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ULTRASOUND
CLINICS
Ultrasound Clin 1 (2006) 273–291
Prenatal Diagnosis of Congenital
Heart Disease: Where Are We Now?
Wesley Lee,
&
&
&
MD
a,b,*
, Christine H. Comstock,
Fetal cardiac screening
What influences the prenatal detection of
congenital heart disease?
Factors influencing adequate examination
of the heart
Unrecognized abnormalities
Evolution of cardiac abnormalities
Standardized images may not demonstrate
the anomalous heart
Fetal cardiac screening guidelines
Basic examination
Extended basic examination
The antenatal detection of birth defects is an
important public health concern with significant
clinical ramifications. In 2002, more than 28,000
infants died within the first year of birth, with an
overall rate of 7.0 deaths per 1000 live births in the
United States [1]. This mortality rate was largely
attributed to birth defects, of which congenital
heart disease has been a leading cause of related
adverse outcomes [2]. Furthermore, data from the
World Health Organization indicates that 42% of
infant deaths were attributed to heart defects [3].
Prenatal sonography has played an important
role for the timely detection of congenital heart
disease (CHD). Despite promising results of early
studies, however, the efficacy of fetal cardiac screening programs has been variably successful. This
article provides an update regarding various factors
affecting the prenatal identification of cardiac de-
&
&
&
MD
a,c
Sonographic detection of selected cardiac
anomalies
Ventricular septal defects
Atrioventricular septal defects
Hypoplastic left heart syndrome
Tricuspid valve abnormalities
Conotruncal abnormalities
Aortic coarctation
Total anomalous pulmonary venous return
Summary
References
fects and summarizes current guidelines for fetal
heart screening during the second trimester of pregnancy. The diagnostic imaging characteristics and
clinical significance of selected fetal cardiac abnormalities are also reviewed.
Fetal cardiac screening
Cardiac abnormalities occur with an estimated incidence of approximately 4–13 per 1000 live births
[4–6]. Most of the affected children will be born
to mothers with no identifiable risk factors for
CHD. Consequently, standardized approaches are
needed to screen low-risk populations for cardiac abnormalities.
Prenatal cardiac screening was introduced in the
mid-1980s when the four-chamber view of the
heart was incorporated into a routine obstetric scan
a
Division of Fetal Imaging, 3601 W. Thirteen Mile Road,William Beaumont Hospital, Royal Oak, MI 48073, USA
Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA
c
Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA
* Corresponding author. Department of Obstetrics and Gynecology, Division of Fetal Imaging, William
Beaumont Hospital, 3601 W. Thirteen Mile Road, Royal Oak, MI 48073.
E-mail address: [email protected] (W. Lee).
b
1556-858X/06/$ – see front matter © 2006 Elsevier Inc. All rights reserved.
ultrasound.theclinics.com
doi:10.1016/j.cult.2006.01.005
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Lee & Comstock
between 18 and 22 weeks, menstrual age [7].
After a training period, several centers in the United
Kingdom were able to detect 77% of all cardiac
anomalies over a 2.5-year period [8]. Copel and
associates [9] also examined fetuses in 1022 pregnancies and found 74 abnormal heart cases using
the four-chamber view. They reported 92% sensitivity and 99.7% specificity for the detection of CHD.
Unfortunately, others have found a wide range of
detection rates for the four-chamber view of the
heart in unselected patient populations [10–15].
Additional diagnostic benefit has been subsequently
demonstrated for the inclusion of cardiac outflow
tracts into routine screening examination of the
heart [11,16,17].
One of the most comprehensive studies regarding
fetal heart screening in a nonselected population
has been recently completed. Tegnander and colleagues [18] analyzed results of a fetal heart screening program over a 10-year period in Norway. Their
study population included 29,460 gravidas, representing 98% of their deliveries at a single institution. Routine fetal examinations were performed at
approximately 18 weeks, and included the fourchamber view and outflow tracts. Beginning in
1995, patients were also asked to return for another
scan if a satisfactory four-chamber view had not
been obtained during the initial visit. Heart defects
were retrospectively classified after delivery as critical when surgery was likely to be required (eg,
transposition of the great arteries, hypoplastic left
heart syndrome, atrioventricular septal defect, aortic coarctation, and large ventricular septal defects)
[19]. This investigation identified 97 critical cases
of CHD, of which 55 (57%) had been detected
before birth. Forty-four percent of affected fetuses
had isolated CHD and 38% had an abnormal karyotype. About one-half (48%) of the abnormal
fetuses with ductal-dependent lesions were detected. Only 27% of infants born with critical
CHD were alive at 2 years after delivery.
What influences the prenatal detection of
congenital heart disease?
Several factors affect the quality of a successful fetal
cardiac screening program. These factors help to
explain why prenatal detection rates have varied
so widely in the medical literature.
Chaoui [20] has summarized key reasons as to
why the four-chamber view does not always provide an optimal detection rate among various centers. The reasons include inadequate examination,
unrecognized abnormalities, evolution of cardiac
lesions, and the inability for this view to detect
specific anomalies that are best identified from
other scanning planes.
Factors influencing adequate examination of
the heart
Inadequate examination of the fetal heart can be
related to timing of scan, fetal position, image
quality, maternal wall thickness, and a history of
prior maternal surgical procedures.
Timing of second trimester fetal heart scans
Satisfactory views of the fetal heart are typically obtained between 18 and 22 weeks, menstrual age. A
prospective and randomized study of 1206 women
found an incomplete four-chamber view more frequently between 18 to 18.9 weeks (18.4%) as compared with scans occurring between 20 to 20.9 weeks
(2.9%) (P<.001) [21]. Many heart structures can
still be satisfactorily visualized beyond this time if
the fetal position is favorable. Many patients, however, prefer to know about major cardiac defects at
an earlier stage of pregnancy.
Fetal position
Optimal views of the fetal heart are often obtained
when the cardiac apex is pointing toward the transducer [Fig. 1] [22]. Suboptimal views occur when
the spine causes acoustic shadowing over cardiac
structures from a prone position. This situation can
be worsened in the presence of oligohydramnios.
Image quality
Technical specifications of the ultrasound system
(eg, beam former, transducer, display screen) can
also affect satisfactory visualization of the fetal
heart. One should always adjust the lowest acoustic power intensity settings (ie, thermal index and
mechanical index) that provide satisfactory diagnostic images from using output display standards
and the ALARA (As Low As Reasonably Achievable)
principle [23].
Image quality relies on the examiner’s efforts to
position the transducer in a manner that is most
suitable for acquiring this information. The degree
of screen magnification, gain, and acoustic focus
should be optimized for the region of interest. The
transducer’s field of view should be minimized
to improve frame rate (ie, temporal resolution). A
color filter can be applied to improve contrast between soft tissue borders. Frame persistence should
not be set too high. Images should be zoomed to fill
at least one-half the display screen with the fetal
heart. Harmonic imaging often improves the image
display [24].
Wavelength (sound velocity divided by frequency) is an important concept that is used to
explain image resolution [25]. Contemporary ultrasound systems usually produce images with axial
resolution between 2 to 4 wavelengths and lateral
Prenatal Diagnosis of Congenital Heart Disease
Fig. 1. Fetal position affects the cardiac screening examination. Satisfactory visualization of the fetal heart
depends on orientation of cardiac structures in relation to the maternal abdomen. The best views are often
obtained with the cardiac apex pointing toward the anterior maternal abdominal wall (A–C ). Anatomicstructures
are usually not well visualized when the cardiac apex is oriented toward the posterior maternal abdominal wall
(D–F ). (Adapted from Lee W. American Institute of Ultrasound in Medicine. Performance of the basic fetal cardiac
ultrasound examination. J Ultrasound Med 1998;17:601–7; with permission.)
resolution between 3 to 10 wavelengths. Depending on the imaging system, the axial resolution
would range between 0.6 and 1.2 mm at 5 MHz.
At the same transducer frequency, lateral resolution
ranges between 0.9 and 3.0 mm. Therefore, the
ultrasound beam resolution and angle of beam
insonation can have important ramifications for
identifying small structures such as 2-mm ventricular septal defects. The highest transducer frequencies, typically 5 MHz and above, often provide the
image resolution necessary to resolve subtle cardiac
defects. This has to be balanced as a trade-off
between image resolution and acoustic penetration.
