191.
11. Lim KI, Pugash D, Dansereau J, Wilson RD. Nuchal index: a gestational age
independent ultrasound marker for the detection of Down syndrome.
Prenat Diagn 2002;22(13):12337.
12. Baumann C, Delagarde R, Vuillard E, Oury JF. Pregnancy outcome and
infant follow-up after diagnosis of nuchal anomalies at the 1st or 2nd trimester ultrasound examination. J Gynecol Obstet Biol Reprod 2001;(30
Suppl 1):6874.
MILD VENTRICULOMEGALY (Figure 6)

Cerebral ventriculomegaly is defined by atrial measurements $ 10 mm. Mean atrial measurements are 7.6 mm,
standard deviation (SD) 0.6 mm. Mild ventriculomegaly
(MVM) is defined as measurements $ 10 to # 15 mm.1 Measurements are obtained from an axial plane at the level of
the thalamic nuclei just below the standard image to measure the BPD. Ventricular measurements are usually
obtained in the far image field because of typical
near-field artifacts. Cursors are positioned perpendicular to
the long axis of the ventricle at the edges of the ventricular
lumen, near the posterior portion of the choroid plexus.
602
When MVM is isolated, the incidence of abnormal fetal

karyotype is estimated at 3.8% (0 to 28.6%).2 Idiopathic lateral ventriculomegaly is found in approximately 0.15% of
chromosomally-normal fetuses,3 whereas 1.4% of trisomy
21 fetuses in the second trimester have idiopathic
ventriculomegaly.4 This suggests a likelihood ratio of 9 for
the risk of karyotype abnormality.
Fetal ventriculomegaly is the most commonly detected

ultrasonographic abnormality of the central nervous system.5 Ventriculomegaly can arise from agenesis of the corpus callosum, cerebral maldevelopment or destruction, vascular anomalies, or an obstruction within the ventricular
system.6 Children with a prenatal diagnosis of MVM have
abnormal neurodevelopment in 10% to 36% of cases
dependent on associated anomalies, etiology,7,8 and ventricular measurement. In combined case series, mortality is
reported at 3.7%.2 When MVM resolves, abnormal outcome has been reported but is infrequent (< 10%).9,10 Unilateral MVM also carries a favourable prognosis when isolated.11,12 After the prenatal diagnosis of MVM, maternal
evaluation for congenital infection is recommended.
Amniocentesis should be offered for karyotype and congenital infection assessment. Other imaging modalities such
as magnetic resonance imaging (MRI) might be considered.13,14
Summary
Lateral ventriculomegaly can be detected on standard cranial biometry planes and should be evaluated on both
screening ultrasounds as well as detailed ultrasound for
higher risk women.15 The ventricles should be measured if
they appear to be larger than the choroid plexus. The finding of ventriculomegaly should prompt a timely referral for
consultation and validation. Evaluation of lateral
ventriculomegaly should include a detailed examination of
fetal anatomy, including the heart. Neonatal assessment and
follow-up are important to rule out associated abnormalities because of the potential for abnormal
neurodevelopment.
Recommendations
1. Fetal cerebral ventricles should be measured if they subjectively appear larger than the choroid plexus (III-B).
2. Cerebral ventricles greater than or equal to 10 mm are
associated with chromosomal and central nervous system
pathology. Expert review should be initiated to obtain the
following: a. a detailed anatomic evaluation looking for
additional malformations or soft markers (III-B); b. laboratory investigation for the presence of congenital infection
or fetal aneuploidy (III-B); and c. MRI as a potential additional imaging technique (II-2 C).
3. Neonatal assessment and follow-up are important to rule
out associated abnormalities and are important because of
the potential for subsequent abnormal neurodevelopment
(II-2 B).
References
1. Cardoza JD, Goldstein RB, Filly RA. Exclusion of fetal ventriculomegaly
with a single measurement: the width of the lateral ventricular atrium. Radiology 1988;169:7114.
2. Pilu G, Falco P, Gabrielli S, Perolo A, Sandri F, Bovicelli L. The clinical significance of fetal isolated cerebral borderline ventriculomegaly: report of 31
cases and review of the literature. Ultrasound Obstet Gynecol
1999;14:3206.
3. Achiron R, Schimmel M, Achiron A, Mashiach S. Fetal mild idiopathic lateral ventriculomegaly: is there a correlation with fetal trisomy? Ultrasound
4. Nyberg DA, Resta RG, Luthy DA, Hickox DE, Mahony BS, Hirsch JH.
Prenatal sonographic findings in Down syndrome. Review of 94 cases.
5. Filly RA, Cardoza JD, Goldstein RB, Barkovich AJ. Detection of fetal central nervous system anomalies: a practical level of effort for a routine
sonogram. Radiology 1989;172:4038.
6. Tsao PN, Teng RJ, Wu TJ, Yau KIT, Wang PJ. Nonprogressive congenital
unilateral ventriculomegaly. Pediatr Neur 1996;14:668.
7. Nicolaides KH, Berry S, Snijders RJ, Thorpe-Beeston JG, Gosden C. Fetal
lateral cerebral ventriculomegaly: associated malformations and chromosomal defects. Fetal Diagn Ther 1990;5(1):514.
8. Tomlinson MW, Treadwell MC, Bottoms SF. Isolated mild
ventriculomegaly: associated karyotypic abnormalities and in utero observations. J Matern Fetal Med 1997;6:2414.
9. Signorelli M, Tiberti A, Valseriati D, Molin E, Cerri V, Grali C, et al. Width

of the fetal lateral ventricular atrium between 10 and 12 mm: a simple variation of the norm? Ultrasound Obstet Gynecol 2004;23:148.
10. Patel HD, Filly AL, Hersh DR, Goldstein RB. Isolated mild fetal cerebral
ventriculomegaly: clinical course and outcome. Radiology 1994;192:75964.
11. Lipitz S, Yagel S, Malinger G, Meizner I, Zalel Y, Achiron R. Outcome of
fetuses with isolated borderline unilateral ventriculomegaly diagnosed at
mid-gestation. Ultrasound Obstet Gynecol 1998;12(1):236.
12. Senat MV, Bernard JP, Schwarzler P, Britten J, Ville Y. Prenatal diagnosis
and follow-up of 14 cases of unilateral ventriculomegaly. Ultrasound Obstet
Gynecol 1999;14(5):32732.
13. Levine D, Barnes PD, Madsen JR, Abbott J, Mehta T, Edelman RR. Central
nervous system abnormalities assessed with prenatal magnetic resonance
imaging. Obstet Gynecol 1999;94(6):10119.
14. Launay S, Robet Y, Valat AS, Thomas D, Devisme L, Rocourt N, et al.
Cerebral fetal MRI and ventriculomegaly. J Radiol 2002;83(6 pt 1):72330.
15. Van den Hof, MC, Deminaczuk NN. Content of a complete obstetrical
CHOROID PLEXUS CYSTS (Figure 7)

