Meng et al. BMC Pediatrics(2024) 24:552
https://doi.org/10.1186/s12887-024-04851-7

BMC Pediatrics

RESEARCH

Open AccessAccurate prenatal diagnosis of coarctationof the aorta by 3-step echocardiographic
diagnostic protocol
Hong Meng1*, Zhi-Ling Luo2, Yan Shen2, Qian-Qian Liu1, Mu-Zi Li1 and Yi-Ming Gao1
Abstract
Background Coarctation of the aorta (CoA) is the most common undiagnosed congenital heart defect during
prenatal screening. High false positive and false negative rates seriously affect prenatal consultation and postnatalmanagement. The objective of the study was to assess the utility of various measurements to predict prenatal CoA
and to derive a diagnostic algorithm.
Methods One hundred and fifty-four fetuses with suspected CoA who presented at Fuwai Hospital between
December 2017 and August 2021 were enrolled and divided into confirmed CoA cases (n = 47) and false positive
cases (n = 107), according to their postnatal outcomes. The transverse aortic arch, isthmus, and descending aorta
were measured in the long-axis view of the aortic arch. The angle between the transverse aortic arch (TAO) and thedescending aortic arch (DAO) was defined as the TAO-DAO angle and measured in the long axis or sagittal view.
Based on the database in GE Voluson E10 and the formula (Z = x−µα ), the standard score (Z-score) of the dimensionsof the aorta were calculated in relation to the gestational age. The main echocardiographic indices were combined
to design a 3-step diagnostic protocol. The TAO-DAO angle was used as the first step in the diagnostic model. The
diameter of the transverse arch and the Z-score of the isthmus were the second step. The third-step indices includeda Z-score of the transverse arch, diameter of the isthmus, distance from the left subclavian artery (LSA) to left common
carotid artery (LCCA), the ratio of isthmus diameter and LSA diameter and ratio of the distances (the distance
between the LSA and LCCA to the distance between the right innominate artery and LCCA). The receiver operating
characteristic (ROC) curve determined the predictive capability of each diagnostic parameter, and the kappa test
determined the diagnostic accuracy of the proposed model.
Results The cases with confirmed CoA had thinner transverse arches (1.92 ± 0.32 mm vs. 3.06 ± 0.67 mm, P = 0.0001),
lower Z-scores of the isthmus (-8.97 ± 1.45 vs. -5.65 ± 1.60, P = 0.0001), smaller TAO-DAO angles (105.54 ± 11.51°
vs. 125.29 ± 8.97°, P = 0.0001) and larger distance between the LSA and LCCA (4.45 ± 1.75 mm vs. 2.74 ± 1.07 mm,
P = 0.0001) than the false positive cases. The area under the curve (AUC) was 0.947 (95% CI 0.91–0.98) for the TAO-DAO
angle ≤ 115.75°, 0.942 (95% CI 0.91–0.98) for the transverse arch diameter ≤ 2.31 mm, 0.937 (95% CI 0.90–0.98) for theZ-score of the isthmus ≤ -7.5, and 0.975 (95% CI 0.95–1.00) for the 3-step diagnostic protocol with 97.8% sensitivity*Correspondence:
Hong Meng
drfwmh@126.com
Full list of author information is available at the end of the article© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use,sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) andthe source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in thisarticle are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not includedin the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you willneed to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The
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in this article, unless otherwise stated in a credit line to the data.

