Prenatal diagnosis of congenital vascular rings and slings sonographic features and perinatal outcom by wen huaxuan

PRENATAL DIAGNOSIS

Prenat Diagn 2011; 31: 334–346. Published online 30 January 2011 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/pd.2678

Prenatal diagnosis of congenital vascular rings and slings: sonographic features and perinatal outcome in 81 consecutive cases Shengli Li1 *, Guoyang Luo2,3 , Errol R. Norwitz3 , Chenhong Wang4 , Shuyuan Ouyang5 , Yuan Yao1 , Congying Chen1 , Huaxuan Wen1 , Xiulan Chen1 and Jingru Bi1 1

Department of Ultrasound, Shenzhen Maternity & Child Healthcare Hospital, Affiliated to Southern Medical University, Shenzhen, China 2 Department of Obstetrics & Gynecology, Danbury Hospital, 24 Hospital Avenue, Danbury, CT, USA 3 Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA 4 Department of Obstetrics & Gynecology, Shenzhen Maternity & Child Healthcare Hospital, Affiliated to Southern Medical University, Shenzhen, China 5 Department of Laboratory Medicine, Shenzhen Maternity & Child Healthcare Hospital, Affiliated to Southern Medical University, Shenzhen, China Objective To describe the sonographic features and perinatal outcome of congenital vascular rings diagnosed prenatally at a single tertiary care institution. Methods All cases of congenital vascular rings diagnosed by prenatal ultrasound between July 2005 and December 2009 were identified at a single referral center using an established perinatal database. The diagnosis was confirmed by postnatal echocardiography for live-born infants or autopsy for terminated cases. Results The overall incidence of vascular ring during this 5-year period was 0.086% (81 cases among 94 321 women undergoing perinatal ultrasound examination). Forty-four cases had complete O-shaped (n = 3) or Ushaped (n = 41) vascular rings, and 37 cases had incomplete C-shaped vascular rings (vascular slings). The most common type of vascular ring seen in 50.6% (41/81) of cases was a right aortic arch with aberrant left subclavian artery. The second most common type was a left aortic arch with an aberrant right subclavian artery [39.5% (32/81)]. Chromosomal analysis was performed prenatally in 46 pregnancies, and six cases (13.0%) of fetal aneuploidy were identified. Conclusions Congenital vascular rings can be diagnosed with prenatal ultrasound using the three-vessel trachea view and subsequent fetal echocardiography with particular attention to the relationship of the aortic arches, ductal arches, and the trachea. Copyright  2011 John Wiley & Sons, Ltd. KEY WORDS:

congenital heart disease; double aortic arch; fetal echocardiography; prenatal diagnosis; vascular

ring

INTRODUCTION Vascular rings refer to a group of congenital vascular anomalies that encircle and compress the esophagus and trachea; incomplete vascular rings are also referred to as vascular slings (Yoo et al., 2003). Vascular rings may compress the trachea and esophagus leading to respiratory distress shortly after birth or the development of milder symptoms and signs of tracheoesophageal compression later in life (Bronshtein et al., 1998). Alternatively, the lesion may remain clinically silent throughout a person’s life. Vascular rings can occur in isolation or may be associated with other congenital heart defects as well as non-cardiac defects and chromosomal or genetic anomalies. With the introduction of the three-vessel view (3VV) on prenatal ultrasound described initially by Yoo et al. *Correspondence to: Shengli Li, Department of Ultrasound, Shenzhen Maternity & Child Healthcare Hospital, Affiliated to Southern Medical University, Shenzhen 518028, China. E-mail: lishengli63@126.com

(1997) and three-vessel trachea view (3VT) described by Yagel et al. (2002) as well as careful attention to the anatomic relationship between the aortic and ductal arch and the fetal trachea, congenital vascular rings can be diagnosed prenatally. However, only a few cases of prenatally diagnosed vascular rings have so far been reported (Achiron et al., 2002; Yoo et al., 2003; Jain et al., 2010). Here, we reported the largest case series of prenatally diagnosed congenital vascular rings. The sonographic features of each type of vascular ring are described along with accompanying perinatal outcome.

MATERIALS AND METHODS Consecutive cases of congenital vascular rings diagnosed by prenatal ultrasound between July 2005 and December 2009 were identified at a single referral center using an established perinatal database. The Prenatal Diagnosis Center at Shenzhen Maternity & Child Received: 17 September Revised: 14 November Accepted: 16 November Published online: 30 January