Choroid plexus cysts (CPCs) are sonographically discrete,

small cysts ($ 3 mm) found in the choroid plexus within the
lateral cerebral ventricles of the developing fetus at 14 to 24
weeks gestation.1 Imaging of the choroid plexus is performed in the transverse plane of the fetal head at the same
level that the lateral cerebral ventricle is evaluated. The
choroid plexus should be inspected bilaterally for the presence of cysts. The size of CPCs is not of clinical relevance.2
Evaluation of the choroid plexus in the near field ventricle
will be more difficult owing to imaging artifact.
CPCs have been identified in 1% of fetuses during the second trimester screening ultrasound.310 The incidence of
CPCs is 50% in fetuses with trisomy 185,11,12; however, only
10% of fetuses with trisomy 18 will have CPCs as the only
identifiable sonographic marker on ultrasound screening.3,4,69,1216 The likelihood ratio for trisomy 18 when an
isolated CPC is identified is 7 (95% CI 412).9 The number
of cysts and the cysts distribution or size does not change
the risk.2 Although it has been suggested that an isolated
CPC may increase the risk for trisomy 21 with a likelihood
ratio of 1.9, the 95% CI crosses 1 (0.784.46) and lacks statistical significance.17,18
The presence of CPCs in chromosomally normal fetuses is

not associated with other fetal abnormalities or abnormal
postnatal development.15
Summary
Evaluation of the fetal cranium, including the ventricles and

choroid plexus, is considered part of the routine screening
603
Figure 7. Choroid plexus cyst
ultrasound at 16 to 20 weeks gestation.19 Identification and

reporting of CPCs should be a part of this screening examination. With the presence of CPCs, caregivers should next
evaluate maternal age risk and, if available, the maternal
serum screen.2 CPCs increase the risk for trisomy 18.
Follow-up ultrasound is not necessary for isolated CPCs.
Referral for counselling and possible invasive testing is only
necessary if maternal age is 35 years or older or the maternal
serum screen is positive for either trisomy 18 or 21.2,20
Recommendations
1. Choroid plexus should be evaluated for the presence of
discrete cysts during the 16- to 20-week ultrasound (III-B).
2. Isolated CPCs require no further investigation when
maternal age or the serum screen equivalent is less than the
risk of a 35-year-old (II-2 E).
3. Fetal karyotyping should only be offered if isolated CPCs
are found in women 35 years or older or if the maternal
serum screen is positive for either trisomy 18 or 21 (II-2 A).
4. All women with fetal CPCs and additional malformation
should be offered referral and karyotyping (II-2 A).
2. Gratton RJ, Hogge WA, Aston CE. Choroid plexus cysts and trisomy 18:
risk of modification based on maternal age and multiple-marker screening.
Am J Obstet Gynecol 1996;175(6):14937.
3. Walkinshaw S, Pilling D, Spriggs A. Isolated choroid plexus cysts the
need for routine offer of karyotyping. Prenat Diagn 1994;14(8):6637.
4. Kupferminc MJ, Tamura RK, Sabbagha RE, Parilla BV, Cohen LS,
Pergament E. Isolated choroid plexus cyst(s): an indication for amniocentesis. Am J Obstet Gynecol 1994;171(4):106871.
5. Gray DL, Winborn RC, Suessen TL, Crane JP. Is genetic amniocentesis
warranted when isolated choroid plexus cysts are found? Prenat Diagn
1996;16(11):98390.
6. Reinsch RC. Choroid plexus cysts association with trisomy: prospective
review of 16,059 patients. Am J Obstet Gynecol 1997;176(6):13813.
7. Geary M, Patel S, Lamont R. Isolated choroid plexus cysts and association
with fetal aneuploidy in an unselected population. Ultrasound Obstet
Gynecol 1997;10(3):1713.
8. Sohn C, Gast AS, Krapfl E. Isolated fetal choroid plexus cysts: not an indication for genetics diagnosis? Fetal Diagn Ther 1997;12(5):2559.
9. Ghidini A, Strobelt N, Locatelli A, Mariani E, Piccoli MG, Vergani P. Isolated fetal choroid plexus cysts: role of ultrasonography in establishment of
the risk of trisomy 18. Am J Obstet Gynecol 2000;182(4):9727.
10. Snijders RJ, Shawa L, Nicholaides KH. Fetal choroid plexus cysts and
trisomy 18: assessment of risk based on ultrasound findings and maternal
age. Prenat Diagn 1994;14(12):111927.
11. Denis E, Dufour P, Valat AS, Vaast P, Subtil D, Bourgeot P, et al. Choroid
plexus cysts and risk of chromosome anomalies. Review of the literature and
proposed management. J Gynecol Obstet Biol Reprod 1998;27(2):1449.
5. All women with CPCs and additional soft markers should

be offered additional counselling and further ultrasound
review (III-B).
12. Gonen R, Kar H, Degani S. The karyotype of fetuses with anomalies

detected by second trimester ultrasonography. Europ J Obstet Gynecol
Reprod Biol 1995;58(2):1535.
References
13. Maieron A, Rustico M, Pecile V, Natale R, DOttavio G, Fischer Tamaro L,

et al. The indications of the management of fetuses with choroid plexus
cysts. Minerva Ginecol 1996;48(4):12533.
1. Chitty LS, Chudleigh RP, Wright E, Campbell S, Pembrey M. The significant of choroid plexus cysts in an unselected population: results of a
multicenter study. Ultrasound Obstet Gynecol 1998;12(6):3917.
604
14. Digiovanni LM, Quinlan MP, Verp MS. Choroid plexus cysts: infant and
early childhood development outcome. Obstet Gynecol 1997;90(2):1914.
Figure 8. Enlarged cisterna magna
15. Morcos CL, Platt LD, Carlson DE, Gregory KD, Greene NH, Korst LM.
The isolated choroid plexus cyst. Obstet Gynecol 1998;92(2):2326.
16. Sullivan A, Giudice T, Vavelidis F, Thiagaraja S. Choroid plexus cysts: is biochemical testing a valuable adjunct to targeted ultrasonography? Am J
Obstet Gynecol 1999;181(2):2605.
17. Yoder PR, Sabbagha RE, Gross SJ, Zelop CM. The second-trimester fetus
with isolated choroid plexus cysts: a meta-analysis of risk of trisomies 18
and 21. Obstet Gynecol 1999;93:86972.
18. Bromley B, Lieberman R, Benacerraf BR. Choroid plexus cysts: not associated with Down syndrome. Ultrasound Obstet Gynecol 1996;8(4):2325.
19. Van den Hof MC, Demianczuk NN. Content of a complete obstetrical ultrasound report. J Soc Obstet Gynaecol Can 2001;23(5):4278.
20. Demasio K, Canterino J, Ananth C, Fernandez C, Smulian J, Vintzileos A.
Isolated choroid plexus cyst in low-risk women less than 35 years old. Am J
ENLARGED CISTERNA MAGNA (Figure 8)