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and 97.2% specificity. The kappa test showed that the model’s diagnostic accuracy was consistent with postnatal
outcomes (kappa value 0.936, P = 0.0001).
Conclusions The 3-step diagnostic protocol included the three most useful measurements and the additional
indices with appropriate cut-off values. The algorithm is useful for the detection of aortic coarctation in fetuses with ahigh degree of accuracy.
Trial registration Retrospectively registered.
Keywords Aortic arch, TAO-DAO angle, Coarctation of the aorta, Fetal echocardiography

BackgroundCoarctation of the aorta (CoA) is the most common
undiagnosed congenital heart defect during prenatal
screening, with a true positive detection rate of < 50%[1, 2]. Accurate prenatal diagnosis allows planning of thedelivery in a center with a pediatric cardiology service,
maintaining arterial duct patency by starting prostaglandin infusion immediately after birth, and performing surgery timely, thus reducing mortality and morbidity. Highfalse positive and false negative rates seriously affect prenatal consultation and postnatal management, causing
unnecessary parental anxiety and hospitalization costs.
The main limitations to the prenatal diagnosis of CoA
are the low specificity of the classic echocardiographic
signs (ventricular disproportion, great vessel asymmetry,shelf of the aortic isthmus) and the hard-to-predict arch
remodeling after the closure of the patent ductus arteriosus (PDA) [3, 4]. Even though some authors have studied the Z-scores of cardiovascular dimensions to identify
fetal CoA [5, 6], it cannot be reliably diagnosed using asingle parameter, and clinicians should maintain a highindex of suspicion when multiple parameters are outsideof the expected ranges.
The objective of this retrospective study was to summarize the diagnostic performance of various echocardiographic measurements for detecting fetal CoA and to
derive an optimal diagnostic algorithm.
Materials and methods
Fetuses presenting with suspected CoA based on rightventricular dominance and a small diameter of the aortic arch or isthmus between December 2017 and August2021 were included in the study. They underwent fetal
echocardiography at Fuwai Hospital and Branch Hospital. The exclusion criteria were prenatally suspectedhypoplastic left heart syndrome, complex congenital
heart defect (CHD), and insufficient technical quality
including suboptimal imaging. The Institutional Review
Board of Fuwai Hospital approved the study protocol(FZX2019-06-01 2022YFKY085), which was in accordance with the “Declaration of Helsinki.”
The participants were divided into confirmed or false
positive cases according to the postnatal echocardiography or cardiac computed tomography (CT) results.

Pregnant women and their families were informed
about the limitations of fetal echocardiography before
the examination and signed an informed consent form
for the performance of the exam. The consent forms tocollect data for research were obtained during followup after birth. Echocardiography was performed by two
experienced doctors (H. M. and L.Z.L.), and all measurements were performed by an experienced doctor (H.M).
Fetal echocardiography was performed on a GE Voluson E10 ultrasound machine (GE Medical Systems,
Austria). Measurements were taken according to published standards and included the right ventricular (RV)
end diastolic dimension (RVEDD), left ventricular (LV)
end diastolic dimension (LVEDD), LV end diastolic area
(LVEDA), RV end diastolic area (RVEDA), mitral valve(MV) and tricuspid valve (TV) annular diameters in the
4-chamber view, aortic valve (AV) annular diameter andascending aorta diameter in the LV outflow view, pulmonary valve (PV) annular diameter and main pulmonary
artery diameter in the RV outflow view, aortic artery(AO) and pulmonary artery (PA) diameters in the threevessels and trachea view (3VT).
The transverse aortic arch, isthmus, and descending aorta should be clearly shown in the long axis viewof the aortic arch. The diameter of the left subclavian
artery (LSA), distance between the LSA and left common carotid artery (LCCA), distance between the rightinnominate artery (RIA) and LCCA, and diameter ofthe distal transverse aortic arch (the aortic arch segment
between the LCCA and LSA) were measured. The aortic
isthmus should either be measured proximal to the insertion of the PDA in the sagittal and coronary views or may
be measured proximal to the orifice of the LSA in thelong axis view.
The angle between the transverse aortic arch (TAO)
and the descending aortic arch (DAO) was defined as
the TAO-DAO angle. In the long axis or sagittal view,
the angle was measured by two straight lines, where one
line was drawn proximal (from the take-off of the second
head vessel) to distal (to the end of the third head vessel) along the internal boundary of the transverse arch,and the second line was drawn proximal (just prior to theisthmus) to distal (to the end of the isthmus) along theinternal boundary of the isthmus (Fig. 1) [3, 7].