2010 2010 2010 2011

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Healthcare Hospital in Shenzhen, China, was designated a national prenatal diagnosis training center in 2004, and it serves as a national referral hospital for patients from throughout China. This study was approved by the Institutional Review Board of the Shenzhen Maternity & Child Healthcare Hospital, which is an affiliation of the Southern Medical University, China. All prenatal ultrasound examinations were performed on Acuson Sequoia machines (Siemens Medical Solutions, Mountain View, CA, USA) using 4- or 6-MHz curvilinear or 8-MHz phased array transducers. Our routine anatomic survey includes a four-chamber cardiac, left and right ventricular outflow tract, and the 3VT views in addition to the other standard views. Fetal echocardiography includes a detailed cardiac assessment, including demonstration of the atrial and visceral situs, systemic and pulmonary venous connections, symmetric four-chamber view, patency and symmetry of the atrioventricular valves, both outflow tracts and great arteries, and the ductal and aortic arches, including their positions relative to the trachea. If an aortic arch anomaly is suspected, additional views are obtained, including a long-axis view of the aortic and ductal arches, a coronal view of the trachea and branches, and a coronal view of the descending aorta (DAO) at the junction of the ductus and arch. In all cases, pulsed and color Doppler flow imaging was also performed to confirm patency of the ventricular inflow tracts, outflow tracts, and arches and to assess the flow patterns in the pulmonary veins, umbilical artery, umbilical vein, and ductus venosus. All perinatal ultrasound examinations were performed by physicians specialized in prenatal diagnosis and fetal echocardiography with up to 10 years of experiences. The diagnosis of vascular ring was confirmed by postnatal echocardiography for live-born infants or autopsy for terminated cases. Demographic and genetic information, pregnancy complications, and perinatal outcome were abstracted from the maternal and neonatal medical records after delivery. Where possible, the long-term outcome of infants and children born with congenital

vascular rings was determined. The sonographic features and perinatal outcome are reported using descriptive statistics.

RESULTS

Incidence and classification of congenital vascular rings During this 5-year time period, a total of 1090 cases of congenital cardiac and vascular defects were identified among the 94 321 women undergoing prenatal ultrasound examination at our institution giving an overall incidence of congenital cardiac and vascular disease of 1.16%. Of these, 81 cases (81/1090, 7.43%) involved congenital vascular rings for an overall incidence of 0.086% (81/94, 321). Forty-four of these had complete O-shaped (n = 3) or U-shaped (n = 41) vascular rings. The specific arrangements of the large vessels are summarized in Table 1. The remaining 37 cases had incomplete C-shaped vascular rings (vascular slings) (Table 1). The most common type of vascular ring seen in 50.6% (41/81) of cases was a complete ring with a right-sided aortic arch (R-ARCH), left ductus arteriosus (LDA), and aberrant left subclavian artery (ALSA) (Figure 1). Among the incomplete vascular rings, the most common was a left-sided aortic arch (L-ARCH) with LDA and an aberrant right subclavian artery (ARSA) (Figure 2), which was seen in 39.5% (32/81) of cases. Among the 81 cases of congenital vascular rings, 46 (56.8%) were isolated lesions not associated with other structural abnormalities (Table 2). All three cases of double aortic arch (DAA) were isolated lesions. Of the remaining 35 cases, 31.4% (n = 11) had associated cardiac defects only, 20.0% (n = 7) had associated noncardiac defects only, and 48.6% (n = 17) had both associated cardiac and non-cardiac anomalies (Table 2). L-ARCH with LDA and an ARSA had the highest rate of associated cardiac [12.5% (4/32)], non-cardiac [9.4%

Table 1—Classification of congenital vascular rings Arrangement of the blood vessels within the congenital vascular ring Double aortic arch Right aorta arch with left ductus arteriosus and aberrant left subclavian artery Left aortic arch with aberrant right subclavian artery Pulmonary artery sling Right aortic arch with left descending aorta Total (%)

Complete type

Incomplete type

‘O’ shape

‘U’ shape

‘C’ shape

Total

Overall incidence (%)

3 0

0 41

0 0

3 (3.7%) 41 (50.6%)

0.003 0.044

32 (39.5%)

0.034

2 (2.5%)

0.002

3 (3.7%)

0.003

3 (3.7%)

41 (50.6%)

37 (45.7%)

81 (100%)

0.086

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(A)

(B)

(C)

(D)

Figure 1—U-shaped complete vascular ring with right aortic arch (R-ARCH), aberrant left subclavian artery (LSA), and left-sided ductus arteriosus (DA). (A) A schematic diagram is included showing R-ARCH with an aberrant LSA, and a left-sided DA forming a U-shaped vascular ring around the esophagus (E) and trachea (T). (B) The three-vessel trachea (3VT) view on prenatal ultrasound shows the aortic arch on the right side of the trachea. (C) A color Doppler image of the 3VT view is shown. (D) On autopsy, the ascending aorta (AAO), R-ARCH, LSA, DA, and main pulmonary artery (MPA) can be seen extending out from the base of the heart and forming a U-shaped vascular ring (highlighted in yellow ) that surrounds the esophagus and trachea. This is regarded as a complete vascular ring as it entirely surrounds the esophagus and trachea. DAO, descending aorta; L, left; LCA, left common carotid artery; LV, left ventricle; R, right; RAA, right atrial appendage; RCA, right common carotid artery; RSA, right subclavian artery; RV, right ventricle; SP, spine; SVC, superior vena cava

(A)

(B)

(C)

(D)

