What is the detailed prenatal workup for a suspected tetralogy of Fallot in a 20‑week gestation fetus?

Prenatal Workup of Tetralogy of Fallot at 20 Weeks Gestation

At 20 weeks gestation with suspected tetralogy of Fallot (TOF), immediately perform a detailed fetal echocardiogram to confirm the diagnosis and characterize cardiac anatomy, followed by genetic counseling with invasive prenatal testing (amniocentesis with chromosomal microarray), systematic evaluation for extracardiac anomalies, and multidisciplinary planning for delivery and postnatal management. 1, 2

Initial Diagnostic Confirmation

Detailed Fetal Echocardiography

A specialized fetal echocardiogram is the cornerstone of TOF diagnosis and must comprehensively evaluate all cardiac structures. 1, 3 The examination should systematically document:

• Right ventricular outflow tract (RVOT) obstruction - the primary pathologic feature requiring detailed characterization of the level and severity of obstruction 4, 5
• Ventricular septal defect (VSD) - specifically the anterior malaligned outlet VSD that defines TOF 3, 6
• Overriding aorta - best visualized in long-axis views showing the aortic root straddling the VSD 5, 6
• Pulmonary valve and main pulmonary artery - including precise measurements to distinguish TOF with pulmonary stenosis (TOF-PS) from pulmonary atresia (TOF-PA) or absent pulmonary valve (TOF-APV) 4, 2
• Branch pulmonary arteries - size and continuity of right and left pulmonary arteries, as hypoplasia significantly impacts surgical planning 4, 5
• Ductus arteriosus - size and direction of flow, as left-to-right ductal flow predicts postnatal ductal dependency requiring prostaglandin therapy 2, 5
• Aortic arch sidedness and morphology - right aortic arch occurs in approximately 25% of TOF cases and is a marker for 22q11.2 deletion syndrome 1, 2
• Systemic and pulmonary venous connections - to exclude associated anomalies 4
• Atrioventricular valves - to identify coexisting defects 4

The three-vessel view is particularly valuable as it most commonly reveals the abnormality on screening ultrasound, showing the characteristic large aortic root and small or absent pulmonary artery 5, 6

Genetic Evaluation

Invasive Prenatal Testing

Amniocentesis with chromosomal microarray analysis (CMA) should be offered to all patients, as genetic anomalies are present in 39% of TOF fetuses who undergo testing. 1, 2

• 22q11.2 deletion syndrome is the most common genetic association with TOF, occurring in a substantial proportion of cases 1, 3, 2
• CMA remains the most comprehensive prenatal diagnostic test for detecting chromosomal abnormalities and microdeletions 1
• Noninvasive prenatal screening may identify some cases but requires confirmatory diagnostic testing via amniocentesis 1

Genetic Counseling

Comprehensive genetic counseling must address:

• Risk of 22q11.2 deletion syndrome and its multisystem implications beyond cardiac disease 1
• Variable expressivity of genetic conditions 1
• Recurrence risk in future pregnancies 1
• Parental testing considerations, as previously undiagnosed maternal 22q11.2 deletion may be identified 1

Systematic Evaluation for Associated Anomalies

Extracardiac Malformations

Extracardiac malformations occur in 53% of TOF fetuses and significantly impact prognosis, requiring comprehensive anatomic survey. 2

The detailed ultrasound examination at 18-22 weeks should specifically evaluate:

• Thymus gland - hypoplastic or absent thymus is a sonographic marker for 22q11.2 deletion syndrome 1, 2
• Central nervous system - brain and spine anomalies 1
• Facial structures - cleft lip/palate, micrognathia 1
• Skeletal system - limb abnormalities, vertebral defects 1
• Gastrointestinal tract - esophageal atresia, duodenal atresia 1
• Genitourinary system - renal anomalies 1
• Amniotic fluid volume - polyhydramnios is associated with TOF, particularly TOF-APV, and is a marker for 22q11.2 deletion 2, 6