The cisterna magna is measured on a transaxial view of the

fetal head angled 15 degrees caudal to the canthomeatal line.
The anterior/posterior diameter is taken between the
inferior/posterior surface of the vemis of the cerebellum to
the inner surface of the cranium. An enlarged cisternal
magna is defined by an anterior/posterior diameter $ 10
mm.1,2 The measurement will be falsely exaggerated by a
steep scan angle through the posterior fossa or
dolichocephaly.3,4
An enlarged cisterna magna has been described in association with fetal aneuploidy, particularly trisomy 18.57 The
association with aneuploidy appears to be strongest in the

absence of ventricular dilatation but in the presence of
other anomalies.46 Isolated enlarged cisterna magna does
not appear to be strongly associated with aneuploidy.2
There are no large prospective studies to evaluate this
marker.
An enlarged cisterna magna is commonly seen in association with other anatomic (arachnoid cyst, Dandy Walker
malformation, and Dandy Walker variant)810 and syndromic (oro-facialdigital syndrome, Meckel-Gruber syndrome, and DiGeorge syndrome)4 abnormalities.
Summary
Review of the fetal cerebellum and cisterna magna is a routine part of the screening ultrasound at 16 to 20 weeks gestation.11,12 If the cisterna magna is subjectively increased, a
measurement should be undertaken. The mean diameter of
a normal cisterna magna is 5 mm, SD 3 mm.3 A measurement $ 10 mm is considered an abnormality and appropriate referral for consultation and validation should be
initiated. A detailed fetal examination should be performed
looking for other anomalies, growth restriction, or abnormal amniotic fluid volume. An isolated enlarged cisterna
magna is not an indication for fetal karyotyping.
Recommendations
1. Review of the fetal cerebellum and cisterna magna is a
routine part of the screening ultrasound at 16 to 20 weeks.
605
If the cisterna magna is subjectively increased, a measurement should be taken (III-B).
4. Nyberg D, Mahony B, Hegge F, Hickok D, Luthy D, Kapur R. Enlarged

cisterna magna and the Dandy-Walker malformation: factors associated
with aneuploidy. Obstet Gynecol 1991;77:436.
2. An isolated enlarged cisterna magna is not an indication

for fetal karyotyping (III-D).
5. Laing FC, Frates MC, Brown DL,Bensen CB, Di Salvo D, Doubilet P.

Sonography of the fetal cisterna magna: false appearance of mega-cisterna
magna and Dandy-Walker variant. Radiology 1994;192:274.
3. With an enlarged cisterna magna, expert review is recommended for follow-up ultrasounds and possible other imaging modalities (for example, MRI) and investigations
(III-B).
6. Chen CP, Hung TH, Jan SW, Jeng CJ. Enlarged cisterna magna in the third
trimester as a clue to fetal trisomy 18. Fetal Diagn Ther 1998;13:2934.
4. If the enlarged cisterna magna is seen in association with

other abnormal findings, fetal karyotyping should be
offered (III-B).
8. Ecker JL, Shipp TD, Bromley B, Benacerraf B. The sonographic diagnosis

of Dandy-Walker and Dandy-Walker variant: associated findings and outcomes. Prenat Diagn 2000;20:32832.
REFERENCES
7. Nyberg DA, Kramer D, Resta RG, Kapur R, Mahony BS, Luthy DA, et al.
Prenatal sonographic findings of trisomy 18: review of 47 cases. J Ultrasound Med 1993;2:10313.
9. Aletebi FA, Fung Kee Fung K. Neurodevelopmental outcome after antenatal diagnosis of posterior fossa abnormalities. J Ultrasound Med
1999;18:6839.
1. Comstock C, Boal D. Enlarged fetal cisterna magna: appearance and significance. Obstet Gynecol 1985;66:25S.
10. Ulm MR, Ulm J, Bernaschek G. Dandy-Walker malformation diagnosed

before 21 weeks of gestation: associated malformations and aneuploidy.
Ultrasound Obstet Gynecol 1997;10:16770.
2. Haimovici J, Doubilet P, Benson C, Frates MC. Clinical significance of isolated enlargement of the cisterna magna (>10mm) on prenatal sonography.
J Ultrasound Med 1997;16:7314.
3. Mahoney B, Callen P, Filly R, Hoddick W. The fetal cisterna magna. Radiology 1984;153:773.
12. Society of Obstetricians and Gynaecologists of Canada. Guidelines for Performance of ultrasound. J Soc Obstet Gynaecol Can 1995;17:2636.
FETAL SOFT MARKERS USEFUL FOR COMPREHENSIVE ULTRASOUND
SHORT FEMUR LENGTH

A short femur length is defined as either a measurement

below the 2.5th percentile for gestational age or a measurement that is less than 0.9 of that predicted by the measured
biparietal diameter.1 The femur should be measured with
the bone perpendicular to the ultrasound beam and with
epiphyseal cartilages visible but not included in the measurement. The relation between bone length and head size
may differ across racial groups.2
Short femur length has been found to have a sensitivity of

16% in the prediction of Down syndrome with a falsepositive rate of 4%. A meta-analysis showed a likelihood
ratio of 2.7 (95% CI 2.16.0).3
Short femur length can also be associated with skeletal

dysplasias or fetal growth restriction.4
If a femur appears abnormal or its length is found to be

below the 2.5th percentile for gestational age, it may be
indicative of fetal growth restriction or a more general skeletal malformation. In this circumstance, other long bones
should be assessed and referral with follow-up ultrasound
considered.
Recommendations
1. Although femur length is standard biometry on the 16- to
20-week ultrasound, the assessment for relative shortness is
not part of the screening evaluation (III-C).
2. Relative femur shortening is an ultrasound marker for
trisomy 21 and should be considered during tertiary level
evaluation (II-1 A).
3. If a femur appears abnormal or measures short on
screening ultrasound, other long bones should be assessed
and referral with follow-up ultrasound considered (III-B).
SHORT HUMERUS LENGTH
Summary
Short femur length is an ultrasound marker for fetal

aneuploidy, particularly trisomy 21. The mathematical
model used to determine a positive result is not amenable to
screening ultrasound; however, it should be included in the
panel of markers used by tertiary centres.
606
A short humerus length is defined as a length below the

