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1. Advances in Fetal Echocardiography: Early Imaging,
Three/Four Dimensional Imaging, and Role of Fetal
Echocardiography in Guiding Early Postnatal
Management of Congenital Heart Disease
Lindsay Rogers, M.D.,* Jun Li, M.D.,† Liwen Liu, M.D., Ph.D.,† Rula Balluz, M.D., M.P.H.,* Jack Rychik, M.D.,‡
and Shuping Ge, M.D.*§
*Heart Center, St. Christopher’s Hospital for Children and Drexel University College of Medicine, Philadelphia,
Pennsylvania; †Department of Ultrasound, Xijing Hospital and Fourth Military Medical University, Xi’an,
Shannxi China; ‡The Fetal Heart Program, Cardiac Center at The Children’s Hospital of Philadelphia,
Phiadelphia, Pennsylvania; and §Pediatric Cardiology, Deborah Heart and Lung Center, Browns Mills, New
Jersey
In this article, we review a number of topics that we believe reflect new and exciting aspects of fetal
echocardiography. These new advances include early fetal cardiovascular imaging around 14 weeks,
the utility of three/four dimensional imaging technology for the fetus, and finally the utility of fetal
echocardiography for antenatal and perinatal care of congenital heart diseases to improve and optimize
outcome. Finally, we briefly discussed future directions in fetal cardiac intervention. (Echocardiography
2013;30:428-438)
Key words: fetal echocardiography, four-dimensional echocardiography, congenital, heart defects,
congenital heart disease
With the advent of cardiac ultrasound, which
gained widespread use in the 1970s, came the
first reports of two-dimensional (2D), spectral
Doppler, and color Doppler fetal cardiac imaging
in the late 1970s and early 1980s.1–7
These initial
reports included detailed descriptions of fetal car-
diac anatomy as well as the diagnosis and moni-
toring of fetal cardiac arrhythmias.8,9
Prior to
cardiac ultrasound, the understanding of fetal
cardiovascular physiology was obtained largely
by studies performed on fetal sheep and angio-
cardiograms of human fetuses as early as the
1960s.10
Over the last two decades, evolving
ultrasound technology has enhanced our ability
to noninvasively study the human fetus and has
lead to a rapid expansion of our understanding
of the anatomy and physiology of the fetal car-
diovascular system. This has cultivated a rapidly
expanding field of clinical research, leading to an
evolving comprehension of the fetal heart and in
utero progression of congenital heart disease
(CHD).
This is an exciting time for the field of fetal
echocardiography. This rapidly evolving spe-
cialty has an abundance of new knowledge
gained through development of novel imaging
techniques, new modalities, and the application
of imaging data toward improved perinatal
management. In this review article, we discuss a
number of topics of interest to our readers with
regards to new and exciting aspects of fetal
echocardiography. We assess the current state of
early cardiovascular imaging around 14 weeks
gestation, evaluate what is known about the role
of three/four dimensional (3D/4D) imaging
technology for the fetus, and finally review fetal
echocardiographic predictors of perinatal out-
come in CHD.
Early Fetal Cardiovascular Imaging:
With the technological advancement of the ultra-
sound imaging systems, cardiac structures in the
fetus can be visualized with some success as early
as 11 weeks gestation. Imaging of normal hearts
shows successful visualization of cardiac structures
from a transvaginal approach at 11–13 weeks
gestation, while transabdominal imaging demon-
strates equivalent visualization by 14 weeks11
(Fig. 1 and movie clip S1). For this review, we will
Addresses for correspondence and reprints requests: Shuping
Ge, M.D., Section of Cardiology, St. Christopher’s Hospital for
Children and Drexel University College of Medicine, 3601 A
Street, Philadelphia, PA 19134, USA. Fax: 215-427-4822;
E-mail: shuping.ge@drexelmed.edu
© 2013, Wiley Periodicals, Inc.
DOI: 10.1111/echo.12211 Echocardiography
428

2. focus on transabdominal early fetal cardiovascular
imaging.
