4/27/2021 Congenital heart disease: Prenatal screening, diagnosis, and management - UpToDate

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Congenital heart disease: Prenatal screening, diagnosis,

and management
Author: Joshua Copel, MD
Section Editors: Louise Wilkins-Haug, MD, PhD, Deborah Levine, MD
Deputy Editor: Vanessa A Barss, MD, FACOG

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Mar 2021. | This topic last updated: Jan 28, 2021.

INTRODUCTION

Prenatal identification and management of fetal cardiac abnormalities are important because
congenital anomalies are a leading cause of infant death, and congenital heart disease (CHD) is
the leading cause of infant death due to congenital anomalies. In the United States, CHD is
diagnosed in approximately 1 percent of births, accounts for 4 percent of neonatal deaths, and
accounts for 30 to 50 percent of deaths related to congenital anomalies [1,2].

Generally, the full spectrum of cardiac lesions diagnosed in a postnatal population can be
detected in the fetus, with the exception of some minor lesions, such as secundum atrial septal
defects, which are less likely to be diagnosed in the prenatal period, and patent ductus
arteriosus, which is a normal fetal shunt.

In addition to adverse cardiac outcome, CHD is also associated with an increased risk for
adverse neurodevelopmental outcome, which has been attributed to factors such as associated
chromosomal abnormalities, syndromes, postnatal cardiac dysfunction, perioperative factors in
infants who require surgical treatment, and possibly in utero hemodynamic abnormalities. In
children with isolated cardiac abnormalities, the frequency of neurodevelopment also depends
on the specific abnormality. (See "Management and outcome of tetralogy of Fallot", section on
'Neurodevelopmental outcome and quality of life' and "Management and outcome of D-
transposition of the great arteries", section on 'Neurodevelopmental outcome' and "Hypoplastic
left heart syndrome: Management and outcome", section on 'Neurodevelopmental outcome'

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and "Management of complications in patients with Fontan circulation", section on 'Psychiatric

disorders'.)

This topic will present an overview of prenatal screening and diagnosis of CHD and
management of affected pregnancies. Newborn screening and evaluation are reviewed
separately. (See "Newborn screening for critical congenital heart disease using pulse oximetry"
and "Identifying newborns with critical congenital heart disease".)

BENEFITS AND RISKS OF PRENATAL SCREENING AND DIAGNOSIS OF CHD

Benefits

● Parental counseling and preparation – Prenatal diagnosis of CHD provides parents an

opportunity to:

• Obtain prognostic information prior to birth.

• Learn about treatment options for their child before and after birth.

• Make decisions concerning the management approach that is best for their family (eg,
whether to terminate pregnancy or undergo in utero intervention, if available;
nonintervention).

• Plan for specific needs at birth (eg, place, timing and route of delivery, pediatric and
obstetric providers, palliative care).

● Improvement in neonatal survival – Prenatal diagnosis of CHD may improve newborn

survival and other outcomes [3-6], but data are limited despite substantial experience in
the identification of fetal cardiac anomalies. In a meta-analysis of eight observational
studies on the effect of prenatal diagnosis of critical CHD on neonatal mortality, prenatal
diagnosis reduced mortality prior to planned cardiac surgery compared with postnatal
diagnosis (pooled odds ratio 0.26, 95% CI 0.08-0.84, 1 death/207 prenatal diagnoses versus
31 deaths/821 postnatal diagnoses) [3]. The analysis was limited to patients with
comparable anatomy, standard risk, a parental desire to treat, and optimal care. The small
number of deaths precludes a clear conclusion about the benefit of prenatal diagnosis, and
the observed survival benefit may not apply to newborns who have a prenatal diagnosis of
noncritical congenital heart defects or who receive nonoptimal care.

● Improvement in neonatal morbidity – Prenatal diagnosis of CHD has also been

associated with a reduction in neonatal morbidity, including severe acidosis [7]. Infants with

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congenital heart defects that require patency of the ductus arteriosus for systemic or
pulmonary blood flow can benefit by early postnatal intervention (prostaglandin E1) to
prevent closure of the ductus [8,9]. Similarly, readiness to perform transcatheter
intervention (eg, balloon atrial septostomy for patients with d-transposition of the great
arteries [TGA] or hypoplastic left heart syndrome [HLHS], balloon valvuloplasty for patients
with critical pulmonic or aortic stenosis) or pacing of complete heart block soon after birth
enables rapid stabilization of the postnatal circulation and thus may improve outcome
[8,10-13].

● Possible opportunity for fetal treatment – In some cases, prenatal diagnosis also
provides an opportunity for in utero interventions. Transplacental medical therapy
improves the prognosis of some fetal arrhythmias, particularly tachycardias (see "Fetal
arrhythmias"). Invasive in utero cardiac intervention (eg, aortic or pulmonary balloon
valvuloplasty [14], atrial needle septoplasty [15]) may improve the prognosis of some
lesions, such as HLHS or severe valvular abnormalities (eg, severe aortic stenosis,
pulmonary atresia); however, these interventions are performed at only a few fetal surgery
centers and are considered investigational [16,17].