2.5th percentile for gestational age or as a measurement less
than 0.9 of that predicted by the measured biparietal diameter.1 The humerus should be measured with the bone
perpendicular to the ultrasound beam and with epiphyseal
cartilages visible but not included in the measurement.
Short humeral length has been found to have a sensitivity of

9% with a false-positive rate of 3%. A meta-analysis showed
a likelihood ratio of 7.5 (95% CI 4.512).3
Short humeral length can also be associated with skeletal

dysplasias or fetal growth restriction.4 Humeral length has
also been recorded as multiples of the median for gestational age. This allows for a graded response including a
negative predictor for the relatively longer humerus.5
Summary
Short humeral length is an ultrasound marker for fetal

aneuploidy, particularly trisomy 21. Humeral length is not
currently part of the screening obstetric ultrasound; however, it should be included in the panel of markers used by
tertiary centres. During screening ultrasound, if the
humerus appears abnormal or its length is short, other long
bones should be assessed and referral with follow-up ultrasound considered.
echogenic line within the bridge of the fetal nose. The fetus
is imaged facing the transducer with the fetal face strictly in
the midline. The angle of insonation is 90 degrees, with the
longitudinal axis of the nasal bone as the reference line.
Calibres are placed at each end of the nasal bone. Absence
of the nasal bone or measurements below 2.5th percentile
are considered significant.24
Preliminary second trimester studies appear to confirm that

hypoplastic or absent nasal bone is an ultrasound marker
for fetal Down syndrome, while, conversely, a normal nasal
bone would reduce significantly the risk.57 The likelihood
ratio for this finding varies depending on ethnic background. Although a hypoplastic nasal bone was associated
with an overall likelihood ratio for Down syndrome at 51, it
was found to be 132 for Caucasians and 8.5 for African
Caribbeans. The negative likelihood ratio was 0.39 for Caucasians and 0.27 for African Caribbeans.7 Nasal hypoplasia
has not been associated with other aneuploidy.
Recommendations
1. Humeral length is not part of the current screening ultrasound at 16 to 20 weeks but should be considered for future
inclusion (III-B).
An absent or hypoplastic nasal bone has not been found to

be associated with chromosomal abnormalities.
2. Relative humeral shortening is an ultrasound marker for

trisomy 21 and should be considered during tertiary level
evaluation (II-1 A).
Hypoplastic or absent nasal bone is an ultrasound marker

for fetal Down syndrome, and a normal nasal bone length
significantly reduces the risk. Although views of the fetal
nasal bone are readily obtained by imaging the facial profile,
this is not considered a part of the routine screening ultrasound.8 In circumstances where the facial profile is seen and
the nasal bone is felt to be absent or hypoplastic, referral is
recommended. Assessment of the nasal bone should be
considered for research or tertiary level evaluation.
3. If the humerus is evaluated and appears abnormal or

short, other long bones should be assessed and referral with
follow-up ultrasound considered (III-B).
References
1. Nyberg DA, Resta RG, Luthy MA, Hickok DE, Williams MA. Humerus
and femur length shortening in the detection of Down syndrome. Am J
2. Shipp TD, Bromley B, Mascola M, Benacerraf B. Variation in fetal femur
length with respect to maternal race. J Ultrasound Med 2001;20:1414.
3. Smith-Bindman R, Hosmer W, Feldstein VA, Deeks JJ, Goldberg JD. Second-trimester ultrasound to detect fetuses with Down syndrome. JAMA
2001;285:104455.
4. Pilu G, Nicolaides KH. Diagnosis of fetal abnormalities: the 18-23-week
scan. London: The Parthenon Publishing Group Inc; 1999.
5. Bahado-Singh RO, Oz AU, Kovanci E, Deren O, Copel J, Baumgarten A,
et al. New Down syndrome screening algorithm: ultrasonographic biometry
and multiple serum markers combined with maternal age. Am J Obstet
Gynecol 1998;179:162731.
Summary
Recommendations
1. Assessment of the fetal nasal bone is not considered a
part of the screening ultrasound at 16 to 20 weeks (III-B).
2. Hypoplastic or absence nasal bone is an ultrasound
marker for fetal Down syndrome, and if suspected, expert
review is recommended (II-2 B).
References
1. Down LJ. Observations on an ethnic classification of idiots. Clinical Lectures and Reports, London Hospital 1866;3:25962.
NASAL BONE
2. Cicero S, Curcio P, Papageorghiou A, Sonek J, Nicolaides K. Absence of

nasal bone in fetuses with trisomy 21 at 11-14 weeks of gestation: an observational study. Lancet 2001;358:16657.
3. Sonek JD. Nasal bone evaluation with ultrasonography: a marker for fetal
aneuploidy. Ultrasound Obstet Gynecol 2003;22:115.
Nasal hypoplasia has been recognized as a feature of

postnatal trisomy 21.1 This has led to prenatal evaluation of
the nasal bone, which has been shown to be a thin
4. Minderer S, Gloning KP, Henrich W, Stoger H. The nasal bone in fetuses

with trisomy 21: sonographic versus pathomorphological findings. Ultrasound Obstet Gynecol 2003;22:1621.
607
5. Vintzileos A, Walters C, Yeo L. Absent nasal bone in the prenatal detection

of fetuses with trisomy 21 in a high-risk population. Obstet Gynecol
2003;101(5 Part l):9058.
6. Bromley B, Lieberman E, Shipp T, Benacerraf B. Fetal nasal bone length: a
marker for Down syndrome in the second trimester. J Ultrasound Med
2002;21:138794.
7. Cicero S, Sonek J, McKenna D, Croom C, Johnson L, Nicolaides K. Nasal
bone hypoplasia in fetuses with trisomy 21. Ultrasound Obstet Gynecol
2003;21:158.
8. Van den Hof MC, Demianczuk NN. Content of a complete obstetrical
FIFTH FINGER CLINODACTYLY