Maternal wall characteristics
DeVore and colleagues [26] examined technical
factors that influence imaging of the fetal heart
during the second trimester of pregnancy. More
than 700 trimester pregnancies were analyzed to
identify independent risk factors that contribute
to difficult cardiac screening examinations. Gestational age, maternal adipose tissue thickness, and
prior lower abdominal surgery were found as the
most significant factors that were associated with
poor visualization of the fetal heart.
now indicates that the embryonic heart results from
a modular process with initial development of a
primary cardiac crescent. Subsequent development
of a second, more anterior heart field is responsible
for the appearance of the right ventricular outflow
tract [27]. Cook and associates [28] have nicely
reviewed cardiac development in the human fetus
as it relates to the prenatal diagnosis of CHD.
Education and training of health care professionals can improve the prenatal recognition of
CHD. As a minimal goal, examiners must understand how to acquire images from standardized
cardiac scanning planes to classify them into normal or abnormal categories. Cardiac screening programs can be further improved after continuous
training of health care professionals based on feedback, a low threshold for echocardiography referrals, and convenient access to fetal heart specialists
[29,30]. As one example, Hunter and colleagues
[31] reported a twofold increase in the detection
rate (17% to 36%) of major cardiac defects after
implementing a targeted training program for fetal
heart screening at 16 ultrasound centers in the
United Kingdom.
Evolution of cardiac abnormalities
Unrecognized abnormalities
Unrecognized abnormalities are another reason
why the prenatal detection rates of CHD have varied so widely. Examiners should be familiar with
development of the human heart and how to translate this information to clinical practice. Anatomic
and molecular methods are clarifying new aspects
of cardiac development. For example, traditional
teaching has suggested that the heart initially
forms from paired linear tubes that fuse and contain all major cardiac segments. More recent work
Evolution of cardiac lesions is another important
reason why these abnormalities are not always
detected at the time of an ultrasound scan. An observational investigation of 22,050 pregnant
women (77.5% low-risk patients) was undertaken
by dividing them into two groups: Group A - 6924
with initial vaginal sonography at 13–16 weeks’
gestation that were followed by abdominal scans
at 20–22 weeks’; and Group B - 15,126 women
who only had initial transabdominal scans at
20–22 weeks’ [32]. Both groups were scanned dur-
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ing the third trimester and diagnoses were confirmed after birth. Two experienced examiners conducted all ultrasound examinations.
Congenital heart disease occurred in 168 infants
(Group A - 66 infants; Group B - 102 infants). Of
the Group A fetuses, 42 (64%) heart anomalies
were detected at the first vaginal scan, and 11
(17%) were subsequently identified during the
abdominal study. Three additional anomalies (4%)
were found during the third trimester exam and
10 more (15%) were only detected after delivery.
Group B fetuses had 80 (78%) cardiac malformations identified at the time of their first abdominal scan at 20–22 weeks’ gestation. An additional 7
(7%) and 15 (15%) cases were identified during
the third trimester and after delivery, respectively.
Ten heart anomalies that were discovered during
the third trimester included aortic stenosis (n=2),
cardiac rhabdomyoma (n=2), subaortic stenosis
(n=1), tetralogy of Fallot (TOF) (n=1), aortic coarctation (n=1), sealed foramen ovale (n=1), ventricular septal defect (n=1), and hypertrophic
cardiomyopathy (n=1).
Their results indicated that fetal heart anomalies
can vary in appearance throughout pregnancy.
In this study, two experienced examiners, using
both early vaginal and second-trimester abdominal
scans, were unable to identify 20% of CHD cases.
Of note, early vaginal scans of the fetal heart were
able to detect nearly two-thirds (64%) of abnormal
hearts. This observation is consistent with the finding of others who have described early detection of
heart anomalies, especially when increased nuchal
translucency is present [33–39]. Although second
trimester fetal heart screening can often be completed between 18 and 22 weeks’ gestation, many
anomalies can still be identified before this stage
of pregnancy.
Standardized images may not demonstrate
the anomalous heart
The inability of specific scanning planes for detecting all forms of CHD can be explained by
considering fetal cardiac anatomy. Although the
four-chamber view across the fetal thorax can be
quite informative, this two-dimensional scanning
plane may not provide satisfactory views of a
small ventricular septal defect or conotruncal
anomalies involving the more anterior ventricular
outflow tracts.
Fetal cardiac screening guidelines
The primary goal of cardiac screening is to identify
which fetuses are likely to have CHD. Current
guidelines emphasize a ‘‘basic examination’’ using
a satisfactory four-chamber view of the heart. If
Box 1: Common indications for fetal
echocardiography
Maternal indications
Family history
1st degree relative of proband
Pre-existing metabolic diseases
diabetes
phenylketonuria
Maternal infections
parvovirus B19
rubella
coxackie
Cardiac teratogen exposure
retinoids
phenyltoin
carbamazepine
lithium carbonate
valproic acid
Maternal antibodies
anti-Ro (SSA)
anti-La (SSB)
Fetal indications
Suspected fetal heart anomaly
Abnormal fetal karyotype
Major extra-cardiac anomaly
Abnormal nuchal translucency
≥3.5 mm before 14 weeks, menstrual age
Abnormal nuchal fold
≥6.0 mm: 15–20 weeks, menstrual age
Abnormal cardiac rate or rhythm
persistent bradycardia
persistent tachycardia
persistent irregular heart rhythm
technically feasible, an ‘‘extended basic’’ examination of the left and right ventricular outflow tracts is
also recommended [40–42]. Fetuses with suspected
anomalies should be referred for fetal echocardiography to assess the seriousness of the anomaly and
the likelihood of a ductal dependent lesion at birth.
Common indications for fetal echocardiography
are summarized in Box 1 [43].
Basic examination
General considerations
The ‘‘basic examination’’ requires specific sonographic criteria using an adequately visualized
four-chamber view of the heart [Table 1; Fig. 2].
This approach must not be mistaken for a simple
count of cardiac chambers. Cardiac rate (120 to
160 beats/minute) and regular rhythm should be
confirmed, although mild fetal bradycardia can
transiently occur during the second trimester. The
heart normally fills no more than a third of the
thoracic area at the level of the four-chamber view.
A small layer of fluid (<2 mm) can appear around
the normal fetal heart, although this finding may
Prenatal Diagnosis of Congenital Heart Disease
Table 1: Basic cardiac screening examination
General
Atria
Ventricles
AV Valves
Normal cardiac situs, axis,
and position
Heart occupies a third of
thoracic area
Majority of heart in left chest
Four cardiac chambers present
No pericardial effusion or
hypertrophy
Atria approximately equal in size
Foramen ovale flap in left atrium
Atrial septum primum present
Ventricles about equal in size
No cardiac wall hypertrophy
Moderator band at right
ventricular apex
Ventricular septum intact (apex
to crux)
Both atrioventricular valves open
and move freely
Tricuspid valve leaflet inserts on
septum closer to the cardiac apex
as compared to the mitral valve
Adapted from [22]; with permission.
be clinically significant in the presence of cardiac
failure, other structural anomalies, or hydrops
[44,45].
Cardiac axis and position should be normal
[Fig. 3] [46]. The cardiac axis can be shifted as a
normal variant, although a detailed examination
should be considered for the possibility of associated abnormalities. Abnormal heart deviation
into the right chest (dextroposition) may be caused
by a chest mass (eg, cystic adenomatoid malformation, pulmonary sequestration, or congenital lo-
bar emphysema), diaphragmatic hernia, or situs
anomalies [46–48].
Cardiac chambers
Both atrial chambers should appear similar in size
with an intact atrial septum primum. The foramen
ovale flap should move freely toward the left
atrium. In the human fetus, more than one-fifth
of combined ventricular output is directed to the
lungs and eventually drained back to the heart
through the pulmonary veins [49,50]. At least one
pulmonary vein should always be seen entering the
left atrium.
The ventricular chambers also appear similar in
size with an intact intervening septum. Relatively
thin ventricular walls usually have no greater than
2 mm of surrounding pericardial fluid. The right
ventricle has a moderator band at the cardiac apex
and normally resides in the anterior chest on the
side opposite the fetal stomach. It usually appears
more triangular in shape as compared with the left
ventricular chamber.
Atrioventricular valves
Both atrioventricular valves should move freely and
not appear thickened. The tricuspid valve leaflet
normally inserts on the ventricular septum at a
position that is closer to the cardiac apex as compared with the mitral valve septal leaflet insertion
[51]. This describes the normal ‘‘offsetting’’ of both
atrioventricular valves.