Harms — The main potential harm of screening for CHD prenatally is parental anxiety in the
time between the screening and diagnostic examinations. False-negative screens engender the
risk of a newborn with critical cardiac disease being born at a facility unprepared to provide
proper intervention, or the neonate becoming unstable even at experienced centers before the
cause of the problem is identified as cardiac in origin. Less commonly, a false-positive diagnosis
could lead to unnecessary intervention, particularly if invasive diagnostic or therapeutic
interventions are performed.

THE 18 TO 22 WEEK SCREENING EXAMINATION

The optimum gestational age for screening for structural fetal cardiac anomalies is 18 to 22
weeks of gestation [18]. Fetal cardiac anatomy can be visualized well at this stage of pregnancy,
a complete fetal anatomic survey can be performed, and there is time for further evaluation
(eg, echocardiogram, chromosomal microarray), if indicated, while the fetus is still previable.

It should be noted that some fetal cardiac conditions may not be detected until, or may first
present after, 18 to 22 weeks of gestation. For example, fetal arrhythmias,
myocarditis/cardiomyopathy, heart failure, valvular insufficiency or obstruction, and cardiac
tumors have variable onset. In addition, small ventricular or atrial septal defects, minor valve

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lesions, partial anomalous pulmonary venous connection, and coronary artery anomalies are
often not detected prenatally.

Screening at other gestational ages — The structure of the fetal heart can be reasonably
assessed as early as 10 weeks of gestation, and consensus guidelines for first-trimester
anatomy evaluation, including cardiac screening, are available [19]. In a systematic review of
studies of the accuracy of first-trimester ultrasound examination for detecting major CHD using
transabdominal or transvaginal ultrasound transducers or a combination of both methods (10
studies, n = 1243 patients), pooled sensitivity and specificity were 85 (95% CI 78-90) and 99
percent (95% CI 98-100), respectively [20]. However, most of the studies were in populations
with fetuses at increased risk for CHD; performance is likely to be lower in the general obstetric
population.

Although the heart is larger after 30 weeks of gestation, optimum cardiac views may be difficult
to obtain due to fetal position and less space for free fetal movement in the amniotic cavity.

STANDARD CARDIAC EVALUATION

Four chambers and ventricular outflow tracts — A standard obstetric ultrasound

examination includes assessment of the four chambers and ventricular outflow tracts of the
fetal heart. The inclusion of views of the outflow tracts increases the likelihood of identifying
conotruncal anomalies such as tetralogy of Fallot, transposition of the great arteries, double
outlet right ventricle, and truncus arteriosus. This examination is consistent with practice
guidelines for sonographic screening of the fetal heart available from the International Society
for Ultrasound in Obstetrics and Gynecology [21] and from a collaboration of the American
Institute of Ultrasound in Medicine, American College of Radiology, American College of
Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine, and Society of
Radiologists in Ultrasound [22].

Formal evaluation of rhythm and cardiac function and detailed examination of cardiopulmonary
anatomy are not part of a standard fetal cardiac evaluation.

A meta-analysis evaluating the performance of different fetal sonographic protocols for

diagnosis of fetal structural heart disease found that inclusion of the outflow tract in the
standard examination increased detection rates of structural cardiac disease substantially:
sensitivity 65 to 90 percent (four chambers with outlet tract or outlet tract and three vessels
with trachea views) versus 52 percent with the four-chamber view alone [23]. However, there
were wide variations in detection rates among screening studies, with some studies reporting

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only 15 percent detection of CHD. Factors affecting sensitivity include type of ultrasound
practice (eg, university versus community hospital), operator training and experience,
gestational age, maternal weight, fetal position, and type of defect [24-26]. Fetal
echocardiography is a more sensitive, but less cost-effective, screening approach for
pregnancies at low risk of CHD [27].

Procedure — Fetal cardiac imaging should always be performed with the highest possible
transducer frequency to maximize image resolution, and at the highest possible frame rate
(preferably >50 Hz), due to the rapid movement of the heart, which normally beats at 110 to 160
beats per minute. The standard four-chamber view can be obtained in 95 to 98 percent of
second-trimester pregnancies [28,29]. It is obtained either from the long axis or apical view (
image 1). Usually it is easiest to start with a standard abdominal circumference plane of the
fetal abdomen and angle the transducer cephalad on the fetus. The four chambers of the fetal
heart are seen with the left atrium most posterior and the right ventricle most anterior. The
right and left atria and ventricles should be approximately symmetric in size. The heart should
occupy approximately one-third of the chest area.

In addition to the four-chamber view, sweeps through the outflow tracts ( image 2 and
image 3) should be obtained.

The mean axis of the fetal heart is approximately 45 degrees to the left of the midline (normal
range 30 to 60 degrees). An increase in the axis can be a marker for outflow tract abnormalities
[30,31]. The evaluation of cardiac axis has also been applied to screening in the first trimester
[32].

ADVANCED FETAL CARDIAC EVALUATION

Indications for echocardiography — Fetal echocardiography provides more detailed

evaluation of fetal cardiovascular structure and function than a basic ultrasound examination. It
is performed in fetuses at a higher risk of CHD than would be expected for the general
population.