Fifth finger clinodactyly is defined by a hypoplastic or

absent mid-phalanx of the fifth digit. Ultrasound identification of the fetal hand must first be undertaken and then
appropriate magnification accomplished. The evaluation
requires stretching of the 5 fingers. The diagnosis is established when the middle phalanx of the fifth finger is markedly smaller than normal or absent, which often causes the
finger to be curved inward.1
Fifth finger clinodactyly is found in 60% of neonates

affected with Down syndrome.2 During antenatal screening, it has been found to be present in 3.4% of normal
fetuses and in 18.8% of fetuses with Down syndrome. This
suggests a likelihood ratio of 5.6 (95% CI 2.511.9).3,4
As an isolated finding, clinodactyly is not associated with

other nonchromosomal anatomic or syndromic
abnormalities.
Summary
Evaluation of the fetal fingers is not an established part of

the screening obstetric ultrasound at 16 to 20 weeks gestation. The risk for fetal aneuploidy in the presence of isolated
clinodactyly has been estimated to increase by 5.5, and
although this finding is considered a significant soft marker,
it has not been confirmed with prospective studies. In the
event that clinodactyly is seen, it is important to initiate
timely referral for consultation, validation, and possibly further investigations. Tertiary centres may use evaluation for
clinodactyly as part of their review for patients at increased
risk for aneuploidy.
Recommendations
1. Imaging of the outstretched hand to evaluate for fifth finger clinodactyly is not an expectation during the 16- to
20-week ultrasound (III-C).
2. Fifth finger clinodactyly is associated with trisomy 21 and
should be considered for research or tertiary-level evaluation (III-B).
References
1. Benacerraf BR, Osathanondh R, Frigoletto FD. Sonographic demonstration
of hypoplasia of the middle phalanx of the fifth digit: a finding associated
with Down syndrome. Am J Obstet Gynecol 1988;159:1814.
2. Hall B. Mongolism in newborn infants. Clin Pediatr 1966;5:4.
3. Vintzileos AM, Campbell WA, Guzman ER, Smulian JC, McLean DA,
Ananth CV. Second-trimester ultrasound markers for detection of trisomy
21: which markers are best? Obstet Gynecol 1997;89:9414.
4. Deren O, Mahoney MJ, Copel JA, Bahado-Singh RO. Subtle
ultrasonographic anomalies: do they improve the Down syndrome detection rate? Am J Obstet Gynecol 1998;178:4415.
FETAL SOFT MARKERS NOT ESTABLISHED FOR CLINICAL PRACTICE

BRACHYCEPHALY
The cephalic index does not vary significantly between

trisomy 21 and euploid fetuses.38 Other calculations of
frontal lobe hypoplasia have shown some screening potential in retrospective studies;911 however, no prospective
studies have been undertaken, and there are no calculated
likelihood ratios. The strawberry shaped cranium has
been specifically described as being associated with trisomy
1812 but has not been evaluated prospectively in a low-risk
population.
Fetuses affected with trisomy 21 are known to be at

increased risk for abnormalities in brain growth and maturation.1 This is known to result in shortening of the frontal
occipital brain length primarily owing to a smaller frontal
lobe.2 The subsequent abnormal skull shape
(brachycephaly) has been evaluated as a screening tool. Initially, brachycephaly was studied with the cephalic
indexthe biparietal diameter over the occipital frontal
diameter. More recent investigations have specifically studied the hypoplastic frontal lobe with various biometric
measurements and calculations.
608
Brachycephaly is not strongly associated with other chromosomal abnormalities.
Summary
Brachycephaly has not been established as an effective

screen for fetal aneuploidy. No recommendations for
follow-up or changes in neonatal care are advised as a result
of a finding of brachycephaly or abnormalities in frontal
lobe biometry. Other abnormal cranial morphologies, such
as strawberry12 or lemon13 shapes, are associated with
fetal pathology and should prompt appropriate referral.
References
1. Golden JA, Hyman BT. Development of the superior temporal neocortex is
anomalous in trisomy 21. J Neuropath Experiment Neurol1994;53(5):51320.
2. Schmidt-Sidor B, Wisniewski KE, Shepart TH, Sersen EA. Brain growth in
Down syndrome subjects 15 to 22 weeks of gestational age and birth to 60
months. Clin Neuropathol 1990;9(4):18190.
one method, the converging lines are drawn along the posterior lateral aspect of the iliac wings, while in the second
method, the converging lines are drawn through the middle
of the iliac wing extremity. It has been suggested that an
angle 90 degrees should be considered the upper limit of
normal when screening for trisomy 21.1,3
Several prospective and retrospective studies have shown

the association between increased iliac angle and trisomy
21.2,48,9 Research to date has been limited to high-risk populations. There is no screening sensitivity for this marker in
the low-risk population.
3. Borrell A, Costa D, Martinez JM, Puerto B, Carrio A, Ojuel J, Fortuny A.

Brachycephaly is ineffective for detection of Down syndrome in early
midtrimester fetuses. Early Human Dev 1997;47:5761.
An increased iliac angle has not been associated with specific chromosomal abnormalities.
4. Lockwood C, Benacerraf B, Krinsky A, Blakemore K, Belanger K,

Mahoney M, Hobbins J. A sonographic screening method for Down syndrome. Am J Obstet Gynecol 1987;157(4 Pt 1):8038.
Summary
5. Shah YG, Eckl CJ, Stinson SK, Woods JR. Biparietal diameter/femur
length ratio, cephalic index, and femur length measurements: not reliable
screening techniques for Down syndrome. Obstet Gynecol 1990;75:186.
6. Perry TB, Benzie RJ, Cassar N, Hamilton EF, Stocker J, Toftager-Larse K,
Lippman A. Fetal cephalometry by ultrasound as a screening procedure for
the prenatal detection of Down syndrome. Br J Obstet Gynaecol
1984;91(2):13843.
7. Rosati P, Guariglia L. Early transvaginal measurement of cephalic index for
the detection of Down syndrome fetuses. Fetal Diagn Ther 1999;14:3840.
8. Buttery B. Occipitofrontal-biparietal diameter ratio. An ultrasonic parameter for the antental evaluation of Down syndrome. Med J Aust
1979;2(12):6624.
9. Bahado-Singh RO, Wyse L, Dorr MA, Copel JA, OConnor T, Hobbins JC.
Fetuses with Down syndrome have disproportionately shortened frontal
lobe dimensions on ultrasonographic examination. Am J Obstet Gynecol
1992;167:100914.
Increased iliac angle is a possible marker for trisomy 21;

