Right aortic arch detected in fetal life

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1 Ultrasound Obstet Gynecol 2006; 28: Published online 6 November 2006 in Wiley InterScience ( DOI: /uog.3883 Right aortic arch detected in fetal life C. BERG*, F. BENDER*, M. SOUKUP*, A. GEIPEL*, R. AXT-FLIEDNER, J. BREUER, U. HERBERG and U. GEMBRUCH* Departments of *Obstetrics and Prenatal Medicine and Pediatric Cardiology, Rheinische Friedrich-Wilhelms-Universität, Bonn and Division of Prenatal Medicine, Department of Obstetrics and Gynecology, University Hospital Schleswig-Holstein, Campus Lübeck, Germany KEYWORDS: cardiac defects; echocardiography; fetus; prenatal diagnosis; right aortic arch ABSTRACT INTRODUCTION Objective To evaluate the prenatal distribution, associated conditions and outcome of the different types of right aortic arch (RAA) detected in fetal life. Methods This was a retrospective review of all cases of RAA detected prenatally between 1998 and 2005 in two tertiary referral centers. Results In the study period 71 cases of RAA were detected; 26 (37%) had RAA with aberrant left subclavian artery, 23 (32%) had RAA with mirror-image branching, 20 (28%) had RAA of unknown type and two (3%) had double aortic arch. While 20/26 cases with RAA and aberrant left subclavian artery were isolated findings, all 23 cases with RAA and mirror-image branching were associated with cardiac defects, namely tetralogy of Fallot (43%) or pulmonary atresia with ventricular septal defect (22%). Of the 20 cases with RAA, 19 of unknown type were associated with heterotaxy syndromes and had additional cardiac malformations and ambiguities of the situs. The two cases with DAA were isolated findings. Seven cases in our series (10%) had a microdeletion 22q11 and these were significantly associated with extracardiac malformations. The outcome in our series depended solely on the associated cardiac and extracardiac malformations, with the exception of one infant with isolated DAA, in whom a surgical correction was warranted. Conclusions RAA detected in fetal life is associated frequently with other cardiac/non-cardiac malformations, heterotaxy syndromes and microdeletions 22q11. The associated conditions vary depending on the branching type of the brachiocephalic vessels and the presence of extracardiac malformations. Copyright 2006 ISUOG. Published by John Wiley & Sons, Ltd. Among the various anomalies of the aortic arch that concern the vessel course and/or its branching pattern, those most commonly seen include: right aortic arch (RAA) with aberrant left subclavian or innominate artery; RAA with mirror-image branching; double aortic arch (DAA); circumflex retroesophageal aortic arch or left aortic arch with an aberrant right subclavian artery 1. Aortic arch abnormalities are the least frequently prenatally diagnosed cardiac abnormalities, with only one major publication reporting 19 cases among over scanned fetuses in a low-risk population 2 ; the remaining body of literature consists of small case series 3 5 and case reports 6 8. Depending on the type of anomaly, important associated conditions in postnatal series are intra- and extracardiac malformations, postnatal tracheal or esophageal compression, left subclavean steal syndrome due to constriction of the aberrant artery and chromosomal anomalies, namely microdeletion of the DiGeorge critical region of chromosome 22q11 3,4,7,9 11. The reported distribution and associated conditions of these anomalies depends mainly on the referral base of the reporting centers: in prenatal low-risk populations, RAA with aberrant left subclavian artery as an isolated finding is predominant 2, while in postnatal populations with cardiac defects, RAA with mirror-image branching is the most frequent finding 10,12. Apart from left aortic arch with an aberrant right subclavian artery and circumflex retroesophageal aortic arch, all of the anomalies listed above have one common sonographic marker: the aortic arch (or one of the arches) can be visualized on the right side of the trachea in the three vessels and trachea view. As this scanning plane has now evolved to become one of the three main pillars in fetal echocardiography (complementary Correspondence to: Dr C. Berg, Abteilung für pränatale Medizin und Geburtshilfe, Zentrum für Geburtshilfe und Frauenheilkunde, Rheinische Friedrich-Wilhelms-Universität, Sigmund-Freud-Str. 25, Bonn, Germany ( christoph.berg@ukb.uni-bonn.de) Accepted: 17 October 2006 Copyright 2006 ISUOG. Published by John Wiley & Sons, Ltd. ORIGINAL PAPER