The American Heart Association, American Society of Echocardiography, and Pediatric and
Congenital Electrophysiology Society define increased risk of CHD as >1 percent since the
baseline risk of CHD in the general population is ≤1 percent [18].

Indications with a high-risk profile (estimated >2 percent absolute risk) include:

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● Maternal pregestational (preexisting) diabetes mellitus or diabetes mellitus diagnosed in

the first trimester. (See "Pregestational (preexisting) diabetes: Preconception counseling,
evaluation, and management".)

● Maternal phenylketonuria (uncontrolled). (See "Overview of phenylketonuria", section on

'Phenylalanine embryopathy (maternal PKU)'.)

● Maternal autoantibodies (SSA/SSB), especially if a previous child had SSA/SSB-related heart

disease. (See "Congenital third degree (complete) atrioventricular block".)

● Maternal use of potential cardiac teratogens (eg, thalidomide, angiotensin-converting

enzyme inhibitors, retinoic acid, nonsteroidal anti-inflammatory drugs [NSAIDs] in the third
trimester).

● Maternal first-trimester rubella infection. (See "Rubella in pregnancy".)

● Suspicion of fetal myocarditis because of poor contractility or effusions on standard four-

chamber cardiac examination. Fetal myocarditis may be related to maternal viral infections,
such as coxsackie virus, adenovirus, parvovirus B19, and cytomegalovirus.

● Pregnancy conceived by assisted reproduction technology (ART). (See "Pregnancy outcome

after assisted reproductive technology", section on 'Congenital anomalies'.)

● CHD in first-degree relative of fetus (maternal, paternal, or sibling). (See "Pregnancy in

women with congenital heart disease: General principles", section on 'Fetal evaluation'.)

● First- or second-degree relative of the fetus with a disorder with Mendelian inheritance-
associated CHD (eg, Noonan syndrome, tuberous sclerosis, Holt-Oram syndrome,
velocardiofacial [DiGeorge] syndrome/22q11.2 deletion, Alagille syndrome, Williams
syndrome). (See "Microdeletion syndromes (chromosomes 12 to 22)".)

● Fetal cardiac abnormality (structural, functional, arrhythmia) suspected on a standard

obstetric ultrasound examination.

● Fetal noncardiac abnormality suspected on a standard obstetric ultrasound examination.

● Fetal genetic testing reveals a pathogenic variant, deletion, rearrangement, or aneuploidy (

table 1).

● Fetal tachycardia or bradycardia, or frequent or persistent irregular heart rhythm. (See

"Fetal arrhythmias".)

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● Fetal increased nuchal translucency >95th percentile (≥3 mm) on first-trimester sonogram (
table 2). (See "Increased nuchal translucency and cystic hygroma", section on 'Congenital
heart disease'.)

● Monochorionic twins. (See "Twin pregnancy: Routine prenatal care", section on 'Screening
for congenital anomalies'.)

● Fetal hydrops or pericardial effusions. (See "Nonimmune hydrops fetalis", section on

'Cardiovascular abnormalities'.)

Indications with a less high-risk profile (estimated >1 and <2 percent absolute risk) include:

● Maternal medications (antiseizure, lithium, vitamin A above recommended daily intake,

paroxetine, NSAIDs in first/second trimester).

● CHD in a second-degree relative of the fetus.

● Fetal intraabdominal venous anomaly (eg, agenesis of the ductus venosus).

Fetal echocardiography is not indicated when the risk of cardiac abnormality is no higher than
the baseline population risk (≤1 percent), such as a more distant relative with CHD or a close
relative with acquired heart disease (eg, mitral valve prolapse).

Procedures for advanced fetal cardiac assessment — A scientific statement from the
American Heart Association stated that a fetal echocardiogram should include standard views
of the four chambers, the left and right ventricular outflow tracts, three vessels and trachea (
image 4), aortic and ductal arch, superior and inferior venae cavae, and short- and long-axis,
as well as color and pulsed Doppler studies and M-mode to evaluate major veins, valves, rate,
rhythm, etc [18]. Guidelines for the performance of fetal echocardiograms are also available
from the International Society for Ultrasound in Obstetrics and Gynecology [33] and from the
American Institute of Ultrasound in Medicine [34].

Ultrasound systems used for fetal echocardiography should be capable of performing two-
dimensional, M-mode, and Doppler imaging [35]. Color and spectral Doppler are used to
identify small vessels such as the pulmonary veins, ductus venosus, and ductus arteriosus, to
assess valvular competence and flow patterns, and to examine the ventricular septum for
defects. M-mode of atrial and ventricular wall motion can be useful for analyzing rate and
rhythm disturbances.

More advanced imaging techniques, which are beyond the scope of this review, include three-
dimensional and four-dimensional echocardiography, tissue Doppler, strain and strain rate

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imaging, fetal electrocardiography, fetal magnetocardiography, and cardiovascular magnetic

resonance imaging [18,36].

Diagnosis of specific cardiac abnormalities — The sonographic appearance of specific

anomalies is beyond the scope of this topic, but can be found in UpToDate topics on specific
anomalies.