Early fetal cardiovascular imaging is becoming
increasingly common for women with high-risk
pregnancies, history of previous child with CHD,
or women with abnormalities identified during
early gestation ultrasound. Early fetal cardiovas-
cular imaging provides much needed reassurance
to families when the scan is normal and also aids
in planning and facilitating further workup for
more timely and comprehensive diagnosis when
an abnormality is suspected.
Given the implications of fetal diagnosis of
CHD, accuracy and diagnostic sensitivity of
images are of the utmost importance. Several
studies have sought to compare the accuracy of
early fetal cardiovascular imaging to more con-
ventional 18–22 week fetal echocardiography.
One large study reports on 230 high-risk fetuses
who had early fetal imaging, median gestational
age of 14 weeks. Investigators identified 21 car-
diac abnormalities; confirming 14 of these either
by later gestation ultrasound or autopsy (7 lacked
confirmatory data). Of the 184 early normal
scans, 2 fetuses were subsequently confirmed to
have CHD requiring intervention, not identified
by early imaging: 1 large ventricular septal defect
(VSD) and 1 valvar pulmonary stenosis.12
Another study of 154 fetuses with early gesta-
tion cardiac imaging at <16 weeks and follow-up
confirmatory scans at 18 weeks, identified 14 of
20 fetuses with CHD by early ultrasound (sensitiv-
ity of 70%). In this study, early fetal cardiac imag-
ing had a specificity of 98%, a positive predictive
value of 87.5% and a negative predictive value of
96%.13
Accuracy of early fetal cardiovascular imaging
was 96% in 1 study with missed diagnoses
including VSD, aortic arch abnormalities, and left
superior vena cava (LSVC).14
Most recently, a
study showed first trimester cardiac imaging
missed major CHD in 6 fetuses (870 total
screened with 36 identified as abnormal).15
The
most commonly missed lesion was VSD, followed
by abnormalities of the aortic arch, arch branch-
ing and coarctation, structural atrioventricular
(AV) valve abnormalities, Tetralogy of Fallot
(TOF), partial AV canal defect, and total anoma-
lous pulmonary venous return (TAPVR).
Overall, early fetal cardiovascular imaging,
starting at 14 weeks by transabdominal
approach, can identify complex CHD and gen-
erally misses only minor cardiac abnormalities.
However, early fetal cardiac imaging should
always be followed by a confirmatory scan at
18–20 weeks gestation. Certain lesions, such as
anomalous pulmonary venous return and coarc-
tation, remain a diagnostic challenge for all
fetal imaging and illustrate the importance of
later gestation scans. With increasing focus on
first trimester fetal assessment will come a
greater need to improve early gestational fetal
echocardiography. Increasing demand for first
trimester echocardiography will ultimately lead
to increased operator skill and improvements in
technology.
Three-Dimensional and STIC for Diagnosis of
Congenital Heart Disease:
Two-dimensional fetal ultrasound is the core
modality used in fetal echocardiography. 2D
imaging utilizes multiple anatomic planes, relying
on mental reconstruction of the spatial relation-
ships of these planes to define fetal cardiac anat-
omy. The introduction of 3D/4D imaging
technology aids in this mental reconstruction,
allowing technology to piece together multiple
imaging planes into a more fluid and representa-
tive depiction of the fetal cardiac structures.
(a)
(b)
Figure 1. A. Early fetal cardiovascular imaging in a normal
fetus of B. 13 weeks of gestation. The four-chamber equiva-
lent view shows a single ventricle with a single atrium con-
nected via a common atrioventricular valve. SV = Single
ventricle; SA = single atrium.
429
Advances in Fetal Echocardiography

3. Spatiotemporal image correlation (STIC) is the
most commonly used 3D/4D modality in fetal
echocardiography. STIC is an offline, motion-
gated scanning mode that incorporates sequen-
tial B-mode images, to form full volume datasets.