2 Right aortic arch 883 to the four- and five-chamber views) 13, these anomalies are now likely to be detected more frequently during fetal echocardiography than they have been in the past. A correct diagnosis will prompt meticulous inspection of the fetal cardiac as well as extracardiac anatomy and prenatal testing for 22q11 microdeletions can be offered to the parents. We reviewed all cases in our centers over the last 8 years in which the aortic arch was found to be located to the right of the trachea in the three vessels and trachea view, in order to evaluate the distribution of the different aortic arch anomalies as well as their associated conditions and outcome. PATIENTS AND METHODS All cases between 1998 and 2005 in which the aortic arch was located to the right of the trachea in the three vessels and trachea view were identified in the perinatal databases of two tertiary referral centers for prenatal medicine and fetal echocardiography (Bonn and Lübeck, Germany). Patient charts, ultrasound video recordings and still frames of all cases were reviewed for associated conditions and outcome. During the study period, the anatomical survey and fetal echocardiography were performed in a standardized fashion. Fetal echocardiography was carried out by a segmental approach using standardized anatomical planes incorporating pulsed-wave, color and power Doppler imaging 13,14. For all ultrasound examinations, Acuson Sequoia 512 (Siemens, Erlangen, Germany), ATL HDI 5000 (Phillips, Solingen, Germany) or Voluson 730 Expert Pro (GE Healthcare, Waukesha, WI, USA) machines were used, equipped with 3.5-, 4-, 5- or 7.5-MHz sector or curved array probes. The three vessels view was obtained as previously described2,5,14 16 and was an integral part of all echocardiographic examinations performed in our centers during the study period. During the time in question, second- and third-trimester echocardiographic examinations were performed in the two centers; 80% of these were routine scans in highrisk patients and 20% were referred for suspected fetal anomalies. RAA with aberrant left subclavian or innominate artery was diagnosed in the presence of an aortic arch running on the right side of the trachea, forming a U-shaped confluence with the ductus arteriosus and resulting in a vascular ring around the trachea and esophagus, with the left subclavian artery arising from the descending aorta near the confluence with the ductus arteriosus. RAA with mirror-image branching was diagnosed when the aortic arch was demonstrated to the right of the trachea and did not form a V- or U-shaped confluence with the ductus arteriosus (suggesting that the ductus arteriosus and aortic arch were colocated on the right side and not associated with an aberrant course of the left subclavian artery), and/or when the left subclavian artery could be demonstrated as the first branch of the arch. DAA was diagnosed in the presence of two aortic arches, one on each side of the trachea and clearly discernable from the ductus arteriosus, with the common carotid and subclavian arteries arising separately and symmetrically, one from each arch. During the last 2 years of the study period, the branching pattern of the brachiocephalic vessels was evaluated prospectively in every case of RAA. In cases diagnosed prior to this period, an attempt was made to differentiate the branching pattern retrospectively, from the recordings. RAA of unknown type was diagnosed when the aortic arch was located to the right of the trachea but the branching pattern was not discernable on the reviewed material. Postnatal follow-up was available for all surviving patients of the study population for a minimum of 1 year. The prenatal diagnosis of right or double aortic arch was confirmed postnatally in 48/71 (68%) cases; in 8/17 (47%) terminations and 2/5 (40%) intrauterine demises, confirmation was provided by a specialized pathologist, and in 38/49 (78%) liveborn children the diagnosis was confirmed during postnatal echocardiography or cardiac surgery. In 15/21 (71%) cases with isolated RAA with aberrant left subclavian artery, postnatal echocardiography was performed. The branching pattern of the aortic arch was described in detail in only 30 (42%) cases. Although the prenatally determined branching pattern was confirmed in all of these, the diagnosis of the branching anomalies in our series relied mainly on the accuracy of prenatal ultrasound. Karyotyping was performed in 58 cases and a fluorescent in-situ hybridization (FISH) test for 22q11 microdeletions was performed in 53 of these. Statistical analysis was performed using the χ 2 and Fisher s exact tests. All values are given as mean ± SD unless otherwise indicated. A P-value of < 0.05 was considered significant. RESULTS Seventy-one cases with RAA or DAA were detected during the study period: 26 (37%) had RAA with aberrant left subclavian artery, 23 (32%) had RAA with mirror-image branching, 20 (28%) had RAA of unknown type and two (3%) had DAA. The type of aortic arch anomaly, the associated conditions and the outcome in our series are summarized in Table 1. The mean ± SD maternal age was 32.9 ± 6.6 yearsand gestational age at detection was 25.6 ± 6.2 weeks. Three cases were detected in the first trimester. Indications for referral were suspected cardiac defect (44%), routine scan in high-risk patients (37%), extracardiac malformation (10%), arrhythmia (6%) and hydrops (3%). One mother had a microdeletion 22q11. Of the 26 fetuses with RAA and aberrant left subclavian artery (Figure 1), 20 (77%) were isolated findings. Of the six with associated findings, three had extracardiac

