Part I. Review of the literature

In a fetus, tetralogy of Fallot (TOF) is a conotruncal cardiac anomaly characterised by ventricular septal defect (VSD), overriding aorta, and right ventricular outflow tract obstruction (RVOTO). In fetal life, right ventricular hypertrophy is usually absent because of decompression through the foramen ovale (FO) and ductus arteriosus (DA) [1]. That is why before birth TOF should rather be called Fallot syndrome. After birth right ventricular hypertrophy gradually occurs, and then full criteria of tetralogy (four components) can be fulfilled.

Tetralogy of Fallot with pulmonary atresia (TOF-PA) represents the most severe end of the TOF spectrum and is characterised by complete interruption of antegrade flow from the right ventricle to the pulmonary arteries [2]. Pulmonary perfusion depends on the ductus arteriosus, MAPCAs, or a combination of both [2, 3]. In TOF-PA fetuses, visualisation of hypoplastic pulmonary arteries and pulmonary valve atresia (PA) might be demanding, and they might be mistakenly diagnosed as common arterial trunk (CAT) (Table 1) [1, 4–6].

The anatomy of pulmonary blood supply is highly variable and critically influences prognosis, postnatal intervention, and surgical strategy [7]. Prenatal echocardiography therefore aims not only to diagnose TOF-PA, but also to identify confluent pulmonary arteries, ductal dependency, and the presence of MAPCAs [3].

MAPCAs are systemic-to-pulmonary collateral arteries that usually arise from the descending thoracic aorta, although they may also originate from the aortic arch or subclavian arteries [4, 8]. Their prenatal detection may significantly affect neonatal management and counselling [4, 7].

Prenatal echocardiographic assessment

Ventricular septal defect and overriding aorta

The malalignment VSD is typically visualised in the four-chamber or five-chamber view. The aorta overrides the interventricular septum and appears enlarged relative to the pulmonary artery [1]. Severity of pulmonary hypoplasia/atresia depends on aortic malalignment. The “Y-sign” in the five-chamber view has been described as a useful prenatal marker of TOF [6]. Nevertheless, the “Y-sign” might be also seen in the case of CAT.

Pulmonary atresia

PA is suspected when no antegrade flow across the pulmonary valve is visualised, the pulmonary trunk is severely hypoplastic or absent, reverse flow is present within the ductus arteriosus, and when pulmonary arteries are supplied retrogradely [1]. Retrograde flow through DA should be visualised to differentiate TOF-PA from CAT. Colour Doppler interrogation is essential to confirm absent antegrade pulmonary flow [3].

Identification of MAPCAs

Prenatal detection of MAPCAs remains challenging but feasible with modern fetal echocardiography [4].

MAPCAs are most commonly visualised as: tortuous vessels, arising from the descending thoracic aorta, coursing toward the pulmonary hilum [8].

Colour Doppler facilitates visualisation of collateral vessels, while pulsed Doppler demonstrates continuous arterial flow with a persistent diastolic component [2].

Collateral vessels may arise from descending thoracic aorta, aortic arch, or subclavian arteries [8].

False-positive diagnoses may occur in cases of aberrant subclavian artery, atypical ductus arteriosus course, or right aortic arch [4].

TOF-associated findings

TOF is frequently associated with additional cardiovascular, extracardiac, and genetic abnormalities that may significantly influence prenatal counselling, perinatal management, and postnatal outcome. The prevalence of associated anomalies appears particularly high in fetuses diagnosed prenatally, especially in severe forms such as TOF-PA and absent pulmonary valve syndrome (TOF-APV) [9].

Associated cardiovascular anomalies are reported in nearly half of fetuses with TOF. The most common cardiovascular association is right aortic arch (RAA), observed in approximately 25% of cases. Other frequently identified anomalies include persistent left superior vena cava (LSVC), atrioventricular septal defect (AVSD), anomalies of the ductus arteriosus, and major aortopulmonary collateral arteries (MAPCAs). AVSD demonstrates a strong association with trisomy 21 and may substantially affect surgical planning and postnatal prognosis [9]. Abnormal cardiac axis is also more common in fetuses with pulmonary atresia and is associated with worse postnatal outcome [5, 6].