Figure 2—C-shaped incomplete vascular ring with left aortic arch, aberrant right subclavian artery (RSA), and left-sided ductus arteriosus (DA). (A) A schematic diagram is included showing a left-sided (normal) aortic arch (ARCH) with an aberrant RSA and a left-sided DA. The aberrant RSA courses behind the esophagus (E) and trachea (T) on its way to the right arm of the fetus, thereby forming a C-shaped vascular ring around the esophagus and trachea. (B) The three-vessel trachea (3VT) view on prenatal ultrasound is shown. (C) A color Doppler image of the 3VT view is shown. (D) On autopsy, the aberrant RSA originates from the descending aorta (DAO) and courses rightward and posteriorly on its way to the right arm of the fetus forming a C-shaped vascular ring (highlighted in yellow ) that surrounds the esophagus and trachea. This is regarded as an incomplete vascular ring as it does not entirely encircle the esophagus and trachea. AAO, ascending aorta; L, left; LCA, left common carotid artery; LPA, left pulmonary artery; LSA, left subclavian artery; LV, left ventricle; MPA, main pulmonary artery; R, right; RAA, right atrial appendage; RCA, right common carotid artery; RPA, right pulmonary artery; RV, right ventricle; SVC, superior vena cava Copyright  2011 John Wiley & Sons, Ltd.

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Table 2—Anomalies associated with congenital vascular rings Type of congenital vascular ring Double aortic arch Right aorta arch with left ductus arteriosus and aberrant left subclavian artery Left aortic arch with left ductus arteriosus and aberrant right subclavian artery Pulmonary artery sling Right aortic arch with left descending aorta Total

Isolated lesion (%)

Associated with cardiac anomalies only (%)

Associated with non-cardiac anomalies only (%)

Associated with cardiac and noncardiac anomalies (%)

Total (%)

3 (3.7%) 29 (35.8%)

0 5 (6.2%)

0 4 (4.9%)

0 3 (3.7%)

3 (3.7%) 41 (50.6%)

14 (17.3%)

4 (4.9%)

3 (3.7%)

11 (13.6%)

32 (39.5%)

2 (2.5%)

1 (1.2%)

3 (3.7%)

46 (56.8%)

11 (13.6%)

7 (8.6%)

17 (21.0%)

81 (100%)

(3/32)], and combined cardiac and non-cardiac structural anomalies [34.4% (11/32)]. Twenty-nine of the 81 cases underwent termination of pregnancy, and all of these had an autopsy which confirmed the diagnosis of vascular ring. There were a number of associated anomalies found at autopsy that were not diagnosed by prenatal ultrasound, including a small ventricular septal defect (n = 3), aortic arch coarctation (n = 1), polydactyly (n = 1), hemivertebrae (n = 1), and esophageal atresia (n = 1).

Types of congenital vascular rings The most common type of congenital vascular ring in our study population seen in 50.6% (41/81) of cases was the R-ARCH with LDA and an ALSA, which forms a U-shaped complete vascular ring (Figure 1). In this type of vascular ring, the R-ARCH gives rise to the left common carotid artery as its first branch followed, in turn, by the right common carotid artery, right subclavian artery (RSA), and left subclavian artery (LSA) (Figure 1A). The LSA originates from the beginning of the DAO and courses leftward and forward behind the esophagus and trachea on its way to the left arm of the fetus. The LDA connects the main pulmonary artery (MPA) and LSA. The 3VT view on perinatal ultrasound shows the aortic arch on the right side of the trachea (Figure 1B). The aortic arch, LSA, ductus arteriosus (DA), and MPA thus form a U-shaped vascular ring that surrounds the esophagus and trachea, and the opening of the ‘U’ is closed by the base of the heart. This can be seen most clearly by color Doppler flow imaging at the 3VT view (Figure 1C) and can be confirmed in selected cases by postnatal autopsy (Figure 1D). Of these 41 cases, 29 (70.7%) were isolated, 5 (12.2%) were associated with cardiac anomalies, 4 (9.8%) with non-cardiac anomalies, and 3 (7.3%) with both cardiac and non-cardiac defects (Table 2). The second most common type of vascular ring in our study population seen in 39.5% (32/81) of cases Copyright  2011 John Wiley & Sons, Ltd.