Extended basic examination
If technically feasible, routine views of the outflow
tracts should also be included as part of an ‘‘ex-
Fig. 2. Four-chamber view of the heart. Key components of a normal four-chamber view include an intact
interventricular septum and atrial septum primum. There is no disproportion between the left (LV) and right
(RV) ventricles. A moderator band helps to identify the morphologic right ventricle. Note how the “offset”
atrioventricular septal valve leaflets insert into the crux. (From Lee W. American Institute of Ultrasound in
Medicine. Performance of the basic fetal cardiac ultrasound examination. J Ultrasound Med 1998;17:601–7;
with permission.)
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Fig. 3. Fetal cardiac axis and position The cardiac axis can be measured from a four-chamber view of the fetal
heart. A line through the interventricular axis is extended to the posterior border of the heart to produce point P,
the location of which can be used to define fetal cardiac position. (Adapted from Comstock CH. Normal fetal heart
axis and position. Obstet Gynecol 1987;70:255–9; with permission.)
tended basic’’ cardiac examination [Figs. 4 and 5].
A four-chamber view of the heart can appear as
normal in the presence of a ventricular septal defect
or conotruncal anomaly that would otherwise be
seen from the extended basic examination.
Scanning planes for both the ‘‘basic’’ and ‘‘extended basic’’ examinations are illustrated in
Fig. 6 [22]. Both outflow tracts are examined as
the transducer is angled from the four-chamber
view toward the fetal head. Another method for
evaluating the outflow tracts has also been described when the fetal interventricular cardiac septum is perpendicular to the ultrasound beam [52].
This approach begins with a four-chamber view of
the heart and involves probe rotation until a left
ventricular outflow tract is visualized. The probe
can then be rocked cephalad until the pulmonary
arterial outflow tract is observed in a plane that
appears perpendicular to the aortic outflow tract.
Others have reported the use of a ‘‘three-vessel
view’’ to describe relative sizes and relationships
between the pulmonary artery, ascending aorta,
and right superior vena cava [53–55].
Most second trimester cardiac screening examinations will permit satisfactory visualization of
the four-chamber view and outflow tracts. Over
18,000 second trimester fetuses underwent cardiac
screening of the outflow tracts to evaluate the standardized practice of incorporating a basic fetal
cardiac exam into a 30-minute scan [56]. When
technically feasible, an extended basic evaluation
of the outflow tracts was also attempted. Of the
studies that included an adequate four-chamber
view, the majority (93%) of scans had satisfactory
Fig. 4. Left ventricular outflow tract. A left ventricular outflow tract view (LVOT) emphasizes that a great vessel can be seen exiting the left ventricle. The aortic valve leaflets should be freely moving and not thickened.
(From Lee W. American Institute of Ultrasound in Medicine. Performance of the basic fetal cardiac ultrasound
examination. J Ultrasound Med 1998;17:601–7; with permission.)
Prenatal Diagnosis of Congenital Heart Disease
Fig. 5. Right ventricular outflow tract. Cardiac axis and position are identical to Fig. 4. A right ventricular outflow
tract (RVOT) view emphasizes that a great vessel can be seen exiting the morphologic right ventricle (RV). The
bifurcation of the pulmonary artery is not always seen in this scanning plane. Note that the RVOT exits the
ventricle at about 90° to the aortic outflow tract. The pulmonary valve leaflets should be freely moving and not
thickened. Sometimes, the right superior vena cava (SVC) can be seen. (Adapted from Lee W. American Institute
of Ultrasound in Medicine. Performance of the basic fetal cardiac ultrasound examination. J Ultrasound Med
1998;17:601–7; with permission.)
views of the outflow tracts. Nonvisualization rates
were: left ventricular outflow tract (4.2%); right
ventricular outflow tract (1.6%); both outflow
tracts (1.3%).
Sonographic detection of selected cardiac
anomalies
This section summarizes the clinical significance
and sonographic findings associated with selected
examples of CHD that may be detected by basic
and extended basic cardiac screening exam.
Ventricular septal defects
Ventricular septal defects are the most common
type of CHD [Fig. 7]. They are caused by incomplete closure of the ventricular septum during fetal
development and can occur at various locations
[Fig. 8]. Although isolated lesions may not be
clinically significant, their presence should raise
the possibility of abnormal karyotype and associated structural findings.
Paladini and colleagues [57] summarized their experience with isolated lesions that are detected using
prenatal sonography. Of 26 fetuses that reached
Fig. 6. Scanning planes for the basic and extended basic cardiac examinations. A four-chamber view of the heart is
obtained from an axial scanning plane across the fetal thorax. Corresponding views of the left (LVOT) and right
(RVOT) ventricular outflow tracts are found by angling the transducer toward the fetal head. (Adapted from Lee
W. American Institute of Ultrasound in Medicine. Performance of the basic fetal cardiac ultrasound examination.
J Ultrasound Med 1998;17:601–7; with permission.)
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Fig. 7. Perimembranous ventricular septal defect. A ventricular septal defect (VSD) is circled on the heart specimen
in an abortus at 20 weeks, menstrual age. This small perimembranous lesion can be compared with President
Thomas Jefferson's nose and can be easily missed if technical factors do not favor satisfactory visualization.
1 year of age, 46.1% (12 cases) of all defects closed
in utero. Trisomy 21 was found in 50% of fetuses
with inlet-type (nine cases) or large (two cases)
defects. Trisomy 18 occurred in 56.3% of ventricular septal defects (VSD) lesions (nine cases)
that were associated with aortic-septal override.
None of the malalignment VSDs closed after birth.
By comparison, 69% of the perimembranous
and 60% of the muscular defects closed within
1 year of delivery. In a related pediatric study, Turner
Fig. 8. Variable locations of ventricular septal defects.
The location of a ventricular septal defect (VSD) can be
used to estimate the likelihood of spontaneous closure and for counseling about therapeutic intervention after birth. An inlet VSD of the posterior septum,
near either the tricuspid or mitral valves, will rarely
close. Infants with this type of lesion are not optimal
candidates for repair using a percutaneous septal
occlusion device. (From Fetal ultrasound simulator [CDROM], Washington, D.C: American College of Obstetricians and Gynecologists; 1998; with permission.)
and colleagues [58] found that the location of
the lesion was relevant to its natural history in
68 infants with VSD. Perimembranous defects accounted for most of the moderate and large defects
that required surgical correction. After more than
6 years, almost a third of all perimembranous
and just over two-thirds of all muscular defects
closed spontaneously.
Tegnander and colleagues [18] studied a nonselected population of 30,149 fetuses: an isolated
VSD occurred in 57% (188/333) of noncritical
heart defects. Of these, 162 (86%) were muscular
and 26 (14%) were perimembranous. During the
first year after birth, 77/162 (48%) of the isolated
muscular and 3/26 (12%) of the isolated perimembranous VSDs closed spontaneously.
Prenatal detection of a small VSD <2 mm can be
particularly difficult and depends on several factors
such as the lateral resolution of the ultrasound system, gestational age, fetal size, maternal wall thickness, and a history of prior abdominal or uterine
surgeries. Aside from optimizing image settings (eg,
depth, gain, focus), the entire ventricular septum
should be systematically examined during both the
basic and extended basic cardiac scans.
Other diagnostic tools include the use of digital cineloop technology and Doppler flow studies.
Direct measurements of intracardiac pressures in
human fetuses indicate that no measurable differences occur between the left and right ventricles [59]. Therefore, color Doppler ultrasonography
may not detect flow across a VSD as easily as in
the case of adult patients. However, VSD lesions
can be identified using frame-by-frame analysis of
the ventricular septum (digital cine-loop), sometimes in conjunction with Doppler flow studies as
well [Figs. 9 and 10]. Some ultrasound systems
provide a ‘‘write priority’’ control that allows the
Prenatal Diagnosis of Congenital Heart Disease
Fig. 9. Intramuscular ventricular septal defect. This 2.6-mm VSD can be easily visualized using gray-scale sonography. Simultaneous use of digital cineloop and color Doppler techniques allow visualization of blood flow
across this defect. This abnormality would be much easier to visualize after birth when a high-pressure gradient
is present between the left and right ventricles.
user to balance the color or power Doppler display
so it doesn’t ‘‘bleed’’ over surrounding intra-cardiac
structures that are visualized with gray scale. Finally, one should remember to verify suspected
VSD lesions from more than one view to avoid
diagnostic errors due to sonographic artifacts.