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Fig. 1 Echocardiographic images depicting the measurement of the TAO-DAO angle. In the long axis or sagittal view, one line is drawn from the origin of
the left common carotid artery to the end of the left subclavian artery parallel with the transverse arch (white arrow), and the second line is drawn prior to
the isthmus to the end of the isthmus (black arrow). The aortic arch has a smooth TAO-DAO angle of 120.5° in a fetus without coarctation of the aorta (A).
The aortic arch presents a rigid contour with a sharp TAO-DAO angle of 100.2° in a fetus with coarctation of the aorta (B). DA, descending thoracic aorta

Based on the formula (Z = x−µα ), the standard score(Z-score) of the valve’s annular diameters and thedimensions of the aorta were calculated in relation to
the gestational age [8]. The RVEDD-to-LVEDD ratio,
RVEDA-to-LVEDA ratio, MV-to-TV ratio, isthmus-toLSA ratio, AO-to-PA ratio, and the ratio of the distances(the distance between the LSA and LCCA to the distance
between the RIA and LCCA) were calculated. The flow
directions across the atrial septum and across the isthmus were observed. Abnormal blood flow across the isthmus were included a retrograde or delayed passage.
After birth, all participants were followed up using
echocardiography, and postnatal outcomes were obtained
through medical records and parental telephonic followup. The diagnosis of CoA after birth was based on (1)the diameters of the proximal and distal transverse aortic arch and aortic isthmus being less than 60%, 50%,
and 40%, respectively, of the distal ascending AO; (2) the
diameter of the transverse aortic arch being less than 50%of the descending AO at the diaphragm; (3) the diameterof the transverse aortic arch being less than one plus theneonatal weight; (4) the peak coarctation velocity being≥ 2.5 m/s (> 2.0 m/s for neonates); and (5) a brachialankle blood pressure difference > 20 mmHg [9]. However,in neonates with a wide-open ductus arteriosus, it is difficult to evaluate the degree of CoA.
Indications for intervention (surgery or catheterization) were (1) systolic upper- to lower extremity bloodpressure gradient > 20 mmHg on non-invasive bloodpressure measurement, echocardiography, or cardiac
catheterization; (2) diminished or absent lower extremity pulses; (3) systemic hypertension in the presence ofsignificant coarctation; (4) heart failure attributable tocoarctation (with increasing severity, the presentation
can extend to diminished cardiac output, poor end organ
perfusion, and cardiogenic shock); (5) radiologic evidence of significant collateralization; (6) neonates with
PGE-dependent CoA [10, 11]. In neonates with these

diagnostic clues, initial treatment consisted of PGE1 followed by intervention. If coarctation correction was not
required in the neonatal period, the children underwent
cardiologic and echocardiographic follow-ups at 3, 6, and12 months of age. Cardiac CT was performed to confirm
the diagnosis before surgery.
The continuous data are expressed as mean ± SD, andcategorical data are expressed as frequency and percentage. Continuous variables were analyzed using the t-test,
and categorical variables were analyzed using the chisquare test. The receiver operating characteristic (ROC)
curve determined the predictive capability of each diagnostic parameter. The cut-off points with the best balance
between specificity and sensitivity were established. The
kappa test measured the disagreement and agreement
between the observers or indices.

