DOI: 10.1002/pd.4380
ORIGINAL ARTICLE
Fetal persistent left superior vena cava in cases with and without chromosomal anomalies Liu Du, Hong-Ning Xie*, Yun-Xiao Zhu, Li-Juan Li, Ruan Peng and Ju Zheng Department of Ultrasonic Medicine and Fetal Medical Centre, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China *Correspondence to: Hong-Ning Xie. E-mail: [email protected]
ABSTRACT Objectives The objectives of this study are to determine and compare the prevalence of persistent left superior vena cava (PLSVC) in chromosomally normal and abnormal fetuses and to evaluate the potential of PLSVC as a screening marker for chromosomal abnormalities. Methods Women undergoing routine fetal sonographic examinations were evaluated once for the presence of PLSVC. PLSVC was diagnosed on the basis of the identification of an additional vessel in the left of the pulmonary artery in a three-vessel trachea view. Associated abnormalities, karyotypes, and outcomes were analyzed. Results A total of 164 (0.7%, 164/25 171) cases of PLSVC were detected and successfully followed-up. The detection rates were 0.5% (81/17 535) and 1.1% (83/7636) in the low-risk and high-risk cases, respectively. The incidence of PLSVC was lower among the chromosomally or clinically normal (0.4%, 110/24 914) compared with chromosomally abnormal fetuses (7.8%, 20/257, p < 0.001). Additional defects were identified in 90% (18/20) of the PLSVC fetuses with chromosomal anomalies, a rate that was higher than those fetuses with chromosomal normal (61.8%, 68/110).
Conclusions Persistent left superior vena cava is more common among chromosomally abnormal than normal fetuses, and PLSVC fetuses with other defects are more highly associated with chromosomal disorders than isolated PLSVC fetuses. Isolated PLSVC is a benign vascular anomaly and may not affect outcomes. © 2014 John Wiley & Sons, Ltd. Funding sources: This study was supported by research grant 81071166 from the National Scientific Foundation Committee of China. Conflicts of interest: None declared
INTRODUCTION Persistent left superior vena cava (PLSVC) is the most common variant of the thoracic venous system.1 Its prevalence is estimated to be approximately 0.3–0.5% in the general population.1–3 However, the true incidence of PLSVC is unknown because this condition is usually asymptomatic and difficult to detect during routine transthoracic echocardiographic studies in postnatal patients.4 Nonetheless, PLSVC can be easily and accurately identified prenatally during ultrasound examination. In particular, the use of the three-vessel trachea (3VT) view of the upper mediastinum during fetal cardiac examinations has facilitated the direct diagnosis of PLSVC (Figure 1a).5 An association between PLSVC and chromosomal defects has previously been reported, and some authors have asserted that fetal karyotyping should be routinely offered whenever PLSVC is detected prenatally.6,7 Other authors have noted that most aneuploid fetuses exhibit other defects that might be more directly associated with chromosomal disorders.8,9 Therefore, the implications of PLSVC for the risk assessment of chromosomal anomalies are unknown. Therefore, the aims of this study were to evaluate and compare the prevalence of PLSVC among chromosomally normal and Prenatal Diagnosis 2014, 34, 797–802
abnormal fetuses and to evaluate the potential value of PLSVC as a prenatal screening marker for chromosomal abnormalities.
METHODS This cross-sectional study was conducted between 1 January 2008 and 30 September 2011 at a tertiary referral center for the prenatal diagnosis and management of fetal and neonatal pathology. Experienced perinatologists performed all sonographic examinations using a Voluson 730 Expert system ultrasound machine (GE Healthcare, Kretztechnik, Zipf, Austria) with a 4 to 8 MHz transabdominal probe. The fetal ultrasonographic examinations included a detailed extracardiac structural survey and a complete echocardiographic examination, which were performed following standardized guidelines. The cardiac scans were performed using a segmental approach that combined a two-dimensional mode and color/ pulsed Doppler flow imaging. The cardiac scans included observations of the situs and the position of the heart and the four-chamber view, the outflow tracts, the 3VT view, the aortic and ductal arches, and both systemic and pulmonary venous returns.10 The 3VT view was obtained as originally described.5,10 © 2014 John Wiley & Sons, Ltd.
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Figure 1 (a) Normal three-vessel trachea (3VT) view at 24 weeks showing the following vessels, from left to right: the arterial duct (AD), the aortic arch (AoA) and the right superior vena cava (RSVC). (b) Abnormal 3VT view at 28 weeks showing a supernumerary vessel located to the left of the arterial duct. LSVC, left superior vena cava; T, trachea
During the study period, all fetal echocardiograms were systematically examined for the presence of PLSVC. The prenatal diagnosis of PLSVC was made on the basis of an abnormal 3VT view showing a supernumerary vessel located to the left of the pulmonary trunk and arterial duct (Figure 1b).5 The diagnosis was then confirmed with a long-axis view that revealed direct or indirect drainage via the coronary sinus into the left or right atrium (Figure 2). The karyotype was determined prenatally from a chorionic villus, amniotic fluid, or fetal blood sample or postnatally from a blood test sample of a neonate with features that were suggestive of a chromosomal anomaly. The indications for a prenatal invasive diagnosis of chromosomal abnormality with cytogenetic analysis included the following: (1) advanced maternal age (≥34 years old), (2) abnormal biochemical markers in the maternal serum, such as in maternal blood Down syndrome screening (>1/270), (3) abnormal ultrasound findings, (4) unexplained recurrent miscarriage or intrauterine fetal death, (5) family history of chromosomal abnormalities, (6) parent with abnormal karyotype, (7) history of abnormal offspring birth, (8) radiation or medication exposure during pregnancy, and (9) other nonspecific indications, such as anxiety, consanguineous marriage, and so on. In cases in which no karyotype was obtained prenatally, the karyotype was considered normal if the newborn appeared clinically normal to the local examining pediatrician. Follow-up scans
were offered every 4–6 weeks in cases of ongoing pregnancies. Perinatal management in an appropriate tertiary center was strongly recommended to the parents, particularly when the fetus had cardiac defects. The prenatal sonograms and postnatal imaging findings, pathologic diagnoses, karyotype, and clinical outcomes were recorded. A chi-squared test or Fisher’s exact test was used to compare the incidences of PLSVC and other defects between the normal and chromosomally abnormal fetuses and to identify the significant differences. Odds ratios for the presence of PLSVC in the chromosomally abnormal fetuses were calculated and are presented with 95% CIs. The statistical analysis was performed using the SPSS software, version 16.0 (SPSS Inc, Chicago, IL), and p < 0.05 was considered statistically significant.