POSTDIAGNOSTIC EVALUATION

When a fetal cardiac abnormality is diagnosed, additional evaluation and follow-up are
indicated. Patients who have a normal standard fetal cardiac evaluation and echocardiography
(if performed) generally do not require further evaluation unless there is an increased risk of
development of fetal heart disease later in pregnancy.

Assessment for extracardiac anomalies — The identification of a fetal cardiac defect should
prompt a thorough search for extracardiac abnormalities, since these are detected in at least 20
to 40 percent of cases, depending on the population (eg, midtrimester fetuses versus live borns
versus stillborns) [37-39]. Furthermore, cardiac anomalies are part of numerous fetal
syndromes [40,41]. An analysis of data compiled from 20 registries of congenital malformations
reported that approximately 4 percent of the patients with cardiac anomalies had an
identifiable syndrome [41].

Although postnatal neurodevelopment may be affected by CHD, fetal brain magnetic resonance
imaging (MRI) is not indicated unless a central nervous system abnormality has been identified
on ultrasound and MRI findings will affect pregnancy management. Neuroimaging findings are
generally not predictive of postnatal neurodevelopmental outcome. A meta-analysis of studies
of prenatal ultrasound and MRI found that brain abnormalities, delay in head growth, and
brain-sparing were observed in subgroups of fetuses with CHD [42]. However, the prognostic
significance of these findings was unclear because large MRI studies were scarce, ultrasound
data were biased toward severe and left-sided heart abnormalities, and long-term follow-up
studies correlating prenatal and postnatal findings were limited [43].

Referral to specialists — Given the complexity of fetal CHD, referral to a multidisciplinary

team, including maternal-fetal medicine specialists, pediatric cardiologists, geneticists, and/or
neonatologists, is recommended.

The purpose is to inform the patient about the suspected diagnosis and prognosis and discuss
management options before and after delivery, including the preferred site for delivery.

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Genetic assessment — Fetal genetic assessment is indicated because genetic abnormalities

are common in fetuses with cardiac defects, even when isolated ( table 3) [26,39,44-47]. In
one series of 1510 fetuses with prenatally diagnosed CHD, 624 (41 percent) had an abnormal
karyotype (aneuploidy in 562 cases, structural chromosomal abnormalities in 62 cases) [48].
Prenatal incidence of genetic abnormalities is higher than postnatal incidence, which was
approximately 15 percent in one study [49], because in utero mortality occurs in many cases,
such as the lethal autosomal trisomies (eg, trisomy 9 or 16).

The frequency of fetal aneuploidy varies depending on the malformation. For example [18]:

● Atrioventricular septal defect (46 to 73 percent)

● Truncus arteriosus (19 to 78 percent)
● Double-outlet right ventricle/conotruncal malformations (6 to 43 percent)
● Coarctation/arch interruption (5 to 37 percent)
● Tricuspid valve dysplasia (including Ebstein malformation, 4 to 16 percent)
● Tetralogy of Fallot (7 to 39 percent)
● Hypoplastic left heart syndrome (HLHS; 4 to 9 percent)
● Pulmonic stenosis/atresia with intact ventricular septum (1 to 12 percent)
● Heterotaxy/cardiosplenic syndromes (0 percent)
● Transposition of great arteries (0 percent)

In addition, the 22q11 deletion has been associated with several cardiac anomalies, including
interrupted aortic arch, truncus arteriosus, ventricular septal defect, and tetralogy of Fallot [18].
(See "DiGeorge (22q11.2 deletion) syndrome: Clinical features and diagnosis".)

The two main approaches for genetic testing are (1) G-banding of fetal cells obtained via
amniocentesis, with fluorescent in situ hybridization (FISH) to assess for microdeletions, such as
22q11, not detectable by visual banding techniques, and (2) chromosomal microarray, which
detects submicroscopic chromosomal abnormalities in 5 percent of fetuses with ultrasound-
detected anomalies and a normal G-band karyotype. Many fetuses with CHD will have
microarray abnormalities, especially if noncardiac anomalies are also present [50,51].
Disadvantages of chromosomal microarray are that balanced rearrangements are not
detectable and variants of unknown significance may be identified. Either approach is
reasonable; the best choice is controversial and depends on factors such as physician/patient
preference, cost, suspicion of trisomy or balanced rearrangement versus a microscopic gene
defect, and time to obtain definitive results. (See "Prenatal diagnosis of chromosomal
imbalance: Chromosomal microarray".)

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If these genetic tests are normal and there is a family history of a similar cardiac defect, long QT
syndrome, or Noonan syndrome, DNA mutation analysis and direct sequence analysis are
options (see "Congenital long QT syndrome: Diagnosis" and "Causes of short stature", section
on 'Noonan syndrome'). The role of exome sequencing is promising but remains unclear [52-
54].

