To determine the frequency of prenatal detection among liveborn patients with an interrupted aortic arch (IAA), the accuracy of prenatal diagnosis, and the anatomic features associated with IAA in the fetus. The prenatal diagnosis of an IAA is challenging. The data on the features and outcomes of fetal IAA are limited. This was a retrospective review of the fetuses and neonates diagnosed with IAA at the Children’s Hospital Boston. From 1988 to 2009, 26 fetuses were diagnosed with an IAA. Of these, 21 were live born, and 5 pregnancies were terminated. Of these 21 patients, 18 were confirmed to have an IAA after birth and 3 had severe aortic coarctation. Of the 56 patients diagnosed with an IAA as neonates, 3 had a prenatal echocardiogram that did not include the correct diagnosis. Among the liveborn patients with a postnatally confirmed IAA, 24% were diagnosed prenatally, which increased from 11% during the first 7-year period to 43% more recently. Also, 15% of the prenatally diagnosed patients with IAA had a family history of structural or genetic anomalies. In fetuses with an IAA, echocardiographic Z-scores for the aortic valve and ascending aorta were significantly lower than in normal fetuses, but the left ventricular dimensions were normal. Aortopulmonary diameter ratios were abnormally low. In conclusion, although the identification of IAA on a prenatal echocardiogram can be challenging, a number of anatomic features can facilitate the diagnosis. In particular, a low aortopulmonary diameter ratio in the absence of a ventricular size discrepancy should prompt consideration of this diagnosis. Despite the diagnostic challenges, the frequency of prenatal diagnosis of the IAA is increasing.
An interrupted aortic arch (IAA) is a rare, but serious, anomaly in which a proportion of the systemic circulation is ductal dependent in the neonatal period. Imaging of the aortic arch in the fetus can be challenging, and it can be difficult to distinguish the ductal arch from the aortic arch. The current recommendations for screening on the obstetric fetal anomaly scan include identification of a 4-chamber view, all 4 valves, and the outflow tracts, all of which can appear to be normal to the ultrasonographer in fetuses with conotruncal anomalies.
Other than case reports, essentially no published data are available concerning the prenatal diagnosis of IAA, and, as such, the frequency, accuracy, outcomes, and specific anatomic features of fetuses with an IAA have not been characterized. The aim of the present study was to determine the frequency of prenatal detection among liveborn patients with an IAA, the accuracy of the prenatal diagnosis of an IAA, and the specific anatomic features associated with an IAA in the fetus that should alert ultrasonographers to the presence of a significant heart defect. The ascending aortic flow might be lower than normal in fetuses with an IAA, owing to the ductal supply of the entire lower body circulation and often the left subclavian artery. Therefore, it was hypothesized that the Z-scores for the aortic valve (AoV) annulus and ascending aortic diameters would be lower than in the normal population, that the pulmonary valve annulus and main pulmonary artery Z-scores would be greater than in the normal population, and that the AoV/pulmonary valve and ascending aorta/main pulmonary artery ratios would be abnormally low.
Methods
Fetuses and neonates diagnosed with an IAA were ascertained by searching the database of the cardiovascular program at the Children’s Hospital Boston (Boston, Massachusetts), using the diagnostic codes for all types of IAA. Patients suspected to have an IAA prenatally who were found to have another diagnosis after birth were also included. The postnatal cohort only included patients who presented to our institution at <1 month of age. Patients with additional major cardiac anomalies who also had IAA, such as transposition of the great arteries, double-outlet right ventricle, and truncus arteriosus, were excluded. The following demographic and historical data were obtained: gestational age at diagnosis, family history of congenital heart disease, a previous serious fetal anomaly or chromosomal defect, pregnancy outcome, and postnatal outcome.
The assigned prenatal and postnatal diagnoses were taken from the official echocardiogram report. The diagnosis of IAA was specified as type A (interruption after the origin of the left subclavian artery), type B (interruption after the origin of the left common carotid artery), or unspecified. The presence and type of ventricular septal defect (VSD) was recorded. Echocardiographic measurements were made off-line by one observer who was unaware of the patient outcomes. All studies obtained after 2004 were recorded in Digital Imaging and Communications in Medicine format. For earlier echocardiograms that were stored on videotape, the studies were digitized and measurements made from the digital version. The anatomic structures measured included the mitral and tricuspid valve diameters (valve hinge points at the annulus during the maximum opening in diastole), left ventricular (LV) and right ventricular lengths at end-diastole, LV short-axis dimension at end-diastole, AoV and pulmonary valve, and ascending aorta and main pulmonary artery diameters in systole. Gestational age-based Z-scores were calculated from unpublished normative data collected at Children’s Hospital Boston from 2005 to 2007 from 232 normal fetuses. To optimize the reporting of the diagnostic accuracy of the fetal echocardiographic findings and the estimates of the frequency of the prenatal diagnosis, the data from newborns with an IAA not diagnosed prenatally at our center were also collected to ascertain whether a fetal diagnosis had been made elsewhere. The postnatal echocardiograms and reports were reviewed to assess for discrepancies between the pre- and postnatal diagnosis.