Atrioventricular septal defects
Complete atrioventricular septal defects (AVSD)
consist of a common atrioventricular junction instead of separate mitral and tricuspid valve orifices
[Fig. 11]. In the past, this lesion has also been
known as an endocardial cushion defect or AV
canal defect. Milder forms of this anomaly (ie, ‘‘incomplete AVSD’’) have only a defect in the inferior
part of the atrial septum, just above the atrioven-
tricular valves. In this case, two separate valve orifices will be visualized.
Allan [60] reviewed the prenatal sonographic findings of 49 fetuses with AVSD; 18 cases appeared
to only involve AVSD only, of which 13 were subsequently found to have trisomy 21. Other abnormalities included heterotaxy syndrome (22 cases),
left ventricular malformations (8 cases), and TOF
(1 case). Increased nuchal translucency has also
been found in embryos with AVSD at 10–14 weeks,
menstrual age [61].
There were 22 cases of heterotaxy syndrome involving isomerism of the atrial appendages. Sixteen
fetuses were suspected to have right atrial isomerism (eg, anomalies of pulmonary venous drainage,
double outlet right ventricle with pulmonary valve
Fig. 10. Perimembranous ventricular septal defect. A small VSD may not be identified on gray-scale sonography (left), although the addition of a color Doppler study can be used demonstrate this lesion in the same
fetus (right).
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Fig. 11. Atrioventricular septal defect. A complete form of atrioventricular septal defect is characterized by
incomplete formation of separate mitral and tricuspid valves. A cross-section demonstrates a common valve
apparatus (inset). RA, right atrium; LA, left atrium; RV, right ventricle; LV, left ventricle. (Adapted from Fetal
ultrasound simulator [CD-ROM]. Washington, D.C: American College of Obstetricians and Gynecologists; 1998;
with permission.)
atresia, bilateral right bronchi and lung lobation,
and asplenia). Six fetuses had sonographic evidence
of left atrial isomerism, where typical findings may
include an interrupted inferior vena cava with azygous continuation, complete heart block, bilateral
left bronchi and lung lobation, and polysplenia.
This series emphasized the high rate of intrauterine
death for fetuses with left atrial isomerism because
only one of six abnormal fetuses survived to delivery, but died soon after birth. Although the prognosis for fetuses with AVSD and right atrial
isomerism typically is to survive pregnancy, there
is a high postnatal mortality rate found in infancy
and early childhood [62].
The sonographic detection of complete AVSD is
usually straightforward because the normal offsetting of the atrioventricular valves is not present.
Instead, the common atrioventricular valve appears
as a straight line [Fig. 12]. Occasionally, a dilated
coronary sinus can simulate an AVSD lesion [63].
Incomplete forms of AVSD also may obscure the
diagnosis because two separate inlet valves are still
seen, in addition to both atrial and ventrticular
septal defects. As a final consideration, ventricular
disproportion may appear as an ‘‘unbalanced’’ form
of AVSD. Complete AVSD can be typically repaired
with low mortality and good intermediate to longterm results [64].
Hypoplastic left heart syndrome
Prenatal identification of hypoplastic left heart syndrome (HLHS), using the basic cardiac screening
examination, is extremely important because of
improved surgical outcome in fetuses in whom
the lesion was detected prenatally [65] [Fig. 13].
Severe ventricular disproportion is the hallmark of
this abnormality where the left ventricle can appear
very small [Fig. 14].
This condition refers to an underdeveloped left
ventricle from abnormal development of the mitral
or aortic valve. Valve obstruction causes a shift of
blood flow back over the foramen ovale to the right
Fig. 12. Atrioventricular septal defect. Sonographic
findings for a complete atrioventricular septal defect
consist of atrial septal defect (asd), ventricular septal
defect (vsd), and lack of the normal offset atrioventricular valve insertion sites. The common valve appears as a straight echogenic line.
Prenatal Diagnosis of Congenital Heart Disease
sion will keep these fetal shunts open temporarily,
but eventually surgery will be necessary. The conventional surgical repair is a three-stage procedure,
the first of which is a Norwood procedure that
involves connecting the aorta to the proximal pulmonary artery, thus allowing the right ventricle to
pump blood to the body [67]. Two lower risk
operations, the hemi-Fontan (4 to 6 months of age)
and Fontan (18 months to 2 years of age) are
subsequently required [68]. Although these children are now reaching young adulthood and are
doing remarkably well, recent studies suggest increased risk for cognitive, neuromotor, and psychosocial problems [69].
Fig. 13. Hypoplastic left heart syndrome Hypoplastic
left heart syndrome consists of a small left ventricle
(LV) with abnormal mitral or aortic valve development. The LV will initially appear slightly small during
early pregnancy, with subsequent development as a
rudimentary slit-like cavity as the pregnancy progresses. The dominant chamber is the right ventricle
(RV). Blood flow across the foramen ovale is reversed
from the right (RA) to left (LA) atrium. (Adapted from
Fetal ultrasound simulator [CD-ROM]. Washington, D.C:
American College of Obstetricians and Gynecologists;
1998; with permission.)
atrium. The left ventricle stays small due to decreased blood flow. A truly anatomic univentricular
heart is very uncommon since a small ‘‘slit’’ can
usuallly be seen to the left of the right ventricle.
In severe mitral valve dysplasia, the left ventricle
is usually quite small at the time of the screening
exam. Milder involvement of the valves causes disparity of the size of the right and left ventricles, but
both are still visible. Another presentation is that of
an enlarged left atrium with a large noncontracting
left ventricle. Although the ventricle is large, blood
does not flow into or out of it. The enlarged ventricle can shrink with advancing pregnancy. Associated findings may include aortic valve atresia,
coarctation of the aorta, and echogenic thickening
of the ventricular walls due to endocardial fibroelastosis [66].
Hypoplastic left ventricle can also occur with
other defects such as atrioventricular septal defect.
It is rare that chromosomes are abnormal, but if
they are, trisomy 18 is the most frequent aneuploidy. Hypoplastic left ventricle can also occur
in left-sided diaphragmatic hernia due to pressure
on the left ventricle. The pregnancy course is usually uneventful in the absence of heart failure (eg,
atrioventricular valve insufficiency, pericardial effusion, cardiomegaly).
After birth the newborn will depend on a patent
foramen ovale and ductus arteriosus to get blood
to the aorta and neck vessels. Prostaglandin infu-
Tricuspid valve abnormalities
Tricuspid valve atresia is caused by marked dysplasia of the leaflets and cords where a connection fails
to develop between the right atrium and ventricle.
Therefore, systemic venous blood return bypasses
the right heart and traverses a patent foramen ovale
(secundum atrial septal defect, ASD) into the left
atrium and ventricle. An inlet VSD typically allows
some blood flow from the left ventricle into an
underdeveloped right ventricle.
Tongsong and colleagues [70] published prenatal
sonographic findings for isolated tricuspid valve
atresia. The four chamber view fails to demonstrate
a patent tricuspid valve and this area appears echogenic [Fig. 15]. A small right ventricle is seen, de-
Fig. 14. Hypoplastic left heart syndrome. Sonographic
findings demonstrate marked underdevelopment
of the left ventricular cavity that gives it a “slitlike” appearance. This degree of ventricular disproportion may not be as obvious at an earlier stage
of pregnancy.
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poor perinatal prognosis with a mortality rate as
high as 85% [73].
Conotruncal abnormalities
Fig. 15. Tricuspid valve atresia. Key findings consist
of an echogenic mass of non-mobile tissue between
the right ventricle (RV) and atrium (RA), small right
ventricle (RV), and the presence of a ventricular septal
defect (*). Increased systemic venous return flows
from the RA through the foramen ovale (FO).
pending on size of the VSD. Right ventricular outflow tract obstruction may occur as subvalvular pulmonary stenosis or pulmonary valve stenosis—a
potential cause of ductal dependency. Approximately
20% of cases will be associated with transposition of the great arteries. Aortic arch abnormalities
have also been reported. Chromosomes are usually
normal and it is rare to have extracardiac defects.
Increased nuchal translucency, however, has been
reported in embryos with triscuspid atresia as early
as 11 weeks, menstrual age [61].