Ultrasound follow-up — The necessity, timing, and frequency of serial assessment should be
guided by the nature and severity of the lesion, presence of heart failure, anticipated timing
and mechanism of progression, and the options available for prenatal and postpartum
intervention [18]. At least one follow-up examination early in the third trimester is reasonable to
look for abnormalities that progressed in severity or may not have been detectable earlier in
gestation, and have peripartum clinical implications. Some causes of progressive fetal cardiac
dysfunction include worsening valvular insufficiency or obstruction, increasing obstruction to
blood flow in the great arteries, or development/worsening of myocarditis or cardiomyopathy,
arrhythmias, or cardiac tumors [18].

The early to mid-third trimester is also an appropriate time to screen for growth restriction,
which may be more prevalent in these fetuses or specific subtypes of CHD [55-58].

Evaluation of fetal well-being — Fetuses with cardiac structural anomalies, functional

disorders, or arrhythmias that have the potential to compromise tissue oxygen delivery are
generally followed with antepartum testing, with intervention if results are abnormal. In one
retrospective cohort study, fetuses with a genetic syndrome, extracardiac anomaly, or severe
valvular regurgitation were at increased risk for fetal demise: 15/197 (7.6 percent) fetuses with
one or more of these risk factors died in utero versus 3/270 (1 percent) of fetuses without any
of these risk factors [59]. Six of the 22 fetal deaths occurred at 20 to 23 weeks and 16 occurred
at 26 to 41 weeks (including three deaths at 37, 39, and 41 weeks).

However, there is no strong evidence of the value of this practice and antepartum fetal testing
with the nonstress test, biophysical profile, or fetal movement count has not been evaluated
specifically in this clinical setting. The type of test depends on the underlying abnormality; for
example, the biophysical profile is particularly useful in fetuses with arrhythmias and provides
an opportunity to monitor for development or progression of hydrops in any fetus with severely
altered hemodynamics. (See "Overview of antepartum fetal surveillance".)

Fetal therapy — Transplacental medical therapy can improve the prognosis of some fetal
arrhythmias. (See "Fetal arrhythmias".)

Invasive in utero cardiac intervention (eg, aortic or pulmonary balloon valvuloplasty [14], atrial
needle septoplasty [15]) may improve the prognosis of some lesions, such as HLHS or severe
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valvular abnormalities (eg, severe mitral regurgitation, aortic stenosis, pulmonary atresia);
however, these interventions are performed at only a few fetal surgery centers and are
considered investigational [16].

DELIVERY PLANNING

Delivery should be planned at a facility with the appropriate level of care for the mother and
neonate. Neonates with ductal-dependent lesions and most with critical cardiac lesions (
table 4) should be delivered at a facility with a level III neonatal intensive care unit (NICU)
and pediatric cardiology expertise. If this is not feasible, transport arrangements should be
established in advance of the delivery.

Timing and route — Cesarean birth is performed for standard obstetric indications, as there is
no evidence that route of delivery of fetuses with CHD affects outcome [60]. Based on
observational data, induction of labor or scheduled cesarean before 39 weeks of gestation is
not recommended in the absence of standard maternal or fetal concerns about well-being, as
even early term delivery has been associated with worse outcomes after neonatal cardiac
surgery [18,61-63]. One exception may be single ventricle defects, where earlier delivery may be
beneficial [64-66]. (See "Hypoplastic left heart syndrome: Anatomy, clinical features, and
diagnosis".)

Delivery room care — Risk assessment for anticipated compromise in the delivery room or
during the first few days of life is specific to the abnormality. Initial management of newborns
with CHD at risk of postnatal hemodynamic instability or respiratory compromise during the
fetal-neonatal transition is reviewed separately. (See "Diagnosis and initial management of
cyanotic heart disease in the newborn", section on 'Initial management'.)

A committee from the American Heart Association made the following recommendations [18]:

Specialized delivery room care is recommended for fetuses with:

● d-transposition of the great arteries.

● Sustained or uncontrolled tachyarrhythmias with heart failure or hydrops fetalis.

Specialized delivery room care planning is reasonable for fetuses with:

● Hypoplastic left heart syndrome with restrictive or intact atrial septum and abnormal
pulmonary vein flow (pulmonary vein forward/reversed flow ratio <3) or abnormal
hyperoxia test in the third trimester.

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● Complete heart block and low ventricular rate, cardiac dysfunction, or hydrops fetalis.

Specialized delivery room care planning may be considered in fetuses with:

● Tetralogy of Fallot with absent pulmonary valve.

● Ebstein anomaly with hydrops fetalis.

● Total anomalous pulmonary venous return, obstructed.

Specialized delivery room care is not needed for fetuses with:

● Mild tetralogy of Fallot, ventricular septal defect, atrioventricular septal defect.

● Shunt lesions.

● Most ductal-dependent lesions, but initiation of prostaglandin E1 may be indicated in the

NICU.

● Controlled arrhythmias.

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Prenatal screening and
diagnosis" and "Society guideline links: Congenital heart disease in infants and children".)

SUMMARY AND RECOMMENDATIONS

● We suggest prenatal screening for fetal cardiac abnormalities (Grade 2C). Prenatal
diagnosis provides parents an opportunity to obtain prognostic information prior to birth,
learn about treatment options before and after delivery, reach decisions concerning the
management approach that is best for their family, and plan for specific needs at birth.
Depending on the lesion, prenatal diagnosis may reduce perinatal morbidity and mortality.
(See 'Benefits and risks of prenatal screening and diagnosis of CHD' above.)

