Advertisement

Evaluation of the trachea in fetuses with double aortic arch using prenatal ultrasound: a retrospective cohort study

  • Xia Yin
    Affiliations
    Department of Ultrasonic Medicine, Fetal Medical Centre, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China (Drs Yin, Wu, Zheng, Peng, and Xie)
    Search for articles by this author
  • Yan Liu
    Affiliations
    and Department of Ultrasonic Medicine, Dalian Municipal Women and Children's Medical Center, Dalian, Liaoning, China (Dr Liu)
    Search for articles by this author
  • Li-Hong Wu
    Affiliations
    Department of Ultrasonic Medicine, Fetal Medical Centre, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China (Drs Yin, Wu, Zheng, Peng, and Xie)
    Search for articles by this author
  • Qiao Zheng
    Affiliations
    Department of Ultrasonic Medicine, Fetal Medical Centre, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China (Drs Yin, Wu, Zheng, Peng, and Xie)
    Search for articles by this author
  • Ruan Peng
    Correspondence
    Corresponding authors: Ruan Peng, PhD.; Hong-Ning Xie, PhD.
    Affiliations
    Department of Ultrasonic Medicine, Fetal Medical Centre, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China (Drs Yin, Wu, Zheng, Peng, and Xie)
    Search for articles by this author
  • Hong-Ning Xie
    Correspondence
    Corresponding authors: Ruan Peng, PhD.; Hong-Ning Xie, PhD.
    Affiliations
    Department of Ultrasonic Medicine, Fetal Medical Centre, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China (Drs Yin, Wu, Zheng, Peng, and Xie)
    Search for articles by this author
Open AccessPublished:September 30, 2022DOI:https://doi.org/10.1016/j.ajogmf.2022.100759

      BACKGROUND

      Double aortic arch is the most common form of complete vascular ring. The trachea and/or esophagus could be compressed by the complete vascular ring, which may lead to early respiratory and/or esophageal symptoms in children with double aortic arch. Accurate prenatal assessment of tracheal compression could provide relevant information for perinatal clinical management of double aortic arch and emergency treatment of infants with double aortic arch. The fetal trachea is filled with amniotic fluid and can be clearly visualized with prenatal ultrasound. Previous studies reported the use of prenatal ultrasound to measure the tracheal internal diameters in normal fetuses and showed a linear correlation between the fetal tracheal internal diameters and gestational age. However, to the best of our knowledge, few studies have quantitatively evaluated tracheal compression in fetuses with double aortic arch using ultrasound.

      OBJECTIVE

      This study aimed to evaluate the tracheal compression caused by the vascular ring in fetuses with double aortic arch using prenatal ultrasound and to analyze the relationship between tracheal compression and postnatal clinical symptoms.

      STUDY DESIGN

      The data of fetuses with double aortic arch diagnosed with prenatal ultrasound at 2 institutions from January 2011 to April 2021 were retrospectively analyzed. Singleton pregnancies with normal fetuses as the control group were prospectively recruited. The tracheal compression—evaluated by comparing the tracheal internal diameter z scores against the gestational age—was assessed in fetuses with double aortic arch and in normal fetuses. The live-born infants with double aortic arch were divided into symptomatic and asymptomatic groups for the comparison of z scores. The receiver operating characteristic curve for the tracheal internal diameter z score cutoffs and prediction of symptomatic infants with double aortic arch was plotted. Intraobserver and interobserver agreements were investigated.

      RESULTS

      A total of 26 fetuses with double aortic arch were diagnosed, and 14 fetuses (53.8%) with double aortic arch were delivered alive. Among the 14 live-born infants, 7 (50.0%) were symptomatic, whereas 7 (50.0%) were asymptomatic. The tracheal internal diameter z scores were significantly lower in the double aortic arch group than in the normal groups (−0.62±1.36 vs 0.00±0.78; P<.001). The tracheal internal diameter z scores were significantly lower in the symptomatic group than in the asymptomatic group (−1.42±0.92 vs −0.49±0.96; P=.018). The area under the curve was 0.878 (95% confidence interval, 0.689–1.000). Using a tracheal internal diameter z scores cutoff of −1.21, the sensitivity was 71%, and the specificity was close to 100%. The intraclass correlation coefficients of interobserver and intraobserver agreements were 0.987 (95% confidence interval, 0.980–0.992) and 0.975 (95% confidence interval, 0.955–0.987), respectively.

      CONCLUSION

      The clinical symptoms in infants with double aortic arch were associated with prenatal tracheal compression, which can be prenatally evaluated using ultrasound. If fetuses are diagnosed with double aortic arch, prenatal surveillance of the tracheal internal diameters and comparison with z score reference ranges could provide pertinent information that would aid perinatal clinical management.

      Key words

      Why was this study conducted?

      The double aortic arch (DAA) may cause severe clinical symptoms; however, few studies have accurately evaluated the extent of tracheal compression in fetuses with DAA.

      Key findings

      The z score reference ranges of the tracheal internal diameter were established in normal fetuses. The tracheal internal diameter z scores were significantly lower in fetuses with DAA than in normal fetuses. The tracheal internal diameter z scores were significantly lower in symptomatic infants than in asymptomatic infants with DAA.

      What does this add to what is known?