was a L-ARCH with LDA and an ARSA, which forms a C-shaped incomplete vascular ring (Figure 2). In this lesion, the L-ARCH gives out its first branch as the right common carotid artery followed, in turn, by the left common carotid artery, LSA, and ARSA (Figure 2A). The ARSA, which originates from the beginning of the DAO, courses behind the esophagus and trachea on its way to the right arm of the fetus, thereby forming a C-shaped vascular ring around the esophagus and trachea. At the 3VT view, both grayscale (Figure 2B) and color Doppler images (Figure 2C) show the C-shaped vascular ring. The diagnosis can be confirmed at autopsy (Figure 2D). Of these 32 cases, 14 (43.8%) were isolated, 4 (12.5%) were associated with cardiac defects, 3 (9.4%) with non-cardiac defects, and 11 (34.4%) with both cardiac and non-cardiac defects (Table 2). A less common type of vascular ring seen in our study population [3.7% (3/81)] was the DAA (Figure 3). This represents an embryologic persistence of both the RARCH and L-ARCH which entirely encircles the trachea and esophagus forming an O-shaped complete vascular ring (Figure 3A). The L-ARCH gives rise to the left common carotid artery and LSA, and the R-ARCH gives rise to the right common carotid artery and RSA. On the 3VT view, the DAA can be seen to encircle the trachea (Figure 3B). The DA located on the left side of the LARCH makes this anomaly appear like the number ‘9’ or ‘6’ on the 3VT view, which is perhaps best seen by color Doppler imaging (Figure 3C). The pregnancy was terminated in one of the three fetuses with a suspected diagnosis of DAA, and the diagnosis was confirmed at autopsy (Figure 3D). In this cohort, all three cases of DAA were isolated lesions with no associated cardiac or non-cardiac anomalies (Table 2). Left pulmonary artery (LPA) sling [aberrant LPA arising from the right pulmonary artery (RPA)] was found in two cases [2.5% (2/81)] (Figure 4). In such cases, the LPA originates from the RPA before the proximal portion of the right bronchus and courses between the trachea and esophagus on its way to the Prenat Diagn 2011; 31: 334–346. DOI: 10.1002/pd

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(B)

(C)

(D)

Figure 3—O-shaped complete vascular ring with double aortic arch (DAA) and left-sided ductus arteriosus (DA). (A) A schematic diagram is included showing a DAA arising from the ascending aorta (AAO) with a left-sided DA. (B) The three-vessel trachea (3VT) view on prenatal ultrasound shows the persistent right (R) and left (L) aortic arches which form an O-shaped vascular ring around the trachea (T) and esophagus. (C) A color Doppler image of the 3VT shows the O-shaped vascular ring. The DA is located on the left side of the left aortic arch, which may take on the shape of the number ‘9’ or ‘6’. (D) On autopsy, the DAA can be seen arising from the AAO and forming an O-shaped vascular ring (highlighted in yellow ) that surrounds the trachea and esophagus. This is regarded as a complete vascular ring as it entirely surrounds the esophagus and trachea. LAA, left atrial appendage; L-ARCH, left aortic arch; LCA, left common carotid artery; L-LU, left lung; LSA, left subclavian artery; LV, left ventricle; MPA, main pulmonary artery; RAA, right atrial appendage; R-ARCH, right aortic arch; RCA, right common carotid artery; R-LU, right lung; RSA, right subclavian artery; RV, right ventricle; SP, spine; SVC, superior vena cava. (The autopsy picture was provided by Dr Ying Wu, MD, Shenzhen First People’s Hospital, Shenzhen, China)

hilus of the left lung, thus forming a C-shaped incomplete vascular ring (Figure 4A). Gray-scale (Figure 4B) and color Doppler imaging (Figure 4C) at the 3VT view show the aberrant course of the LPA as it passes between the trachea and esophagus, forming the C-shaped vascular ring. In many cases, it may not be possible to see the aberrant vessel passing between the trachea and esophagus, as the esophagus is rarely visible on perinatal ultrasound unless it is filled with fluid during fetal swallowing. The diagnosis was confirmed at autopsy (Figure 4D). Both these cases were associated with other cardiac anomalies (Table 2). The final type of vascular ring seen in our study population, although rare [3.7% (3/81)], was a R-ARCH crossing the midline behind the trachea and esophagus and culminating in a left-sided DAO (also called a circumflex retroesophageal aortic arch), thereby forming a C-shaped incomplete vascular ring (Figure 5). In the 3VT view, the DAO can be seen to the left side of the thoracic spine, whereas the ascending aorta and MPA are located to the right of the spine. The R-ARCH can be seen crossing the midline behind the trachea and esophagus to descend on the left side (Figure 5B and C). The diagnosis was confirmed at autopsy (Figure 5D). All three cases were associated with other cardiac anomalies (Table 2). Copyright  2011 John Wiley & Sons, Ltd.

Perinatal outcome Of the 46 cases of isolated vascular rings, 3 (6.5%) ended in elective pregnancy termination, 35 (76.1%) resulted in a live birth at term, 6 (13.0%) were lost to follow-up, 1 (2.2%) ended in intrauterine fetal demise at 30 weeks, and 1 (2.2%) pregnancy is ongoing (Table 3). All live-born infants had a postnatal echocardiogram performed, and the diagnosis was confirmed in all instances. One infant developed symptoms of tracheoesophageal compression requiring surgery at 1 month of age; the infant died a week after surgery. The remaining 34 live-born infants remain asymptomatic. The three pregnancies that ended in elective termination and the stillborn fetus all had the diagnosis confirmed on autopsy. Of the 32 women (69.6%) who chose to undergo amniocentesis and prenatal karyotype analysis, only one case of fetal aneuploidy (trisomy 21) was identified (2.2%). Of the 35 cases of vascular rings with associated structural abnormalities, 26 (74.3%) ended in elective pregnancy termination, 7 (20.0%) resulted in a live birth, 1 (2.9%) was still birth, and 1 (2.9%) was lost to follow-up (Table 4). The diagnosis was confirmed in all cases by either postnatal echocardiography or autopsy. Of the 14 women (40%) who elected to proceed with prenatal karyotype analysis, 5 (35.7%) had fetuses with Prenat Diagn 2011; 31: 334–346. DOI: 10.1002/pd