● The optimum gestational age for screening for structural fetal cardiac anomalies is 18 to 22
weeks of gestation. However, some fetal cardiac conditions may not be detected until, or
may first present, later in gestation. Fetal arrhythmias, myocarditis/cardiomyopathy, heart
failure, valvular insufficiency or obstruction, and cardiac tumors have variable timing of

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onset. Small ventricular or atrial septal defects, minor valve lesions, partial anomalous
pulmonary venous connection, and coronary artery anomalies are often not detected
prenatally. (See 'The 18 to 22 week screening examination' above.)

● A basic fetal cardiac assessment should include a four-chamber view and the outflow tracts
and be a part of every second-trimester fetal evaluation, regardless of risk factors.
Sonologists and sonographers performing these assessments should have a low threshold
for referral to fetal echocardiography to maintain a high detection rate for cardiac
anomalies. (See 'Standard cardiac evaluation' above.)

● Fetal echocardiography should be performed in fetuses at a higher risk of congenital heart

disease (CHD) than would be expected for the general population (see 'Advanced fetal
cardiac evaluation' above). We agree with the American Institute of Ultrasound in Medicine,
International Society for Ultrasound in Obstetrics and Gynecology, American Heart
Association (AHA), American Society of Echocardiography, and Pediatric and Congenital
Electrophysiology Society guidance describing fetal, maternal, and familial factors
conferring an increased risk of fetal cardiac disease. (See 'Indications for echocardiography'
above.)

● In fetuses undergoing echocardiography, a detailed fetal anatomic survey should also be

performed. Extracardiac abnormalities are detected in at least 20 to 40 percent of fetuses
with a cardiac defect. Approximately 4 percent of patients with cardiac anomalies have an
identifiable syndrome. (See 'Assessment for extracardiac anomalies' above.)

● There is an increased risk of genetic abnormalities, particularly aneuploidy or 22q11

deletion, in fetuses with CHD; the frequency of genetic abnormality depends on the specific
lesion. Current approaches for genetic testing include (1) G-banding of fetal cells obtained
via amniocentesis, with fluorescent in situ hybridization (FISH) to assess for microdeletions,
such as 22q11, not detectable by visual banding techniques, and (2) chromosomal
microarray, which detects submicroscopic chromosomal abnormalities in 5 percent of
fetuses with ultrasound-detected anomalies and a normal G-band karyotype. Either
approach is reasonable. (See 'Genetic assessment' above.)

● The necessity, timing, and frequency of follow-up ultrasound assessment should be guided
by the nature and severity of the lesion, presence of heart failure, anticipated timing and
mechanism of progression, and the options available for prenatal and postpartum
intervention. We suggest at least one follow-up examination early in the third trimester to
look for abnormalities that progressed in severity or may not have been detectable earlier
in gestation. For most lesions other than small muscular ventricular septal defects, we

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typically perform serial examinations at least monthly to assess for disease progression
and further patient counseling. (See 'Ultrasound follow-up' above.)

● Delivery should be planned at a facility with the appropriate level of care for the mother
and neonate. Early delivery and cesarean delivery are generally performed only for
standard obstetric indications. (See 'Timing and route' above.)

● Risk assessment for anticipated compromise in the delivery room or during the first few
days of life is specific to the disease. We agree with AHA guidance for delivery room
preparation and neonatal care. (See 'Delivery room care' above.)

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GRAPHICS

Four-chamber view fetal heart

Axial view of the fetal chest in the second trimester. The four-chamber view of the
heart is demonstrated. The hyperechoic spine and ribs are shown. Anteriorly, the
ventricles are seen and are of similar sizes. The atria are posterior and are similarly of
comparable sizes. The atrioventricular valves are both demonstrated, with the right
atrioventricular valve slightly more apically positioned.

Courtesy of Joshua Copel, MD.

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Fetal right ventricular outflow tract

RV: right ventricle; MPA: main pulmonary artery; RT PA: right pulmonary artery; DV: ductus venosus.

Courtesy of Joshua Copel, MD.

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Fetal left ventricular outflow tract

RV: right ventricle; LV: left ventricle; Ascend AO: ascending aorta.

Courtesy of Joshua Copel, MD.