The diagnostic and outcome data are reported in descriptive fashion. A comparison of the gestational age at diagnosis between the liveborn and terminated pregnancies was performed using the Wilcoxon rank sum test. A comparison of categorical data between groups (eg, pre- and postnatally diagnosed patients) was performed using Fisher’s exact test. The echocardiographic data from the fetuses with an IAA were compared with a normative population (mean Z-score = 0) using a 1-sample t test. A comparison of the serial echocardiograms in fetuses with 2 studies was performed using a paired t test analysis.
Results
From June 1988 through April 2009, 26 fetuses and 56 additional neonates ≤30 days old were diagnosed with an IAA at Children’s Hospital Boston. Of the 26 fetuses with a prenatal diagnosis of IAA, 21 were liveborn and 5 families elected to terminate the pregnancy without fetopsy. The median gestational age at diagnosis was 25.7 weeks (range 17.0 to 37.3) overall and 19.8 weeks (range 18.8 to 20.1) for the terminated pregnancies (p <0.001 for comparison of terminated pregnancies with those continued to birth). Of the 21 liveborn patients, 17 were female and 3 were male; for 1 infant, who was born and died at an outside hospital, the gender was unknown. Illustrative echocardiographic images are depicted in Figures 1 and 2 .
All 21 liveborn patients diagnosed prenatally with IAA for whom postnatal echocardiograms were available had a postnatal diagnosis of an IAA or severe coarctation of the aorta (COA). Of the 21 liveborn patients, 18 (86%) were confirmed to have an IAA after birth ( Table 1 ), and 3 were found to have severe COA instead of an IAA. In 2 of these 3, the prenatal diagnosis was “either IAA or severe COA,” and in the third, the prenatal diagnosis was IAA type B. In 2 cases, the prenatal diagnosis specified a particular type of IAA (eg, type A or B), and the postnatal imaging revealed the IAA to be a different type. In 4 cases, the type of IAA was not specified prenatally and was found to IAA type B postnatally. In 8 other cases, the prenatal diagnosis was listed as “either IAA or severe COA” and was found postnatally to be IAA type B (n = 5) or type A (n = 3). Those patients were considered to have had the correct antenatal diagnosis. In the other 4 cases, the prenatal diagnosis of IAA type B was correct.
| Prenatal Diagnosis | Postnatal Diagnosis | Patients (n) |
|---|---|---|
| Liveborn after prenatal diagnosis of IAA | ||
| IAA type B and VSD | IAA type B and VSD | 4 ⁎ |
| IAA type B and VSD | IAA type A and VSD | 1 |
| IAA type B and VSD | Severe COA with hypoplastic aortic arch and VSD | 1 |
| IAA type A | IAA type B and VSD | 1 |
| IAA unspecified and VSD | IAA type B and VSD | 4 |
| IAA type A or severe COA and VSD | IAA type A and VSD | 1 |
| IAA type A or severe COA and VSD | Severe COA and VSD | 1 |
| IAA unspecified or severe COA, VSD, small left ventricle | COA and Shone complex | 1 |
| IAA unspecified or severe COA and VSD | IAA type A and VSD | 2 † |
| IAA unspecified or severe COA and VSD | IAA type B and VSD | 5 |
| Pregnancy terminated after prenatal diagnosis of IAA | ||
| IAA type B and VSD | pregnancy terminated | 2 |
| IAA unspecified | pregnancy terminated | 2 |
| IAA unspecified or severe COA | pregnancy terminated | 1 |
| Prenatal echocardiogram incorrect, postnatal diagnosis of IAA ‡ | ||
| Large VSD, small AoV ‡ | IAA type A and VSD | 1 |
| Normal | IAA type A and VSD | 1 |
| Possible COA and mild ventricular discrepancy | IAA type B and VSD | 1 |
⁎ Co-existing left-sided congenital diaphragmatic hernia in 1, diagnosed prenatally and confirmed postnatally.
† Patient also had dextrocardia.
‡ Prenatal echocardiography was performed at another institution in the first of these patients and at our institution in the other 2.
In all 21 liveborn patients, a VSD was diagnosed prenatally. In 16 cases, all correctly characterized on the prenatal scan, the VSD was a posterior malalignment defect. Of these 16 patients, 14 had type B IAA confirmed postnatally, 1 had type A IAA, and 1 had COA. Of the other 5 patients, 4 had muscular VSDs and 1 a membranous defect. None of these patients had a type B IAA; 3 had type A IAA and 2 had COA. All 5 fetuses in which the pregnancy was terminated were diagnosed with a posterior malalignment VSD.