PRENATAL DIAGNOSIS OF VASCULAR RINGS

(A)

(B)

(C)

(D)

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Figure 4—C-shaped incomplete vascular ring with aberrant left pulmonary artery (LPA, also referred to as pulmonary artery sling). (A) A schematic diagram is included showing the aberrant LPA, which originates from the right pulmonary artery (RPA) before the proximal portion of the right bronchus and courses between trachea (T) and esophagus (E) on its way to the hilus of the left lung. (B) The three-vessel trachea (3VT) view on prenatal ultrasound shows that the diameter of the main pulmonary artery (MPA) is smaller than that of the ascending aorta (AAO). The aberrant LPA can be seen passing between the trachea and esophagus. This particular case was also complicated by a double superior vena cava. (C) A color Doppler image of the 3VT view is shown. (D) At autopsy, the aberrant LPA can be seen originating from the RPA before the proximal portion of the right bronchus and coursing between the trachea and esophagus on its way to the hilus of the left lung, thereby forming a C-shaped vascular ring (highlighted in yellow ) that surrounds the trachea. This is regarded as an incomplete vascular ring as it does not entirely encircle the trachea. DA, ductus arteriosus; DAO, descending aorta; IA, innominate artery; IV, innominate vein; L, left; L-LU, left lung; L-SVC, left superior vena cava; LV, left ventricle; R, right; RAA, right atrial appendage; R-LU, right lung; R-SVC, right superior vena cava; RV, right ventricle; SP, spine; TH, thymus

chromosomal abnormalities (2 cases of trisomy 21 and 3 cases of trisomy 18). All the seven live-born infants had a normal karyotype and remained asymptomatic at this time (Table 4). Overall, five of the six fetuses (83.3%) with congenital vascular rings and aneuploidy also had other associated structural anomalies identified on prenatal ultrasound. DISCUSSION Vascular rings are a group of congenital anomalies of the great vessels and their branches, and account for <1% of all congenital cardiac diseases. Little has been published on the prenatal diagnosis of these disorders or on the outcome of such pregnancies. Here, we report the largest series of prenatally diagnosed congenital vascular rings. In this cohort, all cases of prenatally diagnosed vascular rings were confirmed by postnatal echocardiography or at autopsy, and there were no false-positive diagnoses. These results confirm the feasibility and accuracy of prenatal diagnosis of vascular rings using the standard 3VV view initially described by Yoo et al. (1997). In all cases, the diagnosis should be confirmed with fetal echocardiography using both two-dimensional and color Copyright  2011 John Wiley & Sons, Ltd.

flow imaging for complete assessment of the aortic arch system, with particular attention to the arrangement of the vascular structures coursing around and behind the trachea and esophagus (Patel et al., 2006). The overall incidence of congenital vascular rings in this cohort was 0.9%. However, this may not reflect the true prevalence of these conditions in the general population as this cohort is a high-risk referral population. Approximately half of the cases [56.8% (46/81)] were isolated vascular ring anomalies. The remaining 35 cases (43.2%) had evidence of associated structural abnormalities on prenatal ultrasound, especially cardiac anomalies. For this reason, we strongly suggest a detailed anatomic sonographic evaluation (including fetal echocardiography) by an experienced provider for all cases of suspected congenital vascular ring. In contrast to previous reports in adults (Tuo et al., 2009), but consistent with prior smaller publications in pediatric populations (Yoo et al., 2003), the most common type of vascular ring in our study population was a R-ARCH with ALSA [50.6% (41/81)] followed by L-ARCH with an ARSA [39.5% (32/81)]. A detailed knowledge of the embryologic origins of the heart and great vessels is essential to understand the pathogenesis and diagnosis of congenital vascular rings (Lowe et al., 1991; Yoo et al., 2003). If regression of the L-ARCH Prenat Diagn 2011; 31: 334–346. DOI: 10.1002/pd

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(A)

(C)

(B)

(D)

Figure 5—C-shaped incomplete vascular ring with right-sided aortic arch (R-ARCH) and left descending aorta (DAO) (circumflex retroesophageal aortic arch). (A) A schematic diagram is included showing a R-ARCH crossing the midline behind the trachea (T) and esophagus (E) and continuing as the DAO on the left side. In this case, ductus arteriosus is on the right side (RDA). (B) The three-vessel view (3VV) on prenatal ultrasound shows that the DAO lies on the left side of the thoracic spine (SP), whereas the ascending aorta (AAO) and main pulmonary artery (MPA) lie on the right side. (C) The sonographic three-vessel trachea (3VT) view also illustrates the relationship between the aortic arch (ARCH) and superior vena cava (SVC). (D) At autopsy, the right-sided ARCH can be seen passing from right to left and from anterior to posterior relative to the heart, thereby forming a C-shaped vascular ring (highlighted in red) that surrounds the trachea and esophagus; in this specimen, the trachea and esophagus have been removed. This is regarded as an incomplete vascular ring as it does not entirely encircle the trachea and esophagus. DA, ductus arteriosus; L, left; L-LU, left lung; LPA, left pulmonary artery; R, right; RAA, right atrial appendage; RCA, right common carotid artery; R-LU, right lung; RPA, right pulmonary artery; RSA, right subclavian artery; RV, right ventricle. (The autopsy picture was provided by Dr Guangzhi He, Gongming Hospital of Shenzhen, Shenzhen, China)