Calculation of the fetal heart rate allows correla-
tion of the spatial and temporal position of the B-
mode images; however, interference such as fetal
breathing and maternal motion can affect the
quality of data obtained. Typically, the full sweep
begins just caudal to the traditional four-chamber
view of the heart continuing though the heart,
finishing cranial to takeoff of the arch vessels.16
Real time or live 3D fetal imaging is based on
matrix array transducer and other technologies
to image and process 3D volumetric data.17,18
Published data suggest that the image quality of
real time 3DE is similar to the images acquired
by STIC from the sagittal views and superior to
those obtained by STIC from the four-chamber
views. However, real time 3DE has less motion
artifact. The recent advent of single heart beat
acquisition of the full volume dataset using real
time 3D echocardiography has made it possible
for this technology to be promising in clinical
practice.19
There are multiple postprocessing techniques
that can be applied to these 3D/4D datasets.
Multiplanar reconstruction (MPR) allows visuali-
zation of 3 orthogonal planes at the same time
(Fig. 2). 3D rendering, adds depth to 1 selected
plane from MPR display. Tomographic ultra-
sound imaging (TUI) displays a matrix of sequen-
tial parallel planes, with the reference planes at
center and adjacent slices arranged in order
around the reference plane (Fig. 3).
There are some advantages of 3D/4D imaging
compared with 2D ultrasound. Two-dimensional
imaging is limited to the planes and data
obtained during the study, while 3D manipula-
tion can allow visualization of orthogonal planes
and nontraditional planes at the operator’s
choice. However, continued debate exists as to
the utility of these extra imaging planes and
datasets in improving detection of, or accuracy in
diagnosis of CHD compared with 2D echocardio-
graphic technology.
The accuracy of STIC for the diagnosis of
CHD has been shown in multiple studies. A
recent study showed an accuracy of 91.6% and
sensitivity of 94.2% by STIC alone in diagnosis
of CHD.20
In addition, the accuracy and repro-
ducibility of 4D STIC in diagnosing CHD was
evaluated in a recent cross-sectional study ana-
lyzing 90 volume datasets, from fetuses at 18–
26 weeks.21
Data were evaluated from across 7
international centers with expertise in 4D
ultrasound. The median sensitivity was 93%,
specificity was 96%, positive predictive value
(PV) = 4.8%, and negative PV = 6.8%. Ten
percent of volume data had limited clinical value
secondary to image quality. This study supports
existing literature that at centers with expertise
in 4D fetal echocardiography, STIC may be reli-
ably used to aid in diagnosis of CHD. Impor-
tantly, this study establishes the idea of remote
evaluation of 4D data by expert centers, poten-
tially expanding the role of telemedicine for
diagnosis of CHD.
Furthermore, 3D/4D imaging full volumes can
be used to measure the ventricular volumes and
ejection fraction, potentially improving accuracy
and reproducibility. The left and right ventricular
volumes can be measured by manual or semiau-
tomated 3D methodologies developed for chil-
dren and adults22–24
(Fig. 4). This is an exciting
new development in understanding ventricular
maturation, remodeling, and global systolic
function in normal human fetuses and those with
CHD and various forms of myocardial dysfunc-
tion.
The above data support the accuracy of 3D/
4D imaging in diagnosis of CHD. However,
given the added time, equipment, and training
needed to implement this type of imaging into
A
C
B
Figure 2. Spatiotemporal image correlation (STIC) imaging
of fetal heart in 3 dimensions (3D). A 3D dataset was obtained
by the STIC techniques. Offline analysis shows cardiac struc-
tures in multiple views and planes and views that can be refer-
enced with each other. In this set of views, the A., B., and C.
scans and images are perpendicular to each other and can be
used to assess the cardiac structures in a systematic way. A.
Long-axis view of the left ventricular inflow posteriorly, out-
flow in the middle and right ventricle anteriorly. B. Short-axis
view of the base of the heart: The aorta in the center and left
and right atria and right ventricular inflow and outflow
around the aorta. C. The ascending aorta, aortic arch, and
descending aorta. LV = left ventricle; RV = right ventricle;
LA = left atrium; RA = right atrium; AO = aorta; DAO =
descending aorta; PA = pulmonary artery; RVOT = right
ventricular outflow tract.