3 884 Berg et al. Table 1 Type of aortic arch anomaly, associated conditions at prenatal ultrasound and outcome in 71 fetuses with right (RAA) or double (DAA) aortic arch Outcome (n) Aortic arch anomaly/ associated condition Total TOP IUFD NND CD Survived RAA with aberrant left subclavian artery No associated condition Muscular VSD Malalignment VSD, Pena Shokeir syndrome CAT, cleft lip, retrognathia, del 22q Cleft lip/palate, spina bifida, del 22q Hygroma colli, del 22q Left isomerism, interr. IVC, VCH, polysplenia RAA with mirror-image branching No associated condition TOF Isolated TOF TOF, del 22q TOF, esophageal atresia, del 22q TOF, hexadactyly, trisomy TOF, multicystic right kidney, IUGR PA, VSD Isolated PA, VSD PA, VSD, MAPCA, del 22q CAT isolated CAT CAT, hydrops, hexadactyly, cleft lip, trisomy AVSD AVSD, DORV, PA AVSD, DORV, PA, spina bifida aperta Left isomerism, AVSD, HLV, interr. IVC, VCH MA,HLH,d-TGA,PA,VSD DILV, DORV, PS RAA of unknown type No associated condition Heterotaxy syndrome Right isomerism Left isomerism Isolated DAA AVSD, atrioventricular septal defect; CAT, common arterial trunk; CD, death in infancy or childhood; del 22q11, microdeletion of the DiGeorge critical region of chromosome 22; DILV, double inlet left ventricle; DORV, double outlet right ventricle; d-tga, transposition of the great arteries; HLH, hypoplastic left heart; HLV, hypoplastic left ventricle; interr. IVC, interrupted inferior vena cava; IUFD, intrauterine fetal death; IUGR, intrauterine growth restriction; MA, mitral atresia; MAPCA, major aortopulmonary collateral arteries; NND, neonatal death; PA, pulmonary atresia; PS, pulmonary stenosis; TOF, tetralogy of Fallot; TOP, termination of pregnancy; VCH, viscerocardiac heterotaxy; VSD, ventricular septal defect. malformations in association with a microdeletion 22q11 (Table 2) and one (in which no screening for 22q11 deletions was performed) had Pena Shokeir syndrome with malalignment ventricular septal defect. One had a small muscular ventricular septal defect and the last was associated with left isomerism and had no cardiac defect. All 23 cases of RAA with mirror-image branching (Figure 2) were associated with cardiac defects, most frequently tetralogy of Fallot (n = 10, two of which had 22q11 deletion), pulmonary atresia with ventricular septal defect (n = 5 two of which had 22q11 deletion) and common arterial trunk (n = 3). One fetus in this group was associated with left isomerism. Five of the 23 cases also had extracardiac anomalies, one of them in association with a microdeletion 22q11 (Table 2) and two with trisomy 13; the remaining fetus (in which no screening for 22q11 deletions was performed) had a combination of spina bifida aperta, atrioventricular septal defect, double outlet right ventricle and pulmonary atresia. Nineteen of the 20 cases with RAA of unknown type were associated with heterotaxy syndromes (12 with left isomerism, six of which were associated with a rightward orientation of the cardiac apex; seven with right isomerism, three of which had the cardiac apex to the right). All 19 had additional complex cardiac malformations as well as abnormalities of the situs, including various combinations of atrioventricular septal defect (n = 13), discordant ventriculoarterial connection (n = 13) and right outflow tract obstruction (n = 9). All 19 cases were associated with viscerocardiac heterotaxy (nine with dextrocardia and left stomach; 10 with levocardia and right stomach). The distortion of the

4 Right aortic arch 885 Figure 1 Three vessels and trachea view of right aortic arch with aberrant left subclavian or innominate artery in a 21-week fetus: grayscale (a) and color Doppler (b) images. The aortic arch is visible running on the right side of the trachea, forming a U-shaped confluence with the ductus arteriosus (diverticulum of Kommerell, DK), resulting in a vascular ring around the trachea and esophagus. The aberrant course of the left subclavian artery is not evident. DA, ductus arteriosus; PT, pulmonary trunk; RAA, right aortic arch; SVC, superior vena cava; T, trachea. Table 2 Type of aortic arch anomaly, associated conditions at prenatal ultrasound and outcome in seven fetuses with right aortic arch (RAA) and microdeletion 22q11 GA (weeks) Type of RAA Cardiac defect Additional findings Outcome 21 Mirror-image branching TOF, agenesis of ductus arteriosus Esophageal atresia, TOP polyhydramnios 20 