occurs distally to the origin of the LSA, the end result is a mirror image of the normal L-ARCH. This situation does not result in the formation of a vascular ring surrounding the trachea and esophagus, but has the highest association with other congenital cardiac defects, most commonly tetralogy of Fallot (F4) (Achiron et al., 2002; Yoo et al., 2003). If regression of the L-ARCH occurs between the origins of the left common carotid artery and LSA, then the R-ARCH gives rise to the left common carotid artery as its first branch followed, in sequence, by the right common carotid artery, RSA, and ALSA. The LDA persists and connects to the MPA and ALSA. This situation results in the formation of a complete U-shaped vascular ring, as the ALSA arising from the DAO courses behind the trachea and esophagus on its way to the left arm of the fetus and connects to the main pulmonary via the LDA (Figure 1) (Berg et al., 2006; Galindo et al., 2009). In our study population, this was the most common type of isolated vascular ring (Tables 2 and 3). When other structural anomalies are present, these are most commonly seen other cardiac defects (Tables 2 and 4). The second most common vascular ring in our study population was the L-ARCH with ARSA. In these cases, the L-ARCH gives rise to the right common carotid artery as its first branch followed, in sequence, by the left Copyright  2011 John Wiley & Sons, Ltd.

common carotid artery, LSA, and then the ARSA. The ARSA courses behind the esophagus and trachea on its way to the right arm of the fetus, and the LDA persists, thereby forming an incomplete C-shaped vascular ring around the esophagus and trachea (Figure 2). Compared with the R-ARCH with ALSA, this type of vascular ring is more likely to be associated with other structural defects, especially combined cardiac and non-cardiac defects (Tables 2 and 4). The remaining three types of vascular rings were all less common, each seen in only two or three cases (2.5–3.7%). All three cases of DAA with complete O-shaped vascular ring surrounding the trachea and esophagus represented isolated lesions. In contrast to previous reports (Shum et al., 2007), the one liveborn child with this lesion remains asymptomatic after 13 months of close postnatal follow-up. The two cases of LPA sling (aberrant LPA arising from the RPA) and three cases of circumflex retroesophageal aortic arch were all seen in association with other cardiac anomalies (Table 4). The association between isolated vascular rings and chromosomal abnormalities in our study population was low, with only one case of fetal aneuploidy identified among 32 cases tested (3.1%). In contrast, 5 of the 14 cases (35.7%) of vascular rings with associated structural Prenat Diagn 2011; 31: 334–346. DOI: 10.1002/pd

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Table 3—Perinatal outcomes in cases of isolated congenital vascular rings Arrangement of the congenital vascular rings Double aortic arch

Right aortic arch with left ductus arteriosus and aberrant left subclavian artery

Left aortic arch with aberrant right subclavian artery

GA at diagnosis (weeks)

Karyotype

3 4

1 3

29 32

46, XY 46, XY

21 23

1 1

0 0

23 24

Not performed 46, XX

46, XY

7 8

29 23

1 1

0 0

28 27

Not performed Not performed

46, XY

46, XX

46, XY

46, XX

46, XY

46, XX

46, XY

Not performed

46, XY

Not performed

46, XX

46, XY

24 25

28 22

2 1

0 0

25 22

46, XY 46, XX

26 27 28 29 30 31 32 33

28 28 34 36 26 22 35 24

1 4 1 2 3 1 4 1

0 0 0 0 0 0 0 0

22 25 26 25 26 22 20 26

Not performed 46, XY Not performed Not performed 46, XX Not performed 46, XY 46, XY

Not performed

Case number

MA (years)

1 2

35 44

3 4

Perinatal outcome TOP Live birth; asymptomatic at 13 months Ongoing pregnancy Live birth; asymptomatic at 48 months Live birth; asymptomatic at 42 months Live birth; asymptomatic at 40 months Oligohydramnios, TOP Live birth; asymptomatic at 34 months Live birth; asymptomatic at 37 months Live birth; surgery performed at 1 month of life because of worsening symptoms; infant died 1 week after surgery Live birth; asymptomatic at 23 months Live birth; asymptomatic at 24 months Live birth; asymptomatic at 26 months Live birth; asymptomatic at 18 months Live birth; asymptomatic at 19 months Live birth; asymptomatic at 23 months Live birth; asymptomatic at 36 months Live birth; asymptomatic at 34 months Live birth; asymptomatic at 31 months Live birth; asymptomatic at 36 months Polyhydramnios, vasa previa leading to IUFD at 32 weeks Live birth; asymptomatic at 21 months Live birth; asymptomatic at 11 months Live birth; asymptomatic at 8 months Live birth; asymptomatic at 10 months Lost to follow-up Live birth; asymptomatic at 3 months Lost to follow-up TOP Live birth; asymptomatic at 4 months Lost to follow-up Live birth; asymptomatic at 9 months Live birth; asymptomatic at 34 months Live birth; asymptomatic at 30 months Prenat Diagn 2011; 31: 334–346. DOI: 10.1002/pd