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Data expressed as overall rate of aneuploidy (percent) for individual congenital cardiac defects

Cardiac Overall aneuploid T 21 T 18 T 13 45X0 Other 22q11

anomaly rate percent percent percent percent percent percent deletion

AVSD 46 79 13 8

VSD 46 43 45 2 4 6 10 to 17

TOF 31 43 29 7 21 6 to 30

CoA 33 18 24 24 12 22

CAT 19 25 75 10

IAAb 17 to 50

APVS 20

HLHS 7 56 22 11 11

DORV 21 10 40 20 30 1

Mitral atresia 18

UVH 15

PS/PA + IVS 5

Tricuspid atresia 7

TVD 4

Aortic stenosis 5

ASD 17

TGA 0

cTGA 0

Tumours 0

Cardiomyopathy 0

Cardiosplenic 0
syndromes

DIV 0

AVSD: atrioventricular septal defect; VSD: ventricular septal defect; TOF: tetralogy of Fallot; CoA: coarctation of the aorta; CAT: common
arterial trunk; APVS: absent pulmonary valve syndrome; HLHS: hypoplastic left heart syndrome; DORV: double outlet right ventricle;
UVH: univentricular heart; PS/PA + IVS: pulmonary stenosis/pulmonary atresia with intact ventricular septum; TVD: tricuspid valve
dysplasia; ASD: atrial septal defect; TGA: transposition of the great arteries; cTGA: corrected transposition of the great arteries; DIV:
double inlet ventricle; IAAb: interrupted aortic arch type B.

Adapted from studies by Allan et al. (Allan et al., 1994), Paladinin et al. (Paladini et al., 2002), Boldt et al. (Boldt et al., 2002) and Tennstedt et al.
(Tennstedt et al., 1999). The incidence of individual types of aneuploidy as a percentage of the total number of aneuploid fetuses are adapted
from Paladini et al. (Paladini, et al., 2002), Boldt et al. (Boldt et al., 2002) and Tennstedt et al. (Tennstedt et al., 1999). Incidence of 22q11 deletion
adapted from Marino et al. (Marino et al., 2001), Yamagishi et al., 2000), McElhinney et al. (McHElhinney et al., 2003), Lewin et al., 1997) and
Ryan et al. (Ryan et al., 1997).
Reproduced with permission from: Wimalasundera, RC, Gardiner, HM. Congenital heart disease and aneuploidy. Prenat Diagn 2004; 24:1116.
Copyright © 2004 John Wiley &Sons.

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Prevalence of congenital heart disease in chromosomally normal fetuses according to nuchal

translucency thickness

Nuchal translucency thickness, mm Prevalence per 1000 fetuses

3.5 to 4.4 28.9

4.5 to 5.4 90.9

≥5.5 195.1

Adapted from: Hyett J, Perdu M, Sharland G, et al. BMJ 1999; 318:81.

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Three vessel view of fetal heart

SVC: superior vena cava; Ao Arch: aortic arch; MPA: main pulmonary artery.

Courtesy of Joshua Copel, MD.

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Selected genetic disorders associated with cardiovascular malformations

Syndrome Cardiovascular anomaly

Genetic associations

VATER/VACTERL association Wide-ranging (including VSD, TOF, TGA, and others)

Chromosomal syndromes

Down syndrome (trisomy 21) AV canal defect, VSD, ASD, TOF, PDA, pulmonary hypertension

Edwards syndrome (trisomy 18) ASD, VSD, PDA, PS, AS, CoA, TOF, HLHS, pulmonary
hypertension

Patau syndrome (trisomy 13) ASD, VSD, TOF, PS, AS, CoA, HLHS, DORV, pulmonary
hypertension

Turner syndrome Aortic valve abnormalities, CoA, systemic and pulmonary

venous abnormalities, VSD, HLHS, ASD, aortic dilation/rupture

Chromosomal deletion/microdeletion syndromes

DiGeorge syndrome (22q11 deletion syndrome) TOF, IAA and other aortic arch anomalies, truncus arteriosus,
VSD

Williams syndrome Pulmonary and aortic valve defects, ASD, VSD, coronary ostial
stenosis, branch pulmonary artery stenosis, arteriopathy

Single-gene syndromes – Autosomal dominant inheritance pattern

Alagille syndrome Peripheral pulmonary artery stenosis, ASD, VSD, TOF, CoA

Albright hereditary osteodystrophy Cardiomyopathy

Cardiofaciocutaneous syndrome PS, ASD, VSD, HCM

CHARGE syndrome VSD, ASD, TOF, DORV, PDA, PS, pulmonary vein anomalies

Costello syndrome HCM, PS, ASD, VSD, atrial arrhythmias

Ehlers-Danlos syndrome (vascular type) Rupture of large vessels

Holt-Oram syndrome ASD, VSD, left-sided lesions, conotruncal defects, AV block

Leopard syndrome PS, prolonged PR interval, ASD, VSD, HCM

Marfan syndrome Aortic root dilation/aneurysmal dissection, AI, MVP

Myotonic dystrophy Cardiomyopathy

Neurofibromatosis CoA, renal artery stenosis

Osler-Weber-Rendu disease Multiple telangiectasis, pulmonary AVM

Treacher Collins syndrome ASD, VSD, PDA

Tuberous sclerosis Myocardial rhabdomyoma, Wolff-Parkinson-White syndrome

Noonan syndrome PS, ASD, AS, subaortic stenosis, HCM

Single-gene syndromes – Autosomal recessive inheritance pattern

Carpenter syndrome PDA

Cutis laxa Pulmonary hypertension

Ellis-van Creveld syndrome ASD, AVSD

Friedreich ataxia Cardiomyopathy

MPS type IH (Hurler syndrome) AI, MR, premature CAD, cardiomyopathy

MPS type IS (Scheie syndrome) Aortic valve disease

MPS type IV (Morquio syndrome) Aortic valve disease

MPS type VI (Maroteaux-Lamy syndrome) Aortic valve disease

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Pompe disease (GSD type 2) Cardiomyopathy

