Screening for heart defects in the first trimester
Ultrasound Obstet Gynecol 2010; 36: 658–660
Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/uog.8874
Screening for heart defects in the ﬁrst trimester of pregnancy: food for thought
I would like to start this Opinion by exercising the rights
of a chairperson and going beyond the Editor-in-Chief’s
request for me to comment on two papers in this issue
of the Journal that deal with the fetal heart in the ﬁrst
trimester of pregnancy1,2. I do so in order to acknowledge
Professor Yves Ville’s immense support for me to perform
early fetal echocardiography when we worked together
many years ago3
, as well as to recognize his early vision
about the importance of performing (transabdominal)
ﬁrst-trimester cardiac scans in high-risk pregnancies, at a
time when this was not common practice, but innovative.
To stress his enthusiasm in this important area of fetal
medicine is for me a ‘must do’ in this Opinion, but it is
also a pleasure to write about ﬁrst-trimester cardiac scans
in Yves’s last issue as Editor-in-Chief of Ultrasound in
Obstetrics & Gynecology.
I should also acknowledge that highly-skilled obstetri-
cians have been performing (transvaginal) ﬁrst-trimester
fetal echo since the beginning of the 1990s4–15
cardiologists became interested in the fetal heart in early
pregnancy. However, use of the transabdominal route for
and the ever improving ultrasound resolution
over the years has not only made it possible for cardiolo-
gists to explore the small ﬁrst-trimester fetal heart but has
also paved the way for sonographers, radiographers and
other professionals to incorporate basic cardiac views into
the routine 11 to 13 + 6-week scan. This has obviously
shifted interest in early fetal echo from accurate diagnosis
to screening low-risk pregnancies.
‘Business as usual’ – I must now return to my task and
comment on the two papers in this issue of the Journal.
The studies of Sinkovskaya et al.1
and Timmerman et al.2
are both concerned with screening for major congenital
heart disease (CHD) in early pregnancy. Yet they explore
different aspects of screening.
Sinkovskaya and colleagues1
measured the cardiac axis
on the four-chamber view in a prospective study of 100
consecutive women scanned at 11 + 0 to 14 + 6 weeks of
gestation. Additionally, the outﬂow tracts were imaged
and targeted fetal echocardiography was performed later
in the second trimester. In early pregnancy, the mean
value for the cardiac axis, based on 94 fetuses with no
cardiac abnormalities, was approximately 47◦
of normality set between 35◦ and 60◦. The four-chamber
view was seen in all cases and there was good interobserver
reproducibility. An abnormal axis was seen in four of the
six cases with CHD (of which three showed a structurally
abnormal four-chamber view): one with hypoplastic left
heart syndrome, two with atrioventricular septal defects
(one unbalanced, one associated with isomerism) and one
with tetralogy of Fallot.
The conclusion that followed was an obvious one: it is
possible to measure the cardiac axis in early pregnancy
and this may help to identify pregnancies at risk of
CHD. But, in the context of screening, is it really that
simple or do we have some ‘food for thought’ here?
Whilst the authors report that the four-chamber view
was imaged in all cases, it is of note that women with
a body mass index (BMI) ≥ 30 were excluded from the
study and nearly one in ﬁve cases (19%) required a
combined transabdominal–transvaginal approach. Thus,
for screening purposes, it may be somewhat premature to
extrapolate the ﬁndings of this study to a large low-risk
population that includes women with BMI ≥ 30 and in
an environment where it may be less practical to perform
transvaginal scans in nearly a ﬁfth of cases. Previous
investigators have shown high BMI and small fetal size to
have a negative impact on success rates of ﬁrst-trimester
Timmerman and colleagues2
, on the other hand, aimed
at reﬁning risk assessment to improve prediction of CHD
over and above that associated with an increased nuchal
translucency thickness (NT) in chromosomally normal
fetuses. In a retrospective study of nearly 800 fetuses, they
explored the added predictive value of an abnormal ductus
venosus pulsatility index (DV-PIV, above the 95th
and abnormal a-wave (consistently absent or reversed).
Cardiac defects were present in 35 fetuses, 26 with major
forms of CHD. An abnormal DV-PIV in the context of
increased NT and normal karyotype conferred a three-
fold increase in risk whereas an abnormal a-wave did not
add to the prediction following correction for DV-PIV.