Results
One hundred and fifty-four fetuses with suspected CoA
were enrolled in the study. Postnatal echocardiography
or cardiac CT confirmed the diagnosis of CoA in 47
cases, and that of normal aortic arches in 107 false positive cases. The mean maternal age was 30.0 ± 4.5 years(range, 21–43 years). The mean gestational age at diagnosis was 28.1 ± 4.1 weeks (range, 20–39 weeks) in 154
fetuses. Fifty-four fetuses (35.1%) had ventricular septal
defects (VSD), and 19 (12.3%) had persistent left superior
venae cavae (PLSVC). The flow direction across the atrial
septum was right to left in all fetuses. Fourteen fetuseswith limited atrial shunt (< 3 mm) among 107 false positive cases, while five fetuses among 47 confirmed cases(P > 0.05). The characteristic of the flow across the isthmus was different between the two groups (P = 0.0001).
All of the fetuses were born alive, and twenty-ninechildren underwent cardiac surgeries. Figure 2 shows
the outcomes for the entire group. Compared with thosewith normal arches postnatally, the fetuses with confirmed CoA had a smaller aortic diameter and wider

Meng et al. BMC Pediatrics(2024) 24:552

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Fig. 2 Outcomes of eligible fetal cases

distance from the LSA to LCCA. Confirmed CoA waspositively associated with the presence of VSD and
PLSVC (Table 1).
The ROC curve determined that the 3-step diagnostic protocol was the strongest indicator of fetal CoA,with area under the curve (AUC) was 0.975 (95% CI
0.95–1.00). The single strong diagnostic indicators werea TAO-DAO angle ≤ 115.75°, a transverse arch diameter ≤ 2.31 mm, and a Z-score of the isthmus ≤ -7.5. The
AUC was 0.947 (95% CI 0.91–0.98) for the TAO-DAO
angle, 0.942 (95% CI 0.91–0.98) for the transverse archdiameter, and 0.937 (95% CI 0.90–0.98) for the Z-scoreof the isthmus (Fig. 3). The following indices showed astrong specificity for the diagnosis of fetal CoA: a Z-scoreof the transverse arch of ≤ -5.29, diameter of the isthmus of ≤ 1.64 mm, distance from the LSA to LCCA of≥ 3.5 mm, the ratio of isthmus diameter and LSA diameter ≤ 0.89, and ratio of the distances of ≥ 1.81 (Table 2).
When all of the first three measurements (the TAODAO angle, a transverse arch diameter and a Z-score of
the isthmus) were abnormal, the diagnosis of fetal CoA
was supported in 34 cases (72.3%, 34/47). Conversely,
when all of these indices were within the normal range,
a postnatal normal arch was predicted in 81 cases (75.7%,
81/107). Subsequently, five additional measurements
were utilized to improve specificity in the algorithm.
According to their diagnostic performance, the indiceswere incorporated into a diagnostic flow chart (Fig. 4)that forms the basis of our proposed three-step diagnostic protocol. The kappa test showed that the diagnostic
model’s evaluation was consistent with the postnatal outcome of the aortic arch with 97.8% sensitivity and 97.2%
specificity (kappa value 0.936, P = 0.0001), whereas theaccurate diagnosis rate from the two experienced doctors(H.M; L.Z.L.) was 77%.
Four neonatal deaths occurred among the 154 cases
due to duodenal atresia (1.3%, 2/154), cerebral anomalies (0.65%, 1/154), and premature birth (0.65%, 1/154).
Among the 47 children with postnatally confirmed CoA,
22 children underwent arch corrections, including 15
in the neonatal period and 7 in childhood. Comparedwith the other 32 children who did not require neonatal intervention, the 15 children with duct-dependent
CoA had a smaller transverse arch Z-score (-7.90 ± 1.40
vs. -7.05 ± 1.08; P = 0.031) although they had similar otherechocardiographic data. Among the 107 children with anormal arch postnatally, six underwent VSD repairs, andone underwent ductus arteriosus ligation. No postoperative deaths occurred. Their echocardiographic and clinical follow-up findings, growth, and development werenormal.