RESULTS During the study period, 29 227 second-trimester and thirdtrimester echocardiographic examinations were performed in our center, and 25 171 (86.1%, 25 171/29 227) cases were successfully followed-up with karyotype or postnatal data. The majority of the women (n = 17 535, 69.7%) were attending our hospital primarily for standard prenatal care and routine scans for low-risk factors. The remaining women (n = 7636, 30.3%) were referred from their local hospitals because of the suspicion of fetal anomalies during routine scans; the women
Figure 2 (a) Longitudinal view of the coronary sinus (CS) draining into the right atrium in a normal fetus at 24 weeks. (b) Longitudinal view of the persistent left superior vena cava (LSVC) showing drainage into the dilated CS at 28 weeks. AO, aorta; IVC, inferior vena cava; LA, left atrium; PA, pulmonary artery; RA, right atrium; RV, right ventricle
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received detailed anomaly scans, counseling, and perinatal management as needed. In total, 725 cases were found to have a congenital heart defect in our center during the observation period, and 577 cases were successfully followed-up. Fetuses with PLSVC were detected in 181 cases, and 17 (9.4%, 17/181) were lost to follow-up. The median gestational age at detection was 25 weeks (range: 16–35 weeks). These cases represent 0.7% (164/25 171) of all echocardiographic examinations performed during that period; 81 were from low-risk populations (0.5%, 81/17 535), and 83 were from high-risk populations (1.1%, 83/ 7636). Within this group of 164 fetuses, 110 were chromosomally or clinically normal, whereas 20 fetuses (15.4%, 20/130) exhibited abnormal karyotypes (seven with trisomy 18, six with trisomy 21, three with trisomy 13, one with X chromosome monosomy, and three with other chromosomal defects). The remaining 34 cases (20.7%, 34/ 164) lacked fetal karyotype data or postnatal follow-up data. Chromosomal abnormalities were diagnosed by prenatal screening after detailed ultrasonographic examinations or postnatal karyotyping or by clinical assessment of the newborn. All PLSVC fetuses with chromosomal anomalies were detected prenatally, and there are two cases of Turner syndrome, six cases of trisomy 21, and 16 cases of abnormal chromosome segment were diagnosed postnatally. The PLSVC assessments are summarized in Table 1 according to the fetal karyotype or the outcome. The incidence of PLSVC was significantly lower among the chromosomally or clinically normal fetuses (0.4%, 110/ 24 914) compared with those fetuses with chromosomal anomalies (7.8%, 20/257, p < 0.001). The highest incidence of PLSVC (12.1%) was noted in the fetuses with trisomy 18. Similarly, PLSVC was more common among the fetuses with trisomy 21 (p < 0.001) and those fetuses with all other chromosomal abnormalities (p < 0.001) compared with the normal fetuses. The odds ratio for PLSVC in the chromosomally abnormal fetuses compared with the normal fetuses was 27.5 (95% CI, 15.8–47.8). There were 44 (26.8%, 44/164) cases with isolated PLSVC, 120 (73.2%, 120/164) cases associated with other anomalies (32 with other cardiac defects, 29 with extracardiac anomalies, 45 with both cardiac and extracardiac anomalies, and 14 with
Table 1 A summary of the karyotypes of the studied fetuses and the assessments of persistent left superior vena cava according to karyotype [n (%)] N
Karyotype Normal karyotype
Without PLSVC
With PLSVC
4626
4583
57 (1.2)
20 288
20 235
53 (0.3)
Trisomy 21
84
78
6(7.1)
Trisomy 18
58
51
7(12.1)
Normal clinical assessment
Other chromosomal defects No follow-up data Total
115
108
7(6.1)
4056
4005
51 (1.3)
29 227
25 240
181 (0.6)
PLSVC, persistent left superior vena cava.
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heterotaxy syndromes). Within the group of chromosomally or clinically normal fetuses with PLSVC, 42 (38.2%, 42/110) fetuses had isolated PLSVC; 68 (61.8%, 68/110) cases were associated with other defects (17 fetuses had cardiac defects, 16 had extracardiac anomalies, 21 had both cardiac and extracardiac anomalies, and 14 had heterotaxy syndromes). Among the 20 chromosomally abnormal PLSVC fetuses, only two (10%, 2/20) had PLSVC as an isolated finding; this difference was significant (p < 0.05). The ultrasonographic features of all chromosomally abnormal fetuses are presented in Table 2. The numbers and types of congenital heart defect in fetuses with and without PLSVC are presented in Table 3. All chromosomally abnormal fetuses and 87 of the normal fetuses with PLSVC underwent termination of pregnancy, including eight fetuses with isolated PLSVC, two cases with abnormal chromosomes, two women with severe pregnancy complications, and four childbearing women who violated the family planning restrictions in China. There were 57 births (36 fetuses had isolated PLSVC, three had cardiac defects, 10 had extracardiac anomalies, and eight had both cardiac and extracardiac anomalies), of which three infants died (one had isolated extracardiac anomalies and two had both cardiac and extracardiac anomalies); however, all cases of isolated PLSVC survived and were healthy at the time of this writing. Among the cases with postnatal follow-up for a minimum of 1 year, the overall survival rate was 29.8% (54/181); this rate increases to 94.7% (54/57) if the termination of pregnancy cases are excluded. Furthermore, there were two cases of prenatally detected extracardiac anomalies combined with other defects revealed at birth that were either not detected or not considered detectable by prenatal ultrasound. One newborn had microtia, dysaudia, and abnormal brain development and survived; the other infant had atretorrhinia and intestinal malrotation and died after surgery.
DISCUSSION Persistent left superior vena cava can be easily and accurately identified prenatally during a fetal echocardiographic examination. It is logical to assume that the rate of falsenegative diagnoses by specialists is extremely low, and PLSVC should be differentiated from anomalous pulmonary venous connection, for which few false-positive diagnoses have been reported.6,9,11 Previous prenatal diagnoses of PLSVC have been based on indirect findings, such as a ‘cystic’ structure corresponding to a cross-section of the dilated coronary sinus adjacent to the lateral wall of the left atrium and a ‘tubular’ structure crossing behind the left atrium and draining blood toward the right atrium.12 In recent years, the addition of the 3VT view of the upper mediastinum to fetal cardiac examinations has facilitated the direct diagnosis of PLSVC, showing four vessels instead of the normal three, with a supernumerary vessel to the left of the arterial duct.5 However, in the rare instances where the right superior vena cava is absent but the innominate vein is present, such as three cases in our study (two cases with isolated PLSVC and one with heterotaxy syndrome), there will again be three vessels, but they will be ‘abnormally’ arranged: from right to left, the aorta, pulmonary artery, and PLSVC. Therefore, the definitive © 2014 John Wiley & Sons, Ltd.