Of the 56 patients diagnosed with an IAA in the newborn period (27 males and 29 females), 53 had not undergone prenatal echocardiography and 3 had a prenatal echocardiogram that did not include the correct diagnosis. Of these 3 patients, 1 had a fetal echocardiogram from a different institution and was diagnosed with a small AoV and a large VSD but was found to have type A IAA and a VSD on postnatal scanning. The other 2 fetuses were scanned at our institution: 1 was reported to have normal findings but had type A IAA; the other was diagnosed prenatally with a “possible COA” and a VSD and was found to have type B IAA and a VSD postnatally.
The frequency of the prenatal diagnosis over time was assessed by dividing the 21-year study period into 3 equivalent periods. Of the liveborn patients with a confirmed postnatal diagnosis of IAA (n = 74), 24% were diagnosed prenatally. This frequency increased from 11% during the first 7-year period to 16% during the second and 43% during the third (p = 0.01). In 2 (40%) of 5 fetuses diagnosed with an IAA during the first 7-year period, the pregnancy was terminated compared to 1 (17%) of 6 during the second period and 2 (13%) of 15 during the most recent period. Of the 56 patients first diagnosed during the neonatal period, 24 were diagnosed during the first 7-year period and 16 each were diagnosed in the second and third periods.
Of the 18 prenatally diagnosed patients with postnatally confirmed IAA, 12 (67%) had an identified chromosomal abnormality or syndrome, chromosome 22q11 deletion in 10 patients, Turner syndrome in 1, and VACTERL association (vertebral anomalies; anal atresia; cardiac defect, most often VSD; tracheoesophageal fistula with esophageal atresia; renal abnormalities; and limb abnormalities, most often radial dysplasia) in 1. One of the patients diagnosed with IAA in utero who was found to have COA after birth had Turner syndrome. The genetic status was unknown in 1 of 21 liveborn patients with a prenatal diagnosis of IAA and in 4 of the 5 in which the pregnancy was terminated. A malformation syndrome or chromosome abnormality was diagnosed in 30 of 56 patients with a neonatal diagnosis of IAA. Of the 30 patients, 27 had a chromosome 22q11 deletion (1 with Klippel-Feil syndrome in addition and 1 with VACTERL association), and 1 patient each had CHARGE syndrome, trisomy 21, and chromosome 4 deletion. The genetic status was unknown in 9 of 56 patients with a confirmed neonatal diagnosis of IAA. The chromosomal abnormalities were similarly common in patients diagnosed pre- and postnatally.
A known family history of cardiac, severe noncardiac, or chromosomal/genetic abnormalities was reported in 10 patients, including 4 (15%) of those with a prenatal diagnosis ( Table 2 ).
| Family History | Patient Diagnosis | Prenatal or Neonatal Diagnosis of IAA |
|---|---|---|
| Father with 22q11 deletion | IAA type B, 22q11 deletion | Prenatal |
| Father with tetralogy of Fallot and probably 22q11 deletion | IAA type B, 22q11 deletion | Prenatal |
| Mother and maternal aunt with tetralogy of Fallot and 22q11 deletion | IAA type B, 22q11 deletion | Prenatal |
| Previous sibling with IAA type A, deceased | IAA type unknown | Prenatal (terminated) |
| Previous fetus with IAA type unknown, pregnancy terminated | IAA type A | Neonatal |
| Mother and brother with 22q11 deletion | IAA type B, 22q11 deletion | Neonatal |
| Previous fetus with anencephaly | IAA type B, 22q11 deletion | Neonatal |
| Sibling with HLHS | IAA type B, 22q11 deletion | Neonatal |
| Mother with 22q11 deletion | IAA type B, 22q11 deletion | Neonatal |
| Maternal grandmother with COA | IAA type A | Neonatal ⁎ |
⁎ Prenatal scan at 20 weeks’ gestation was interpreted as showing normal cardiac anatomy.
The fetal echocardiographic data are summarized in Table 3 . Overall, the Z-scores for the AoV, ascending aorta, and mitral valve were significantly (p <0.001) lower in the study cohort than in normal fetuses, and were less than normal (Z-score ≤2) in 69%, 73%, and 19% of fetuses, respectively ( Figure 3 and Table 3 ). The LV short- and LV long-axis Z-scores, however, were normal. The pulmonary valve, main pulmonary artery, and right ventricular length Z-scores were all larger than normal, although only modestly so for the right ventricle ( Table 3 ). The AoV/pulmonary valve diameter ratio (0.54 ± 0.11) and the ascending aorta/main pulmonary artery diameter ratio (0.50 ± 0.09) were lower than normal, but both were noticeably greater and closer to normal in fetuses diagnosed earlier in gestation ( Figure 3 ). The fetuses found to have IAA type A and COA postnatally tended to have greater ascending aorta/main pulmonary artery diameter ratios on the prenatal scan than those with IAA type B.