430
Rogers, et al

4. practice, evaluating the added value of 3D/4D
imaging is imperative to justify its use. Recently
1 study evaluated 181 cases of CHD, comparing
diagnoses made by viewing either 2D or 4D
imaging.25
An added value of about 6% using
3D/4D imaging was reported in diagnosing
CHD. Specific modalities were found to be
helpful in certain lesions: VSD—virtual planes;
Figure 3. Spatiotemporal image correlation (STIC) imaging of fetal heart in 3 dimensions. A series of 7 parallel two-dimensional
cross-sectional images can be obtained and used to assess the cardiac structures, for example, the right and left ventricular outflow
in their long-axis views in a systematic way that is similar to scanning from the right to the left ventricular outflow using traditional
2D imaging.
Figure 4. Real time 3D/4D fetal echocardiography to assess left ventricular volume and function. Right panel displays final mea-
surements stroke volume (SV), end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF).
431
Advances in Fetal Echocardiography

5. TAPVR—multiplanar reconstruction; right ven-
tricular aneurysm—B-flow; transposition of the
great arteries (TGA) with pulmonary atresia and
interrupted aortic arch—tomographic ultrasound
imaging (TUI); agenesis of ductus venosus to the
coronary sinus—MPR and B-flow.25
As with all ultrasound technology, 3D/4D
ultrasound has limitations such as acoustic shad-
owing, Doppler dropout, and loss of resolution at
greater scanning depths. In experienced centers,
3D/4D ultrasound can be accurately used to
diagnose CHD. However, its added value over
traditional 2D evaluation remains limited, quanti-
fied as of added value of only 6% in 1 study. It is
likely that as 3D/4D technology improves, the
modality will become increasingly valuable in the
diagnosis of CHD. Currently, telemedicine pro-
vides a potential new avenue for utilization of
STIC at smaller centers, electronically accessing
the expertise of larger centers.
Fetal Echocardiography, Congenital Heart
Disease, and Stability in the Newborn:
Identification of CHD in fetal life offers many
advantages, including parental preparation,
physical readiness, and improved stability at birth
with decreased infant morbidity and mortality.26
Identification and characterization of congenial
heart disease is the first goal of fetal echocardiog-
raphy. Once CHD is identified, serial assessments
are aimed at evaluation of disease progression
and predicting clinical outcomes. Fetal echocar-
diographic predictors of antenatal stability are a
vital part to each analysis and are unique to each
individual form of CHD. The following is a review
of the more common forms of critical CHD and a
discussion of some of the fetal echocardiographic
predictors of immediate postnatal stability.
Coarctation of the Aorta:
Isolated aortic coarctation is 1 of the most com-
monly missed forms of CHD, both prenatally and
prior to hospital discharge.27
Undiagnosed, aor-
tic coarctation often manifests as neonatal shock
after ductus arteriosus closure forces full cardiac
output across the narrowed aortic isthmus,
resulting in decreased peripheral perfusion and
development of left ventricular failure. Therefore,
identification of these infants prior to ductal clo-
sure, that is, in fetal life, could prevent danger-
ously low cardiac output and potential infant
death.28
Distinguishing physiologic aortic arch/isthmus
narrowing in the fetus from true coarctation is a
challenge. Echocardiographic findings that raise
suspicion of coarctation include left and right
ventricular size discrepancy, the presence of an
LSVC to coronary sinus and bicuspid aortic valve.
In addition, other forms of CHD seen in associa-
tion with coarctation include anatomic abnor-
malities of the MV, anomalous pulmonary
venous connection, and interrupted IVC with
azygous continuation to right superior vena
cava.29
However, evaluation of the aortic arch
and isthmus can be challenging even in cases
with heightened suspicion.
Standard views used to assess the aortic arch
by fetal echocardiography include the long-axis
aortic arch view, which allows visualization of the
arch originating from the heart and coursing cau-
dally into the fetal abdomen (Fig. 5 and movie
clip S2). In addition, the aortic isthmus, defined
as the region of the aorta just distal to the left
subclavian artery and proximal to the insertion of
the ductus arteriosus, can be well seen in the
3-vessel tracheal view (Fig. 6). This 3-vessel view
is helpful in assessing the size of the isthmus,
especially in cases where coarctation of the aorta
is suspected.
