1. Ultrasound Obstet Gynecol 2010; 36: 676–681
Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/uog.8814
Defining the fetal cardiac axis between 11 + 0 and
14 + 6 weeks of gestation: experience with 100 consecutive
pregnancies
E. SINKOVSKAYA*, S. HORTON*, E. M. BERKLEY*, J. K. COOPER*, S. INDIKA†
and A. ABUHAMAD*
*Division of Maternal-Fetal Medicine of the Department of Obstetrics & Gynecology and †Epidemiology and Biostatistics Core, Eastern
Virginia Medical School, Norfolk, VA, USA
KEYWORDS: cardiac axis; echocardiography; fetal heart; first trimester; heart defects
ABSTRACT
Objective The purpose of this study was to establish
normal fetal cardiac axis values during the first and early
second trimesters of pregnancy.
Methods This was a prospective observational cohort
study in which the fetal cardiac axis was assessed
during ultrasound examinations in 100 consecutive
fetuses between 11 + 0 and 14 + 6 weeks of gestation.
Transabdominal, and, when indicated, transvaginal,
approaches were used. Intraobserver and interobserver
reproducibility were calculated.
Results The cardiac axis ranged from 34.5 to 56.8◦
(mean (SD) 47.6 ± 5.6◦) in 94 fetuses with normal cardiac
anatomy. The fetal cardiac axis tended to be significantly
higher in fetuses at 11 + 0 to 11 + 6 weeks of gestation
than in fetuses at 12 + 0 to 14 + 6 weeks of gestation.
Congenital heart defects were found in six out of 100
fetuses, four of which had abnormal cardiac axis values
at 11 + 0 to 14 + 6 weeks of gestation.
Conclusion Cardiac axis measurement is possible in
the first and early second trimesters of pregnancy. The
assessment of cardiac axis at an early gestational age may
help to identify pregnancies at high risk for congenital
heart defects. Copyright  2010 ISUOG. Published by
John Wiley & Sons, Ltd.
INTRODUCTION
The ability to obtain images of the fetal heart, at an
early gestational age, of sufficient clarity to diagnose
cardiac malformations, was made possible by the advent
of high-resolution transvaginal and transabdominal
ultrasonography. Furthermore, the growing acceptance of
nuchal translucency (NT) thickness measurements made
between 11 and 14 weeks’ gestation to assess the risk
for chromosomal abnormalities led to the identification
of fetuses at high risk for major congenital heart disease
(CHD)1
. Detailed evaluation of the fetal heart in early
gestation may therefore allow the early detection of
CHD2–4
.
Evaluation of the fetal cardiac axis (CAx) is part of the
fetal cardiac examination performed in the mid-second
and third trimesters of pregnancy5. In this gestational age
window, the normal CAx is defined at a 45◦
angle to the
left of the midline with a range of plus or minus 20◦6
.
Several studies have suggested fetal CAx measurement
as a possible screening tool for CHD, with a reported
sensitivity of 79.3% and a specificity of 97.6%7
. Left CAx
deviation is largely associated with cardiac abnormalities,
especially conotruncal anomalies, which are commonly
difficult to detect from the four-chamber view alone8,9.
It was also demonstrated that an abnormally narrow
CAx with a normal cardiac position may occur in cases
of cardiac anomalies10
. The specific embryologic event
that results in an abnormal CAx in some fetuses with
cardiac abnormalities is not currently known; however,
an over-rotation of the bulboventricular loop in early
embryogenesis has been proposed as the underlying
mechanism6,7
.
The aim of this prospective study was to establish
normal fetal CAx values during the first and early second
trimesters of normal pregnancy as well as to determine
if routine assessment of the CAx in early gestation may
identify fetuses with CHD.