Discussion
It is important to accurately diagnose fetal CoA; however,fetal prediction of postnatal CoA continues to be a challenge [12]. Even several echocardiographic indices areMeng et al. BMC Pediatrics(2024) 24:552

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Table 1 Prenatal characteristics of the fetuses with suspected coarctation of the aorta and echocardiography indexes predicting
postnatal coarctation of the aorta
Maternal age, years
Gestational age at diagnosis, weeks
RVEDD-to-LVEDD ratio
RVEDA-to-LVEDA ratio
AO-to-PA ratio
AV annular diameter
Z-score of AV
MV-to-TV ratio
Diameter of transverse arch
Z-score of transverse arch
Diameter of isthmus
Z-score of isthmus
TAO-DAO angle
Diameter of LSA
Isthmus-to-LSA ratio
Distance between LCCA and LSA
Distance between RIA and LCCA
Ratio of the distances
Presence of VSD
Presence of PLSVC
Peak aortic velocity
Flow direction across IAS
≥ 3mm
< 3mm
Flow direction across isthmus
Antegrade
With retrograde
With delayed passage

With confirmed CoA n = 47
29 ± 4.3
27 ± 2.9
1.27 ± 0.27
1.31 ± 0.47
0.68 ± 0.13
4.36 ± 0.70
-0.01 ± 1.15
0.79 ± 0.14
1.92 ± 0.32
-7.30 ± 1.29
1.43 ± 0.31
-8.97 ± 1.45
104.54 ± 11.51
1.61 ± 0.39
0.92 ± 0.23
4.45 ± 1.75
1.99 ± 0.79
2.39 ± 0.89
59.6% (28/47)
23.4% (11/47)
71.39 ± 13.63

With normal arch n = 107
31 ± 4.6
28 ± 4.5
1.24 ± 0.21
3.14 ± 18.14
0.72 ± 0.86
4.67 ± 1.03
0.1 ± 0.99
0.81 ± 0.10
3.06 ± 0.67
-4.02 ± 1.31
2.30 ± 0.58
-5.65 ± 1.60
125.29 ± 8.97
1.74 ± 0.49
1.37 ± 0.35
2.74 ± 1.07
1.99 ± 0.65
1.41 ± 0.51
24.3% (26/107)
7.5% (8/107)
68.54 ± 15.54

89.4% (42/47)
10.6% (5/47)

13.1% (14/107)
86.9% (93/107)

63.8% (30/47)
4.3% (2/47)
31.9% (15/47)

90.7% (97/107)
3.7% (4/107)
5.6% (6/107)

P
0.669
0.079
0.444
0.510
0.145
0.036
0.573
0.330
0.00010.00010.00010.00010.00010.103
0.00010.00010.980
0.00010.0001
0.014
0.349
0.447

0.0001RVEDD-to-LVEDD ratio: the ratio of right ventricular end-diastolic dimension to left ventricular end-diastolic dimension; RVEDA-to-LVEDA ratio: the ratio of rightventricular end-diastolic area to left ventricular end-diastolic area; AO-to-PA ratio: the ratio of aortic artery diameter to pulmonary artery diameter; AV: aortic valve;standard score: Z-score; MV-to-TV ratio: ratio of mitral valve annular diameter to tricuspid valve annular diameter; TAO-DAO angle: the angle between the transverse
aortic arch and isthmus; LSA: left subclavian artery; isthmus-to-LSA ratio: ratio of isthmus diameter to LSA diameter; LCCA: left common carotid artery; RIA: rightinnominate artery; VSD: ventricular septal defect; PLSVC: persistent left superior vena cava; R-to-L shunt: right to left shunt

used to diagnose fetal CoA, no single parameter has good
diagnostic accuracy [13, 14]. In this retrospective study,
we validated that postnatal CoA can be predicted with ahigh degree of accuracy using a 3-step echocardiographic
diagnostic model.
Step one Previous studies demonstrated that a tortuous
and rigid aortic arch is the most intuitive sign of CoA
diagnosis in children. Some researchers have used the
TAO-DAO angle to digitally evaluate the arch contour
rather than relying on the operator’s subjective evaluation. Drs. Arya [3] and Freeman [15] defined one angle
between the ascending and descending aorta (≤ 20.31°)
and another angle between the transverse and descending
aorta (≥ 96.15°) to detect fetal CoA. These two measurements could not be obtained if the aortic arch was too
tortuous or if no standard view of the entire aortic arch
was present. So they suggested combining the distance