Several studies have sought to determine fetal
echocardiographic characteristics that identify
(a)
(b)
Figure 5. Long-axis aortic arch view. A. Normal fetal aorta. B.
Aortic coarctation in 40 week gestation fetus, isthmus
measures 1.8 mm (fetal z-score = À6.7). Ao = Aorta; DAo =
descending aorta; AAo = ascending aorta; AN = innominate
artery; LCCA = left common carotid artery
432
Rogers, et al

6. aortic coarctation requiring neonatal surgery
after birth. A recent study evaluated the sensitiv-
ity of previous reported echocardiographic
predictors of coarctation in 39 fetuses: isthmus
z-score, the ratio of isthmus diameter to ductal
diameter, continuous diastolic flow at the isth-
mus, and presence of a coarctation shelf.30
The
z-score is a standard value indicating the number
of standard deviations a given measurement is
above or below the mean (mean values based on
fetal weight and gestational age normals). A z-
score of +1 represents 1 standard deviation
above the mean, while À1 is 1 standard deviation
below the mean. Normal z-scores fall between
À2 and +2, that is, within 2 standard deviations
of the mean. In this study, the presence of all 4
findings yielded a diagnostic accuracy of 86% in
the 30 fetuses who required surgery for coarcta-
tion after birth. The isthmus z-score of 2 (more
than 2 standard deviations below the mean) at
the final fetal scan was the most important pre-
dictor of the need for coarctation repair. It is
important to note that there was no statistically
significant difference between any 1 of the 4
parameters listed above between with 30
patients with coarctation and the 7 patients
incorrectly identified to have coarctation.
Matsui et al. previously evaluated 44 fetuses
referred with suspected coarctation, secondary
to ventricular, or great artery disproportion.31
They found that isthmus z-scores and the ratio of
isthmus diameter to ductal diameter were sensi-
tive in predicting the need for infant coarctation
repair. The overall specificity for the suspected
coarctation group was 77%. In addition, the
presence of both a posterior shelf (found in 45%
of true coarctation) and flow disturbance across
the isthmus (found in 65% of coarctation
patients) increased the specificity of diagnosis to
90% and 94%, respectively. Finally, serial mea-
surements of isthmus and isthmus:ductal ratio
helped decrease the number of false positive
diagnoses, as isthmus z-scores have been shown
to normalize in some patients as gestation pro-
gresses.
Another study, evaluating fetuses referred for
suspicion of coarctation, compared the diame-
ter of main pulmonary artery (MPA) to that of
the ascending aorta (AA) in the mediastinal 3-
vessel view.32
In this cohort, mediastinal MPA:
AA ratio of 1.6 had a sensitivity of 83% in dis-
tinguishing true coarctation from great vessel
discrepancy without coarctation. The specificity
was 85%.
These studies exemplify the difficulty in diag-
nosis of fetal coarctation. The above echocardio-
graphic predictors provide tools with good
sensitivity for predicting coarctation in the fetal
population referred for suspicion of arch narrow-
ing. Given the potential morbidity associated
with missed diagnosis of coarctation, a certain
false positive rate should be expected, taking into
consideration the associated morbidity and cost
burden that observation of infants in the inten-
sive care unit incurs, while awaiting ductal
closure.
Hypoplastic Left Heart Syndrome:
Hypoplastic left heart syndrome (HLHS) is 1 of
the most common forms of CHD diagnosed in
fetal life.33
HLHS is a critical form of left-sided
heart disease where the left heart structures are
incapable of supporting systemic circulation; this
makes the infant dependent on ductus arteriosus
flow after birth. Prenatal detection of HLHS can
provide a more stable transition at birth and has
been shown to improve preoperative stability
Figure 6. Three-vessel tracheal views. SP = spine; T =
trachea; SVC = superior vena cava; Ao = aorta; PA = pulmo-
nary artery.
Figure 7. Fetus with hypoplastic left heart syndrome (HLHS).
The left atrium (LA) and left ventricle (LV) are severely hypo-
plastic. The pulmonary veins appear dilated entering the left
atrium. RA = right atrium; RV = right ventricle.