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26
26
32
28
38
33
28
29
38
28
39
23
41
34
29
38
24
26
29
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
23
29
32
20
30
25
24
20
17
30
26
21
18
23
27
27
26
31
29
27
GA at examination (weeks)
46, XX, t(1;2)(q44;q41)
46, XY, inv9(p11q13)
46, XY, der(21;21)(q10;q10)
46, XX, der(18;18)(q10;q10)
45, XO
47, XY, +13
47, XY, +13
47, XY, +13
47, XY, +18
47, XX, +18
47, XY, +18
47, XY, +18
47, XY, +18
47, XX, +18
47, XX, +21
47, XY, +21
47, XX, +21
47, XY, +21
47, XX, +21
47, XX, +mar[20]/46, XX[20]
Karyotype
No
No
No
No
CoA
DORV
VSD
DORV, HLHS
VSD, MA, ARSA
DORV, VSD
VSD
VSD
SV, CAT
AVSD
AVSD
AVSD
No
No
No
No
Cardiac defects
No
Long bone dysplasia, mild ventriculomegaly, increased iliac wing angle, hypoplasia of the fifth middle phalanx
Nasal bone dysplasia, long bone dysplasia, ICEF, renal echogenicity
Holoprosencephaly, proboscis, digestive obstruction
Long bone dysplasia, thickened nuchal fold
Strawberry head, micrognathia, microtia, polyhydramnios
Monophthalmia, proboscis, holoprosencephaly, clubfeet, polydactyly, polyhydramnios
Holoprosencephaly, proboscis, anophthalmia, cleft lip and palate, renal echogenicity
Hydrops, cystic hygroma, strawberry head, CPC, micrognathia, low-set ears, nasal bone dysplasia, omphalocele, clenched hands with overlapping fingers
ACC, enlarged cisterna magna, clenched hands with overlapping fingers
Lemon head, aplasia radii, ectrodactyly, clenched hands with overlapping fingers, esophageal atresia, SUA, cord cyst, polyhydramnios
Clenched hands with overlapping fingers, strawberry head
Absence of the nasal bone, micrognathia, meningoencephalocele, CPC, thickened nuchal fold, echogenic bowel, horseshoe kidney, omphalocele, aplasia radii, polydactyly, ectrodactyly, SUA
Absence of the nasal bone, hypoplasia of the fifth middle phalanx, echogenic bowel
Digestive obstruction, absence of nasal bone, increased iliac wing angle, echogenic liver, renal echogenicity, polyhydramnios
No
Pyelectasis, echogenic bowel, thickened nuchal fold, long bone dysplasia, nasal bone dysplasia, SUA
Enlarged cisterna magna, nasal bone dysplasia, long bone dysplasia, renal echogenicity
Thickened nuchal fold, mild ventriculomegaly, absence of the nasal bone, long bone dysplasia, echogenic bowel
No
Extracardiac anomalies
ACC, agenesis of the corpus callosum; ARSA, aberrant right subclavian artery; AVSD, atrioventricular septal defect; CAT, common arterial trunk; CoA, coarctation of the aorta; CPC, choroid plexus cysts; DORV, double-outlet right ventricle; GA, gestational age; HLHS, hypoplastic left heart syndrome; ICEF, intracardiac echogenic focus; MA, mitral atresia; SUA, single umbilical artery; VSD, ventricular septal defect.
25
MA (years)
1
Case
Table 2 The sonographic findings of 20 fetuses with persistent left superior vena cava and abnormal karyotypes
800 L. Du et al.
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Table 3 The numbers and types of congenital heart defects in fetuses with and without persistent left superior vena cava [n (%)] Type
N
Without PLSVC
VSD
169
TOF AVSD
With PLSVC
149 (30.9)
20 (21.1)
51
41 (8.5)
10 (10.5)
47
41 (8.5)
6 (6.3)
DORV
43
30 (6.2)
13 (13.7)
TGA
34
31 (6.4)
3 (3.2)
RAA
29
27 (5.6)
2 (2.1)
HLHS
26
22 (4.6)
4 (4.2)
Heterotaxy
25
11 (2.3)
14 (14.7)
CoA
24
14 (2.9)
10 (10.5)
CAT
22
19 (4.0)
3 (3.2)
ARSA
18
16 (3.3)
2 (2.1)
HRH
18
16 (3.3)
2 (2.1)
SV
15
13 (2.7)
2 (2.1)
PS/PA with IVS
12
11 (2.3)
1 (1.1)
TVD
13
13 (2.7)
0
IAA
7
7 (1.5)
0
APVC
6
6 (1.3)
0
AS/AA
5
5 (1.0)
0
CAF
3
3 (0.6)
0
IIVC
3
2 (0.4)
1 (1.1)
DAA
2
2 (0.4)
0
3 (0.6)
2 (2.1)
Dextrocardia Total
5 577
482
95
APVC, anomalous pulmonary venous connection; ARSA, aberrant right subclavian artery; AS/AA, aortic stenosis/aortic atresia; AVSD, atrioventricular septal defect; CAF, coronary artery fistula; CAT, common arterial trunk; CoA, coarctation of the aorta; DAA, double aortic arch; DORV, double-outlet right ventricle; HLHS, hypoplastic left heart syndrome; HRH, hypoplastic right heart; IAA, interruption of the aortic arch; IIVC, interruption of the inferior vena cava; PLSVC, persistent left superior vena cave; PA/PS with IVS, pulmonary stenosis/pulmonary atresia with intact ventricular septum; RAA, right aortic arch; SV, single ventricle; TGA, transposition of the great arteries; TOF, tetralogy of Fallot; TVD, tricuspid valve dysplasia; VSD, ventricular septal defect.
