Received: 29 December 2020

DOI: 10.1002/pd.6007

ORIGINAL ARTICLE
- -Revised: 21 March 2021 Accepted: 30 May 2021

Dilated ascending aorta in the fetus

Ioana Dumitrascu‐Biris1,2 | Vita Zidere1,2 | Trisha Vigneswaran1,2 |

Marietta Charakida1,2,3 | Sujeev Mathur1 | Nick Kametas2 | John Simpson1,2,3

1
Fetal Cardiology Unit, Department of
Congenital Heart Disease, Evelina London ABSTRACT
Children's Healthcare, Guy's and St Thomas'
Introduction: Prenatal recognition of dilated aortic root is extremely rare and there
NHS Foundation Trust, London, UK
2 are significant challenges in counselling these patients. The primary aim of this case
Harris Birthright Centre, Fetal Medicine
Research Institute, King's College Hospital, series is to describe the prevalence, associations and outcome of dilated ascending
NHS Foundation Trust, London, UK
aorta diagnosed during fetal life.
3
School of Biomedical Engineering, Division of
Imaging Sciences, King's College London,
Methods: This is a retrospective cohort study from two tertiary fetal cardiology
London, UK centres. Dilated ascending aorta was defined as gestation‐specific standard devia-
tion > 1.96 at some point during gestation.
Correspondence
Ioana Dumitrascu‐Biris, Fetal Cardiology Unit, Results: Sixteen infants were live born and underwent postnatal echocardiography.
Department of Congenital Heart Disease, Prenatally suspected bicuspid aortic valve (BAV) (n = 6) was confirmed in 5 cases
Evelina London Children's Healthcare, Guy's
and St Thomas' NHS Foundation Trust, (83%) postnatally. Thirteen children have been followed up for a period of minimum
London, UK. one year. No connective tissue disease was found.
Email: ioana.dumitrascu@gstt.nhs.uk
Conclusions: Prenatal dilated ascending aorta is a rare finding (0.06%). It is asso-
ciated with BAV in 37% of cases and extracardiac abnormalities in 15.7%. Nuchal
translucency measurement was >3.5 in 13% of cases. Connective tissue disease was
not diagnosed postnatally. This is the largest prenatal cohort with dilated ascending
aorta and postnatal outcomes to date. We showed a postnatal persistence of
ascending aortic dilatation in 43% of babies. In the absence of extra‐cardiac ab-
normalities, medium term outcome appears good but postnatal surveillance of
aortic dilation is required.

KEYWORDS
aortic annulus, bicuspid aortic valve, congenital heart disease, dilated ascending aorta, fetus

Key points
What is already known about this topic?
� Dilation of the ascending aorta in patients with bicuspid aortic valve (BAV) may be present
from infancy.

What does this study add?

� Dilatation of the ascending aorta can be recognized during fetal life.
� The most common association of dilated ascending aorta in fetal life is of a bicuspid aortic
valve.
� In the absence of extra‐cardiac abnormalities, medium term outcome appears good but
postnatal surveillance of aortic dilation is required.

Prenatal Diagnosis. 2021;1–7. wileyonlinelibrary.com/journal/pd © 2021 John Wiley & Sons Ltd.