      Clinical symptoms in infants with DAA are associated with prenatal tracheal compression, which can be prenatally evaluated using ultrasound. For fetuses with DAA, prenatal assessment of the tracheal internal diameters and comparison with the z score reference ranges can guide perinatal DAA management and emergency treatment of infants with DAA.
      Congenital vascular rings consist 0.5% to 1.0% of all congenital cardiovascular malformations.
      • Backer CL
      • Mavroudis C
      Congenital Heart Surgery Nomenclature and Database Project: vascular rings, tracheal stenosis, pectus excavatum.
      • Licari A
      • Manca E
      • Rispoli GA
      • Mannarino S
      • Pelizzo G
      • Marseglia GL
      Congenital vascular rings: a clinical challenge for the pediatrician.
      • Yoshimura N
      • Fukahara K
      • Yamashita A
      • et al.
      Congenital vascular ring.
      Double aortic arch (DAA) is the most common form of a complete vascular ring, and it accounts for 41% to 49% of all congenital vascular rings.
      • Van Son JA
      • Julsrud PR
      • Hagler DJ
      • et al.
      Surgical treatment of vascular rings: the Mayo Clinic experience.
      ,
      • Backer CL
      • Mongé MC
      • Popescu AR
      • Eltayeb OM
      • Rastatter JC
      • Rigsby CK
      Vascular rings.
      The pathogenesis of DAA involves the persistent existence of a fourth aortic arch during embryonic development.
      • Priya S
      • Thomas R
      • Nagpal P
      • Sharma A
      • Steigner M
      Congenital anomalies of the aortic arch.
      DAA can be accurately diagnosed using fetal echocardiography in the 3-vessel and tracheal (3VT) view.
      • Gardiner H
      • Chaoui R
      The fetal three-vessel and tracheal view revisited.
      The left and right aortic arches arise from the ascending aorta, encircle the esophagus and trachea, and converge to the descending aorta.
      • Priya S
      • Thomas R
      • Nagpal P
      • Sharma A
      • Steigner M
      Congenital anomalies of the aortic arch.
      Thus, the trachea and/or esophagus could be compressed by the complete vascular ring, which may lead to early respiratory and/or esophageal symptoms in approximately 74% of children with DAA.
      • Bravo C
      • Gámez F
      • Pérez R
      • Álvarez T
      • De León-Luis J
      Fetal aortic arch anomalies: key sonographic views for their differential diagnosis and clinical implications using the cardiovascular system sonographic evaluation protocol.
      Respiratory symptoms that may occur in neonates with DAA include wheezing, coughing, dyspnea, asphyxia, neonatal respiratory failure, and even pseudo-congenital high airway obstruction syndrome (pseudo-CHAOS).
      • Backer CL
      • Mongé MC
      • Popescu AR
      • Eltayeb OM
      • Rastatter JC
      • Rigsby CK
      Vascular rings.
      • Priya S
      • Thomas R
      • Nagpal P
      • Sharma A
      • Steigner M
      Congenital anomalies of the aortic arch.
      • Gardiner H
      • Chaoui R
      The fetal three-vessel and tracheal view revisited.
      • Bravo C
      • Gámez F
      • Pérez R
      • Álvarez T
      • De León-Luis J
      Fetal aortic arch anomalies: key sonographic views for their differential diagnosis and clinical implications using the cardiovascular system sonographic evaluation protocol.
      • Griswold Jr, HE
      • Young MD
      Double aortic arch; report of two cases and review of the literature.
      • Lee M
      • Kumar TKS
      • Paudel G
      Double aortic arch presenting as neonatal respiratory failure in the delivery room.
      • Naidu DP
      • Wohlmuth C
      • Gardiner HM
      Prenatal diagnosis of double aortic arch: can we predict airway obstruction (pseudo-CHAOS) and need for airway EXIT?.
      • Shum DJ
      • Clifton MS
      • Coakley FV
      • et al.
      Prenatal tracheal obstruction due to double aortic arch: a potential mimic of congenital high airway obstruction syndrome.
      Accurate prenatal assessment of tracheal compression could provide relevant information for perinatal clinical management of DAA and emergency treatment of infants with DAA.
      Pediatric studies reported that computed tomography (CT), magnetic resonance imaging, and bronchoscopy can be used to evaluate the airway condition and guide the diagnosis and treatment of DAA in infants.
      • Priya S
      • Thomas R
      • Nagpal P
      • Sharma A
      • Steigner M
      Congenital anomalies of the aortic arch.
      ,
      • Mogra R
      • Kesby G
      • Sholler G
      • Hyett J
      Identification and management of fetal isolated right-sided aortic arch in an unselected population.
      Fetal trachea is filled with amniotic fluid and can be clearly visualized with prenatal ultrasound.
      • Achiron R
      • Rotstein Z
      • Heggesh J
      • et al.
      Anomalies of the fetal aortic arch: a novel sonographic approach to in-utero diagnosis.
      Previous studies reported the use of prenatal ultrasound to measure the tracheal internal diameters in normal fetuses and showed a linear correlation between the fetal tracheal internal diameters and gestational age (GA).
      • Kalache KD
      • Franz M
      • Chaoui R
      • Bollmann R
      Ultrasound measurements of the diameter of the fetal trachea, larynx and pharynx throughout gestation applicability to prenatal diagnosis of obstructive anomalies of the upper respiratory-digestive tract.
      However, to the best of our knowledge, few studies have quantitatively evaluated tracheal compression in fetuses with DAA using ultrasound.
      • Achiron RR
      • Kassif E
      • Gilboa Y
      • et al.
      Congenital aortic vascular ring: in-utero sonographic assessment of tracheal patency and postnatal outcome.
      This study aimed to establish the tracheal internal diameter z score reference range in normal fetuses and compare the z scores in fetuses with DAA and normal fetuses. The secondary aim was to compare the tracheal internal diameter z scores in symptomatic and asymptomatic infants with DAA, thereby demonstrating the feasibility and effectiveness of the prenatal evaluation of tracheal compression in fetuses with DAA.