Mirror-image branching PA, VSD, MAPCA Polyhydramnios TOP 26 Mirror-image branching PA, VSD, MAPCA None CD 36 Mirror-image branching TOF, agenesis of ductus arteriosus Polyhydramnios Delivery at term, correction pending 22 Aberrant left subclavian artery None Unilateral cleft lip, TOP spina bifida aperta, bilateral clubfoot 14 Aberrant left subclavian artery None Hygroma colli TOP 32 Aberrant left subclavian artery CAT type II Unilateral cleft lip, retrognathia, polyhydramnios NND CAT, common arterial trunk; CD, death in infancy or childhood; GA, gestational age at detection; MAPCA, major aortopulmonary collateral arteries; NND, neonatal death; PA, pulmonary atresia; TOF, tetralogy of Fallot; TOP, termination of pregnancy; VSD, ventricular septal defect. thoracic situs as well as the complex combination of cardiac defects prevented a retrospective evaluation of the brachiocephalic branching pattern in most cases of heterotaxy syndromes in our series. The autopsy reports as well as the reports on postnatal corrective surgery in this group confirmed the presence of RAA, but lacked specific details on the branching pattern. The remaining case in this group that was not associated with heterotaxy had RAA with right ductus arteriosus and no further cardiac or extracardiac defects. Again, the branching pattern of the brachiocephalic vessels could not be assessed retrospectively. Postnatal echocardiography suggested mirror-image branching in this case. The two cases with DAA (Figure 3) were isolated findings. A FISH test for 22q11 deletions was performed in 53 of the 71 (75%) cases in our series. Three of the 17 tested fetuses (18%) in the group with RAA with aberrant subclavian artery and four of the 16 tested fetuses (25%) in the group with RAA with mirror image branching had 22q11 deletions (Table 2). All fetuses with RAA of unknown type tested negative for monosomy 22q11. The

5 886 Berg et al. Figure 2 Right aortic arch with mirror-image branching in a 31-week fetus with tetralogy of Fallot. The aortic arch is visible arising from an overriding aorta and running to the right of the trachea in the five-chamber view (a), and does not form a confluence with the ductus arteriosus in the three vessels and trachea view (b). The ductus arteriosus could not be demonstrated in any plane and was found to be absent in the postnatal period. LPA, left pulmonary artery; LV, left ventricle; overr. A, overriding aorta; PT, pulmonary trunk; RAA, right aortic arch; RPA, right pulmonary artery; RV, right ventricle; SVC, superior vena cava; T, trachea. Figure 3 Color Doppler images showing double aortic arch with patent left ductus arteriosus in a 22-week fetus. In the three vessels and trachea view, two aortic arches, one on each side of the trachea, are visible (a) and clearly discernable from the left ductus arteriosus (b). The subclavian arteries are seen arising separately and symmetrically from both arches. A, aortic root; LAA, left aortic arch; LDA, left ductus arteriosus; LSA, left subclavian artery; RAA, right aortic arch; RSA, right subclavian artery; T, trachea. two fetuses with DAA were not tested for 22q11 deletions; however, there were no dysmorphic features in any of the survivors in our series (apart from the surviving fetus with 22q11 microdeletion), which included those with DAA, suggesting a normal karyotype. The presence of extracardiac anomalies (other than situs anomalies in heterotaxy syndromes) was significantly associated with 22q11 deletions (P = 0.004). The outcome in our series depended on the associated cardiac and extracardiac malformations as well as the presence of chromosomal anomalies (Table 1), with the exception of one fetus with isolated DAA that had to

6 Right aortic arch 887 undergo surgical correction at the age of 6 months due to persistent wheezing. DISCUSSION The frequency of occurrence of RAA among adults is approximately 0.1% 10, and a similar incidence was found in a prenatal low-risk cohort 2. It has two major variants: mirror-image branching and retroesophageal, aberrant, left subclavian artery 10. The predominant variant of RAA in the general population is with aberrant subclavian artery. Achiron et al. 2 found 19 cases of RAA among prenatal screening echocardiograms; 18 of them were associated with a U-sign, suggesting RAA with aberrant subclavian artery, and the remaining fetus had DAA. In cases of RAA with aberrant subclavian artery, the trachea and esophagus are usually entrapped between the RAA and the left ductus arteriosus. Therefore, a vascular ring is found around the trachea at prenatal ultrasound, the so-called U-sign 2,16. In this condition, the left common carotid artery arises first from the aortic arch, followed by the right common carotid, right subclavian artery, and finally a retroesophageal vessel segment from which the left subclavian artery arises and to which