The surgical outcome of infants born with this
lesion depends on the presence of associated
anomalies and relies on use of the Fontan procedure. The Hospital for Sick Children recently summarized a total of 137 infants who underwent a
Fontan procedure [71]. Cohort survival was 90% at
the age of 1 month, 81% at 1 year, 70% at 10 years,
and 60% at 20 years.
The tricuspid valve septal leaflet is normally
not formed before 12 weeks, menstrual age [28].
However, Ebstein’s malformation is another tricuspid valve anomaly that is caused by failure of
the inferior atrioventricular cushion to properly
develop this leaflet from the right side of the ventricular septum. This anomaly is characterized by
increased offsetting of the atrioventricular valves
and tricuspid valve insufficiency that leads to an
enlarged right atrium. A nomogram of the mitral to
tricuspid valve distance is helpful for confirming
this diagnosis [51]. Melendres and colleagues [72]
recently reported a missed case of Ebstein’s anomaly that was obscured by misinterpretation of an
atrioventricular groove. Ebstein’s anomaly has a
A primitive endocardial heart tube, superior to
the primitive ventricles, becomes divided in half
by a spiral septum to form great arteries early in
gestation. This process may be interrupted for
unknown reasons, leading to a spectrum of developmental cardiac anomalies such as truncus
arteriosus, transposition of the great arteries,
double-outlet right ventricle, and TOF. The fundamental lesion depends on where formation of the
spiral septum is disrupted and where the great
arteries are positioned in relation to each other at
that time. Sonographic distinction between these
specific abnormalities may be very difficult before
birth [74,75].
Some conotruncal abnormalities, such as TOF
and double outlet right ventricle, are also at increased risk for chromosomal abnormalities [76].
In a recent population-based study of 255,849 births,
43 children were found to have 22q11.2 deletion
with an overall prevalence of 1 in 5950 births
(95% CI, 1 in 4417 – 1 in 8224 births) [77]. Most
affected children (81%) had a heart defect that
included conotruncal anomalies (46%), interrupted
aortic arch (19%), ventricular septal defects (16%),
and other assorted extra-cardiac vascular anomalies
(51%). Conotruncal aberrations are more frequent
in diabetics and in those women who have a congenital abnormality themselves or have had a child
with a genetic disorder.
The basic cardiac examination, using a fourchamber view alone, is notoriously unreliable for
detecting these anomalies. However, an extended
basic examination of the outflow tracts is the key
for their effective prenatal detection. The cardiac
axis may provide an initial sonographic indication
of a conotruncal anomaly during the basic examination [78,79]. DeVore [80] has also described the
use of color Doppler sonography to visualize great
vessel relationships for second and third trimester pregnancies.
Truncus arteriosus
Truncus arteriosus occurs when one great artery
arises from the base of the heart and gives rise to
the coronary, pulmonary, and aortic circulations.
The truncus usually overrides a VSD. The pulmonary arteries arise from the truncal root as a common trunk (Type I, most frequent) [Fig. 16A, B],
close but separate (Type II), or widely separate
(Type III) [81]. Fortunately, they are not ductaldependent lesions.
Fetal echocardiography should focus on the ventricular origin of the truncus, truncal valve annular
Prenatal Diagnosis of Congenital Heart Disease
Fig. 16. Truncus arteriosus. (A) Axial view of the fetal thorax reveals a small pulmonary artery (arrow) that directly
originates from a large truncal root (Tr). The fetal spine (Sp) is seen as a point of reference. (B) Oblique coronal
view of the left hemithorax demonstrates a large truncal vessel, with ventricular septal defect, that exits the right
(RV) and left (LV) ventricles. This truncal vessel overrides the ventricular septum and gives off a small pulmonary
vessel (arrow).
diameter, and evidence for valvular dysplasia.
Doppler studies may reveal truncal valve stenosis
or insufficiency [82]. In a pathology study of
28 Type I and Type II cases, other cardiovascular
lesions included anomalous position of the left
coronary artery (18.5%), right aortic arch (36%),
and interrupted aortic arch (11%) [83]. The distinction between truncus arteriosus and pulmonary
valve atresia with VSD can be very difficult [84].
An investigation from the University of Michigan
described 46 infants with truncus arteriosus undergoing early primary repair and found an actuarial
survival rate of 81 ± 6% at 90 days and beyond [85].
More recently, an observational study of 23 affected
fetuses indicates the following outcomes: termination of pregnancies (34.8%); intrauterine death
(8.7%); postnatal deaths (21.7%) [84]. The eight
remaining neonates (34.8%) were alive and doing
well after surgery (n=6) or awaiting repair (n=2).
Major cardiac surgical centers currently favor a primary repair of truncus arteriosus during the neonatal period.
Transposition of the great arteries
Transposition of the great arteries (TGA) occurs
when the aorta arises from the right ventricle and
the pulmonary artery arises from the left ventricle.
The usual spiral relationship of the great arteries
is lost so that the outflow tracts are parallel to
each other [Fig. 17] [86]. In about half of cases
there is no VSD. Affected newborns without a large
VSD may not have adequate mixing of oxygenated
blood and can experience rapid hemodynamic
decompensation as the ductus arteriosus closes.
This abnormality can be easily missed from the
four-chamber view unless a very large VSD is pre-
sent. In this case, an extended basic examination
of the outflow tracts is likely to identify TGA. Congenitally corrected transposition of the great arteries can also rarely occur where parallel vessels
are also seen exiting the heart. In this situation, the
atria connect with anatomically discordant ventricles and the ventricles connect with discordant and
transposed great arteries [87]. Careful attention to
the chamber morphology, presence of moderator
band, and papillary muscle relationships can pro-
Fig. 17. Transposition of the great arteries. The maindiagnostic findings is the manner by which the great
arteries exit the ventricles in a parallel manner. Fetal
echocardiography would demonstrate that the aortic root originates from the right ventricle (RV),
whereas the pulmonary artery would exit the left
ventricle (LV). A small ventricular septal defect is also
present (arrow).
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Lee & Comstock
vide important clues to help the examiner accurately distinguish between right and left ventricles.
The potential impact of early prenatal diagnosis is
illustrated by a study that examined clinical outcome in 68 affected neonates in whom a prenatal
diagnosis of TGA was suspected [88]. Results were
compared with 250 affected neonates who were
first identified with TGA after delivery. Newborns
with late diagnosis had increased delay between
birth and admission for special care and were
more likely to present with metabolic acidosis
and multi-organ failure. Preoperative mortality was
6% for the neonatal group as compared with no
deaths in the prenatal group. Postoperative morbidity was not different between groups, although
the hospital stay was slightly longer in babies diagnosed after birth. Postoperative death was significantly higher in the neonatal group (20 of
235 versus 0 of 68, P<.01. Their results suggest that
prenatal diagnosis of TGA reduces mortality and
morbidity. Timely detection of TGA before delivery
provides adequate planning for monitoring and
antepartum care. This information also facilitates
in utero transfer of fetuses to a tertiary care facility
that can appropriately treat newborns with ductal
dependent lesions.
Double-outlet right ventricle
Double-outlet right ventricle (DORV) describes a
condition in which most of the aorta and pulmonary artery arise from the right ventricle [89].
The sonographic findings may closely resemble
TOF or transposition of the great arteries with VSD
[Fig. 18]. The outcome of infants with DORV depends largely on the associated anomalies.
Fig. 18. Double-outlet right ventricle. Both great vessels exit the right ventricle (RV). The most lateral one
represents the aortic arch (Ao) because neck vessels
are present (arrows). No arteries are seen exiting the
left ventricle (LV). Sp = spine.
Fig. 19. Tetralogy of Fallot. The initial diagnostic clue
for tetralogy of Fallot is the presence of an overriding
aorta (ao) over a ventricular septal defect (*) during
the extended basic examination of the heart. Sonographic evidence for a small pulmonary artery (not
seen in this image) may not occur until a much later
time in pregnancy. s, ventricular septum; sp, spine.
As in TOF there is always an accompanying VSD
but, unlike TOF the relationship of the great vessels
is often abnormal; the aorta is commonly transposed anterior and to the right of the pulmonary
artery. Other defects are not infrequent such as
pulmonary valve stenosis, right cardiac axis deviation, right aortic arch, atrial septal defect, and total
anomalous pulmonary venous return. DORV with
transposition is known as a Taussig-Bing defect
and is commonly associated with coarctation. The
combination of DORV and AVSD is difficult to repair surgically.