801
diagnosis is achieved in the long-axis view, which allows the course of the PLSVC to be followed to its junction with the dilated coronary sinus, which then drains into the right atrium.8 Persistent left superior vena cava represents the most common variation of systemic venous return. The incidence of PLSVC in the normal population has been reported to be approximately 0.3–0.5% in prenatal and postmortem studies; however, its true incidence is unknown.1–3 Galindo et al.9 reported that PLSVC was identified in 0.9% of all fetal echocardiographic examinations; another fetal study by Berg et al.8 calculated a 0.8% rate of PLSVC. Nevertheless, it is important to emphasize that these two studies were conducted in high-risk populations; therefore, the true benefits of detecting this venous anomaly in an unselected population remain unknown. Our results suggest that PLSVC is identified in approximately 0.7% of all fetal echocardiographic examinations; nonetheless, this finding is also from a mixedrisk population. When we divided the study population according to the indication for an ultrasound examination, the incidences were approximately 0.5% in the unselected prenatal group and 1.1% in the high-risk group. An association between PLSVC and chromosomal defects has been previously reported in which 9% of the PLSVC fetuses had chromosomal abnormalities, most commonly trisomy 18 and trisomy 21.6,7 Some authors have advocated that fetal karyotyping should be routinely offered with the prenatal detection of PLSVC. Our research confirms from another perspective that the incidence of PLSVC in the chromosomally abnormal group was significantly higher (27.5-fold) than that in the normal fetuses. Among the fetuses with PLSVC, 11% had chromosomal abnormalities; the highest incidence of PLSVC was observed in the trisomy 18 fetuses. Additional associated defects, which were identified in almost all chromosomally abnormal PLSVC fetuses, were also significantly more common than in the normal cases. These observations are similar to those reported by Berg et al. and Galindo et al.8,9 The common cardiac defects in fetuses with PLSVC are ventricular septal defect, heterotaxy, aortic coarctation, and double-outlet right ventricle. However,
Figure 3 Pathologic specimen of fetal heart with persistent superior vena cava (LSVC) at 28 weeks. The views are from the anterior (a) and the left lateral (b), showing the LSVC junction with the dilated coronary sinus (CS), which then drains into the right atrium (RA). AO, aorta; BA, brachiocephalic artery; LCCA, left common carotid artery; LSA, left subclavian artery; LVN, left vagus nerve; PA, pulmonary artery; PV, pulmonary vein; RA, right atrium; RCCA: right common carotid artery; RSA: right subclavian artery; RSVC, right superior vena cava
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fetuses with abnormal chromosomes are more likely to be detected prenatally, given their phenotypic appearance, than those with a normal karyotype, which may have biased this aspect of our results. Although in our experience PLSVC alone does not significantly increase the risk for an abnormal karyotype, several fetuses that had isolated findings had an abnormal karyotype. This observation would suggest that even if PLSVC has a higher association with abnormal chromosomes when other fetal malformations are detected, that fact should not preclude the physician from offering invasive testing, particularly with the advent of microarray analysis. Although this series was small, our study is noteworthy for identifying the associations between PLSVC and several extracardiac anomalies that were either undetected or considered to be undetectable by prenatal ultrasound (e.g. microtia, atretorrhinia, and intestinal malrotation). The left superior vena cava may be considered as a marker of embryopathy that deserves more attention during morphological examinations.6,8 However, it is notable that in this study, the majority of extracardiac anomalies occurred in association with cardiac anomalies. Therefore, the identification of PLSVC in a screening ultrasound examination should alert the examiner, and these patients should be referred for complete fetal echocardiography studies and thorough fetal anatomical surveys. One limitation of our study was our inability to confirm all of the PLSVC diagnoses, or indeed the false negative rate for PLSVC, because postnatal echocardiography or further testing was not routinely performed on asymptomatic newborns. Therefore, the relationship between PLSVC and chromosomal defects may have been overestimated. However, PLSVC was confirmed in 56 cases by autopsy (Figure 3), in 12 cases by postnatal echocardiography or computed tomography, and six of the newborns who exhibited intracardiac defects in the prenatal diagnosis underwent cardiac surgery. Furthermore, the outcomes of 9.4% of the PLSVC cases are unknown, as they were lost to follow-up. An additional limitation is that in the cases without prenatal karyotyping, the karyotype was assumed to be normal if the newborn appeared clinically normal to the local examining pediatrician.
The advantages of our study include the large number of fetuses examined in a single Asian center and the establishment of the incidence of PLSVC in an unselected low-risk population. Moreover, to our knowledge, this study contains the largest number of chromosomal defect cases to date and is the first to report a difference in the incidence of PLSVC between chromosomally normal and abnormal fetuses.
CONCLUSIONS Persistent left superior vena cava is much more common in chromosomally abnormal fetuses than in normal fetuses. However, the associated cardiac and/or extracardiac defects themselves are more highly correlated with and thus may be more directly related to chromosomal disorders. The detection of PLSVC in the fetus must be followed with a meticulous inspection of the fetal anatomy because PLSVC is frequently associated with heterotaxy syndromes, other cardiac/ noncardiac malformations, and aneuploidies, which affect infant outcomes. Isolated PLSVC is a benign vascular anomaly and may not affect patient outcomes.
WHAT’S ALREADY KNOWN ABOUT THIS TOPIC? • The incidence of PLSVC in fetal echocardiographic examinations has been reported to be 0.9% in studies conducted in high-risk populations. An association between PLSVC and chromosomal defects has been reported, with 9% of PLSVC fetuses having chromosomal abnormalities. Some authors have advocated karyotyping whenever PLSVC is detected prenatally. However, other authors have noted that most aneuploid fetuses exhibit other defects that may be more directly associated with chromosomal disorders.
WHAT DOES THIS STUDY ADD? • In this study, we establish the incidence of PLSVC in an unselected low-risk population and confirm from another perspective that the incidence of PLSVC in chromosomally abnormal group was significantly higher (27.5-fold) than in the normal fetuses.
REFERENCES 1. Cherian S, Ramesh B, Madhyastha S. Persistent left superior vena cava. Clin Anat 2006;19:561–5. 2. Nsah E, Moore G, Hutchins G. Pathogenesis of persistent left superior vena cava with a coronary sinus connection. Pediatr Pathol 1991;11:261–9. 3. Parikh S, Prasad K, Iyer R, et al. Prospective angiographic study of the abnormalities of systemic venous connections in congenital and acquired heart disease. Cathet Cardiovasc Diagn 1996;38:379–86. 4. Pasquini L, Belmar C, Seale A, et al. Prenatal diagnosis of absent right and persistent left superior vena cava. Prenat Diagn 2006;26:700–2. 5. Yagel S, Arbel R, Anteby EY, et al. The three vessels and trachea view (3VT) in fetal cardiac scanning. Ultrasound Obstet Gynecol 2002;20:340–5. 6. Machevin-Surugue E, David N, Verspyck E, et al. Dilated coronary sinus in prenatal echocardiography; identification, associations and outcome. Prenat Diagn 2002;22:898–902. 7. Kalache K, Romero R, Conoscenti G, et al. Prenatal diagnosis of dilated coronary sinus with persistent left superior vena cava in a fetus with trisomy 18. Prenat Diagn 2003;23:108–10.