      Materials and Methods

      Study design and population

      All patients diagnosed prenatally with DAA at 2 institutions between January 2011 and April 2021 were retrospectively assessed. Fetuses whose tracheal internal diameters could not be measured using ultrasound images, volume data, or video clips were excluded. Cases involving women with normal fetuses (singleton pregnancies) who underwent second- and third-trimester ultrasound screening between 20 and 40 gestational weeks in these 2 institutions between December 2020 and February 2021 were prospectively recruited. We excluded the cases involving fetuses with cardiac and extracardiac abnormalities, fetal growth restriction, maternal complications (diabetes mellitus, hypertension, preeclampsia, and autoimmune diseases), and abnormal postnatal phenotypes. The formula for the z scores of the tracheal internal diameters against the GA in the normal fetuses was calculated. GA was established on the basis of the mother's last menstruation period and confirmed during first-trimester screening using ultrasound. If the discordance was more than 1 week, the ultrasound-based GA was used for analyses. The study was approved by the ethics committee of the 2 institutions. Written consent was obtained from all participants, and for the postnatal follow-up, written consent for the children was provided by their legal guardians.
      DAA was diagnosed with the prenatal ultrasound examination in the 3VT view. A normal left aortic arch demonstrated a V-shaped appearance of the junction between the ductus arteriosus and the aortic arch in the 3VT view. The prenatal ultrasonographic diagnostic criteria for DAA are that the great vessels appear U shaped or O shaped, with an intermediate location of the trachea. The composition of the vascular structure was determined using color Doppler or high-definition (HD) Doppler imaging (Figure 1).
      • Hunter L
      • Callaghan N
      • Patel K
      • Rinaldi L
      • Bellsham-Revell H
      • Sharland G
      Prenatal echocardiographic diagnosis of double aortic arch.
      ,
      • Yoo SJ
      • Min JY
      • Lee YH
      • Roman K
      • Jaeggi E
      • Smallhorn J
      Fetal sonographic diagnosis of aortic arch anomalies.
      The branches of cephalic and cervical arteries (the subclavian and common carotid arteries) should be displayed with HD Doppler. A detailed structural evaluation was performed after the diagnosis of DAA to exclude cases with intracardiac and extracardiac defects. For fetuses with a prenatally suspected diagnosis of DAA, karyotype analysis and genetic testing with chromosomal microarray analysis (CMA) using amniotic fluid or umbilical cord blood were recommended.
      • Levy B
      • Wapner R
      Prenatal diagnosis by chromosomal microarray analysis.
      Postnatal data, including those about CT angiography (CTA), autopsy, or corrective surgery, were collected to confirm the diagnosis of DAA. For live-born infants, clinical outcomes, including symptoms related to the tracheal or esophageal compression by the vascular ring, were noted by the pediatricians.
      Figure 1
      Figure 1Fetal echocardiography of the 3-vessel and tracheal view showing a complete double aortic arch vascular ring
      Yin. Evaluation of the trachea in fetuses with double aortic arch. Am J Obstet Gynecol MFM 2022.
      A, A 3-vessel and tracheal view: the ascending aorta divides into the right aortic arch and the left aortic arch around both sides of the trachea and merges into the descending aorta behind the trachea, forming a complete “O”-shaped vascular ring that connects with the left arterial duct. B, Color Doppler ultrasound confirms retrograde flow in 2 aortic arches.
      AO, ascending aorta; DA, ductus arteriosus; DO, descending aorta; L-ARCH, left aortic arch; PA, pulmonary artery; R-ARCH, right aortic arch; T, trachea.

      Ultrasound methodology and measurements

      All prenatal scans in fetuses with DAA were performed by experienced operators using a Voluson 730 Expert, Voluson E6, Voluson E8, or Voluson E10 ultrasound machine with a 4- to 8-MHz transabdominal transducer (GE Medical Systems, Kretztechnik, Zipf, Austria), whereas the scans in normal fetuses were performed using a Voluson E10 ultrasound machine with a 4- to 8-MHz transabdominal transducer. Detailed fetal echocardiography, structural evaluation, and biometric measurements were performed following the guidelines provided by the International Society of Ultrasound in Obstetrics and Gynecology.
      Cardiac screening examination of the fetus: guidelines for performing the ‘basic’ and ‘extended basic’ cardiac scan.
      Fetal biometry measurements included those of the biparietal diameter, head circumference, transverse cerebellar diameter, abdominal circumference, femur length, and humeral length. Video clips or volume datasets were acquired during the episode of fetal apnea and were stored for analysis. The operators were blinded to the results of other evaluations and clinical data. In the fetuses with DAA, the tracheal internal diameters were measured during real-time examination or by using video clips or volume datasets at the first time being diagnosed with DAA. The coronal view of the fetal trachea was identified and confirmed using color Doppler imaging. Moreover, the probe was slightly rotated so that the long axis of the trachea and the left and right main bronchi were seen clearly. A cross section of the aortic arch on each side of the trachea should be seen in fetuses with DAA, which could be determined using color Doppler. The tracheal internal diameters were measured in this view, and the measurements of the tracheal internal diameters (measured from the inner edge to the inner edge) were obtained just at the level where the 2 aortic arches crossed the trachea (Figure 2). In normal fetuses, the tracheal internal diameter was measured during real-time screening using ultrasound prospectively. A coronal view showing the bronchial bifurcation was used for the measurements. In this plane, the vessel has an oblique left-to-right course crossing the trachea anteriorly, and the calipers were located at the level of the aortic arch crossing the trachea (Figure 3). Measurements were repeated 3 times, and the average value was used for analysis. Interobserver agreements were investigated by 2 independent operators (R.P. and X.Y.). Intraobserver agreement was calculated by comparing measurements obtained twice by 1 observer (R.P.). Neither of them was informed about the clinical outcomes. They examined 30 tracheal inner diameters of normal fetuses independently and were blinded to each other's measurements.
      Figure 2
      Figure 2Coronal view of the fetus showing the trachea, left principal bronchus, and right principal bronchus
      Yin. Evaluation of the trachea in fetuses with double aortic arch. Am J Obstet Gynecol MFM 2022.
      A, Image captured from the cineloop video sequence on coronal view of the fetus shows the view of the longitudinal axis of the fetal trachea and the branches of the left and right main bronchi, left principal bronchus, and right principal bronchus. The trachea is compressed by the left and right aortic arches located on either side of the trachea. The internal diameter of the trachea (measured from the inner edge to the inner edge) is measured at the level where the 2 aortic arches cross the trachea (double-headed arrow: the trachea compressed by the vascular ring). B, Color Doppler ultrasound shows the left and right aortic arches on either side of the trachea.
      L-ARCH, left aortic arch; LPB, left principal bronchus; R-ARCH, right aortic arch; RPB, right principal bronchus; T, trachea.
      Figure 3
      Figure 3The 2-dimensional ultrasound image of normal singleton fetuses on the coronal longitudinal view of the fetal trachea
      Yin. Evaluation of the trachea in fetuses with double aortic arch. Am J Obstet Gynecol MFM 2022.
      The internal tracheal diameter (measured from the inner edge to the inner edge) is measured at the level where the aortic arch crosses the trachea (double-headed arrow).
      AOA, aortic arch; LPB, left principal bronchus; RPB, right principal bronchus; T, trachea.

      Clinical outcome

      The prenatal ultrasound findings, prenatal genetic test findings, neonatal complications, and anatomic findings determined using neonatal echocardiography or CTA or surgical procedure were collected and reviewed. Pediatricians acquired the clinical findings, postnatal examination findings, and treatment data. Fetuses with DAA were classified into the symptomatic group if the following symptoms were noted: respiratory symptoms, such as wheezing, cough, dyspnea, or asphyxia; esophageal symptoms, such as feeding difficulty or dysphagia; and growth retardation. Those without the aforementioned symptoms were included in the asymptomatic group.