between the LCCA-to-LSA and Z-score of the ascending
aorta to decrease the rate of misdiagnosis.
Coarctation occurs mostly at the isthmus, so a change
in the angle due to a tortuous or rigid lumen is most
likely to occur at this point, which may explain why the
TAO-DAO angle between the transverse arch and isthmus in our study was found to be the best index to judge
the shape of the arch, as it had the largest AUC (0.95) andthe best sensitivity and specificity (both 92%). Difficulty
in clearly displaying the entire arch contour in one view
may lead to incorrect measurements, which may explain
why we found that some fetuses with confirmed CoA hada normal TAO-DAO angle or that a fetus with a postnatal normal arch had an abnormal TAO-DAO angle. We
found the TAO-DAO angle as the main index in the diagnostic protocol but still utilized the subsequent two steps
to minimize errors in diagnosis.

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Fig. 3 Receiver operating characteristics curve of the 3-step diagnostic protocol and the main three parameters for fetal coarctation of the aorta diagnosis, including the 3-step protocol (red line), the TAO-DAO angle (purple line), the diameter of the transverse arch (blue line), and the Z-score of theisthmus (green line)

Table 2 The optimal critical values of echocardiographic indices for fetal coarctation of the aorta diagnosis, determined by receiver
operating characteristic (ROC)
Index
TAO-DAO angle
Diameter of transverse arch
Z-score of transverse arch
Diameter of isthmus
Z-score of isthmus
Ratio of the distances
Distance between LCCA and LSA
Isthmus-to-LSA ratio

Cut-off value
115.75
2.31
-5.29
1.64
-7.5
1.81
3.50
0.89

AUC
0.947
0.942
0.968
0.918
0.937
0.84
0.823
0.758

Sen
91.6%
86.9%
86.9%
87.9%
92.5%
80.9%
76.6%
98.1%

Sep
91.5%
89.4%
97.9%
83%
87.2%
85.8%
85.8%
41%

AUC: area under curve; Sen: sensitivity; Sep: specificity; TAO-DAO angle: the angle between the transverse aortic arch and isthmus; standard score: Z-score; LCCA: leftcommon carotid artery; LSA: left subclavian artery

Step two The diameter of the transverse arch was measured, and the Z-score of the isthmus was calculated. In
agreement with published data [13, 16], we found thatthe presence of a hypoplastic aortic arch had a good diagnostic performance in detecting CoA. Since the diameter of transverse arch and isthmus must be different at
respective gestational age, the Z-scores of the aorta were
calculated. Considering that a 0.5 mm difference in theisthmus diameter may result in a Z-score of − 2 instead of− 1, we prefer to propose that the Z-scores, instead of theabsolute data, should be used to increase the diagnostic
sensitivity to 92.5%, while concurrently using the transverse arch diameter to improve the specificity to 89.4%.
The two indices used together would balance any false
negative and false positive rates. Gómez-Montes [7] pro-

posed the cut-off value of the Z-score of the isthmus to be≤ -2 when measured in 3VT view, which is larger than ourdata. In our study, the measurement of the isthmus had
to be taken at the insertion of the PDA in the sagittal andcoronary views or proximal to the orifice of the LSA in thelong axis view, and the cut-off value was ≤ -7.5. We holdthat a strict protocol is more suitable for clear display andstandard measurements, facilitating diagnostic accuracy.
The first three indices used in steps 1 and 2, representing the arch contour and dimension, could differentiate
the cases of true narrowing from those of suspected CoA
most of the time. When all of these indices were abnormal, the diagnosis of fetal CoA was supported, and conversely, when all of these indices were within the normal
range, a postnatal normal arch was predicted. Among