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8. Berg C, Knuppel M, Geipel A, et al. Prenatal diagnosis of persistent left superior vena cava and its associated congenital anomalies. Ultrasound Obstet Gynecol 2006;27:274–80. 9. Galindo A, Gutierrez-Larraya F, Escribano D, et al. Clinical significance of persistent left superior vena cava diagnosed in fetal life. Ultrasound Obstet Gynecol 2007;30:152–61. 10. Yagel S, Cohen S, Achiron R. Examination of the fetal heart by five shortaxis views: a proposed screening method for comprehensive cardiac evaluation. Ultrasound Obstet Gynecol 2001;17:367–9. 11. Papa M, Camesasca C, Santoro F, et al. Fetal echocardiography in detecting anomalous pulmonary venous connection: four false positive cases. Br Heart J 1995;73:355–8. 12. Chaoui R, Heling KS, Kalache KD. Caliber of the coronary sinus in fetuses with cardiac defects with and without left persistent superior vena cava and in growth-restricted fetuses with heart-sparing effect. Prenat Diagn 2003;23:552–7.
© 2014 John Wiley & Sons, Ltd.
ORIGINAL ARTICLE
Fetal persistent left superior vena cava in cases with and without chromosomal anomalies Liu Du, Hong-Ning Xie*, Yun-Xiao Zhu, Li-Juan Li, Ruan Peng and Ju Zheng Department of Ultrasonic Medicine and Fetal Medical Centre, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China *Correspondence to: Hong-Ning Xie. E-mail: [email protected]
ABSTRACT Objectives The objectives of this study are to determine and compare the prevalence of persistent left superior vena cava (PLSVC) in chromosomally normal and abnormal fetuses and to evaluate the potential of PLSVC as a screening marker for chromosomal abnormalities. Methods Women undergoing routine fetal sonographic examinations were evaluated once for the presence of PLSVC. PLSVC was diagnosed on the basis of the identification of an additional vessel in the left of the pulmonary artery in a three-vessel trachea view. Associated abnormalities, karyotypes, and outcomes were analyzed. Results A total of 164 (0.7%, 164/25 171) cases of PLSVC were detected and successfully followed-up. The detection rates were 0.5% (81/17 535) and 1.1% (83/7636) in the low-risk and high-risk cases, respectively. The incidence of PLSVC was lower among the chromosomally or clinically normal (0.4%, 110/24 914) compared with chromosomally abnormal fetuses (7.8%, 20/257, p < 0.001). Additional defects were identified in 90% (18/20) of the PLSVC fetuses with chromosomal anomalies, a rate that was higher than those fetuses with chromosomal normal (61.8%, 68/110).
Conclusions Persistent left superior vena cava is more common among chromosomally abnormal than normal fetuses, and PLSVC fetuses with other defects are more highly associated with chromosomal disorders than isolated PLSVC fetuses. Isolated PLSVC is a benign vascular anomaly and may not affect outcomes. © 2014 John Wiley & Sons, Ltd. Funding sources: This study was supported by research grant 81071166 from the National Scientific Foundation Committee of China. Conflicts of interest: None declared
INTRODUCTION Persistent left superior vena cava (PLSVC) is the most common variant of the thoracic venous system.1 Its prevalence is estimated to be approximately 0.3–0.5% in the general population.1–3 However, the true incidence of PLSVC is unknown because this condition is usually asymptomatic and difficult to detect during routine transthoracic echocardiographic studies in postnatal patients.4 Nonetheless, PLSVC can be easily and accurately identified prenatally during ultrasound examination. In particular, the use of the three-vessel trachea (3VT) view of the upper mediastinum during fetal cardiac examinations has facilitated the direct diagnosis of PLSVC (Figure 1a).5 An association between PLSVC and chromosomal defects has previously been reported, and some authors have asserted that fetal karyotyping should be routinely offered whenever PLSVC is detected prenatally.6,7 Other authors have noted that most aneuploid fetuses exhibit other defects that might be more directly associated with chromosomal disorders.8,9 Therefore, the implications of PLSVC for the risk assessment of chromosomal anomalies are unknown. Therefore, the aims of this study were to evaluate and compare the prevalence of PLSVC among chromosomally normal and Prenatal Diagnosis 2014, 34, 797–802
abnormal fetuses and to evaluate the potential value of PLSVC as a prenatal screening marker for chromosomal abnormalities.
METHODS This cross-sectional study was conducted between 1 January 2008 and 30 September 2011 at a tertiary referral center for the prenatal diagnosis and management of fetal and neonatal pathology. Experienced perinatologists performed all sonographic examinations using a Voluson 730 Expert system ultrasound machine (GE Healthcare, Kretztechnik, Zipf, Austria) with a 4 to 8 MHz transabdominal probe. The fetal ultrasonographic examinations included a detailed extracardiac structural survey and a complete echocardiographic examination, which were performed following standardized guidelines. The cardiac scans were performed using a segmental approach that combined a two-dimensional mode and color/ pulsed Doppler flow imaging. The cardiac scans included observations of the situs and the position of the heart and the four-chamber view, the outflow tracts, the 3VT view, the aortic and ductal arches, and both systemic and pulmonary venous returns.10 The 3VT view was obtained as originally described.5,10 © 2014 John Wiley & Sons, Ltd.
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Figure 1 (a) Normal three-vessel trachea (3VT) view at 24 weeks showing the following vessels, from left to right: the arterial duct (AD), the aortic arch (AoA) and the right superior vena cava (RSVC). (b) Abnormal 3VT view at 28 weeks showing a supernumerary vessel located to the left of the arterial duct. LSVC, left superior vena cava; T, trachea
During the study period, all fetal echocardiograms were systematically examined for the presence of PLSVC. The prenatal diagnosis of PLSVC was made on the basis of an abnormal 3VT view showing a supernumerary vessel located to the left of the pulmonary trunk and arterial duct (Figure 1b).5 The diagnosis was then confirmed with a long-axis view that revealed direct or indirect drainage via the coronary sinus into the left or right atrium (Figure 2). The karyotype was determined prenatally from a chorionic villus, amniotic fluid, or fetal blood sample or postnatally from a blood test sample of a neonate with features that were suggestive of a chromosomal anomaly. The indications for a prenatal invasive diagnosis of chromosomal abnormality with cytogenetic analysis included the following: (1) advanced maternal age (≥34 years old), (2) abnormal biochemical markers in the maternal serum, such as in maternal blood Down syndrome screening (>1/270), (3) abnormal ultrasound findings, (4) unexplained recurrent miscarriage or intrauterine fetal death, (5) family history of chromosomal abnormalities, (6) parent with abnormal karyotype, (7) history of abnormal offspring birth, (8) radiation or medication exposure during pregnancy, and (9) other nonspecific indications, such as anxiety, consanguineous marriage, and so on. In cases in which no karyotype was obtained prenatally, the karyotype was considered normal if the newborn appeared clinically normal to the local examining pediatrician. Follow-up scans
were offered every 4–6 weeks in cases of ongoing pregnancies. Perinatal management in an appropriate tertiary center was strongly recommended to the parents, particularly when the fetus had cardiac defects. The prenatal sonograms and postnatal imaging findings, pathologic diagnoses, karyotype, and clinical outcomes were recorded. A chi-squared test or Fisher’s exact test was used to compare the incidences of PLSVC and other defects between the normal and chromosomally abnormal fetuses and to identify the significant differences. Odds ratios for the presence of PLSVC in the chromosomally abnormal fetuses were calculated and are presented with 95% CIs. The statistical analysis was performed using the SPSS software, version 16.0 (SPSS Inc, Chicago, IL), and p < 0.05 was considered statistically significant.