433
Advances in Fetal Echocardiography

7. and postoperative outcomes after stage 1 pallia-
tion compared to those who are diagnosed after
birth34
(Fig. 7 and movie clip S3).
Once the prenatal diagnosis of HLHS is made,
there are several echocardiographic factors that
can be used to determine antenatal stability and
postnatal outcome. Survival after the first pallia-
tive surgery for HLHS, the Norwood operation,
was evaluated in 240 consecutive fetuses diag-
nosed at a single center with HLHS.35
The cohort
was divided into 2 main risk groups; overall
Norwood operative survival was 92.8% in the
“standard risk” group and 56.5% in the “high
risk” group. High risk was defined as any fetus
with 1 or more of the following: extracardiac,
genetic, or chromosomal anomalies; prematurity
<34 weeks gestation; additional cardiac findings
such as intact or highly restrictive atrial septum,
severe degree of tricuspid regurgitation, or severe
ventricular dysfunction. Therefore, presence or
absence of high-risk criteria can guide accurate
prognostication.
Stability in the immediate postnatal period in
most patients with HLHS is easily obtained with
initiation of prostaglandin therapy to maintain
patency of the ductus arteriosus. However, there
is a subset of patients with HLHS that may
develop left atrial hypertension shortly after birth
secondary to an intact or highly restrictive atrial
septum. With no left atrial egress, the increase in
pulmonary blood flow and pulmonary venous
return at birth results in significant left atrial
hypertension, pulmonary edema, and severe
hypoxemia. Predicting which patients will
develop clinically significant LA hypertension can
aid in delivery planning, allowing immediate
access to cardiac catheterization with balloon
dilation and/or stenting of the atrial septum to
relieve LA hypertension; a life saving measure in
these patients. In this setting, Doppler evaluation
of pulmonary venous flow reversal has proven to
be useful in predicting patients who will develop
clinically significant left atrial hypertension requir-
ing intervention36
(Fig. 8). A recent study com-
pared the velocity time integral (VTI) of
antegrade to retrograde flow in the pulmonary
veins in 39 fetuses with left heart obstruction and
suspected atrial septal restriction, yielding a for-
ward/reverse ratio. They found that a forward/
reverse VTI ratio of 5 was 100% sensitive and
94% specific for the need for emergent atrial sep-
tostomy.37
The authors recommended using a
cutoff value of 3 to eliminate false positive
diagnosis, given implication of change in delivery
plan and potential maternal morbidity associated
with a false positive diagnosis. However, patients
with forward/reverse VTI ratios of 5 should
raise suspicion and warrant close evaluation after
birth for potential clinically significant LA hyper-
tension.
In addition, reactivity of the pulmonary vascu-
lar bed to maternal oxygen administration may
aid in predicting which patients with HLHS will
need atrial septal intervention at birth. Pulsitility
index (PI), calculated from branch pulmonary
artery Doppler (PI = [peak systolic velocity À
end-diastolic velocity]/mean velocity), was used
as a measure of pulmonary impedance. Previous
studies have shown a decrease in PI in normal
fetuses with maternal oxygen administration in
the third trimester.38
A recent study evaluated
reactivity of the pulmonary vasculature in
patients with HLHS using maternal oxygen ther-
apy.39
They compared changes in pulmonary
artery PI with maternal oxygen administration in
HLHS fetuses with and without atrial septum
restriction. They found that fetuses with HLHS
and a restrictive atrial septum, requiring immedi-
ate intervention at birth, had no significant
change in PI with maternal oxygen administra-
tion. A cutoff value of 10% change in PI with oxy-
gen administration yielded 100% sensitivity and
94% specificity for the need for immediate post-
natal intervention. This provides another tool for
predicting antenatal stability in patients with
HLHS.