however, measurement techniques do not make it amenable
to a screening exam, and it has not been evaluated to be
effective in a low-risk population. This marker may be useful for tertiary centres investigating high-risk patients or as a
possible negative predictor.9
References
1. Kliewer MA, Hertzberg BS, Freed KS, DeLong DM, Kay HH, Jordan SG,
et al. Dysmorphologic features of the fetal pelvis in Down syndrome: prenatal sonographic depiction and diagnostic implications of the iliac angle.
Radiology 1996;201(3):6814.
2. Bork MD, Egan JFX, Cusick W, Borgida AF, Campbell WA, Rodis JF. Iliac
wing angle as a marker for trisomy 21 in the second trimester. Obstet
Gynecol 1997(Part 1); 89(5):7357.
10. Winter TC, Reichman JA, Luna JA, Cheng EY, Doll AM, Komarniski CA, et
al. Frontal lobe shortening in second-trimester fetuses with trisomy 21: usefulness as an US marker. Radiology 1998;207(1):21522.
3. Shipp TD, Bromley B, Lieberman E, Benacerraf BR. The iliac angle as a

sonographic marker for Down syndrome in second-trimester fetuses.
11. Winter TC, Ostrovksy AA, Komarniski CA, Uhrich SB. Cerebellar and frontal lobe hypoplasia in fetuses with trisomy 21: usefulness as combined US
markers. Radiology 2000;214(2):5338.
4. Shipp TD, Bromley B, Lieberman E, Benacerraf BR. The second-trimester

fetal iliac angle as a sign of Down syndrome. Ultrasound Obstet Gynecol
1998;12(1):158.
12. Nicolaides KH, Salvesen DR, Snijders RJ, Gosden CM. Strawberry-shaped
skull in fetal trisomy 18. Fetal Diagn Ther 1992;7(2):1327.
5. Zook PD, Winter TC, Nyberg DA. Iliac angle as a marker for Down syndrome in second-trimester fetuses: CT measurement. Radiology
1999;211(2):44751.
13. Van den Hof MC, Nicolaides KH, Campbell J, Campbell S. Evaluation of
the lemon and banana signs in one hundred thirty fetuses with open spina
bifida. Am J Obstet Gynecol 1990;162(2):3227.
6. Freed KS, Kliewer MA, Hertzberg BS, DeLong DM, Paulson EK, Nelson
RC. Pelvic CT morphometry in Down syndrome: implications for prenatal
US evaluationpreliminary results. Radiology 2000;214(1):2058.
INCREASED ILIAC ANGLE
7. Grange G, Thoury A, Dupont J-M, Pannier E, LeRhun F, Souchet M, et al.

Sonographic measurement of the fetal iliac angle cannot be used alone as a
marker for trisomy 21. Fetal Diagn Ther 2000;15:415.
8. Lee W, Blanckaert K, Bronsteen RA, Huang R, Romero R. Fetal iliac angle

measurements by three-dimensional sonography. Ultrasound Obset
Gynecol 2001;18:1504.
It has been identified that postnatal trisomy 21 is associated

with a wider lateral flare of the iliac bones. Two techniques
have been described to measure the fetal iliac angle.1,2 Both
methods use the axial (transverse) view of the fetal pelvis. In
9. Massez A, Rypens F, Metens T, Donner C, Avni FE. The iliac angle: a

sonographic marker of trisomy 21 during midtrimester: dependency of fetal
lying? Eur Radiol 2003; 13:207581.
609
SMALL FETAL EAR LENGTH

Small low-set ears are a clinical feature in newborns with

trisomy 21 and other aneuploidy.1 Although fetal ear position is difficult to determine sonographically, ear length is
possible,2 and normal ranges have been established.24 Ear
length is measured in a coronal view and defined as the
maximal distance between the superior and inferior border
of the external ear.
Although sandal gap has been reported as a finding in

fetuses with Down syndrome in the third trimester,3 it is a
subtle sonographic finding in the second trimester.4,5 No
studies have been undertaken to establish a risk for
aneuploidy based on this finding.
The finding of sandal gap may be a normal variant and is not

associated with other chromosomal abnormalities.
Summary
A prospective study has been undertaken to evaluate fetal

ear length and its association with fetal aneuploidy. A sensitivity of 32% and a specificity of 93% was found.5 This
might suggest a likelihood ratio between 3 and 5; however,
in 29% of fetuses, appropriate imaging was not able to be
obtained. Actual likelihood ratios with confidence intervals
have not been published.
No further investigations or follow-up are necessary if isolated sandal gap is detected. It is not part of the screening
ultrasound.
Small, low-set, and malformed ears are associated with

other genetic abnormalities; however, antenatal detection
and evaluation are difficult.
Summary
References
1. Wilkins I. Separation of the great toe in fetuses with Down syndrome. J
Ultrasound Med 1994;13:22931.
2. Hill LM. The sonographic detection of trisomies 13, 18, and 21. Clin Obstet
Gynecol 1996;39:83150.
3. Ranzini AC, Guzman ER, Ananth CV, Day-Salvatore D, Fisher AJ,
Vintzileos AM. Sonographic identification of fetuses with Down syndrome:
a matched control study. Obstet Gynecol 1999;93(5):7026.
4. Rotmensch S, Liberati M, Bronshtein M, Schonfeld-Dimaio M, Shalev J,
Ben-Rafael Z, et al. Prenatal sonographic findings in 187 fetuses with
Down syndrome. Prenat Diagn 1997;17(11):10019.
5. Shipp TD, Benacerraf BR. Second trimester ultrasound screening for chromosomal abnormalities. Prenat Diagn 2002;22: 296307.
Although short fetal ear length may be a marker for fetal

aneuploidy, adequate evaluation has not been undertaken to
establish its usefulness as either a screening tool or as part of
a panel of markers for tertiary centres. The use of fetal ear
length remains relegated to research protocols.
Recommendations
1. Brachycephaly, increased iliac angle, sandal gap, and fetal
ear length are not considered a part of the screening ultrasound at 16 to 20 weeks (III-C).
References
2. Brachycephaly, increased iliac angle, sandal gap, and fetal

ear length should only be evaluated in research protocols or
tertiary centres (II-3 D).
1. Aase JM, Wilson AC, Smith DW. Small ear in Downs syndrome: a helpful
diagnostic aid. J Pediatr 1973;82:8457.
2. Birnholz JC, Farrell EE. Fetal ear length. Pediatrics 1988;81:5558.
3. Shimizu T, Salvador L, Allanson J, Hughes-Benzie R, Nimrod C.
Ultrasonographic measurements of fetal ear. Obstet Gynecol
1992;80:3814.
4. Chitkara U, Lee L, El-Sayed Y, Holbrook RH, Bloch DA, Oehlert JW, et al.
Sonographic ear length measurement in normal second-and third-trimester
fetuses. Am J Obstet Gynecol 2000;183: 2304.
5. Chitkara U, Lee L, Oehlert JW, Bloch DA, Holbrook RH Jr, El-Sayed YY,
et al. Fetal ear length measurement: a useful predictor of aneuploidy? Ultrasound Obstet Gynecol 2002;19(2):1315.
SANDAL GAP
Sandal gap is described as the separation of the great and