RESULTS During the study period, 29 227 second-trimester and thirdtrimester echocardiographic examinations were performed in our center, and 25 171 (86.1%, 25 171/29 227) cases were successfully followed-up with karyotype or postnatal data. The majority of the women (n = 17 535, 69.7%) were attending our hospital primarily for standard prenatal care and routine scans for low-risk factors. The remaining women (n = 7636, 30.3%) were referred from their local hospitals because of the suspicion of fetal anomalies during routine scans; the women
Figure 2 (a) Longitudinal view of the coronary sinus (CS) draining into the right atrium in a normal fetus at 24 weeks. (b) Longitudinal view of the persistent left superior vena cava (LSVC) showing drainage into the dilated CS at 28 weeks. AO, aorta; IVC, inferior vena cava; LA, left atrium; PA, pulmonary artery; RA, right atrium; RV, right ventricle
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received detailed anomaly scans, counseling, and perinatal management as needed. In total, 725 cases were found to have a congenital heart defect in our center during the observation period, and 577 cases were successfully followed-up. Fetuses with PLSVC were detected in 181 cases, and 17 (9.4%, 17/181) were lost to follow-up. The median gestational age at detection was 25 weeks (range: 16–35 weeks). These cases represent 0.7% (164/25 171) of all echocardiographic examinations performed during that period; 81 were from low-risk populations (0.5%, 81/17 535), and 83 were from high-risk populations (1.1%, 83/ 7636). Within this group of 164 fetuses, 110 were chromosomally or clinically normal, whereas 20 fetuses (15.4%, 20/130) exhibited abnormal karyotypes (seven with trisomy 18, six with trisomy 21, three with trisomy 13, one with X chromosome monosomy, and three with other chromosomal defects). The remaining 34 cases (20.7%, 34/ 164) lacked fetal karyotype data or postnatal follow-up data. Chromosomal abnormalities were diagnosed by prenatal screening after detailed ultrasonographic examinations or postnatal karyotyping or by clinical assessment of the newborn. All PLSVC fetuses with chromosomal anomalies were detected prenatally, and there are two cases of Turner syndrome, six cases of trisomy 21, and 16 cases of abnormal chromosome segment were diagnosed postnatally. The PLSVC assessments are summarized in Table 1 according to the fetal karyotype or the outcome. The incidence of PLSVC was significantly lower among the chromosomally or clinically normal fetuses (0.4%, 110/ 24 914) compared with those fetuses with chromosomal anomalies (7.8%, 20/257, p < 0.001). The highest incidence of PLSVC (12.1%) was noted in the fetuses with trisomy 18. Similarly, PLSVC was more common among the fetuses with trisomy 21 (p < 0.001) and those fetuses with all other chromosomal abnormalities (p < 0.001) compared with the normal fetuses. The odds ratio for PLSVC in the chromosomally abnormal fetuses compared with the normal fetuses was 27.5 (95% CI, 15.8–47.8). There were 44 (26.8%, 44/164) cases with isolated PLSVC, 120 (73.2%, 120/164) cases associated with other anomalies (32 with other cardiac defects, 29 with extracardiac anomalies, 45 with both cardiac and extracardiac anomalies, and 14 with
Table 1 A summary of the karyotypes of the studied fetuses and the assessments of persistent left superior vena cava according to karyotype [n (%)] N
Karyotype Normal karyotype
Without PLSVC
With PLSVC
4626
4583
57 (1.2)
20 288
20 235
53 (0.3)
Trisomy 21
84
78
6(7.1)
Trisomy 18
58
51
7(12.1)
Normal clinical assessment
Other chromosomal defects No follow-up data Total
115
108
7(6.1)
4056
4005
51 (1.3)
29 227
25 240
181 (0.6)
PLSVC, persistent left superior vena cava.
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heterotaxy syndromes). Within the group of chromosomally or clinically normal fetuses with PLSVC, 42 (38.2%, 42/110) fetuses had isolated PLSVC; 68 (61.8%, 68/110) cases were associated with other defects (17 fetuses had cardiac defects, 16 had extracardiac anomalies, 21 had both cardiac and extracardiac anomalies, and 14 had heterotaxy syndromes). Among the 20 chromosomally abnormal PLSVC fetuses, only two (10%, 2/20) had PLSVC as an isolated finding; this difference was significant (p < 0.05). The ultrasonographic features of all chromosomally abnormal fetuses are presented in Table 2. The numbers and types of congenital heart defect in fetuses with and without PLSVC are presented in Table 3. All chromosomally abnormal fetuses and 87 of the normal fetuses with PLSVC underwent termination of pregnancy, including eight fetuses with isolated PLSVC, two cases with abnormal chromosomes, two women with severe pregnancy complications, and four childbearing women who violated the family planning restrictions in China. There were 57 births (36 fetuses had isolated PLSVC, three had cardiac defects, 10 had extracardiac anomalies, and eight had both cardiac and extracardiac anomalies), of which three infants died (one had isolated extracardiac anomalies and two had both cardiac and extracardiac anomalies); however, all cases of isolated PLSVC survived and were healthy at the time of this writing. Among the cases with postnatal follow-up for a minimum of 1 year, the overall survival rate was 29.8% (54/181); this rate increases to 94.7% (54/57) if the termination of pregnancy cases are excluded. Furthermore, there were two cases of prenatally detected extracardiac anomalies combined with other defects revealed at birth that were either not detected or not considered detectable by prenatal ultrasound. One newborn had microtia, dysaudia, and abnormal brain development and survived; the other infant had atretorrhinia and intestinal malrotation and died after surgery.