      Statistics

      Statistical analysis was performed using SPSS statistical software (version 23.0; IBM Corporation, Armonk, NY). Continuous variables were presented as mean±standard deviation (SD) or median (interquartile range), and categorical variables were presented as proportion (percentage). The tracheal internal diameter z score reference ranges were established as a function of the GA. First, the normal distribution of the tracheal internal diameter was analyzed using the Kolmogorov-Smirnov test. Later, the linear, quadratic, cubic, and logarithmic models were compared and analyzed, and an optimal model was determined. When a more complex model was not able to significantly improve the goodness of fit, a simpler model was used. The Kolmogorov-Smirnov test (residuals normally distributed when P>.05) was used to test the normality of residuals (differences between observed and predicted values). Residuals were converted to absolute residuals when they followed a normal distribution. Otherwise, the original data were transformed, and the new residuals were tested again and converted to absolute residuals. Finally, according to the method described by Altman,
      • Altman DG
      Construction of age-related reference centiles using absolute residuals.
      linear regression of the absolute residuals and independent variables was performed, and the predicted SDs were determined by multiplying the value by a constant of π2, after which the linear regression of the predicted SDs against GA was obtained. The z score formula was constructed as follows: (1) predicted tracheal internal diameters = mx + c; (2) predicted SD = m’ x + c’; and (3) z scores = observed tracheal internal diameters − predicted tracheal internal diameters/predicted SD (x is the GA, and m, m’, c, and c’ are the slope and intercept of the regression equation). The z scores ±2 represent 2 SDs above or below the mean (corresponding to 97.7th percentiles and 2.3th percentiles, respectively). The median and range of the z scores of the tracheal internal diameters in normal fetuses and fetuses with DAA were calculated. The differences in the tracheal internal diameter z scores were compared using the Mann-Whitney U test. A receiver operating characteristic (ROC) curve analysis was performed to illustrate the tracheal internal diameter z score cutoffs and the corresponding predictive value for symptomatic infants with DAA. Statistical significance was defined as P<.05.