second toe and has been reported to be present in 45% of
newborns with trisomy 21.1,2 Prenatal diagnosis requires
imaging the foot and toes from the plantar view.
610
3. With specific abnormal cranial morphology such as clover leaf, strawberry, or lemon shapes, referral should
be considered (II-2 A).
Discussion
Prenatal diagnosis of fetal aneuploidy is of varying importance to individuals. Diagnosis can only be undertaken with
invasive tests that are accompanied by procedure-related
risks. Although uncommon, when a complication does
occur, it usually results in the loss of a normal fetus. A
womans decision to proceed with testing will involve an
assessment of the risk for the procedure versus the chance
of detecting an abnormality. For some, no level of risk
assessment for aneuploidy will lead to invasive testing, and
as such, screening for the abnormality is of less relevance. It
is important to remember that the process of prenatal
screening and the decision to proceed with invasive testing
Table 2. Ultrasound soft markers performance summary in the detection of aneuploidy

(trisomy 21, 18) and other genetic/congenital anomalies
Aneuploidy (LR)2
Ultrasound soft markers
(evidence and classification) 1
T21
T18
Congenital/Anomaly
Association3
Nuchal fold (III, A)
17
Congenital heart disease
Echogenic bowel (II-2, A)
CF2%, infection 3%, GI 6%
Ventriculomegaly (II-2, A)
AC, CNS, infection, obstruction
Echogenic cardiac focus (III, A)
A. Screening scan (16-20 weeks)
Choroid plexus cyst (II-2, A)

Single umbilical artery (III, A)
Enlarged cisterna magna (III, A)
Renal pyelectasis (II-2, A)
Renal, cardiac
OFD, MG, DiG
Hydronephrosis; reflux
B. Comprehensive scan (calculation; detail)

Clinodactyly (II-2, A)
5.6
Humerus (short) (II-2, A)
7.5
skeletal dysplasia; IUGR
Femur (short) (II-2, A)
2.7
skeletal dysplasia; IUGR
51
Nasal bone absent/hypo (II-2, A)

C. Research/Not useful
Brachycephaly (III, B)
Iliac angle (II-2, A)
TBD
Ear length (III, B)
35
Sandal toe (III, B)
Canadian Task Force on Periodic Health Examination, Health Canada; Quality of Evidence;Classification of Recommendation (Ann Intern
Med 1993; 118:731-7).
LR: likelihood ratio; TBD: to be determined.
CF: cystic fibrosis; CNS: central nervous system; GI: gastrointestinal; OFD: oro-facial-digital syndrome; MG: Meckel Gruber Syndrome;
DiG: Di George Syndrome; IUGR: intrauterine growth restriction; AC: agenesis corpus callosum
is voluntary. Caregivers who counsel women must be

knowledgeable, must have the ability to integrate various
risk factors, and must maintain a nondirective approach.1
The diagnosis of and screening for fetal abnormalities make
the 16- to 20-week obstetric ultrasound both clinically
effective and cost effective.24 Based on ultrasound findings, further investigations or treatment may be offered that
are gestational-age dependent and thus time limited. If any
fetal abnormalities or soft markers are discovered on routine ultrasound, it is important that findings be expeditiously communicated to primary caregivers. Waiting for
transcription, editing, and the mail service is unacceptable in
this circumstance. Persons who report these findings
should do so verbally, electronically, or by fax. Primary