Transposition of the Great Arteries:
The stability of patients with transposition of the
great arteries and intact ventricular septum
(TGA/IVS) after birth is dependent on mixing of
the systemic and pulmonary circulations, allow-
ing oxygenated blood to circulate to the vital
organs. The primary and most effective site of
mixing is at the atrial level via foramen ovale or
atrial septal defect (ASD). In addition, a patent
ductus arteriosus (DA) can provide additional
Figure 8. Pulmonary Vein (PV) Doppler in HLHS (patient
seen in Fig. 7). There is a small amount of flow reversal in
atrial systole. This is a typical PV Doppler for patients with
HLHS and unrestrictive atrial septum.
434
Rogers, et al

8. sources of mixing, increasing pulmonary blood
flow, adding preload to the LA, and promoting
atrial mixing (Fig. 9).
Predicting the degree of postnatal cyanosis in
TGA is focused on prenatal evaluation of the
foramen ovale and ductus arteriosus as sites
for potential mixing. Restriction of the ductus
arteriosus in utero is associated with extremely
poor neonatal outcome in these patients.40
Evaluation of the foramen ovale (specifically
hypermobility of septum primum) and direction
of flow in the DA was undertaken in 26 fetuses
with TGA/IVS, with 14 newborns needing urgent
BAS secondary to significant cyanosis.41
There
were 5 patients with both diastolic flow reversal
in the ductus arterious and hypermobility of sep-
tum primum (flopping into both atria), all
needed urgent BAS. In addition, only 1 patient
with diastolic flow reversal in the DA did not
need BAS. However, the sensitivity and negative
predictive value of these parameters were low as
there were 5 patients with normal septal mobility
and 6 patients with normal ductal flow patterns
that also required urgent BAS after birth.
Such studies provide some general fetal pre-
dictors of patients with TGA/IVS who may need
immediate postnatal intervention. However, over
one-third of patients who needed an urgent bal-
loon atrial septostomy did not have either predic-
tor. Therefore, it is still prudent to anticipate the
need for BAS in all patients with TGA, regardless
of fetal appearance of the atrial septum and DA.
Given the lack of predictability and the efficacy of
early intervention through balloon atrial septos-
tomy, all fetuses with TGA should be delivered at
a site where immediate neonatal evaluation can
take place and early access to potential cardiac
intervention is possible.
Right Ventricular Outflow Obstruction:
Right ventricular outflow tract obstruction
(RVOTO) occurs in many varieties. In patients
with an intact ventricular septum (IVS), RVOTO
can occur with isolated valvar pulmonary stenosis
(PS), pulmonary atresia with varying degrees of
RV hypoplasia, and Ebstein’s anomaly. Conotrun-
cal anomalies associated with RVOTO typically
occur with a VSD and include TOF, TGA, and
Double outlet right ventricle (DORV). RVOTO in
the setting of IVS has a more predictable postna-
tal course with degree of RVOTO being deter-
mined by the size of the pulmonary valve,
gradient across the RVOT by Doppler, and direc-
tion of shunting at the ductus arteriosus. How-
ever, the second group of anomalies, specifically
TOF and DORV occurring with a large VSD, pres-
ent a greater prognostic challenge in determin-
ing the degree of cyanosis that may be present at
birth.
In the setting of a large VSD, the velocity across
the pulmonary outflow is not reflective of the
degree of pulmonary stenosis and the need for
supplemental pulmonary blood flow after birth.42
Predicting the degree of cyanosis and the
dependence of adequate pulmonary blood flow
on the ductus arteriosus after birth are the pri-
mary focus points for predicting postnatal stabil-
ity of this patient population. Reversal of flow in
the ductus arteriosus in fetal life has been
reported in the setting of severe right ventricular
outflow tract obstruction and/or pulmonary atre-
sia and can be a poor prognostic marker for post-
natal outcome.43,44
In addition, main pulmonary
artery size to aortic size ratio was found to be
smaller in patients with severe TOF (ductal
dependent after birth) compared to mild TOF on
initial fetal echocardiogram: 0.5 Æ 0.15 cm ver-
sus 0.73 Æ 0.14 cm.45
Another study in patients with right ventricu-
lar outflow tract obstruction (RVOTO) and large
VSD (TOF) found the strongest predictor for the
need for neonatal intervention to be flow rever-
sal in the ductus arteriosus.46
In addition, these
investigators reported that PV:AV ratio of <0.6
and a PV z-score of <À3 was 92% sensitive, but
only 46% specific for the need for neonatal
intervention (Fig. 10 and movie clip S4). This
study noted pulmonary valve growth rate
throughout gestation of 0.6 mm/month for
those who required neonatal intervention and
0.9 mm/month for those who did not. The
authors also analyzed 13 patients with single-
ventricle heart disease and RVOTO, 46% of who
required neonatal intervention; however, the
above parameters noted for predicting the need
for neonatal intervention did not reach statistical
significance in this smaller single-ventricle
cohort.