DISCUSSION Persistent left superior vena cava can be easily and accurately identified prenatally during a fetal echocardiographic examination. It is logical to assume that the rate of falsenegative diagnoses by specialists is extremely low, and PLSVC should be differentiated from anomalous pulmonary venous connection, for which few false-positive diagnoses have been reported.6,9,11 Previous prenatal diagnoses of PLSVC have been based on indirect findings, such as a ‘cystic’ structure corresponding to a cross-section of the dilated coronary sinus adjacent to the lateral wall of the left atrium and a ‘tubular’ structure crossing behind the left atrium and draining blood toward the right atrium.12 In recent years, the addition of the 3VT view of the upper mediastinum to fetal cardiac examinations has facilitated the direct diagnosis of PLSVC, showing four vessels instead of the normal three, with a supernumerary vessel to the left of the arterial duct.5 However, in the rare instances where the right superior vena cava is absent but the innominate vein is present, such as three cases in our study (two cases with isolated PLSVC and one with heterotaxy syndrome), there will again be three vessels, but they will be ‘abnormally’ arranged: from right to left, the aorta, pulmonary artery, and PLSVC. Therefore, the definitive © 2014 John Wiley & Sons, Ltd.
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26
26
32
28
38
33
28
29
38
28
39
23
41
34
29
38
24
26
29
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
23
29
32
20
30
25
24
20
17
30
26
21
18
23
27
27
26
31
29
27
GA at examination (weeks)
46, XX, t(1;2)(q44;q41)
46, XY, inv9(p11q13)
46, XY, der(21;21)(q10;q10)
46, XX, der(18;18)(q10;q10)
45, XO
47, XY, +13
47, XY, +13
47, XY, +13
47, XY, +18
47, XX, +18
47, XY, +18
47, XY, +18
47, XY, +18
47, XX, +18
47, XX, +21
47, XY, +21
47, XX, +21
47, XY, +21
47, XX, +21
47, XX, +mar[20]/46, XX[20]
Karyotype
No
No
No
No
CoA
DORV
VSD
DORV, HLHS
VSD, MA, ARSA
DORV, VSD
VSD
VSD
SV, CAT
AVSD
AVSD
AVSD
No
No
No
No
Cardiac defects
No
Long bone dysplasia, mild ventriculomegaly, increased iliac wing angle, hypoplasia of the fifth middle phalanx
Nasal bone dysplasia, long bone dysplasia, ICEF, renal echogenicity
Holoprosencephaly, proboscis, digestive obstruction
Long bone dysplasia, thickened nuchal fold
Strawberry head, micrognathia, microtia, polyhydramnios
Monophthalmia, proboscis, holoprosencephaly, clubfeet, polydactyly, polyhydramnios
Holoprosencephaly, proboscis, anophthalmia, cleft lip and palate, renal echogenicity
Hydrops, cystic hygroma, strawberry head, CPC, micrognathia, low-set ears, nasal bone dysplasia, omphalocele, clenched hands with overlapping fingers
ACC, enlarged cisterna magna, clenched hands with overlapping fingers
Lemon head, aplasia radii, ectrodactyly, clenched hands with overlapping fingers, esophageal atresia, SUA, cord cyst, polyhydramnios
Clenched hands with overlapping fingers, strawberry head
Absence of the nasal bone, micrognathia, meningoencephalocele, CPC, thickened nuchal fold, echogenic bowel, horseshoe kidney, omphalocele, aplasia radii, polydactyly, ectrodactyly, SUA
Absence of the nasal bone, hypoplasia of the fifth middle phalanx, echogenic bowel
Digestive obstruction, absence of nasal bone, increased iliac wing angle, echogenic liver, renal echogenicity, polyhydramnios
No
Pyelectasis, echogenic bowel, thickened nuchal fold, long bone dysplasia, nasal bone dysplasia, SUA
Enlarged cisterna magna, nasal bone dysplasia, long bone dysplasia, renal echogenicity
Thickened nuchal fold, mild ventriculomegaly, absence of the nasal bone, long bone dysplasia, echogenic bowel
No
Extracardiac anomalies
ACC, agenesis of the corpus callosum; ARSA, aberrant right subclavian artery; AVSD, atrioventricular septal defect; CAT, common arterial trunk; CoA, coarctation of the aorta; CPC, choroid plexus cysts; DORV, double-outlet right ventricle; GA, gestational age; HLHS, hypoplastic left heart syndrome; ICEF, intracardiac echogenic focus; MA, mitral atresia; SUA, single umbilical artery; VSD, ventricular septal defect.
25
MA (years)
1
Case
Table 2 The sonographic findings of 20 fetuses with persistent left superior vena cava and abnormal karyotypes
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Table 3 The numbers and types of congenital heart defects in fetuses with and without persistent left superior vena cava [n (%)] Type
N
Without PLSVC
VSD
169
TOF AVSD
With PLSVC
149 (30.9)
20 (21.1)
51
41 (8.5)
10 (10.5)
47
41 (8.5)
6 (6.3)
DORV
43
30 (6.2)
13 (13.7)
TGA
34
31 (6.4)
3 (3.2)
RAA
29
27 (5.6)
2 (2.1)
HLHS
26
22 (4.6)
4 (4.2)
Heterotaxy
25
11 (2.3)
14 (14.7)
CoA
24
14 (2.9)
10 (10.5)
CAT
22
19 (4.0)
3 (3.2)
ARSA
18
16 (3.3)
2 (2.1)
HRH
18
16 (3.3)
2 (2.1)
SV
15
13 (2.7)
2 (2.1)
PS/PA with IVS
12
11 (2.3)
1 (1.1)
TVD
13
13 (2.7)
0
IAA
7
7 (1.5)
0
APVC
6
6 (1.3)
0
AS/AA
5
5 (1.0)
0
CAF
3
3 (0.6)
0
IIVC
3
2 (0.4)
1 (1.1)
DAA
2
2 (0.4)
0
3 (0.6)
2 (2.1)
Dextrocardia Total
5 577
482
95
APVC, anomalous pulmonary venous connection; ARSA, aberrant right subclavian artery; AS/AA, aortic stenosis/aortic atresia; AVSD, atrioventricular septal defect; CAF, coronary artery fistula; CAT, common arterial trunk; CoA, coarctation of the aorta; DAA, double aortic arch; DORV, double-outlet right ventricle; HLHS, hypoplastic left heart syndrome; HRH, hypoplastic right heart; IAA, interruption of the aortic arch; IIVC, interruption of the inferior vena cava; PLSVC, persistent left superior vena cave; PA/PS with IVS, pulmonary stenosis/pulmonary atresia with intact ventricular septum; RAA, right aortic arch; SV, single ventricle; TGA, transposition of the great arteries; TOF, tetralogy of Fallot; TVD, tricuspid valve dysplasia; VSD, ventricular septal defect.