Tetralogy of Fallot
TOF is the only conotruncal anomaly in which the
usual spiral relationship of the great vessels is maintained. The aorta overrides a ventricular sepal defect
[Fig. 19]. The pulmonary artery may be small due
to uneven division of the primitive truncus. In the
fetus, unlike in children, the right ventricle is not
hypertrophied because of shunting across the foramen ovale and the VSD reduces the load on the
right heart.
Early fetal TOF may simply present as a VSD with
aortic septal override. This anomaly can be missed
on a screening four-chamber view if the VSD is
small [Fig. 20]. Left cardiac axis deviation may
provide an initial diagnostic clue for this lesion
[79]. However, the extended basic cardiac examination is most likely to demonstrate a VSD with aortic
override. The aortic root itself can also be enlarged,
although pulmonary valve stenosis may be become
Prenatal Diagnosis of Congenital Heart Disease
These newborns may experience hemodynamic
decompensation if the pulmonary valve diameter
is small (≤ 5 mm at term) or if there is retrograde
flow across the ductus arteriosus. Immediate surgery may not be required for affected infants with
sufficient pulmonary valve flow and absence of
ductal dependency.
One variation, in which the pulmonary valve is
atretic and the pulmonary artery is not visible, is
known as ‘‘pseudotruncus’’ as only a solitary large
vessel is seen straddling the VSD. Another variation
of TOF involves absence of the pulmonary valve so
that there is regurgitation back and forth. The pulmonary artery may enlarge to massive proportions
and hydrops may occur.
Fig. 20. Tetralogy of Fallot with normal four-chamber
view The same fetus with tetralogy of Fallot appears
in Fig. 19. This four-chamber view appears normal
despite the presence of this conotruncal anomaly. lv,
left ventricle; rv, right ventricle; ra, right atrium; la,
left atrium.
apparent until later pregnancy [90,91]. The aortic
to pulmonary size ratio will be high despite normal
valve diameter measurements. In TOF, this ratio
increases as gestational age advances because
there is less than the usual growth of the pulmonary diameter [92]. The 90% confidence interval
for the pulmonary artery to aortic diameter (Pa/Ao)
ratio ranges from 0.84 to 1.41 and remains constant throughout pregnancy [93]. The right ventricular outflow tract should be re-evaluated before
delivery to identify affected fetuses at greatest risk
for ductal dependency.
Aortic coarctation
Cardiac ventricular disproportion can occur as a
normal variant, a consequence of fetal growth
restriction, or an indirect sign of aortic coarctation
[Fig. 21]. Aortic coarctation is usually difficult
to directly visualize, especially in the context of a
cardiac screening examination. However, the prenatal diagnosis of aortic coarctation has been
reported to improve survival and reduce morbidity [94].
Allan and colleagues [95] found that 24 fetuses
had dilatation of the right heart as compared with
the left side. In 18 of these cases, the diagnosis of
aortic coarctation or interruption was correctly
inferred from indirect sonographic findings. Hornberger and associates [96] summarized a multicenter investigation for 20 infants with coarctation.
They found quantitative hypoplasia of the aortic
isthmus and transverse arch as the best predictors
Fig. 21. Ventricular disproportion A disparity in ventricular dimensions can represent a normal variant. However,
one should also consider that this could be caused by several other conditions that include intrauterine growth
restriction, aortic coarctation, or an evolving hypoplastic left heart syndome.
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Lee & Comstock
for coarctation and emphasized the importance of
conducting serial studies for suspected cases. Ventricular disproportion has only a moderate degree
of sensitivity (62%) for the detection of coarctation that occurs with a high false-positive rate after
34 weeks [97]. The 90% confidence interval for the
right ventricular to left ventricular diameter ratio is
constant throughout pregnancy and ranges from
0.79 to 1.24 [93].
Total anomalous pulmonary venous return
The left atrium is normally positioned near the
descending aorta. In the space between these two
structures are the main left and right pulmonary
veins. They can be followed to their drainage point
in the back of the left atrium. In total anomalous
pulmonary venous return (TAPVR), both main pulmonary veins drain into the right atrium via a
vertical vein which then drains into a coronary
sinus, persistent left superior vena cava, innominate vein, the hepatic veins, or even below the
diaphragm (20%) into the inferior vena cava.
Thus oxygenated blood from the lungs never
reaches the body and brain but rather circulates
around and around in the lungs with the only
mixing available across a patent foramen ovale.
TAPVR can lead to cardiorespiratory decompensation of the newborn that is unresponsive to prostaglandin infusion. This circulatory abnormality
should be considered when a dilated coronary sinus, cardiac chamber disproportion, or size dis-
Fig. 22. Total anomalous pulmonary venous return At
least two pulmonary veins (arrows) drain into the
right atrium instead of the left. A ventricular septal
defect is also present between the two markers. LV,
left ventricle. Increased volume loading of the right
heart and cyanosis are the key clinical findings for this
condition. An atrial septal defect is desirable because
this defect will allow blood to flow from the right
atrium into the left heart.
parity between the great arteries is seen. It is particularly common in fetuses with heterotaxic abnormalities. Direct documentation of pulmonary
venous flow into the left atrium is the most reliable
way to exclude TAPVR [98] [Fig. 22].
A nonlethal variation is partial anomalous
venous return in which the right vein drains to
the right atrium but the left still drains to the left
atrium. As long as some return goes to the left
atrium, oxygenated blood is available to the body
and brain.
Summary
CHD is a leading cause of infant morbidity and
mortality that results from birth defects. Diagnosticians who use ultrasonography to evaluate the fetal
heart must be familiar with key factors that can
impact the success of their cardiac screening programs. A good understanding of practice guidelines
for the ‘‘basic’’ and ‘‘extended basic’’ cardiac examination is essential. Efforts should also be made to
standardize diagnostic training of these who perform these examinations in an ongoing manner.
The primary goal is for these individuals to accurately identify who should be referred for a more
detailed evaluation of the fetus.
References
[1] Kochanek KD, Murphy SL, Anderson RN, Scott C.
Deaths: final data for 2002. Natl Vital Stat Rep
2004;53:1–115.
[2] Centers for Disease Control and Prevention.
Trends in infant mortality attributable to birth
defects - United States, 1980–1995. MMWR Morb
Mortal Wkly Rep 2005;47:773–8.
[3] Rosano A, Botto LD, Botting B, Mastroiacovo P.
Infant mortality and congenital anomalies from
1950 to 1994: an international perspective. J Epidemiol Community Health 2000;54:660–6.
[4] Ferencz C, Rubin JD, McCarter RJ, et al. Congenital heart disease: prevalence at livebirth. The
Baltimore-Washington infant study. Am J Epidemiol 1985;121:31–6.
[5] Meberg A, Otterstad JE, Froland G, et al. Outcome of congenital heart defects–a populationbased study. Acta Paediatr 2000;89:1344–51.
[6] Cuneo BF, Curran LF, Davis N, Elrad H. Trends
in prenatal diagnosis of critical cardiac defects in
an integrated obstetric and pediatric cardiac imaging center. J Perinatol 2004;24:674–8.
[7] Allan LD, Crawford DC, Chita SK, Tynan MJ.
Prenatal screening for congenital heart disease.
BMJ 1986;292:717–9.
[8] Sharland GK, Allan LD. Screening for congenital
heart disease prenatally. Results of a 2 1/2 year
study in the South East Thames Region. Br J
Obstet Gynaecol 1992;99:220–5.
Prenatal Diagnosis of Congenital Heart Disease
[9] Copel JA, Pilu G, Green J, Hobbins JC, Kleinman
CS. Fetal echocardiographic screening for congenital heart disease: the importance of the fourchamber view. Am J Obstet Gynecol 1987;157:
648–55.
[10] Crane JP, LeFevre ML, Winborn RC, et al. A
randomized trial of prenatal ultrasonographic
screening: impact on the detection, management,
and outcome of anomalous fetuses. The RADIUS
Study Group. Am J Obstet Gynecol 1994;171:
392–9.
[11] Kirk JS, Riggs TW, Comstock CH, et al. Prenatal
screening for cardiac anomalies: the value of
routine addition of the aortic root to the fourchamber view. Obstet Gynecol 1994;84:427–31.
[12] Ott WJ. The accuracy of antenatal fetal echocardiography screening in high and low risk
patients. Am J Obstet Gynecol 1995;172:1741–7.
[13] Tegnander E, Eik-Nes SH, Johansen OJ, Linker
DT. Prenatal detection of heart defects at the
routine fetal examination at 18 weeks in a nonselected population. Ultrasound Obstet Gynecol
1995;5:372–80.