      Results

      During the study period, a total of 26 fetuses with DAA were identified by prenatal ultrasound screening, and 344 normal fetuses were recruited at the 2 institutions. The most common intracardiac anomalies noted in fetuses with DAA were persistent left superior vena cava (PLSVC) and tetralogy of Fallot (TOF). There were 11 fetuses with DAA that underwent karyotyping and genetic testing with CMA. Karyotype anomalies were not identified, whereas pathogenic copy number variants (CNVs) (22q11 microdeletion) were identified in 2 fetuses. All the prenatal findings on ultrasound were confirmed using postnatal histopathologic or CTA or ultrasound examination (Figure 4). The baseline characteristics of the fetuses with DAA are shown in Table 1. Detailed information on all 26 fetuses with DAA are shown in Supplemental Table.
      Figure 4
      Figure 4Postnatally confirmed diagnosis of double aortic arch by multidetector row computed tomography angiography with volume-rendering processing
      Yin. Evaluation of the trachea in fetuses with double aortic arch. Am J Obstet Gynecol MFM 2022.
      A and B, Transaxial view: the ascending aorta divides into the right and left aortic arches, which surround the trachea and esophagus, and converges behind the trachea into the descending aorta, forming a complete “O”-vascular ring. The transaxial view shows the trachea compressed by the vascular ring (arrowhead). C, The coronal view shows the trachea, left principal bronchus, right principal bronchus, and 2 aortic arches (arrowhead). D, The front view of a volume-rendered image: the branches (the LCCA and LSA originating from the left arch and the RCCA and RSA originating from the right arch) and the arches surrounding the trachea and esophagus appear more intuitively. E, The view from above of the volume-rendered image shows the “O”-shaped complete vascular ring more clearly. F, The view from the back of the volume-rendered image: the left and right aortic arches join to form the descending aorta.
      AO, ascending aorta; DO, descending aorta; L-ARCH, left aortic arch; LCCA, left common carotid artery; LSA, left subclavian artery; R-ARCH, right aortic arch; RCCA, right common carotid artery; RSA, right subclavian artery; T, trachea.
      Table 1Baseline characteristics of fetuses with DAA
      Yin. Evaluation of the trachea in fetuses with double aortic arch. Am J Obstet Gynecol MFM 2022.
      CharacteristicsValues (n=26)
      Maternal age (y)28.2 (25.0–30.1)
      Gestational age at diagnosis (wk)26 6/7 (23 1/7 to 29 6/7)
      Type
       Right arch dominant16 (61.5)
       Left arch dominant5 (19.2)
       Double arch balanced5 (19.2)
      Isolated DAA16 (61.5)
      Intracardiac anomalies7 (26.9)
      Extracardiac anomalies8 (30.8)
      Chromosomal karyotype abnormalities0 (0)
      Copy number variations2/11 (18.2)
      Copy number variations in isolated DAA1/10 (10.0)
      Clinical outcomes
       Termination of pregnancies12 (46.2)
       Live birth14 (53.8)
        Symptomatic7/14 (50.0)
        Asymptomatic7/14 (50.0)
        Surgery4/14 (28.6)
      Data are presented as median (interquartile range), number (percentage), or number/total number (percentage).
      DAA, double aortic arch.
      The relationship between the tracheal internal diameters and GA was best described using a simple linear regression model (Figure 5). The other models did not improve the linear models. Regression equations showing the relationship between the tracheal internal diameters of normal fetuses with the GA and fetal biometric variables are shown in Table 2. Regression standardized residuals of the linear regression of the tracheal internal diameters in normal fetuses against GA were tested to be normally distributed, according to using the Kolmogorov-Smirnov test. The z scores of the tracheal internal diameters against GA were calculated as follows: (1) predicted tracheal internal diameters = (−1.423 × GA) + 0.147; (2) predicted SD = π2 × 0.029 × GA; and (3) z scores = (observed tracheal internal diameters − predicted tracheal internal diameters)/predicted SD.
      Figure 5
      Figure 5Scatterplots of tracheal internal diameters in relation to the gestational age in normal fetuses and in fetuses with double aortic arch, with or without symptoms
      Yin. Evaluation of the trachea in fetuses with double aortic arch. Am J Obstet Gynecol MFM 2022.
      Table 2Regression equations showing the relationship between the tracheal internal diameters of normal fetuses with the GA and fetal biometric variables
      Yin. Evaluation of the trachea in fetuses with double aortic arch. Am J Obstet Gynecol MFM 2022.
      Fetal biometric variablesInterceptSlopeP value
      GA (wk)−1.4230.1470.855<.001
      Biparietal diameter (mm)−1.1730.0570.809<.001
      Transverse cerebellar diameter (mm)0.0250.0800.845<.001
      Head circumference (mm)−1.3960.0160.787<.001
      Femur length (mm)−0.7950.0690.827<.001
      Humerus length (mm)−1.2170.0870.811<.001
      Abdominal circumference (mm)−0.6660.0140.835<.001
      GA, gestational age.
      Compared with normal fetuses, the tracheal internal diameter z scores were significantly lower in the fetuses with DAA. The comparison of the z scores (−0.62±1.36 vs 0.00±0.78; P<.001) is shown in Figure 6, A. Table 3 shows a comparison between the fetuses with DAA and normal fetuses.
      Figure 6
      Figure 6Boxplots of the tracheal internal diameter z scores against the GA in fetuses with DAA and normal fetuses and asymptomatic and symptomatic fetuses with DAA
      Yin. Evaluation of the trachea in fetuses with double aortic arch. Am J Obstet Gynecol MFM 2022.
      A, Boxplots of the tracheal internal diameter z scores against the GA in fetuses with DAA and in normal fetuses. B, Boxplots of the tracheal internal diameter z scores against the GA in asymptomatic fetuses and symptomatic fetuses with DAA.
      DAA, double aortic arch; GA, gestational age.
      Table 3Comparisons of fetuses with DAA and normal fetuses
      Yin. Evaluation of the trachea in fetuses with double aortic arch. Am J Obstet Gynecol MFM 2022.
      VariablesDAA (n=26)Normal (n=334)P value
      Maternal age (y)28.2 (25.0–30.1)27.9 (25.4–30.4).741
      Gestational age (wk)26 6/7 (23 1/7 to 29 6/7)30 0/7 (23 4/7 to 36 4/7).017
      Tracheal internal diameter z scores−0.62 ± 1.360.00 ± 0.78<.001
      Data are presented as median (interquartile range) or mean±standard deviation, unless otherwise indicated.
      DAA, double aortic arch.
      A total of 14 fetuses (53.8%) with DAA were delivered alive, and live-born infants with DAA were followed up by pediatricians for at least 200 days. Among the 14 infants with DAA, 7 (50.0%) had different degrees of clinical symptoms during the follow-up period, whereas 7 (50.0%) had no obvious symptom. Among the 7 symptomatic infants with DAA, 4 mainly presented with a mild cough, 1 presented with wheezing, and 2 presented with severe dyspnea for several hours after birth. Moreover, 4 infants underwent surgical treatment during the follow-up period. The detailed characteristics of all 14 live-born fetuses with DAA are shown in Table 4. Compared with the asymptomatic group, the median z scores were significantly lower in the symptomatic group (−1.42±0.92 vs −0.49±0.96; P=.018) (Figure 6, B). The comparison of z scores between the normal, symptomatic, and asymptomatic groups is shown in Figure 5. Table 5 summarizes the comparison between the characteristics and z scores of live-born infants with DAA.
      Table 4Details of the 14 fetuses with double aortic arch who were born alive
      Yin. Evaluation of the trachea in fetuses with double aortic arch. Am J Obstet Gynecol MFM 2022.
      CaseGestational age (wk)TypeAssociated anomaliesSymptomsSurgeryFollow-up time (d)Tracheal internal diameter (mm)z scores
      130 0/7RightNoCoughNo2001.50−1.36
      233 0/7BalancedNoBronchopneumoniaNo2312.50−0.77
      332 0/7RightNoCoughNo4891.50−1.53
      427 3/7RightNoCoughNo9310.76−1.85
      523 0/7RightPLSVCNoNo10621.49−0.56
      829 4/7RightNoNoNo19741.80−1.05
      1123 2/7LeftNoWheezeNo23251.30−0.83
      1330 2/7RightNoNoNo27162.01−0.90
      1828 4/7RightNoNoNo35092.69−0.06
      2022 6/7LeftNoNoNo39341.86−0.10
      2238 2/7BalancedNoNoYes8844.400.14
      2328 6/7BalancedNoDyspneaYes2531.00−1.73
      2522 6/7LeftNoNoYes3431.20−0.89
      2627 6/7BalancedNoDyspneaYes2600.80−1.85
      PLSVC, persistent left superior vena cava.
      Table 5Comparisons of the clinical characteristics and tracheal internal diameter z scores between the asymptomatic and symptomatic groups in infants with DAA
      Yin. Evaluation of the trachea in fetuses with double aortic arch. Am J Obstet Gynecol MFM 2022.
      CharacteristicsTotal (N=14)Asymptomatic (n=7)Symptomatic (n=7)P value
      Maternal age (y)26.5 (23.0–30.8)23.0 (23.0–26.5)30.0 (26.0–31.0).132
      GA at diagnosis (wk)28 4/7 (24 2/7 to 30 0/7)28 3/7 (22 6/7 to 29 6/7)28 6/7 (27 4/7 to 31 0/7).442
      Type1.000
       Right arch dominant9 (64.3)4 (57.1)5 (71.4)
       Left arch dominant1 (7.1)1 (14.3)0 (0)
       Double arch balanced4 (28.6)2 (28.6)2 (28.6)
      Isolated DAA13 (92.8)6 (85.7)7 (100.0)
      Intracardiac anomalies1.000
       No13 (92.9)6 (85.7)8 (100.0)
       Yes1 (7.1)1 (14.3)0 (0)
      Extracardiac anomalies1.000
       No13 (92.9)6 (85.7)7 (100.0)
       Yes1 (7.1)1 (14.3)0 (0)
      Chromosomal abnormalities0 (0)0 (0)0 (0)1.000
      CNVs0 (0)0 (0)0 (0)1.000
      Surgery.580
       No10 (71.4)5 (71.4)5 (71.4)
       Yes4 (28.6)1 (28.6)3 (28.6)
      Tracheal internal diameter (mm)1.5 (1.2–2.0)1.9 (1.6–2.4)1.3 (0.9–1.5).064
      Tracheal internal diameter z scores−0.95 ± 1.32−0.49 ± 0.96−1.42 ± 0.92.018
      Data are presented as median (interquartile range), number (percentage), or mean±standard deviation, unless otherwise indicated.
      CNV, copy number variant; DAA, double aortic arch; GA, gestational age.
      The area under the curve (AUC) of the ROC was 0.878 (95% confidence interval [CI], 0.689–1.000) (Figure 7). Using a tracheal internal diameter z score cutoff of −1.21, the sensitivity was 71%, and the specificity was close to 100%.
      Figure 7
      Figure 7ROC curve for the tracheal internal diameter z score cutoffs and prediction of symptomatic infants with double aortic arch
      Yin. Evaluation of the trachea in fetuses with double aortic arch. Am J Obstet Gynecol MFM 2022.
      The area under the curve was 0.878 (95% confidence interval, 0.689–1.000). Using a tracheal internal diameter z score cutoff of −1.21, the sensitivity was 71%, and the specificity was close to 100%.
      ROC, receiver operating characteristic.
      The intraclass correlation coefficient (ICC) of interobserver agreement was 0.987 (95% CI, 0.980–0.992), and the ICC of intraobserver agreement was 0.975 (95% CI, 0.955–0.987).