801
diagnosis is achieved in the long-axis view, which allows the course of the PLSVC to be followed to its junction with the dilated coronary sinus, which then drains into the right atrium.8 Persistent left superior vena cava represents the most common variation of systemic venous return. The incidence of PLSVC in the normal population has been reported to be approximately 0.3–0.5% in prenatal and postmortem studies; however, its true incidence is unknown.1–3 Galindo et al.9 reported that PLSVC was identified in 0.9% of all fetal echocardiographic examinations; another fetal study by Berg et al.8 calculated a 0.8% rate of PLSVC. Nevertheless, it is important to emphasize that these two studies were conducted in high-risk populations; therefore, the true benefits of detecting this venous anomaly in an unselected population remain unknown. Our results suggest that PLSVC is identified in approximately 0.7% of all fetal echocardiographic examinations; nonetheless, this finding is also from a mixedrisk population. When we divided the study population according to the indication for an ultrasound examination, the incidences were approximately 0.5% in the unselected prenatal group and 1.1% in the high-risk group. An association between PLSVC and chromosomal defects has been previously reported in which 9% of the PLSVC fetuses had chromosomal abnormalities, most commonly trisomy 18 and trisomy 21.6,7 Some authors have advocated that fetal karyotyping should be routinely offered with the prenatal detection of PLSVC. Our research confirms from another perspective that the incidence of PLSVC in the chromosomally abnormal group was significantly higher (27.5-fold) than that in the normal fetuses. Among the fetuses with PLSVC, 11% had chromosomal abnormalities; the highest incidence of PLSVC was observed in the trisomy 18 fetuses. Additional associated defects, which were identified in almost all chromosomally abnormal PLSVC fetuses, were also significantly more common than in the normal cases. These observations are similar to those reported by Berg et al. and Galindo et al.8,9 The common cardiac defects in fetuses with PLSVC are ventricular septal defect, heterotaxy, aortic coarctation, and double-outlet right ventricle. However,
Figure 3 Pathologic specimen of fetal heart with persistent superior vena cava (LSVC) at 28 weeks. The views are from the anterior (a) and the left lateral (b), showing the LSVC junction with the dilated coronary sinus (CS), which then drains into the right atrium (RA). AO, aorta; BA, brachiocephalic artery; LCCA, left common carotid artery; LSA, left subclavian artery; LVN, left vagus nerve; PA, pulmonary artery; PV, pulmonary vein; RA, right atrium; RCCA: right common carotid artery; RSA: right subclavian artery; RSVC, right superior vena cava
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fetuses with abnormal chromosomes are more likely to be detected prenatally, given their phenotypic appearance, than those with a normal karyotype, which may have biased this aspect of our results. Although in our experience PLSVC alone does not significantly increase the risk for an abnormal karyotype, several fetuses that had isolated findings had an abnormal karyotype. This observation would suggest that even if PLSVC has a higher association with abnormal chromosomes when other fetal malformations are detected, that fact should not preclude the physician from offering invasive testing, particularly with the advent of microarray analysis. Although this series was small, our study is noteworthy for identifying the associations between PLSVC and several extracardiac anomalies that were either undetected or considered to be undetectable by prenatal ultrasound (e.g. microtia, atretorrhinia, and intestinal malrotation). The left superior vena cava may be considered as a marker of embryopathy that deserves more attention during morphological examinations.6,8 However, it is notable that in this study, the majority of extracardiac anomalies occurred in association with cardiac anomalies. Therefore, the identification of PLSVC in a screening ultrasound examination should alert the examiner, and these patients should be referred for complete fetal echocardiography studies and thorough fetal anatomical surveys. One limitation of our study was our inability to confirm all of the PLSVC diagnoses, or indeed the false negative rate for PLSVC, because postnatal echocardiography or further testing was not routinely performed on asymptomatic newborns. Therefore, the relationship between PLSVC and chromosomal defects may have been overestimated. However, PLSVC was confirmed in 56 cases by autopsy (Figure 3), in 12 cases by postnatal echocardiography or computed tomography, and six of the newborns who exhibited intracardiac defects in the prenatal diagnosis underwent cardiac surgery. Furthermore, the outcomes of 9.4% of the PLSVC cases are unknown, as they were lost to follow-up. An additional limitation is that in the cases without prenatal karyotyping, the karyotype was assumed to be normal if the newborn appeared clinically normal to the local examining pediatrician.
The advantages of our study include the large number of fetuses examined in a single Asian center and the establishment of the incidence of PLSVC in an unselected low-risk population. Moreover, to our knowledge, this study contains the largest number of chromosomal defect cases to date and is the first to report a difference in the incidence of PLSVC between chromosomally normal and abnormal fetuses.
CONCLUSIONS Persistent left superior vena cava is much more common in chromosomally abnormal fetuses than in normal fetuses. However, the associated cardiac and/or extracardiac defects themselves are more highly correlated with and thus may be more directly related to chromosomal disorders. The detection of PLSVC in the fetus must be followed with a meticulous inspection of the fetal anatomy because PLSVC is frequently associated with heterotaxy syndromes, other cardiac/ noncardiac malformations, and aneuploidies, which affect infant outcomes. Isolated PLSVC is a benign vascular anomaly and may not affect patient outcomes.
WHAT’S ALREADY KNOWN ABOUT THIS TOPIC? • The incidence of PLSVC in fetal echocardiographic examinations has been reported to be 0.9% in studies conducted in high-risk populations. An association between PLSVC and chromosomal defects has been reported, with 9% of PLSVC fetuses having chromosomal abnormalities. Some authors have advocated karyotyping whenever PLSVC is detected prenatally. However, other authors have noted that most aneuploid fetuses exhibit other defects that may be more directly associated with chromosomal disorders.
WHAT DOES THIS STUDY ADD? • In this study, we establish the incidence of PLSVC in an unselected low-risk population and confirm from another perspective that the incidence of PLSVC in chromosomally abnormal group was significantly higher (27.5-fold) than in the normal fetuses.
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8. Berg C, Knuppel M, Geipel A, et al. Prenatal diagnosis of persistent left superior vena cava and its associated congenital anomalies. Ultrasound Obstet Gynecol 2006;27:274–80. 9. Galindo A, Gutierrez-Larraya F, Escribano D, et al. Clinical significance of persistent left superior vena cava diagnosed in fetal life. Ultrasound Obstet Gynecol 2007;30:152–61. 10. Yagel S, Cohen S, Achiron R. Examination of the fetal heart by five shortaxis views: a proposed screening method for comprehensive cardiac evaluation. Ultrasound Obstet Gynecol 2001;17:367–9. 11. Papa M, Camesasca C, Santoro F, et al. Fetal echocardiography in detecting anomalous pulmonary venous connection: four false positive cases. Br Heart J 1995;73:355–8. 12. Chaoui R, Heling KS, Kalache KD. Caliber of the coronary sinus in fetuses with cardiac defects with and without left persistent superior vena cava and in growth-restricted fetuses with heart-sparing effect. Prenat Diagn 2003;23:552–7.
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