[14] Stumpflen I, Stumpflen A, Wimmer M, Bernaschek G. Effect of detailed fetal echocardiography as part of routine prenatal ultrasound
screening on detection of congenital heart disease. Lancet 1996;348:854–7.
[15] Buskens E, Grobbee DE, Frohn-Mulder IME.
Efficacy of routine ultrasound screening for
congenital heart disease in normal pregnancy.
Circulation 1996;94:67–72.
[16] Bromley B, Estroff JA, Sanders SP, et al. Fetal
echocardiography: accuracy and limitations in a
population at high and low risk for heart defects.
Am J Obstet Gynecol 1992;166:1473–81.
[17] Wigton TR, Sabbagha RE, Tamura RK, et al.
Sonographic diagnosis of congenital heart disease: comparison between the four-chamber
view and multiple cardiac views. Obstet Gynecol
1993;82:219–24.
[18] Tegnander E, Williams W, Johansen OJ, et al.
Prenatal detection of heart defects in a nonselected population of 30,149 fetuses—detection
rates and outcome. Ultrasound Obstet Gynecol
2006;27:252–65.
[19] Mitchell SC, Korones SB, Berendes HW. Congenital heart disease in 56,109 births. Incidence
and natural history. Circulation 1971;43:323–32.
[20] Chaoui R. The four-chamber view: four reasons
why it seems to fail in screening for cardiac abnormalities and suggestions to improve detection
rate. Ultrasound Obstet Gynecol 2003;22:3–10.
[21] Senat MV, Holden D, Bernard JP, et al. Feasibility
of the second-trimester fetal ultrasound examination in an unselected population at 18, 20
or 22 weeks of pregnancy: a randomized trial.
Ultrasound Obstet Gynecol 1999;14:92–7.
[22] Lee W. American Institute of Ultrasound in
Medicine. Performance of the basic fetal cardiac
ultrasound examination. J Ultrasound Med 1998;
17:601–7.
[23] Barnett SB, Ter Haar GR, Ziskin MC, et al.
International recommendations and guidelines
for the safe use of diagnostic ultrasound in medicine. Ultrasound Med Biol 2000;26:355–66.
[24] Paladini D, Vassallo M, Tartaglione A, et al. The
role of tissue harmonic imaging in fetal echocardiography. Ultrasound Obstet Gynecol 2004;
23:159–64.
[25] Kossof G. Basic physics and imaging characteristics of ultrasound. World J Surg 2000;24:
134–42.
[26] DeVore GR, Medearis AL, Bear MB, et al. Fetal
echocardiography: factors that influence imaging
of the fetal heart during the second trimester of
pregnancy. J Ultrasound Med 1993;12:659–63.
[27] Moorman A, Webb S, Brown NA, et al. Development of the heart: (1) formation of the cardiac
chambers and arterial trunks. Heart 2003;89:
806–14.
[28] Cook AC, Yates RW, Anderson RH. Normal and
abnormal fetal cardiac anatomy. Prenat Diagn
2004;24:1032–48.
[29] Carvalho JS, Mavrides E, Shinebourne EA, et al.
Improving the effectiveness of routine prenatal
screening for major congenital heart defects.
Heart 2002;88:387–91.
[30] Cuneo BF, Curran LF, Davis N, Elrad H. Trends
in prenatal diagnosis of critical cardiac defects
in an integrated obstetric and pediatric cardiac
imaging center. J Perinatol 2004;24:674–8.
[31] Hunter S, Heads A, Wyllie J, Robson S. Prenatal diagnosis of congenital heart disease in the
northern region of England: benefits of a training
programme for obstetric ultrasonographers.
Heart 2000;84:294–8.
[32] Yagel S, Weissman A, Rotstein Z, et al. Congenital heart defects: natural course and in utero
development. Circulation 1997;96:550–5.
[33] Achiron R, Rotstein Z, Lipitz S, et al. Firsttrimester diagnosis of fetal congenital heart
disease by transvaginal ultrasonography. Obstet
Gynecol 1994;84:69–72.
[34] Hyett J, Moscoso G, Papapanagiotou G, et al.
Abnormalities of the heart and great arteries in
chromosomally normal fetuses with increased
nuchal translucency thickness at 11–13 weeks of
gestation. Ultrasound Obstet Gynecol 1996;7:
245–50.
[35] Hyett JA, Perdu M, Sharland GK, et al. Increased
nuchal translucency at 10–14 weeks of gestation
as a marker for major cardiac defects. Ultrasound
Obstet Gynecol 1997;10:242–6.
[36] Rustico MA, Benettoni A, D’Ottavio G, et al. Early
screening for fetal cardiac anomalies by transvaginal echocardiography in an unselected population: the role of operator experience. Ultrasound
Obstet Gynecol 2000;16:614–9.
[37] Huggon IC, Ghi T, Cook AC, et al. Fetal cardiac
abnormalities identified prior to 14 weeks’ gestation. Ultrasound Obstet Gynecol 2002;20:22–9.
[38] Carvalho JS. Fetal heart scanning in the first
trimester. Prenat Diagn 2004;24:1060–7.
289
290
Lee & Comstock
[39] Carvalho JS, Moscoso G, Tekay A, et al. Clinical
impact of first and second trimester fetal echocardiogaphy on high risk pregnancies. Heart
2004;90:921–6.
[40] American Institute of Ultrasound in Medicine.
Guidelines for the performance of the antepartum obstetrical ultrasound examination. J Ultrasound Med 2003;22:1116–25.
[41] American College of Radiology. ACR practice
guideline for the performance of antepartum
obstetrical ultrasound. In: Practice guidelines
& technical standards. Reston, VA: ACR; 2004.
p. 689–95.
[42] American College of Obstetricians and Gynecologists. ACOG Practice Bulletin. Ultrasonography in
pregnancy. Obstet Gynecol 2004;104:1449–58.
[43] Small M, Copel JA. Indications for fetal echocardiography. Pediatr Cardiol 2004;25:201–22.
[44] Di Salvo DN, Brown DL, Doubilet PM, et al.
Clinical significance of isolated fetal pericardial
effusion. J Ultrasound Med 1994;13:291–3.
[45] Yoo SJ, Min JY, Lee YH. Normal pericardial fluid
in the fetus: color and spectral Doppler analysis.
Ultrasound Obstet Gynecol 2001;18:248–52.
[46] Comstock CH. Normal fetal heart axis and position. Obstet Gynecol 1987;70:255–9.
[47] Smith RS, Comstock CH, Kirk JS, Lee W. Ultrasonographic left cardiac axis deviation: a marker
for fetal anomalies. Obstet Gynecol 1995;85:
187–91.
[48] Comstock CH, Smith R, Lee W, Kirk JS. Right
fetal cardiac axis: clinical significance and associated findings. Obstet Gynecol 1998;91:495–9.
[49] Sutton MS, Groves A, MacNeill A, et al. Assessment of changes in blood flow through the lungs
and foramen ovale in the normal human fetus
with gestational age: a prospective Doppler
echocardiographic study. Br Heart J 1994;71:
232–7.
[50] Rasanen J, Wood DC, Weiner S, et al. Role of
the pulmonary circulation in the distribution of
human fetal cardiac output during the second
half of pregnancy. Circulation 1996;94:1068–73.
[51] Vettraino IM, Huang R, Comstock CH. The normal offset of the tricuspid septal leaflet in the
fetus. J Ultrasound Med 2002;21:1099–104.
[52] DeVore G. The aortic and pulmonary outflow
tract screening examination in the human fetus.
J Ultrasound Med 1992;11:345–8.
[53] Yoo SJ, Lee YH, Cho KS. Abnormal three-vessel
view on sonography: a clue to the diagnosis of
congenital heart disease in the fetus. AJR Am J
Roentgenol 1999;172:825–30.
[54] Vinals F, Heredia F, Giuliano A. The role of the
three vessels and trachea view (3VT) in the
diagnosis of congenital heart defects. Ultrasound
Obstet Gynecol 2003;22:358–67.
[55] Yagel S, Arbel R, Anteby EY, et al. The three
vessels and trachea view (3VT) in fetal cardiac
scanning. Ultrasound Obstet Gynecol 2002;20:
340–5.