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1 | INTRODUCTION
Dilatation of the ascending aorta is well described in children and
adults most commonly in association with a bicuspid aortic valve
(BAV) or connective tissue disorders such as Marfan syndrome and
Loeys‐Dietz syndrome. With respect to BAV, which is present in 1%–
2% of the population, recent data has confirmed that dilation of the
ascending aorta may be present in infancy.1–3 This is clinically
important because severe dilatation of the ascending aorta is asso-
4
ciated with an increased risk of aortic dissection. Aortic valve
morphology and coexistence of aortic stenosis and/or regurgitation
are important predictors of progressive aortic dilatation.1–3 Howev-
er, even in the absence of BAV dysfunction, aortic dilation may occur,
5
reflecting abnormal aortic wall properties with aortic elasticity.
Abnormalities of the great arteries are being increasingly
recognized during fetal life following the incorporation of the three
vessel and trachea views into screening programmes.6 In recent
years, dilation of the ascending aorta has been identified during fetal
life, detected either during screening examinations or during detailed
fetal echocardiography, but literature is sparse on the sonographic
features and outcome of this group of fetuses. Viassolo et al., in his
case report described an isolated aortic dilatation in the fetus at
19 weeks' gestation, although postnatally the aortic measurements
were normal, a de Novo mutation in TGFBR2 and Loeys‐Dietz syn-
drome was confirmed.7 The aims of our report are to describe the
associations and outcome of dilated ascending aorta diagnosed dur-
ing fetal life.
2 | METHODS
This is a retrospective cohort study of fetuses diagnosed with a
dilated ascending aorta from two tertiary fetal cardiology centres.
Fetuses diagnosed with a dilated ascending aorta were identified
from our departmental database between January 2010 and August
2019. Fetuses with abnormal cardiac structure including abnormal
cardiac connections, aortic valve stenosis and fetal arrhythmia were
excluded. A dilated ascending aorta was defined as a gestation‐
specific standard deviation > 1.96 at some point during gestation
and was measured on the long axis view of the left ventricle where
the diameter was at its greatest value.8 Fetal measurements of the
aortic valve were performed in systole hinge points to hinge points
and the ascending aorta was measured at its widest diameter in
systole. The z‐score were calculated using the Cardio Z App (https://
www.ncbi.nlm.nih.gov/pmc/articles/PMC3487208/), using the data of
Schneider et al.9
Postnatal measurements of the aortic root and ascending aorta
were made using the parasternal long axis view in mid‐systole using
the inner‐edge to inner edge dimensions.10
This is a retrospective analysis of clinically acquired data which
was approved by the Institutional Clinical Governance Board of
Guy's & St Thomas' Hospital, audit no. 9875/2019. Parental consent
was not considered necessary for the study.
ET AL.
2.1 | Statistical analysis
Normality of distribution for continuous variables was assessed by
the Kolmogorov‐Smirnov test. As these were not normally distrib-
uted, they are presented as median (interquartile range). Mann
Whitney‐U test was used for comparison between babies with
tricuspid and BAV and the Friedman test for comparison between the
first and second visit. Statistical analyses were performed using SPSS
(IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version
25.0. Armonk, NY: IBM Corp).
3 | RESULTS
The fetal databases (Viewpoint version 5.6, GE Corporation, Mil-
waukee, USE and Filemaker Pro, Claris Corporation) were searched
for fetuses with a dilated ascending aorta. The search identified 20
cases (0.06%) with dilated ascending aorta during the study period. In
three cases pregnancy was terminated (two with major extracardiac
anomalies and one with trisomy 21) and in one case the postnatal
outcome was not available. Hence, these four fetuses were not
included in the further analysis.
3.1 | Prenatal findings
The median (IQR) gestation at diagnosis was 20.8 weeks (20.2–
21.1). In one case, suspicion of aortic dilatation was raised at
14 weeks gestation and confirmed in the second trimester. In-
dications for fetal echocardiography included abnormal three‐vessel
view (n = 10), family history of major congenital heart disease
(n = 2), family history of BAV (2) and increased nuchal translucency
(n = 2).
There were no extracardiac abnormalities evident on ultrasound
in the 16 fetuses where pregnancy continued. The nuchal trans-
lucency (NT) measurement was available in 14/16 patients and in two
(14%) it was above 99th centile. In our study 3/16 fetuses had inva-
sive testing (two with associated increase NT) yielding a normal array
CGH in all three cases. In six cases, short axis views of the aortic
valve suggested that this was bicuspid (Figure 1), in nine cases it was
felt to be tricuspid and in one case the short axis view could not be
achieved.
The absolute measurements and z‐scores of the aortic valve
annulus and ascending aorta and the morphology of the aortic valve
are demonstrated in the Table 1.
The first visit was at a median of 20.8 weeks gestation (IQR
20.2–21.1) and the second visit at a median 28.3 weeks gestation
(IQR 28.0–28.9). In the whole cohort, ascending aorta increased
with gestation from 4.8 mm (IQR 4.6–5.0 mm) to 7.7 mm (IQR 6.3–