Fetal MRI Considerations

If ultrasound findings are incomplete or additional anatomic detail is needed, fetal MRI without contrast may be performed at or after 22 weeks gestation to further characterize extracardiac anomalies, particularly central nervous system abnormalities 1

Cardiovascular Subtype Classification

Precise classification of TOF subtype is essential as it directly impacts perinatal management and prognosis. 2

• TOF with pulmonary stenosis (TOF-PS) - accounts for 73% of cases and generally has better prognosis 2
• TOF with pulmonary atresia (TOF-PA) - represents 22% of cases and requires assessment for major aortopulmonary collateral arteries (MAPCAs) 1, 2
• TOF with absent pulmonary valve (TOF-APV) - comprises 5% of cases and carries the worst prognosis, often associated with severe pulmonary artery dilation, airway compression, and hydrops fetalis 2, 6

Distinguishing TOF-PA from truncus arteriosus requires careful examination along the ascending aorta to confirm no pulmonary arteries arise from the aortic root 6

Additional Cardiovascular Anomalies

The echocardiogram must identify coexisting cardiac defects that occur in 49% of TOF fetuses:

• Aberrant subclavian artery 1
• Vascular ring causing tracheoesophageal compression 1
• Atrial septal defects 4
• Atrioventricular canal defects 4
• Additional VSDs 4

Ongoing Surveillance Protocol

Serial Ultrasound Monitoring

Follow-up ultrasound examinations are required throughout pregnancy to monitor for progression of cardiac and extracardiac findings. 1

• Repeat detailed fetal echocardiography at 28-32 weeks to reassess cardiac anatomy, as some features evolve with advancing gestation 1, 4
• Monitor for development of hydrops fetalis, particularly in TOF-APV 2, 6
• Assess fetal growth, as intrauterine growth restriction may occur 1
• Monitor amniotic fluid volume for polyhydramnios 1, 2

Maternal-Fetal Medicine Comanagement

Close monitoring by maternal-fetal medicine specialists is warranted given:

• Elevated risk of preterm birth 1
• Need for delivery planning at a tertiary center with pediatric cardiac surgery capabilities 1, 3
• Potential for cesarean delivery depending on associated anomalies and fetal status 1

Delivery Planning and Postnatal Preparation

Delivery Location and Timing

Delivery should occur at a tertiary care center with immediate access to neonatal intensive care, pediatric cardiology, and pediatric cardiac surgery. 1, 3

• Mode and timing of delivery are influenced by TOF subtype, presence of extracardiac anomalies, and fetal status 1
• Neonatology and pediatric cardiology teams must be present at delivery 3

Postnatal Management Preparation

Prenatal counseling should address:

• Prostaglandin E1 therapy - required for ductal-dependent lesions (predicted by left-to-right ductal flow on fetal echocardiography) 2
• Timing of surgical repair - typically within the first year of life, either primary repair or staged with initial palliation 3
• Long-term prognosis - TOF is a lifelong condition requiring ongoing cardiology follow-up and potential reinterventions in adulthood 3
• Impact of associated anomalies - particularly 22q11.2 deletion syndrome with multisystem involvement including immune deficiency, developmental delays, and psychiatric disorders 1

Critical Pitfalls to Avoid

• Do not assume isolated cardiac disease - systematically evaluate for extracardiac anomalies and genetic syndromes, as they are present in the majority of cases and significantly impact prognosis 1, 2
• Do not rely on screening ultrasound alone - specialized fetal echocardiography is mandatory for complete anatomic characterization 1, 4
• Do not defer genetic testing - amniocentesis with CMA should be offered at the time of diagnosis, not delayed, as results inform counseling and management 1, 2
• Do not overlook ductal flow assessment - direction of ductal flow predicts postnatal ductal dependency and need for immediate prostaglandin therapy 2
• Do not confuse TOF-PA with truncus arteriosus - careful examination of the ascending aorta distinguishes these conditions 6
• Do not underestimate the importance of thymus assessment - absent or hypoplastic thymus is a key sonographic marker for 22q11.2 deletion syndrome 1, 2