[56] Vettraino IM, Lee W, Bronsteen RA, Comstock
[57]
[58]
[59]
[60]
[61]
[62]
[63]
[64]
[65]
[66]
[67]
[68]
[69]
[70]
[71]
[72]
CH. Sonographic evaluation of the ventricular
cardiac outflow tracts [Letter to the Editor].
J Ultrasound Med 2005;24:566.
Paladini D, Palmieri S, Lamberti A, et al. Characterization and natural history of ventricular
septal defects in the fetus. Ultrasound Obstet
Gynecol 2000;16:118–22.
Turner SW, Hunter S, Wyllie JP. The natural
history of ventricular septal defects. Arch Dis
Child 1999;81:413–6.
Johnson P, Maxwell DJ, Tynan MJ, Allan LD.
Intracardiac pressures in the human fetus. Heart
2000;84:59–63.
Allan LD. Atrioventricular septal defect in the
fetus. Am J Obstet Gynecol 1999;181(5 Pt 1):
1250–3.
Galindo A, Comas C, Martinez JM, et al. Cardiac
defects in chromosomally normal fetuses with
increased nuchal translucency at 10–14 weeks of
gestation. J Matern Fetal Neonatal Med 2003;13:
163–70.
Gentles TL, Mayer Jr JE, Gauvreau K, et al. Fontan operation in five hundred consecutive patients: factors influencing early and late outcome.
J Thorac Cardiovasc Surg 1997;114:376–91.
Park JK, Taylor DK, Skeels M, Towner DR.
Dilated coronary sinus in the fetus: misinterpretation as an atrioventricular canal defect. Ultrasound Obstet Gynecol 1997;10:126–9.
Bando K, Turrentine MW, Sun K, et al. Surgical
management of complete atrioventricular septal
defects. A twenty-year experience. J Thorac Cardiovasc Surg 1995;110:1543–52.
Tworetzky W, McElhinney DB, Reddy VM, et al.
Improved surgical outcome after fetal diagnosis
of hypoplastic left heart syndrome. Circulation
2001;103:1269–73.
McCaffrey FM, Sherman FS. Prenatal diagnosis of
severe aortic stenosis. Pediatr Cardiol 1997;18:
276–81.
Norwood WI, Kirkland JK, Sanders SP. Hypoplastic left heart syndrome: experience with
palliative surgery. Am J Cardiol 1980;45:87–91.
Bove EL, Ohye RG, Devaney EJ. Hypoplastic left
heart syndrome: conventional surgical management. Semin Thorac Cardiovasc Surg Pediatr
Card Surg Annu 2004;7:3–10.
Mahle WT, Wernovsky G. Neurodevelopmental
outcomes in hypoplastic left heart syndrome.
Semin Thorac Cardiovasc Surg Pediatr Card Surg
Annu 2004;7:39–47.
Tongsong T, Sittiwangkul R, Wanapirak C,
Chanprapaph P. Prenatal diagnosis of isolated
tricuspid valve atresia: report of 4 cases and
review of the literature. J Ultrasound Med 2004;
23:945–50.
Sittiwangkul R, Azakie A, Van Arsdell GS, et al.
Outcomes of tricuspid atresia in the Fontan era.
Ann Thorac Surg 2004;77:889–94.
Melendres G, Ormsby EL, McGahan JP, et al.
Prenatal diagnosis of Ebstein anomaly: a potential pitfall. J Ultrasound 2004;23:551–5.
Prenatal Diagnosis of Congenital Heart Disease
[73] Pavlova M, Fouron JC, Drblik SP, et al. Factors
affecting the prognosis of Ebstein’s anomaly
during fetal life. Am Heart J 1998;135:1081–5.
[74] Allan LD, Sharland GK, Milburn A, et al.
Prospective diagnosis of 1,006 consecutive cases
of congenital heart disease in the fetus. J Am Coll
Cardiol 1994;23:1452–8.
[75] Tometzki AJ, Suda K, Kohl T, et al. Accuracy of
prenatal echocardiographic diagnosis and prognosis of fetuses with conotruncal anomalies.
J Am Coll Cardiol 1999;33:1696–701.
[76] Paladini D, Rustico M, Todros T, et al. Conotruncal anomalies in prenatal life. Ultrasound
Obstet Gynecol 1996;8:241–6.
[77] Botto LD, May K, Fernhoff PM, et al. A
population-based study of the 22q11.2 deletion:
phenotype, incidence, and contribution to major
birth defects in the population. Pediatrics 2003;
112:101–7.
[78] Comstock CH, Smith RS, Lee W, Kirk JS. Right
fetal cardiac axis: clinical significance and associated findings. Obstet Gynecol 1998;85:495–9.
[79] Smith RS, Comstock CH, Kirk JS, Lee W. Ultrasonographic left cardiac axis deviation: a marker
for fetal anomalies. Obstet Gynecol 1995;85:
187–91.
[80] DeVore GR. Color Doppler examination of the
outflow tracts of the fetal heart: a technique for
identification of cardiovascular malformations.
Ultrasound Obstet Gynecol 1994;4:463–71.
[81] Collett RW, Edwards JE. Persistent truncus arteriosus: a classification according to anatomic
types. Surg Clin N Am 1949;29:1245–70.
[82] Duke C, Sharland GK, Jones AM, Simpson JM.
Echocardiographic features and outcome of
truncus arteriosus diagnosed during fetal life.
Am J Cardiol 2001;88:1379–84.
[83] Butto F, Lucas Jr RV, Edwards JE. Persistent truncus arteriosus: pathologic anatomy in 54 cases.
Pediatr Cardiol 1986;7:95–101.
[84] Volpe P, Paladini D, Marasini M, et al. Common
arterial trunk in the fetus: characteristics, associations, and outcome in a multicentre series of
23 cases. Heart 2003;89:1437–41.
[85] Bove EL, Lupinetti FM, Pridjian AK, et al. Results
of a policy of primary repair of truncus arteriosus
in the neonate. J Thorac Cardiovasc Surg 1993;
105:1057–65.
[86] Allan LD. Sonographic detection of parallel great
[87]
[88]
[89]
[90]
[91]
[92]
[93]
[94]
[95]
[96]
[97]
[98]
arteries in the fetus. AJR Am J Roentgenol 1997;
168:1283–6.
McEwing RL, Chaoui R. Congenitally corrected
transposition of the great arteries: clues for prenatal diagnosis. Ultrasound Obstet Gynecol 2004;
23:68–72.
Bonnet D, Solti A, Butera G, et al. Detection of
transposition of the great arteries in fetuses
reduces neonatal morbidity and mortality. Circulation 1999;99:916–8.
Smith RS, Comstock CH, Kirk JS, et al. Doubleoutlet right ventricle: an antenatal diagnostic
dilemma. Ultrasound Obstet Gynecol 1999;14:
315–9.
DeVore GR, Siassi B, Platt LD. Fetal echocardiography. VIII. Aortic root dilatation—a marker for
tetralogy of Fallot. Am J Obstet Gynecol 1988;
159:129–36.
Lee W, Smith RS, Comstock CH, et al. Tetralogy
of Fallot: prenatal diagnosis and postnatal survival. Obstet Gynecol 1995;86:583–8.
Hornberger LK, Sanders SP, Sahn DJ, et al. In
utero pulmonary artery and aortic growth and
potential for progression of pulmonary outflow
tract obstruction in tetralogy of Fallot. J Am Coll
Cardiol 1995;25:739–45.
Kirk JS, Comstock CH, Lee W, et al. Fetal cardiac
asymmetry: a marker for congenital heart disease.
Obstet Gynecol 1999;93:189–92.
Franklin O, Burch M, Manning N, et al. Prenatal
diagnosis of coarctation of the aorta improves
survival and reduces morbidity. Heart 2002;87:
67–9.
Allan LD, Chita SK, Anderson RH, et al. Coarctation of the aorta in prenatal life: an echocardiographic, anatomical, and functional study.
Br Heart J 1988;59:356–60.
Hornberger LK, Sahn DJ, Kleinman CS, et al.
Antenatal diagnosis of coarctation of the aorta:
a multicenter experience. J Am Coll Cardiol
1994;23:417–23.
Brown DL, Durfee SM, Hornberger LK. Ventricular discrepancy as a sonographic sign of coarctation of the fetal aorta: how reliable is it?
J Ultrasound Med 1997;16:95–9.
Allan LD, Sharland GK. The echocardiographic
diagnosis of totally anomalous pulmonary venous connection in the fetus. Heart 2001;85:
433–7.
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