8.0 mm) at the first and second visits, respectively (p < 0.0001). The
ascending aorta z‐score did not increase significantly between the
first visit (median z score +2.2 (IQR 1.9 to + 2.9)) and the second
visit (median z ‐score +2.8 (IQR1.5 to + 3.3)) (p = 0.61). In the
DUMITRASCU‐BIRIS ET AL.
F I G U R E 1 Fetal short axis view of the aortic valve showing a
bicuspid aortic valve (white arrow)
whole cohort, the aortic valve size increased with gestation from
3.3 mm (3.1–3.9 mm) to 5.8 mm (5.5–6.2 mm) at the first and
second visits, respectively (p < 0.0001). The aortic valve z‐score
increased with gestation from +0.74 (IQR 0.23 to +1.74) to +2.01
(IQR 1.42 to + 2.34) between the first and second visits (p = 0.003)
(Table 2).
At the first visit, there was a non‐significant trend (p = 0.07) for
the ascending aorta z‐score to be higher in fetuses with a tricuspid
aortic valve than those with a bicuspid aortic valve. The aortic valve
z‐score was significantly higher at the first visit in fetuses with a BAV
compared to those with a tricuspid aortic valve (p = 0.04). At the
second visit, the ascending aortic z‐scores were no different between
the two group and there was a non‐significant trend for the z‐score
of the BAV to be higher than the tricuspid aortic valve group
(Table 3: Figures 2 and 3).
3.2 | Postnatal outcome
There were sixteen live‐born babies who were all assessed by a pe-
diatric cardiologist in the first three months of life. Postnatal echo-
cardiography confirmed persistent dilation of the ascending aorta in
7/16 infants with median z‐score +2.9 (2.3–3.6). The median z‐score
of aortic valve annulus was −0.4 (range −1.6 to +0.4) and aortic sinus
median z score (range‐0.9 to +1.5).
Prenatally suspected BAV (n = 6) was confirmed in five cases
(83%) postnatally. There was a further one patient where a BAV was
confirmed postnatally but not suspected prenatally. There were 67%
(n = 4) male and 33% (n = 2) female patients in the group with
confirmed bicuspid aortic valve.
Five children underwent postnatal cardiac magnetic resonance
imaging (MRI). This investigation demonstrated dilated ascending
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aorta in all cases (Figure 4). In one of the patients a significant arterial
tortuosity was identified (Figure 5).
None of the 16 patients had dysmorphic features on postnatal
examination, nor were there other echocardiographic signs of con-
nective tissue disease such as mitral valve prolapse. Patients with
persisting aortic dilatation without a BAV were generally referred to
clinical geneticist. Five patients were evaluated by a clinical geneti-
cist, none of whom had additional clinical features of connective
tissue disease, and all had normal array CGH. One child with a grossly
dilated ascending aorta had whole exome sequencing with normal
findings.
One patient was discharged at one year of age (with a resolution
of findings) and the remaining cases are under cardiology follow‐up
and have not required any treatment.
3.3 | Discussion
This is the first study describing the prenatal features and post-
natal outcome of fetuses presenting with dilation of the ascending
aorta during fetal life. The majority of our cases were referred
because of abnormal screening views during a second trimester
anomaly scan. Isolated dilation of the ascending aorta is a rare
prenatal finding – the 20 cases identified represent 0.06% cases
evaluated at our referral units. The diameter of the ascending
aorta is not routinely measured during screening examinations of
the fetal heart which are done according to standards set down as
part of the National Health System Fetal Anomaly Screening
Programme (NHS FASP). The majority of the patients were
referred for detailed fetal echocardiography due to the sonogra-
pher observing an abnormal three vessel or three vessels + tra-
chea view, following an observation of disproportionate
enlargement of the aorta compared to adjacent vessels such as the
superior vena cava or ductal arch. The most frequent associated
finding was a BAV which was diagnosed prenatally or postnatally
in six of the 16 affected fetuses. None of our cases has shown
clinical or echocardiographic evidence of an underlying connective
tissue disease to date.
BAV is described as the most common form of congenital heart
disease with an incidence between 1% and 2% and a male predom-
inance of 3:1.11,12 In our cohort, there was male predominance of 2:1
in patients with isolated BAV.
BAV disease has a recognized association with aortic valve ste-
nosis and/or aortic valve regurgitation as well as dilation of the
ascending aorta. However, fetuses with aortic valve stenosis were
excluded from our cohort as were fetuses with other lesions such as
coarctation of the aorta with a known association with bicuspid
aortic valve. However, in pediatric patients with BAV early signs of
dilated ascending aorta in the absence of aortic stenosis or regurgi-
tation and irrespective of the pattern of aortic cusp fusion has been
reported.1–3 Abnormal flow dynamics in the ascending aorta have
been implicated in dilation of the ascending aorta in the presence of a
bicuspid aortic valve, even in the absence of aortic valve stenosis.3,13
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TABLE 1 Antenatal absolute measurements and z‐scores of the aortic valve annulus, ascending aorta and aortic valve morphology