      Discussion

      Principal findings

      The z score reference ranges of the tracheal internal diameter were established in normal fetuses. The tracheal internal diameter z scores were significantly lower in fetuses with DAA than in normal fetuses. The scores were significantly lower in symptomatic infants than in asymptomatic infants with DAA.

      Results in the context of what is known

      DAA, the most common form of a complete vascular ring, may lead to tracheal or esophageal compression. Severe respiratory failure or pseudo-CHAOS presentation has been reported in infants.
      • Lee M
      • Kumar TKS
      • Paudel G
      Double aortic arch presenting as neonatal respiratory failure in the delivery room.
      ,
      • Cannioto Z
      • Ngalikpima CJ
      • Dall'Amico R
      A newborn with double aortic arch.
      • Griffiths AL
      • Massie J
      • South M
      Double aortic arch presenting as severe bronchiolitis in a 2-week-old infant.
      • Moon S
      • Mayor J
      • Younis R
      Congenital airway anomaly of double aortic arch in a 2-day-old infant.
      However, to the best of our knowledge, few studies have evaluated the tracheal compression in fetuses with DAA accurately by prenatal ultrasound. This study measured the tracheal internal diameters of fetuses with DAA by prenatal ultrasound and established the z score reference ranges of the tracheal internal diameters based on the GA. In our study, the GA was significantly correlated with the tracheal internal diameter, in accordance with a previous report.
      • Kalache KD
      • Franz M
      • Chaoui R
      • Bollmann R
      Ultrasound measurements of the diameter of the fetal trachea, larynx and pharynx throughout gestation applicability to prenatal diagnosis of obstructive anomalies of the upper respiratory-digestive tract.
      We found that the tracheal internal diameter z scores were significantly different between the DAA and the normal groups. In addition, the tracheal internal diameter z scores were significantly different between the symptomatic and asymptomatic infants with DAA; thus, this study confirmed that the prenatal evaluation of tracheal compression in fetuses with DAA was feasible and effective.
      DAA is often associated with intracardiac and extracardiac abnormalities. The most common intracardiac abnormality is TOF,
      • Alsenaidi K
      • Gurofsky R
      • Karamlou T
      • Williams WG
      • McCrindle BW
      Management and outcomes of double aortic arch in 81 patients.
      which may be related to the conical septum and macrovascular dysplasia during embryonic development caused by 22q11 microdeletion.
      • Yang Y
      • Jin X
      • Pan Z
      • Li Y
      • Wu C
      Diagnosis and surgical repair of congenital double aortic arch in infants.
      In our study, the most common intracardiac abnormalities were the PLSVC and TOF. If PLSVC is considered a normal variation, TOF is the most common coexisting intracardiac malformation in this study. Detailed fetal echocardiography and fetal structural evaluation should be performed following the diagnosis of DAA. Prenatal chromosomal detection of a DAA has been rarely reported. McElhinney et al
      • McElhinney DB
      • Clark 3rd, BJ
      • Weinberg PM
      • et al.
      Association of chromosome 22q11 deletion with isolated anomalies of aortic arch laterality and branching.
      reported that the incidence rates of chromosome 22q11 deletion were up to 24% in infants with isolated anomalies of the aortic arch and 14% in infants with isolated DAA. However, most of the previous studies have included populations with aortic arch anomalies. Here, 2 of 11 cases that underwent CMA examination were found to have pathogenic CNVs, and 1 of them had no intracardiac abnormality. We recommend that once DAA is diagnosed by prenatal ultrasound, chromosome karyotyping and CMA examination should be considered.
      Symptoms because of tracheal or esophageal compression were the most severe complications in infants with DAA. The rate of symptomatic neonates varies between 41% and 98% in different studies, and the most common symptom was stridor.
      • Trobo D
      • Bravo C
      • Alvarez T
      • Pérez R
      • Gámez F
      • De León-Luis J
      Prenatal sonographic features of a double aortic arch: literature review and perinatal management.
      ,
      • Razon Y
      • Berant M
      • Fogelman R
      • Amir G
      • Birk E
      Prenatal diagnosis and outcome of right aortic arch without significant intracardiac anomaly.
      Here, 50% of infants were symptomatic, and the symptoms developed before 3 years of age, which was consistent with the findings reported by previous studies.
      • Bravo C
      • Gámez F
      • Pérez R
      • Álvarez T
      • De León-Luis J
      Fetal aortic arch anomalies: key sonographic views for their differential diagnosis and clinical implications using the cardiovascular system sonographic evaluation protocol.
      ,
      • Trobo D
      • Bravo C
      • Alvarez T
      • Pérez R
      • Gámez F
      • De León-Luis J
      Prenatal sonographic features of a double aortic arch: literature review and perinatal management.
      • Razon Y
      • Berant M
      • Fogelman R
      • Amir G
      • Birk E
      Prenatal diagnosis and outcome of right aortic arch without significant intracardiac anomaly.
      • Tuo G
      • Volpe P
      • Bava GL
      • et al.
      Prenatal diagnosis and outcome of isolated vascular rings.
      The most common symptom was cough.