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Table 3—(Continued ) Arrangement of the congenital Case vascular rings number 35 36 37 38 39 40 41 42 43 44 45

46 Totala

MA (years)

GA at diagnosis (weeks)

Karyotype

Perinatal outcome

46, XX

Live birth; asymptomatic at 36 months 26 2 0 24 46, XY Live birth; asymptomatic at 33 months 35 2 0 23 46, XX Live birth; asymptomatic at 31 months 29 2 0 34 Not performed Lost to follow-up 26 2 0 26 46, XX Live birth; asymptomatic at 30 months 31 1 0 25 Not performed Lost to follow-up 28 2 0 30 46, XY Live birth; asymptomatic at 4 months 28 2 0 25 46, XX Live birth; asymptomatic at 15 months 27 1 0 25 46, XY Live birth; asymptomatic at 4 months 29 3 0 28 Not performed Lost to follow-up 27 1 0 23 47, XX, +21 Live birth; symptomatic at 12 months; postnatal chromosome analysis confirmed Down syndrome 27 1 0 29 46, XX Live birth; asymptomatic at 14 months 28.4 ± 4.9 1.9 ± 1.0 0.17 ± 0.56 26.0 ± 4.0 Normal karyotype Live births = 35 (76.1%) = 31 (67.4%) Trisomy 21 = 1 IUFD = 1 (2.2%) (2.2%) Not performed = TOP = 3 (6.5%) 14 (30.4%) Ongoing pregnancy = 1 (2.2%) Lost to follow-up = 6 (13.0%)

G, gravidity; GA, gestational age; MA, maternal age; IUFD, intrauterine fetal demise (stillbirth); P, parity; TOP, termination of pregnancy. a Data are presented as mean ± SD.

abnormalities had an abnormal karyotype. In a series of 66 cases of isolated anomalies of laterality or branching of the aortic arch, McElhinney et al. (2001) found the 22q11.2 deletion to be present in 24%, including 14% of patients with DAA and 32% with a R-ARCH and ALSA. Testing for microdeletion of 22q11 was not done in this series. Given these data, it is reasonable to offer amniocentesis and karyotype analysis for all cases of congenital vascular rings, but especially when seen in association with other structural abnormalities. After birth, children with congenital vascular rings may develop clinical symptoms resulting from compression of the esophagus and/or trachea, including dysphagia and shortness of breath due to large airway obstruction. Interestingly, these symptoms may only begin later in life. Of all the lesions, the DAA has been reported to have the strongest association with clinical symptoms (Shum et al., 2007) due to the significant tracheal and esophageal obstruction caused by both aortic arches as they pass over the corresponding bronchi and join posteriorly to form the DAO, Copyright  2011 John Wiley & Sons, Ltd.

thereby completely surrounding the esophagus and trachea (Figure 3). Our one live-born child with confirmed DAA has been followed for 13 months and remains asymptomatic. Indeed, the only case that developed clinical symptoms was a case of R-ARCH with ALSA, which required surgery at 1 month of age. Unfortunately, the infant died a week after the procedure from surgical complications. All the remaining live-born cases of vascular ring in our study population remain asymptomatic at present. These children continued to be followed closely for potential lateonset symptoms, including airway obstruction or dysphagia. In conclusion, this study—which represents the largest series of prenatally diagnosed congenital vascular rings yet reported—confirms that vascular rings can be diagnosed by prenatal ultrasound with careful attention to the relationship between the large vessels of the aortic and ductal arches and the trachea. Prenatal detection of these congenital vascular anomalies, whether isolated or associated with other structural defects, should be followed by detailed counseling in consultation with specialists in maternal-fetal medicine, perinatology, and/or Prenat Diagn 2011; 31: 334–346. DOI: 10.1002/pd

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PRENATAL DIAGNOSIS OF VASCULAR RINGS

Table 4—Perinatal outcomes in cases of congenital vascular rings associated with other anomalies Arrangement of the congenital vascular rings Right aortic arch with left ductus arteriosus and aberrant left subclavian artery

Left aortic arch with aberrant right subclavian artery

GA at diagnosis (weeks)

Associated anomalies

Tetralogy of Fallot

Not performed

TOP

VSD

Lost to follow-up TOP

4 5

40 26

2 2

0 0

24 24

VSD, DORV, LSVC, and pulmonary stenosis Tetralogy of Fallot LSVC

Not performed Not performed 46, XY 46, XY

Persistent right umbilical vein

46, XX

Partial phocomelia

Persistent right umbilical vein

Not performed 46, XY

TOP Live birth; asymptomatic at 10 months Live birth; asymptomatic at 23 months TOP