Extracardiac malformations are highly prevalent and may be identified in more than half of fetuses with TOF. The most commonly affected systems the following [6, 9]: genitourinary, skeletal, gastrointestinal, and central nervous systems, thymic hypoplasia, cleft palate, renal anomalies, and growth restriction.

Multiple extracardiac anomalies and fetal growth restriction substantially increase the likelihood of underlying chromosomal abnormalities [9].

The most important prenatal sonographic markers associated with 22q11.2 deletion include hypoplastic thymus, right aortic arch, and polyhydramnios.

Among these findings, thymic hypoplasia appears to be the most specific prenatal marker, and it can be reliably evaluated in the three-vessel and trachea view [9].

Genetic associations

TOF-PA demonstrates a strong association with chromosomal abnormalities, particularly 22q11.2 deletion syndrome. The most common chromosomal abnormalities included trisomy 21, trisomy 18, trisomy 13, triploidy, and microdeletion 22q11.2 [9].

The prevalence of specific genetic anomalies differed between TOF subtypes. Trisomy 21 was most frequently associated with TOF with pulmonary stenosis (TOF-PS), whereas microdeletion 22q11.2 was particularly common in TOF with absent pulmonary valve syndrome (TOF-APV) and TOF with pulmonary atresia (TOF-PA), especially in fetuses with MAPCAs [1]. In fetuses with TOF-PA and MAPCAs, the prevalence of 22q11.2 deletion was significantly higher compared with fetuses with ductus-dependent pulmonary circulation [9]. The prevalence of 22q11 deletion appears especially high in fetuses with MAPCAs and right aortic arch [2, 6].

Several prenatal sonographic markers may increase suspicion for underlying genetic abnormalities. Hypoplastic thymus was identified as the most specific prenatal marker for 22q11.2 deletion syndrome. Additional findings associated with microdeletion 22q11.2 included right aortic arch and polyhydramnios. Increased cardiac axis was also more frequently observed in fetuses with 22q11.2 deletion [9].

Extracardiac malformations were strongly associated with chromosomal abnormalities and were present in more than half of fetuses with TOF [9]. The risk of genetic aberration increased with the number of extracardiac anomalies, particularly in the presence of fetal growth restriction or atrioventricular septal defect [9].

Prenatal genetic testing, including fluorescence in situ hybridisation or chromosomal microarray analysis, could therefore be considered in all fetuses with TOF-PA [6, 9].

Prognostic and clinical implications

Prenatal diagnosis of TOF-PA allows the following: multidisciplinary counselling, delivery planning in tertiary cardiac centres, anticipation of prostaglandin dependence, postnatal angiographic planning, and optimisation of neonatal management [1, 3].

The prognosis depends largely on the following: pulmonary artery anatomy, ductal dependency, number and distribution of MAPCAs, associated chromosomal anomalies, and extracardiac malformations [7].

Fetuses with MAPCA-dependent circulation often require complex staged surgical repair and may not be candidates for early complete repair [3].

Part II. Pictorial review

The fetal photos come from the Department of Prenatal Cardiology, Polish Mother’s – Research Institute in . Chief: Prof. Maria Respondek-Liberska.

Conclusions

TOF-PA with MAPCAs represents a complex fetal cardiovascular anomaly requiring meticulous prenatal echocardiographic evaluation. TOF-PA with MAPCAs in itself is not an indication for delivery by caesarean section. Identification of pulmonary blood supply, including ductus arteriosus and MAPCAs, is fundamental for prenatal counselling and postnatal management planning. Colour Doppler and spectral Doppler interrogation of the descending thoracic aorta and pulmonary hilar regions significantly improve prenatal detection of MAPCAs. Fetal echocardiography enables multidisciplinary counselling, delivery planning in tertiary cardiac centres, anticipation of prostaglandin dependence, postnatal angiographic planning, and optimisation of neonatal cardiological and cardiosurgical management.

Disclosures

Ethical considerations: none.

This research received no external funding.

The authors declare no conflict of interest.