AAo (mm) z‐score AAo AoV (mm) z‐score AoV AAo (mm) Z‐score AAo AoV (mm) z‐score AoV

Patient Second trimester Third trimester Suspected BAV

1 4.8 1.55 4.2 1.55 8.3 2.52 7.1 2.38 Yes

2 5.8 3.91 3.8 1.74 9.0 4.30 5.5 1.66 Unknown

3 4.6 1.97 3.9 1.74 6.5 1.67 6.2 2.34 Yes

4 4.4 1.76 3.4 0.81 6.1 1.09 5.6 1.45 No

5 4.6 1.97 3.4 0.67 6.5 1.03 5.9 1.29 No

6 4.8 2.48 2.8 −0.64 7.9 3.32 5.3 1.32 No

7 5.0 2.99 3.3 0.85 8.0 3.37 5.4 1.42 No

8 4.7 2.13 3.3 0.44 8.0 3.23 6.2 2.34 Yes

9 5.0 3.12 3.8 2.09 7.0 2.61 5.8 2.22 Yes

10 4.8 2.29 3.1 −0.05 6.3 1.02 6.3 2.04 No

11 3.9 1.19 2.9 −0.09 8.0 3.61 6.0 2.49 No

12 5.1 3.27 3.0 0.25 7.8 3.28 5.5 1.66 No

13 4.5 2.06 4.0 2.21 6.3 1.48 5.9 2.01 Yes

14 5.1 2.81 4.0 2.01 8.2 4.00 6.3 3.08 Yes

15 5.0 2.85 3.1 0.22 7.6 2.98 5.0 0.81 No

16 4.6 2.10 3.2 0.34 6.0 1.65 5.5 2.02 No

Abbreviations: AAo, ascending aorta; AoV, aortic valve; BAV, bicuspid aortic valve; mm, millimetres.

T A B L E 2 Gestational age, ascending

First visit Second visit p‐value
aorta and aortic valve measurements in
Gestational age (weeks) 20.8 (20.2–21.1) 28.3 (28.0–28.9) ‐ the first and second visit for the whole
cohort
Ascending aorta (mm) 4.8 (4.6–5.0) 7.7 (6.3–8.0) < 0.0001

Ascending aorta z‐score 2.2 (1.9–2.9) 2.8 (1.5–3.3) 0.61

Aortic valve (mm) 3.3 (3.1–3.9) 5.8 (5.5–6.2) < 0.0001

Aortic valve z‐score 0.74 (0.23–1.74) 2.01 (1.42–2.34) 0.003

Note: The bold values denote statistically significant.

T A B L E 3 Gestational age, ascending aorta and aortic valve measurements in the first and second visit for babies with tricuspid or
bicuspid aortic valve

Tricuspid aortic valve (N = 10) BAV (N = 6) p‐value

First visit Gestational age (weeks) 20.4 (20.0–20.9) 21.1 (20.8–21.6) 0.04

Ascending aorta (mm) 4.9 (4.6–5.0) 4.6 (4.4–4.8) 0.26

Ascending aorta z‐score 2.66 (2.06–3.15) 2.01 (1.75–2.30) 0.07

Aortic valve (mm) 3.15 (2.9–3.5) 3.9 (3.4–4.0) 0.007

Aortic valve z‐score 0.29 (−0.06–1.07) 1.64 (0.72–2.06) 0.04

Second visit Gestational age (weeks) 28.1 (27.9–28.7) 28.7 (28.2–29.7) 0.2

Ascending aorta (mm) 7.7 (6.4 ‐ 8.0) 7.2 (6.2–8.2) 1.0

Ascending aorta z‐score 3.13 (1.49–3.4) 2.09 (1.3–3.4) 0.5

Aortic valve (mm) 5.5 (5.3–5.9) 6.2 (5.8–6.5) 0.02

Aortic valve z‐score 1.66 (1.31–2.08) 2.34 (1.87–2.55) 0.07

Note: The bold values denote statistically significant.