Not performed

Right-sided congenital diaphragmatic hernia, persistent right umbilical vein VSD, echogenic bowel, and hypoplasia of the fifth middle phalanx LSVC, hypoplasia of corpus callosum, Dandy–Walker complex, ventriculomegaly, hemivertebrae, and bilateral renal hypoplasia HLHS, VSD, DORV, pulmonary stenosis, LSVC, and situs inversus HLHS, aortic arch coarctation, and LSVC

Tetralogy of Fallot

Case number

MA (years)

Karyotype

Perinatal outcome

Live birth; asymptomatic at 5 months TOP

47, XX, +21

TOP

Not performed

TOP

Not performed

TOP

46, XX

TOP

Not performed

TOP

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Table 4—(Continued ) Arrangement of the congenital vascular rings

Case number

MA (years)

GA at diagnosis (weeks)

Associated anomalies

Karyotype

Perinatal outcome

Not performed

TOP

Not performed

TOP

HLHS, endocardial fibroelastosis, mitral stenosis, premature closure of foramen ovale, and LSVC Aortic arch coarctation, single atrium, and single ventricle Increased nuchal fold

46, XY

Polydactyly

Not performed

47, XY, +21 47, XY, +18

Cystic hygroma and nasal bone hypoplasia HLHS, VSD, growth restriction, clenched hands, and micrognathia Tetralogy of Fallot, VSD, choroid plexus cyst, strawberry-shaped head, single umbilical artery, micrognathia, and clenched hands Aortic arch coarctation, single umbilical artery, and persistent right umbilical vein

Live birth; asymptomatic at 2 months Live birth; asymptomatic at 13 months TOP

Not performed

VSD, complete transposition of the great arteries, Dandy–Walker complex, microtia, and esophageal atresia VSD, hypoplasia of corpus callosum, maga cisterna magna, micrognathia, strawberry-shaped head, clenched hands, rocker-bottom foot, and umbilical cord cyst HLHS, pulmonary stenosis, bilateral renal agenesis, severe oligohydramnios, single umbilical artery, and sirenomelia sequence LSVC and single umbilical artery

HLHS, cystic hygroma, and fetal hydrops Mirror-image dextrocardia, left radial ray aplasia, radial deviation left hand, clubhand, and micrognathia

Not performed Not performed

TOP

47, XX, +18

TOP

46, XX

Live birth; required surgical closure of patent ductus arteriosus at 2 years of age; asymptomatic at 35 months TOP

47, XX, +18

TOP

Not performed

TOP

46, XX

Live birth; asymptomatic at 27 months TOP TOP

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PRENATAL DIAGNOSIS OF VASCULAR RINGS

Table 4—(Continued ) Arrangement of the congenital Case vascular rings number

Right aortic arch with left descending aorta

MA (years)

GA at diagnosis (weeks)

Pulmonary artery sling with aberrant left pulmonary artery

Totala

Associated anomalies VSD, tricuspid regurgitation, Dandy–walker complex, posterior fossa cyst, ventricular dilatation, hypoplasia of corpus callosum, and omphalocele VSD, hypoplasia of tricuspid valve, LSVC, radial ray aplasia of hands, and clubhand Truncus arteriosus, single atrium, and single ventricle

Karyotype

Perinatal outcome

Not performed

TOP

Not performed

TOP

Not performed

TOP

Tetralogy of Fallot Not performed 23 1 0 26 Levoversion of Not heart, single performed ventricle, pulmonary stenosis, and situs inversus 26 1 0 26 Hypoplasia of 46, XX right heart, LSVC, right-sided pulmonary agenesis Not 30 1 0 23 Dextroversion of performed heart, and right-sided pulmonary agenesis 28.5 ± 4.6 1.7 ± 1.0 0.1 ± 0.4 25.2 ± 3.6 Associated cardiac Normal malformations karyotype = only = 13 (37.1%) 9 (25.7%) Associated Trisomy 21 non-cardiac = 2 (5.7%) malformations only = 7 (20.0%) Both associated Trisomy 18 cardiac and = 3 (8.6%) non-cardiac malformations = 15 (42.9%) Not performed = 21 (60.0%)

TOP TOP

IUFD

TOP

Live births = 7 (20%) IUFD = 1 (2.9%) TOP = 26 (74.2%)

Lost to follow-up = 1 (2.9%)

DORV, double outlet right ventricle; G, gravidity; GA, gestational age; HLHS, hypoplastic left heart syndrome; IUFD, intrauterine fetal demise (stillbirth); LSVC, left superior vena cava; MA, maternal age; P, parity; VSD, ventricular septal defect; TOP, termination of pregnancy. a Data are presented as mean ± SD.

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genetics. Additional prenatal testing may be indicated, including karyotype analysis. Patients with prenatally diagnosed congenital vascular rings should be followed closely for clinical symptoms of airway obstruction or dysphagia. ACKNOWLEDGEMENT

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