caregivers should then relay information to the patient and
offer referral for consultation, validation, and possibly further investigation. These referrals will often be to genetic
and (or) prenatal diagnostic services that should be capable
of urgent accommodation.
Patients who receive news of potential or real fetal abnormalities will experience anxiety and distress.5 Information
should only be given to patients by individuals who can
answer preliminary questions and initiate subsequent counselling, referrals and (or) investigations. Although patients
will look for answers in the Diagnostic Imaging department, this is seldom the appropriate setting. Patients should
611
be told about general concerns and assured that their primary caregiver will receive the report as quickly as possible.
Sixteen potential second trimester soft markers for fetal
aneuploidy are reviewed in this document (Table 2). Only 5
markers are considered useful for evaluation for fetal
aneuploidy at the time of a screening ultrasound. Increased
nuchal fold, echogenic bowel, mild ventriculomegaly,
echogenic foci in the heart, and choroid plexus cysts are
associated with an increased risk of aneuploidy. Choroid
plexus cysts are only associated with trisomy 18 and, in this
circumstance, adjustment should only be made for this specific risk. The markers clinodactyly, short humerus, short
femur, and hypoplastic or absent nasal bone are all associated with aneuploidy but should be used in tertiary level
ultrasounds and (or) research protocols. The mathematical
evaluation for short long bones is not part of the screening
process and the images for clinodactyly and the nasal bone
are not established as a standard part of the 16- to 20-week
scan. Three other markerssingle umbilical artery,
enlarged cisterna magna, and pyelectasisdo not have a
well-established association with aneuploidy when seen in
isolation and should not be used to adjust risk when there
are no other significant risk factors. However, these latter
findings have other potential perinatal implications, and
thus evaluation and reporting remain important during the
screening process. Four markersbrachycephaly, iliac
angle, ear length, and sandal gapare not established as
markers for screening a low-risk population and should not
be evaluated except in a research setting or at a tertiary level.
The reduction in risk that accompanies the absence of ultrasound markers is dependent on the diligence with which an
entire panel of markers is evaluated. Risk reduction has only
been validated in single institutions or with prospective
studies using rigorous research protocols.68 Although this
may be recreated in dedicated prenatal diagnosis centres, a
reduction should not be applied on the basis of a 16- to
20-week screening scan, owing to the variety of imaging
locations involved. In the event that multiple (more than 2)
markers are identified, it is recommended that patients be
referred for confirmation, counselling, and possible further
investigation. It is widely accepted that individual markers
function independently, and as a result, when clustered
together, they convey an even greater risk. This may be true
even for markers that do not have a statistically-significant
association with fetal aneuploidy when seen in isolation.9,10
This document deals with the adjustment in risk for fetal
aneuploidy based on the presence or absence of second trimester ultrasound markers; however, this risk adjustment
has not been validated in a population with a lower prevalence for fetal aneuploidy owing to first trimester prenatal
612
screening and diagnosis. As early screening (nuchal translucency, early maternal serum testing) and diagnosis (chorionic villus sampling) become established, the significance
of second trimester markers will decrease and require readjustment.1113
In summary, the screening ultrasound at 16 to 20 weeks
should evaluate 8 markers, of which 5 (thickened nuchal
fold, echogenic bowel, mild ventriculomegaly, echogenic
intracardiac focus, and choroid plexus cyst) are associated
with an increased risk of fetal aneuploidy as well as
nonchromosomal problems, while 3 (single umbilical
artery, pyelectasis, and enlarged cisterna magna) are only
associated with an increased risk of nonchromosomal problems when seen in isolation.
References
1. Society of Obstetricians and Gynaecologists of Canada. Canadian guidelines
for prenatal diagnosis, techniques of prenatal diagnosis. JOGC Clinical
Practice Guidelines No. 105; July 2001.
2. Saari-Kemppainen A, Karjalainen O, Ylostalo P, Heinonen OP. Ultrasound
screening and perinatal mortality: controlled trial on systematic one-stage
screening in pregnancy. The Helsinki Ultrasound Trial. Lancet
1990;336(8712):38791.
3. Leivo T, Tuominen R, Saari-Kemppainen A, Ylostalo P, Karjalainen O,
Heinonen OP. Cost-effectiveness of one-stage ultrasound screening in
pregnancy: a report from the Helsinki ultrasound trial. Ultrasound Obstet
Gynecol 1996;7(5):30914.
4. Long G, Sprigg A. A comparative study of routine versus selective fetal
anomaly ultrasound scanning. J Med Screen 1998;5(1):610.
5. Kowalcek I, Huber G, Lammers C, Brunk J. Bieniakiewicz I, Gembrunch
U. Anxiety scores before and after prenatal testing for congenital anomalies.
Arch Gynecol Obstet 2003;267(3):1269.
6. Vintzileos AM, Guzman ER, Smulian JC, Yeo L, Scorza WE, Knuppel RA.
Down syndrome risk estimation after normal genetic sonograph. Am J
Obstet Gynecol 2002;187(5):12269.
7. Winter TC, Uhrich SB, Souter VL, Nyberg DA. The genetic sonogram:
comparison of the index scoring system with the age-adjusted US risk
assessment. Radiology 2000;215(3):77582.
8. DeVore GR. The genetic sonogram: its use in the detection of aneuploidy
in fetuses of women of advanced maternal age. Prenat Diagn
2001;21(1):405.
sonogram: a method of risk assessment for Down syndrome in the second
trimester. J Ultrasound Med 2002;21:108796.
10. Sohl B, Scioscia A, Budorick, NE, Moore TR. Utility of minor
prenatal diagnostic center. Am J Obstet Gynecol 1999;181:898903.
11. Verdin SM, Whitlow BJ, Lazanakis M, Kadir RA, Chatzipapas I,
Economides DL. Ultrasonographic markers for aneuploidy in women with
negative nuchal translucency and second trimester maternal serum biochemistry. Ultrasound Obstet Gynecol 2000;16(5):4026.
12. Thompson MO, Thilaganathan B. Effect of routine screening for Down
syndrome on the significance of isolated fetal hydronephrosis. Br J Obstet
Gynaecol 1998;105(8):8604.
13. Prefumo F, Presti F, Mavrides E, Sanusi AF, Bland JM, Campbell S, et al.
Isolated echogenic foci in the fetal heart: do they increase the risk of trisomy
21 in a population previously screened by nuchal translucency? Ultrasound

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Disclaimer: This guideline was peer reviewed by the SOGCs Genetics Committee in

SOGC CLINICAL PRACTICE GUIDELINES

No 162, June 2005

Fetal Soft Markers in Obstetric Ultrasound

Outcomes: The use of ultrasound in pregnancy has significant health

Phil Wyatt, MD, North York ON

Benefits, Harms, Costs: It is not possible at this time to determine

David C. Young, MD, Halifax NS

Valerie Desilets, MD, Montreal QC

Key Words: Ultrasound, soft marker, prenatal screening, fetus,

1. The screening ultrasound at 16 to 20 weeks should evaluate 8

lJUNE JOGC JUIN 2005

Fetal Soft Markers in Obstetric Ultrasound

The presence of soft markers increases the risk for fetal

JUNE JOGC JUIN 2005 l

SOGC CLINICAL PRACTICE GUIDELINES

Table 1. Criteria for quality of evidence assessment and classification of recommendations

A. There is good evidence to support the recommendation for

Evidence obtained from at least one properly designed

II-1: Evidence from well-designed controlled trials without

B. There is fair evidence to support the recommendation for

D. There is fair evidence not to support the recommendation

FETAL SOFT MARKERS USEFUL FOR SCREENING ULTRASOUND

ECHOGENIC INTRACARDIAC FOCUS (Figure 1)

Echogenic intracardiac focus (EICF) is defined as a focus

The association between isolated EICF and fetal

l JUNE JOGC JUIN 2005

Although the numbers are small, studies suggest that the

EICF has not been associated with congenital heart disease

EICF is readily diagnosed on the 4-chamber view of the

Fetal Soft Markers in Obstetric Ultrasound

Figure 1. Echogenic intracardiac focus in the left ventricle of the heart

4. Manning JE, Ragavendra N, Sayre J, Laifer-Narin SL, Melany ML, Grant

JUNE JOGC JUIN 2005 l

SOGC CLINICAL PRACTICE GUIDELINES

Figure 2. Bilateral renal pyelectasis with anterior/posterior measurement

l JUNE JOGC JUIN 2005

MILD PYELECTASIS (Figure 2)

Mild pyelectasis is defined as a hypoechoic spherical or

Isolated pyelectasis is seen in 0.7% of fetuses at 16 to 26

Fetal pyelectasis is associated with congenital

Fetal Soft Markers in Obstetric Ultrasound

those having measurements > 10 mm should also have a

7. Aviram R, Pomeran A, Sharony R, Beyth Y, Rathaus V, Tepper R. The

8. Van den Hof MC, Demianczuk NN. Content of a complete obstetrical

Evaluation of fetal kidneys, which includes possible

SINGLE UMBILICAL ARTERY (Figure 3)

Single umbilical artery (SUA) is the absence of one of the

Isolated SUA has been associated with both underlying fetal

JUNE JOGC JUIN 2005 l

SOGC CLINICAL PRACTICE GUIDELINES

Figure 3. Single umbilical artery on cross-section of cord

anomalies, Doppler findings and perinatal outcome. Ultrasound Obstet

echogenicity of fetal bowel and surrounding bone relative

ECHOGENIC BOWEL (Figure 4)

The presence of echogenic bowel is associated with an

Definition and Imaging Criteria

Association With Nonchromosomal Abnormalities

The presence of echogenic bowel has been associated with