      Clinical and research implications

      This study provided a tracheal internal diameter z score reference range, which could be used to evaluate tracheal compression prenatally and to predict whether clinical symptoms could occur in infants with DAA. To the best of our knowledge, there were few studies on the relationship between prenatal diagnosis of tracheal compression and postnatal prognosis or management.
      • Achiron RR
      • Kassif E
      • Gilboa Y
      • et al.
      Congenital aortic vascular ring: in-utero sonographic assessment of tracheal patency and postnatal outcome.
      Studies have shown that early evaluation of tracheal compression and surgical intervention should be considered to promote the normal development of tracheal cartilage.
      • Anand R
      • Dooley KJ
      • Williams WH
      • Vincent RN
      Follow-up of surgical correction of vascular anomalies causing tracheobronchial compression.
      • Backer CL
      • Ilbawi MN
      • Idriss FS
      • DeLeon SY
      Vascular anomalies causing tracheoesophageal compression. Review of experience in children.
      • Gross RE
      Arterial malformations which cause compression of the trachea or esophagus.
      • McLaughlin Jr, RB
      • Wetmore RF
      • Tavill MA
      • Gaynor JW
      • Spray TL
      Vascular anomalies causing symptomatic tracheobronchial compression.
      • Stephens EH
      • Eltayeb O
      • Kennedy C
      • et al.
      Influence of fetal diagnosis on management of vascular rings.
      • Vigneswaran TV
      • Kapravelou E
      • Bell AJ
      • et al.
      Correlation of symptoms with bronchoscopic findings in children with a prenatal diagnosis of a right aortic arch and left arterial duct.
      • Wailoo MP
      • Emery JL
      Normal growth and development of the trachea.
      Vigneswaran et al
      • Vigneswaran TV
      • Van Poppel MP
      • Griffiths B
      • et al.
      Postnatal impact of a prenatally diagnosed double aortic arch.
      reported that children with a prenatal diagnosis of vascular ring, including DAA, underwent surgery at a younger age than those with a postnatal diagnosis (13 months vs 24 months). Therefore, we speculate that prenatal diagnosis of DAA and simultaneous assessment of tracheal compression will help promptly to find those infants with tracheal compression, benefitting the performance of surgery for relieving tracheal compression at exactly the correct time. Here, we found that if the tracheal internal diameter z score was less than −1.2, the infant with significant tracheal compression may present symptoms after birth, and early surgical treatment was necessary. There is no consensus about the operative intervention time for patients with DAA. Several reports suggested operating at 6 to 9 months.
      • Stephens EH
      • Eltayeb O
      • Kennedy C
      • et al.
      Influence of fetal diagnosis on management of vascular rings.
      We recommend that if trachea compression is diagnosed prenatally, operative intervention should be performed as soon as possible after birth.
      In addition, if neonates present with severe symptoms, first aid treatment or surgical intervention would be required.
      • Vigneswaran TV
      • Kapravelou E
      • Bell AJ
      • et al.
      Correlation of symptoms with bronchoscopic findings in children with a prenatal diagnosis of a right aortic arch and left arterial duct.
      Here, 2 infants presented with severe dyspnea immediately after birth and underwent surgery during the neonatal period. The tracheal internal diameter z scores of the 2 infants were −1.73 and −1.83, which indicated severe tracheal compression. Prenatal identification of severe tracheal compression could provide important information for clinicians to make preparations perinatally. Further studies should be prospectively performed to investigate the neonatal management approaches for patients with DAA according to the prenatal diagnosis of tracheal compression.

      Strengths and limitations

      The main strengths of this study included the following: (1) our study population included infants with DAA, who may develop severe respiratory distress after birth; (2) the tracheal internal diameter z score reference ranges that were established in this study could be used to evaluate cases with obscure last menstruation period; and (3) this study provided a reliable postnatal confirmatory diagnosis. Detailed prenatal ultrasound and postnatal CTA or echocardiography assessments were performed on all participants. Finally, we divided all infants with DAA into 2 different groups and compared the tracheal internal diameter z scores between them, thus providing more information for predicting the prognosis in infants with DAA.
      However, this study had some limitations. Here, the follow-up was carried out for a short period of 7 months, and thus, it is not certain whether the infants in the asymptomatic group developed symptoms in the future. Serial and further follow-ups should be conducted to follow the progress of clinical symptoms in infants with DAA.

      Conclusion

      The prenatal tracheal internal diameter z scores were significantly different between the asymptomatic and symptomatic infants with DAA. The clinical symptoms in infants with DAA are associated with prenatal tracheal compression, which can be prenatally evaluated using ultrasound. If fetuses are diagnosed with DAA, prenatal surveillance of the tracheal internal diameters and comparison with the z score reference ranges could provide pertinent information for perinatal clinical management.

      Acknowledgments

      The authors are grateful to Dr Mei-Qin Li for her help with the preparation of the figures in this article.