Abbreviation: BAV, bicuspid aortic valve.
DUMITRASCU‐BIRIS ET AL.
F I G U R E 2 Ascending aorta z‐score during
second and third trimester. Comparisons
between tricuspid and bicuspid aortic valve
F I G U R E 3 Fetal aortic valve z‐score during
second and third trimester. Comparison
between tricuspid and bicuspid aortic valve
F I G U R E 4 Postnatal magnetic resonance imaging at 6 months
confirming dilated ascending aorta (red arrow)
- 5
Furthermore, genetic predisposition linked to an underlying abnor-
mality of the aortic wall has also been implicated.14,15 Recently, our
group has demonstrated the feasibility of 4D flow in the ascending
aorta during fetal life.16 This might provide a useful technique to
provide further understanding of the pathophysiology in future but
was not available at the time any of the fetuses in this cohort were
studied.
None of our study group cases had evidence of aortic stenosis
or regurgitation before or after birth so the findings cannot be
attributed to post‐stenotic dilatation. The ascending aorta and
aortic valve annulus z‐scores had a trend to increase through
gestation in our patients (Figures 2 and 3). Moreover, the aortic
valve annular dilatation was statistically significant in those with
bicuspid aortic valve.
Although a BAV was observed in over a third of our cohort, the
remaining two thirds had a normally formed tricuspid aortic valve. In
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- DUMITRASCU‐BIRIS
F I G U R E 5 Postnatal magnetic resonance imaging showing
significant arterial tortuosity (white arrow)
the pediatric population Marfan Syndrome and Loeys‐Dietz syn-
drome are major causes of aortic dilatation.17 In those conditions the
dilation of the aorta typically begins at the aortic root rather than
ascending aorta as observed in our cohort. Furthermore, no stigmata
of an underlying connective tissues disorder have been observed to
date. Our current policy includes referral of all infants with unex-
plained dilation of the ascending aorta to clinical geneticists for
further evaluation, and to consider further testing for single gene
disorders which are not detected on the array CGH. We also consider
postnatal imaging such as MRI of the aortic arch to serve as a
baseline for follow‐up and also to investigate for other features of a
vasculopathy such as arterial tortuosity which was observed in one of
our cases and may not be detected on echocardiography alone.
3.4 | Limitations
The ascending aorta is not routinely measured in prenatal screening
and therefore, only those who were subjectively suspected to have
an abnormal appearance of the three‐vessel view/ascending aorta
were referred from a screening setting.
Cardiac MRI was only performed in a minority of cases (n = 5)
with the most significant progression of the dilatation of the
ascending aorta. Assessment of the remaining infants was based on
echocardiography alone.
Newer methods to assess for single gene defects , for example,
whole exome sequencing, was only undertaken in one patient in this
series following clinical genetics assessment. With increased appli-
cation of such techniques, a higher proportion of single gene disor-
ders may be identified in future.
ET AL.
4 | CONCLUSION
Isolated dilatation of the ascending aorta in the fetus is a rare finding.
The most common association is of a bicuspid aortic valve; however,
two thirds of our cohort had a normally formed tricuspid aortic valve.
In the absence of extra‐cardiac abnormalities, medium term outcome
appears good but postnatal surveillance of aortic dilation may be
required. Connective tissue disease was not diagnosed postnatally in
any of our cases to date. A prospective prenatal population‐based
study is warranted.
AC K NO W L ED G E M EN T S
We wish to thank the clinical genetics team at King's College Hospital
and Guy's and St Thomas' Hospital who reviewed our patients in fetal
and postnatal life.
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the
corresponding author upon reasonable request.
OR C I D
Ioana Dumitrascu‐Biris https://orcid.org/0000-0002-0804-6690
Vita Zidere https://orcid.org/0000-0001-7505-6621
Trisha Vigneswaran https://orcid.org/0000-0002-4084-4203
Marietta Charakida https://orcid.org/0000-0003-4214-5059
Nick Kametas https://orcid.org/0000-0002-7992-6038
John Simpson https://orcid.org/0000-0002-9773-7441
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How to cite this article: Dumitrascu‐Biris I, Zidere V,
Vigneswaran T, et al. Dilated ascending aorta in the fetus.
Prenatal Diagnosis. 2021;1–7. https://doi.org/10.1002/pd.
6007