Figure 9. Transposition of the great arteries. The pulmonary
artery (PA) can be seen arising from the left ventricle (LV) and
the aorta (Ao) can be seen arising from the right ventricle
(RV).
435
Advances in Fetal Echocardiography

9. Currently, assessment of pulmonary outflow
tract obstruction in the setting of a VSD is
focused on determining, with high sensitivity,
the need for neonatal intervention to augment
pulmonary blood flow. Given the reported data,
it appears that the direction of flow in the ductus
arteriosus is the most sensitive indicator for the
need for neonatal intervention. In addition, serial
measurements of the pulmonary outflow and its
ratio to the aortic outflow can provide additional
data in determining the likelihood of ductal-
dependent pulmonary blood flow after birth.
These key pieces of information can be used in
prenatal family counseling, decision making
about location of delivery, and planning for sta-
bilization in the immediate postnatal period.
Future Directions in Fetal Cardiology: Fetal
Cardiac Intervention:
As we continue to gain knowledge about the nat-
ural progression of CHD in utero, the potential to
alter disease progression, with the goal of
decreasing the severity of disease and/or optimiz-
ing stable transition to postnatal circulation, pre-
sents itself. Alteration of the fetal heart was
reported as early at 1975 with maternal adminis-
tration of propranolol to control fetal ventricular
tachycardia.47
Since that time maternal adminis-
tration of medication has become a mainstay of
treatment of fetal arrhythmias, altering the
course of this disease process. However, attempts
at more invasive alterations of the fetal heart are
still in their early stages.
Currently, percutaneous fetal cardiac inter-
vention remains experimental, occurring at only
the most highly specialized centers and reserved
for those fetuses with the most severe diseases.
To date, the most common percutaneous fetal
interventions have been: balloon aortic valvulopl-
asty in patients with critical aortic stenosis and
evolving HLHS; atrial septal intervention in HLHS
with highly restrictive or intact atrial septum; and
pulmonary valvuloplasty in the setting of pulmo-
nary atresia and hypoplastic right ventricle.48
A
comprehensive discussion of the indications and
results of fetal cardiac interventions is beyond the
scope of this review and the authors refer inter-
ested readers to the references herein.49–54
Conclusions:
There is an increasing utility for early fetal cardio-
vascular imaging, with early diagnosis of CHD
facilitating comprehensive fetal evaluation. In
some cases, early diagnosis may allow opportuni-
ties for early sustained management and possibly
even for fetal intervention, but more often allows
families more timely information and physicians
the opportunity to plan for a safe transition at
birth. 3D/4D imaging has proven to be an accu-
rate way to diagnose CHD at experienced cen-
ters, opening potential avenues for the use of
telemedicine and has slightly improved diagnos-
tic accuracy in some cases of CHD. The contribu-
tion of 3D/4D imaging will likely continue to
grow as technology in the field improves. Ulti-
mately, our ability to predict postnatal stability of
patients with significant CHD is improving as
studies are undertaken to identify fetal echocar-
diographic predictors of perinatal outcome. The
future of fetal cardiovascular imaging research
will likely focus on continued identification of
fetal imaging risk factors of postnatal outcome
and the role of evolving ultrasound technology in
facilitating early diagnosis, assessment, progno-
sis, and guidance of fetal intervention to improve
outcome of CHD.
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Supporting Information
Additional Supporting Information may be found
in the online version of this article:
Movie clip S1 for Figure 1B.
Movie clip S2 for Figure 5B.
Movie clip S3 for Figure 7.
Movie clip S4 for Figure 10A.
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