      Appendix. Supplementary materials

      References

        • Backer CL
        • Mavroudis C
        Congenital Heart Surgery Nomenclature and Database Project: vascular rings, tracheal stenosis, pectus excavatum.
        Ann Thorac Surg. 2000; 69: S308-S318
        • Licari A
        • Manca E
        • Rispoli GA
        • Mannarino S
        • Pelizzo G
        • Marseglia GL
        Congenital vascular rings: a clinical challenge for the pediatrician.
        Pediatr Pulmonol. 2015; 50: 511-524
        • Yoshimura N
        • Fukahara K
        • Yamashita A
        • et al.
        Congenital vascular ring.
        Surg Today. 2020; 50: 1151-1158
        • Van Son JA
        • Julsrud PR
        • Hagler DJ
        • et al.
        Surgical treatment of vascular rings: the Mayo Clinic experience.
        Mayo Clin Proc. 1993; 68: 1056-1063
        • Backer CL
        • Mongé MC
        • Popescu AR
        • Eltayeb OM
        • Rastatter JC
        • Rigsby CK
        Vascular rings.
        Semin Pediatr Surg. 2016; 25: 165-175
        • Priya S
        • Thomas R
        • Nagpal P
        • Sharma A
        • Steigner M
        Congenital anomalies of the aortic arch.
        Cardiovasc Diagn Ther. 2018; 8: S26-S44
        • Gardiner H
        • Chaoui R
        The fetal three-vessel and tracheal view revisited.
        Semin Fetal Neonatal Med. 2013; 18: 261-268
        • Bravo C
        • Gámez F
        • Pérez R
        • Álvarez T
        • De León-Luis J
        Fetal aortic arch anomalies: key sonographic views for their differential diagnosis and clinical implications using the cardiovascular system sonographic evaluation protocol.
        J Ultrasound Med. 2016; 35: 237-251
        • Griswold Jr, HE
        • Young MD
        Double aortic arch; report of two cases and review of the literature.
        Pediatrics. 1949; 4: 751-768
        • Lee M
        • Kumar TKS
        • Paudel G
        Double aortic arch presenting as neonatal respiratory failure in the delivery room.
        Cardiol Young. 2018; 28: 476-478
        • Naidu DP
        • Wohlmuth C
        • Gardiner HM
        Prenatal diagnosis of double aortic arch: can we predict airway obstruction (pseudo-CHAOS) and need for airway EXIT?.
        Ultrasound Obstet Gynecol. 2017; 49: 660-661
        • Shum DJ
        • Clifton MS
        • Coakley FV
        • et al.
        Prenatal tracheal obstruction due to double aortic arch: a potential mimic of congenital high airway obstruction syndrome.
        AJR Am J Roentgenol. 2007; 188: W82-W85
        • Mogra R
        • Kesby G
        • Sholler G
        • Hyett J
        Identification and management of fetal isolated right-sided aortic arch in an unselected population.
        Ultrasound Obstet Gynecol. 2016; 48: 739-743
        • Achiron R
        • Rotstein Z
        • Heggesh J
        • et al.
        Anomalies of the fetal aortic arch: a novel sonographic approach to in-utero diagnosis.
        Ultrasound Obstet Gynecol. 2002; 20: 553-557
        • Kalache KD
        • Franz M
        • Chaoui R
        • Bollmann R
        Ultrasound measurements of the diameter of the fetal trachea, larynx and pharynx throughout gestation applicability to prenatal diagnosis of obstructive anomalies of the upper respiratory-digestive tract.
        Prenat Diagn. 1999; 19: 211-218
        • Achiron RR
        • Kassif E
        • Gilboa Y
        • et al.
        Congenital aortic vascular ring: in-utero sonographic assessment of tracheal patency and postnatal outcome.
        Ultraschall Med. 2020; ([Epub ahead of print])
        • Hunter L
        • Callaghan N
        • Patel K
        • Rinaldi L
        • Bellsham-Revell H
        • Sharland G
        Prenatal echocardiographic diagnosis of double aortic arch.
        Ultrasound Obstet Gynecol. 2015; 45: 483-485
        • Yoo SJ
        • Min JY
        • Lee YH
        • Roman K
        • Jaeggi E
        • Smallhorn J
        Fetal sonographic diagnosis of aortic arch anomalies.
        Ultrasound Obstet Gynecol. 2003; 22: 535-546
        • Levy B
        • Wapner R
        Prenatal diagnosis by chromosomal microarray analysis.
        Fertil Steril. 2018; 109: 201-212
      1. Cardiac screening examination of the fetus: guidelines for performing the ‘basic’ and ‘extended basic’ cardiac scan.
        Ultrasound Obstet Gynecol. 2006; 27: 107-113
        • Altman DG
        Construction of age-related reference centiles using absolute residuals.
        Stat Med. 1993; 12: 917-924
        • Cannioto Z
        • Ngalikpima CJ
        • Dall'Amico R
        A newborn with double aortic arch.
        J Pediatr. 2013; 163: 917
        • Griffiths AL
        • Massie J
        • South M
        Double aortic arch presenting as severe bronchiolitis in a 2-week-old infant.
        J Paediatr Child Health. 2005; 41: 297-299
        • Moon S
        • Mayor J
        • Younis R
        Congenital airway anomaly of double aortic arch in a 2-day-old infant.
        Ear Nose Throat J. 2014; 93: E51-E53
        • Alsenaidi K
        • Gurofsky R
        • Karamlou T
        • Williams WG
        • McCrindle BW
        Management and outcomes of double aortic arch in 81 patients.
        Pediatrics. 2006; 118: e1336-e1341
        • Yang Y
        • Jin X
        • Pan Z
        • Li Y
        • Wu C
        Diagnosis and surgical repair of congenital double aortic arch in infants.
        J Cardiothorac Surg. 2019; 14: 160
        • McElhinney DB
        • Clark 3rd, BJ
        • Weinberg PM
        • et al.
        Association of chromosome 22q11 deletion with isolated anomalies of aortic arch laterality and branching.
        J Am Coll Cardiol. 2001; 37: 2114-2119
        • Trobo D
        • Bravo C
        • Alvarez T
        • Pérez R
        • Gámez F
        • De León-Luis J
        Prenatal sonographic features of a double aortic arch: literature review and perinatal management.
        J Ultrasound Med. 2015; 34: 1921-1927
        • Razon Y
        • Berant M
        • Fogelman R
        • Amir G
        • Birk E
        Prenatal diagnosis and outcome of right aortic arch without significant intracardiac anomaly.
        J Am Soc Echocardiogr. 2014; 27: 1352-1358
        • Tuo G
        • Volpe P
        • Bava GL
        • et al.
        Prenatal diagnosis and outcome of isolated vascular rings.
        Am J Cardiol. 2009; 103: 416-419
        • Anand R
        • Dooley KJ
        • Williams WH
        • Vincent RN
        Follow-up of surgical correction of vascular anomalies causing tracheobronchial compression.
        Pediatr Cardiol. 1994; 15: 58-61
        • Backer CL
        • Ilbawi MN
        • Idriss FS
        • DeLeon SY
        Vascular anomalies causing tracheoesophageal compression. Review of experience in children.
        J Thorac Cardiovasc Surg. 1989; 97: 725-731
        • Gross RE
        Arterial malformations which cause compression of the trachea or esophagus.
        Circulation. 1955; 11: 124-134
        • McLaughlin Jr, RB
        • Wetmore RF
        • Tavill MA
        • Gaynor JW
        • Spray TL
        Vascular anomalies causing symptomatic tracheobronchial compression.
        Laryngoscope. 1999; 109: 312-319
        • Stephens EH
        • Eltayeb O
        • Kennedy C
        • et al.
        Influence of fetal diagnosis on management of vascular rings.
        Ann Thorac Surg. 2022; 113: 630-636
        • Vigneswaran TV
        • Kapravelou E
        • Bell AJ
        • et al.
        Correlation of symptoms with bronchoscopic findings in children with a prenatal diagnosis of a right aortic arch and left arterial duct.
        Pediatr Cardiol. 2018; 39: 665-673
        • Wailoo MP
        • Emery JL
        Normal growth and development of the trachea.
        Thorax. 1982; 37: 584-587
        • Vigneswaran TV
        • Van Poppel MP
        • Griffiths B
        • et al.
        Postnatal impact of a prenatally diagnosed double aortic arch.
        Arch Dis Child. 2021; 106: 564-569