The sensitivity and speciﬁcity of DV-PIV for major CHD
were 71% and 61%, respectively. While this approach
is important to streamline referrals so that the limited
resources (in this case, availability of diagnostic early
fetal echocardiography) can be allocated to those families
who are at the highest risk, obtaining a technically good
DV Doppler signal may not be so straightforward18,
bringing into question its widespread use for screening
low-risk pregnancies. Factors such as the learning curve19
observer variability and reproducibility of the signal20–22
may have a negative impact on its potential utility as a
method of screening for CHD worldwide, as highlighted
by the authors.
This study also offers more food for thought in that,
of all cases of CHD which had fetal cardiac scans
and required postnatal intervention, half were false-
negative cases. Excluding those with a patent arterial
Copyright 2010 ISUOG. Published by John Wiley & Sons, Ltd. OPINION
duct and a secundum atrial septal defect, 12 children
had cardiac intervention and six were thought to have
‘no anomalies’ on fetal scans2. The reasons behind this
ﬁnding are unclear. While it is well known that certain
cardiac defects evolve during pregnancy and may not be
amenable to diagnosis prenatally23
, an abnormality of
the atrioventricular connection such as tricuspid atresia
can (and should?) indeed be diagnosed if a cardiac
scan is performed. In one additional case, the diagnosis
of atrioventricular and ventriculoarterial discordance
was made postnatally. The ISUOG consensus statement
regarding ‘What constitutes a fetal echocardiogram’24
reﬂects the need for a multidisciplinary approach to fetal
cardiac scans, which should involve cardiologists and
Of relevance to both these studies and of utmost
importance to early screening for CHD in general
is: how soon after identifying markers in the general
population, prior to 14 weeks of gestation, are we
able to refer the pregnant woman for diagnostic fetal
echocardiography? This question goes beyond the studies
of Sinkovskaya et al.1
and Timmerman et al.2
as it applies
to all potential early markers of CHD (abnormal cardiac
axis, increased NT, abnormal DV, tricuspid regurgitation
and even aberrant subclavian artery25,26
a suspected cardiac abnormality in mid-gestation, the
accepted recommendation in the UK is that the pregnant
woman be offered an appointment as soon as possible,
but preferably within a week.
An unexpected abnormal ultrasound ﬁnding leads to
parental anxiety, vacillation between emotional confusion
and sense of reality. Parents adapt but they need
additional information about diagnosis and treatment
. The magnitude of such anxiety may
be difﬁcult to measure but is potentially devastating for
some families. When the abnormality at stake in the ﬁrst
trimester is a chromosomal defect, resolving the issue may
be relatively easy (albeit with a small risk of miscarriage
through invasive procedures), but deﬁnition of the cardiac
anatomy accurately in the ﬁrst or early second trimester
when major CHD is suspected, or following identiﬁcation
of a high-risk pregnancy, is certainly not widely available.
For many women, therefore, identifying the risk early but
having to wait until the 20-week scan may be associated
with a period of excessive stress. Rosenberg et al.28 found,
after controlling for race and maternal age, that referral
for fetal echocardiography was an independent predictor
of maternal ‘state anxiety’, i.e. how patients feel at the
time of the scan.
Revealing to parents that the fetal heart shows an
abnormality is likely to raise maternal and family anxiety
levels. Thus, it is important that we think further about
the implications of incorporating new markers for CHD
in early pregnancy. Identifying the high-risk group but
being unable to offer the appropriate means to clarify
whether there is an abnormality at an early gestational
age may not be appropriate. Furthermore, deﬁnition of
an abnormality must come hand in hand with diagnostic
To conclude, identifying cases at risk of CHD in the
ﬁrst and early second trimesters of pregnancy poses
two important questions: how soon can early fetal
echocardiography be offered to families so that the
diagnosis of normality or abnormality can be made, and
how accurately can this be achieved?
J. S. Carvalho
Fetal & Paediatric Cardiology, Royal Brompton &
St George’s Hospitals and Fetal Cardiology, St George’s
University of London, London, UK
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Copyright 2010 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2010; 36: 658–660.