the ductus arteriosus connects. The retroesophageal vessel segment is known as the diverticulum of Kommerell 1,7. Prenatal diagnosis of a markedly enlarged diverticulum of Kommerell, as can be seen in the postnatal period in cases of RAA with aberrant left subclavian artery, is rare 2. This marked dilation of the proximal part of the aberrant subclavian or innominate artery that carried the ductal blood flow to the descending aorta becomes apparent with the regression of the ductus arteriosus in the postnatal period. It represents the partial remnant of the fourth aortic arch from the side opposite the dominant arch. In the prenatal period this segment is as wide as the descending aorta and the ductus arteriosus, and it therefore does not appear dilated in the presence of a normally sized ductus arteriosus. Accordingly, in our series, only two of 26 fetuses with RAA and aberrant left subclavian artery were diagnosed with a dilated Kommerell s diverticulum. In these fetuses the ductal arch was narrower than the aortic arch. In cases with RAA with mirror-image branching, both the aorta and the ductus arteriosus usually lie to the right of the trachea and do not form a vascular ring. The left innominate (brachiocephalic) artery arises first from the aortic arch, followed by the right common carotid and right subclavian arteries, thus representing a mirror image of the usual branching pattern 1,7. The branching pattern of the aortic arch has gained attention only recently among prenatal sonographers. Following the pictorial essay of Yoo et al. 1, which demonstrated the feasibility of detailed prenatal diagnosis, and the work of Chaoui et al. 17, who proposed the aberrant right subclavian artery in the presence of a left aortic arch and left ductus arteriosus as a cardiac sign in fetuses with Down syndrome, many centers included the branching pattern of the brachiocephalic vessels in their cardiac work-up, even in the absence of RAA. Previous to this, the determination of the branching type relied mainly on the presence or absence of the U-sign in the three vessels and trachea view, as in the study of Achiron et al. 2 and our own study in the first 6 years of the study period. Due to the limited postnatal follow-up on the branching pattern in our series, we are unable to comment on the reliability of either diagnostic approach. However, in the 30 cases with detailed postnatal description, the prenatally determined branching pattern was always confirmed. The risk of concomitant congenital heart disease is over 90% with the mirror-image branching type of RAA and only 10% with RAA and aberrant left subclavian artery 18. Accordingly, 22 of 26 fetuses in our series with RAA and aberrant left subclavian artery were diagnosed during screening ultrasound examinations in high-risk patients and 20 of them had no further anomalies. All 23 fetuses with the mirror-image type of RAA were referred for and proved to have cardiac defects. The most common association is tetralogy of Fallot, where the incidence of RAA (usually the mirror-image branching pattern) ranges from 13 to 35% 10,19,20. Other frequent associations are pulmonary atresia with ventricular septal defect, and common arterial trunk, with incidences of RAA of 31 36% and 15 36%, respectively 10,19. These figures were largely confirmed in our prenatal series, with tetralogy of Fallot being the most frequent association of RAA with mirror image branching (43%), followed by pulmonary atresia with ventricular septal defect (22%) and common arterial trunk (13%). In a fetal autopsy series, Ho et al. 21 found RAA in five of 20 hearts with left isomerism (only one of these being associated with a rightward orientation of the cardiac apex) and in five of 10 hearts with right isomerism (two of which had the cardiac apex to the right). Similar incidences in the postnatal period were reported by other authors 22,23. Although no details on the branching pattern were given, the absence of a vascular ring suggests that mirror-image branching was the predominant variant in these cases. Among the 78 fetuses diagnosed prenatally with heterotaxy syndromes in our institutions 24,25 21 were found to have RAA and were included in this study. In 19 of these cases the branching pattern could not be assessed retrospectively; however, none of them was associated with a vascular ring and the postnatal reports, although lacking details on the branching pattern, never mentioned an aberrant (retroesophageal) course of the left subclavian artery, therefore suggesting mirror-image branching. The remaining two fetuses were both associated with left isomerism. One had RAA with aberrant left subclavian artery and a vascular ring and the other had the mirrorimage type with aplasia of the arterial duct. Due to their vessel course, RAA with aberrant subclavian artery and DAA may cause a compression of the trachea and esophagus. In RAA with mirror-image branching, the vascular ring is incomplete and symptoms due to compression are unlikely to occur 1. As in the series of Achiron et al. 2, the only child with symptomatic