Pseudoxanthoma elasticum Premature CAD, MVP

Smith-Lemli-Opitz syndrome VSD, PDA, HLHS

Thrombocytopenia absent radii syndrome ASD, TOF

Single-gene syndromes – X-linked inheritance pattern

MPS II (Hunter syndrome) Valvular disease, premature CAD, cardiomyopathy

Duchenne muscular dystrophy Cardiomyopathy

Emery-Dreifuss muscular dystrophy Cardiomyopathy

X-linked heterotaxy Heterotaxy

Incontinentia pigmenti PDA, hypertension

Genetic mutations associated with nonsyndromic congenital heart disease

NKX2-5 mutation ASD, VSD, TOF, HLHS

GATA4 mutation ASD, VSD, TOF

TAB2 mutation Valvular disease, VSD, TOF

VATER/VACTERL: Vertebral anomalies, anal atresia, cardiac defects, tracheoesophageal fistula and/or esophageal atresia, renal & radial
anomalies, and limb defects; VSD: ventricular septal defect; TOF: tetralogy of Fallot; TGA: transposition of the great arteries; AV:
atrioventricular; ASD: atrial septal defect; PDA: patent ductus arteriosus; PS: pulmonic stenosis; AS: aortic stenosis; CoA: coarctation of
the aorta; HLHS: hypoplastic left heart syndrome; DORV: double-outlet right ventricle; IAA: interrupted aortic arch; HCM: hypertrophic
cardiomyopathy; CHARGE: Coloboma, heart defect, atresia choanae, retarded growth and development, genital abnormality, and ear
abnormality; AI: aortic insufficiency; MVP: mitral valve prolapse; AVM: arteriovenous malformation; AVSD: atrioventricular septal defect;
MPS: mucopolysaccharidosis; MR: mitral regurgitation; CAD: coronary artery disease; GSD: glycogen storage disease.

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Common critical congenital heart defects and their association with cyanosis and dependence
upon the ductus arteriosus

Cyanosis? Ductal-dependent?

Left-sided obstructive lesions

Hypoplastic left heart syndrome Yes Yes

Valvar AS

Critical AS Cyanosis or differential cyanosis * Yes

Moderate to severe AS No No

COA

Critical COA Differential cyanosis * Yes

Moderate to severe COA No No

Interrupted aortic arch Differential cyanosis* (pattern of Yes

cyanosis varies based upon type)

Right-sided obstructive lesions

Tetralogy of Fallot Variable Possibly ¶

Tetralogy of Fallot with pulmonary Yes Yes (unless multiple or large

atresia aortopulmonary collaterals are present)

Pulmonary atresia with intact Yes Yes

interventricular septum

PS

Critical PS Yes Yes

Severe PS No No

Tricuspid atresia Yes Possibly ¶

Severe neonatal Ebstein anomaly Yes Possibly Δ

Parallel circulations

Transposition of the great arteries Yes ◊ Yes

Other

TAPVC Yes No §

Large VSD No No

AV canal defect No No

Truncus arteriosus Yes No

This table summarizes the key features of some of the more common critical CHD lesions. Critical CHD refers to lesions
requiring surgery or catheter-based intervention in the first year of life. The most common lesions are listed in this table;
however, there are other less common congenital heart lesions that may require intervention within the first year of life.

AS: aortic stenosis; COA: coarctation of the aorta; PS: pulmonic stenosis; TAPVC: total anomalous pulmonary venous connection; VSD:
ventricular septal defect; AV: atrioventricular; CHD: congenital heart disease; RV: right ventricle; PDA: patent ductus arteriosus.

* In these lesions, the upper one-half of the body (preductal) is pink and the lower one-half (postductal) is cyanotic.
¶ Infants with tetralogy of Fallot or tricuspid atresia may have ductal-dependent circulation if there is severe RV outflow tract obstruction
(ie, critical pulmonary stenosis or atresia).
Δ In cases of severe Ebstein anomaly with extreme cyanosis, a PDA may be necessary to maintain pulmonary blood flow until pulmonary
vascular resistance drops.
◊ Reversed differential cyanosis (ie, oxygen saturation higher in the lower than upper extremity) may occur if there is coexisting
coarctation of the aorta or pulmonary artery hypertension.

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§ Some patients with obstructed TAPVC may require a PDA to maintain systemic cardiac output. However, a PDA may also increase the
degree of cyanosis.

Graphic 103087 Version 5.0

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Contributor Disclosures
Joshua Copel, MD Consultant/Advisory Boards: Jubel LLC [Infertility]; Nuvo [Wearable fetal monitor
device]. Louise Wilkins-Haug, MD, PhD Nothing to disclose Deborah Levine, MD Nothing to
disclose Vanessa A Barss, MD, FACOG Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.

Conflict of interest policy

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