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Fig. 4 Comprehensive 3-step echocardiographic diagnostic process to identify a normal fetal aortic arch (A) and fetal coarctation of the aorta (B). LCCA:
left common carotid artery; LSA: left subclavian arterythe 47 fetuses with true CoA, the accurate diagnosis rate
was 72.3% (34/47), when all the first three measurements
were abnormal. Conversely, when all these indices were
within the normal range, a postnatal normal arch waspredicted in 81 cases among 107 false-positive cases(75.7%).
Step Three When the two-step measurements were completed, the diagnosis of CoA was still undetermined with

Meng et al. BMC Pediatrics(2024) 24:552

24.3% false-negative fetus and 27.7% false-positive fetus.
So the following five indices should be added to improvethe diagnostic accuracy further.
1. The distance from the LCCA to the LSA always
increased in patients with CoA, which is theorized
to be secondary to a stretch in the contour of thetransverse arch [17]. Therefore, we measured the
distances and calculated the ratio. The distance fromthe LCCA to the LSA and ratio of the distances had
a high specificity of 86%, which could reduce thefalse-positive rate and provide an indirect evaluationof the arch contour.
2. The aortic arch was further assessed using theZ-score of the transverse arch and the diameter ofthe isthmus [18]. The two indices compensated forthe contradictory judgment in step 2. A reduced
Z-score of the transverse arch would strongly
support the diagnosis of fetal CoA. If isthmus
stenosis is associated with a smaller transverse arch’s
Z-score, the duct-dependent CoA that requires
intervention in the neonatal period should beconsidered.
3. Prior studies have indicated that the diameter of theisthmus should be smaller than that of the LSA in
fetal CoA [19]. Therefore, the isthmus-to-LSA ratio
is considered an important clue to the diagnosisof fetal CoA, which was confirmed in our study.
However, the isthmus-to-LSA ratio had a lowest
specificity (41%). Therefore, the isthmus-to-LSA
ratio may suggest CoA, but it is not specific enoughto independently diagnose CoA. The diagnosis must
be made in conjunction with more specific indices.
Dr. Dodge-Khatami [17] first defined the carotid-subclavian artery index as the ratio of the isthmus diameterto the distance between the LCCA and LSA, and provedthat the parameters had high sensitivity and specificity
for detecting fetal CoA [20]. In our study, the isthmus
diameter and the distance between the LCCA and LSA
were also assessed in this algorithm.
We found that the arterial duct often appears as a tortuous aneurysm in CoA, especially in the third trimester.
The tortuous arterial duct is often mistaken for the aortic
arch, resulting in both a missed diagnosis and misdiagnosis. Therefore, a key point of prenatal echocardiography
is to clearly show the isthmus where the LSA originatesor the arterial duct inserts.
A close relationship between postnatal arch intervention and a higher peak ascending aorta Doppler velocity(OR, 2.51, per 20 cm/s; P = 0.001) was found in a previous
study [21]. One explanation could be that the pulsed wave
Doppler with the best alignment at the ascending aorta
just above the AV is easier to record, whereas Doppler

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tracing of the transverse aortic arch or isthmus is difficult
due to the tortuous and stenotic lumen and the angledependence. In our study, abnormal flow direction acrossthe isthmus was found in the fetuses with true CoA,
however, the index was not put into the algorithm due
to low diagnostic sensitivity. In future research, the peak
Doppler velocity across the aorta should be recorded to
explore the diagnostic sensitivity and realizability.
In addition, Dr Fruitman [22] also established a score
to predict CoA, including gestational age, Z-score of RV
mid-cavitary dimension, and Z-score of isthmal diameter,
which presented a good diagnostic performance with
90% sensitivity and 83% specificity. However, gestationalage, RV dimension and its Z-score were not confirmed asindicators of fetal CoA in our study. One possible explanation could be that the measurement of RV dimension
is non-standard, since there are at least two different fetal
four-chamber views (the apical 4-chamber view and thesubcostal 4-chamber view).
The proposed algorithm in our study is better than theother scoring systems [17–20, 22] due to the standardized measurements. Recently, some researchers havereported that three-dimensional printing and speckletracking peak global longitudinal strain might be helpful
in detecting fetal congenital heart diseases [23, 24]. Thesenovel tools could be verified in future research.