7 888 Berg et al. vascular ring that warranted surgical intervention in our series had DAA, while 21 fetuses with isolated RAA and aberrant subclavian artery had an uneventful postnatal period. This is explained well by the tight vascular ring that is formed in DAA in contrast to the situation in RAA with aberrant left subclavian artery, in which the ring is probably loose 18. However, as the onset of symptoms in cases of RAA with aberrant left subclavian artery has a broad time range from infancy into adulthood 18,and the reported cases in the literature represent mainly the symptomatic subset of individuals with vascular rings, the true incidence of complications in this group remains largely unknown. Conotruncal malformations have a clear association with 22q11 deletion syndromes (CATCH 22) 26. The incidence of this microdeletion is 60% among patients with interrupted aortic arch 27, 33% among patients with common arterial trunk 28,29, 23% in patients with pulmonary atresia with ventricular septal defect (predominately in the presence of major aortopulmonary collateral arteries (MAPCA)) and 16% in tetralogy of Fallot 30. Accordingly, in our series, the incidence of 22q11 deletions was 25% among patients with conotruncal anomalies and a normal situs that were tested for these microdeletions. Among four fetuses with pulmonary atresia and ventricular septal defect, the two with MAPCA tested positive for monosomy 22q11. Rauch et al. 9 showed that in patients with conotruncal malformations, the anomalies of the subclavian arteries are the most important anatomical marker for the presence of monosomy 22q11, independent of the laterality of the aortic arch. Fetuses with aberrant origin from the descending aorta, isolation, distal ductal origin from the pulmonary artery and cervical origin of the subclavian artery contralateral to the aortic arch had significantly higher rates of 22q11 deletions than had those with mirror-image branching. In our series, 20 fetuses had conotruncal anomalies and were screened for monosomy 22q11 (five with 22q11 deletion). Only one of them had an aberrant origin of the left subclavian artery from the descending aorta and this one indeed tested positive for a 22q11 deletion. However, the low incidence of anomalous origin of the left subclavian artery in our series might have been due to our sonographic approach, that did not allow clear differentiation between mirrorimage branching and cervical origin of the subclavian artery from the carotid artery, a variant that was the second most frequent anomaly of the branching pattern in the series of Rauch et al. 9 and was highly associated with 22q11 deletions. None of the 20 fetuses with aberrant subclavian artery and otherwise normal anatomy was associated with a 22q11 deletion, while three of six cases with additional cardiac or extracardiac anomalies had monosomy 22q11. In the whole series, extracardiac anomalies (excluding those associated with the situs ambiguities in heterotaxy syndromes) were significantly associated with 22q11 deletions, and therefore represent an important diagnostic marker in fetuses with RAA. Although a sporadic association with 22q11 deletions has been reported previously 31,32, heterotaxy syndromes were not associated with chromosomal abnormalities in our series. In summary, RAA detected in fetal life is frequently associated with other cardiac and/or non-cardiac malformations, heterotaxy syndromes and microdeletions 22q11. The associated conditions vary depending on the branching type of the brachiocephalic vessels and the presence of extracardiac malformations. Therefore, a meticulous inspection of the fetal cardiac and extracardiac anatomy, including the brachiocephalic branching pattern, should be performed in prenatally detected cases, and cytogenetic testing for 22q11 deletions should be considered carefully. Although this is the largest cohort of fetuses with RAA reported so far, the incompleteness of the postnatal confirmation and follow-up and, consequently, the relative limitation of this study must be kept in mind. Further prospective studies are warranted to evaluate the accuracy of prenatal ultrasound in the determination of the anatomical variants of the aortic arch as well as their clinical consequences. REFERENCES 1. Yoo SJ, Min JY, Lee YH, Roman K, Jaeggi E, Smallhorn J. Fetal sonographic diagnosis of aortic arch anomalies. Ultrasound Obstet Gynecol 2003; 22: Achiron R, Rotstein Z, Heggesh J, Bronshtein M, Zimand S, Lipitz S, Yagel S. Anomalies of the fetal aortic arch: a novel sonographic approach to in-utero diagnosis. 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