Limitation
The proposed algorithm has not been tested in morepatients. In the future, the algorithm based on our retrospective study requires to be validated by a prospective
multicenter registry of suspected CoA fetuses. Furthermore, the main purpose of this proposed algorithm
was not to detect the fetuses with PGE-dependent CoA
requiring neonatal coarctation correction. In this retrospective study, 29 children met the diagnostic criteria
and did not undergo neonatal arch correction. In further
studies, a larger number of cases should be included to
specify the algorithm to predict the severity of CoA andthe timing of intervention.
Conclusion
The 3-step diagnostic protocol starts with a measurement of the aortic TAO-DAO angle, followed by measurements of the transverse arch and isthmus, and finallyincorporates additional indices. The algorithm is usefulfor the detection of aortic coarctation in fetuses with ahigh degree of accuracy.
Abbreviations
CoA	Coarctation of the aorta
PDA	Patent ductus arteriosus
CHD	Congenital heart defectCT	Computed tomography
RV	Right ventricular
RVEDD	Right ventricular end diastolic dimension

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RVEDA	Right ventricular end diastolic area
LV	Left ventricular
LVEDD	Left ventricular end diastolic dimension
LVEDA	Left ventricular end diastolic area
MV	Mitral valve
TV	Tricuspid valve
AV	Aortic valve
PV	Pulmonary valve
AO	Aortic artery
PA	Pulmonary artery3VT	Three vessels and trachea view
LSA	Left subclavian artery
LCCA	Left common carotid artery
RIA	Right innominate artery
Z-score	Standard score
ROC	Receiver operating characteristic
AUC	Area under the curve
CI	Confidence interval
VSD	Ventricular septal defects
PLSVC	Persistent left superior venae cavae

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Acknowledgements
We would like to thank Editage for English language editing.
Author contributions
HM designed the study, performed the echocardiographic examinations,collected and analyzed the data, and drafted the manuscript. Z-L L performed
echocardiographic examinations. YS and Q-QL followed up the patients. M-Z
L and Y-M G collected the clinical data. All authors reviewed and approved thefinal manuscript.
Funding
This study was supported by the CAMS Clinical and Translational Fund for
Medical Sciences (Grant No. 2022-I2M-C&T-B-051) and Yunnan Provincial
Cardiovascular Disease Clinical Medical Center Project (No. FZX2019-06-01
2022YFKY085).
Data availability
The datasets used and/or analyzed during the current study are available fromthe corresponding author on reasonable request.

Declarations
Ethics approval and consent to participate
The study was approved by the institutional review board of Fuwai Hospital(November 5, 2020, Ethics approval number: 2020-063) and performed inaccordance with the Declaration of Helsinki. Informed consent was obtained
from the parents.
Consent to publish
Not Applicable.
Competing interests
The authors declare no competing interests.
Author details
1
Department of Echocardiography, Fuwai Hospital, National Center for
Cardiovascular Diseases, Chinese Academy of Medical Sciences andPeking Union Medical College, 167 Beilishi Rd, Xicheng District,
Beijing 100037, P. R. China
2
Department of Echocardiography, Fuwai Yunnan Cardiovascular Hospital
Kunming, Kunming 650102, China
Received: 28 August 2022 / Accepted: 22 May 2024

Meng et al. BMC Pediatrics(2024) 24:552

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