Correspondence to: Dr E. Sinkovskaya, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, 825 Fairfax
Avenue, Suite 310, Norfolk, VA 23507, USA (e-mail: sinkove@evms.edu)
Accepted: 18 August 2010
Copyright  2010 ISUOG. Published by John Wiley & Sons, Ltd. ORIGINAL PAPER

2. Fetal cardiac axis 677
METHODS
This study was approved by the Human Investigation
Board of the Eastern Virginia Medical School (EVMS),
and was conducted at EVMS’s Division of Maternal-Fetal
Medicine ultrasound laboratories. After receiving writ-
ten informed consent, a total of 100 consecutive women,
≥ 18 years of age and with singleton pregnancies between
11 + 0 and 14 + 6 weeks’ gestation, were enrolled in the
study. Exclusion criteria included maternal obesity (body
mass index (BMI) ≥ 30) and refusal to participate in the
study.
Transabdominal ultrasound was initially performed in
all study patients to examine the fetus. The transvaginal
approach was used if visualization of the fetus (because of
its position) was insufficient or if suboptimal transabdom-
inal images were obtained. All ultrasound examinations
were performed using Voluson 730 Expert and Voluson
E8 ultrasound equipment (GE Healthcare Ultrasound,
Zipf, Austria) with a 4–8-MHz transabdominal trans-
ducer and a 5–9-MHz transvaginal transducer.
The ultrasound examination included a crown–rump
length (CRL) measurement of the fetus followed by a
NT measurement when requested by the patient. The
CAx was assessed by obtaining an axial view of the fetal
chest at the level of the four-chamber view with a single
full rib visible on each side and then by measuring the
CAx as the angle of two lines. The first line started at
the spine posteriorly and ended in mid-chest anteriorly,
bisecting the chest into two equal halves. The second line
traced the long axis of the heart and ran through the
interventricular septum (IVS) (Figure 1). Color or power
Doppler was occasionally used to confirm the location
of the IVS, which then guided the accurate placement of
the intersecting angle line when the IVS was not clearly
imaged on two-dimensional (2D) ultrasound (Figure 2). In
each case one of the authors (E.S.) measured the CAx three
times. The average of these three measurements was used
to represent the CAx for each participant. In addition,
the CAx was also measured by another author (S.H.).
Both investigators were blinded to each other’s results.
In addition to measurement of the CAx, an evaluation of
the fetal heart was performed, which included imaging
of the four-chamber view and the outflow tracts. All
patients underwent ultrasound examination during the
second and/or third trimesters, which included a targeted
evaluation of fetal anatomy, fetal echocardiography and
CAx measurement. Postnatal follow up was obtained
for all patients by reviewing the medical records and by
telephone interview.
Statistical analysis
Statistical analysis was performed using the SAS 9.1.3
software (SAS, Cary, NC, USA). Normal distribu-
tion of continuous variables was assessed using the
Kolmogorov–Smirnov test. Continuous variables are
reported as mean ± SD or as median (range), depending
on the data distribution. Categorical data are expressed
Figure 1 Cardiac axis measurement in a fetus at 13 + 4 weeks’
gestation. The angle shown in this case is 43◦ (normal). LV, left
ventricle; RV, right ventricle; S, spine.
as frequencies and percentages. A P < 0.05 was consid-
ered significant. The Tukey test was applied to examine
the variance of the CAx at different gestational ages. The
effect of CRL on the CAx was evaluated using regres-
sion analyses. Repeated-measures ANOVA was used
to assess intraobserver variations. Interobserver repro-
ducibility was evaluated by calculating the limits of
agreement using the Bland–Altman analysis11
and the
coefficient of variation (CV). The following formula was
used to assess the CV: CV (%) = (SD/mean of measure-
ment (Observer 1; Observer 2)) × 100.
RESULTS
Demographic characteristics, gestational age and NT
measurements at first presentation of the study patients
are shown in Table 1. Seventy-two patients underwent
first-trimester screening with NT measurement for
chromosome abnormalities. Of the 72 fetuses in which
NT thickness was measured, 2/72 had an NT of ≥ 3.5 mm
and both had CHD.
A transabdominal ultrasound alone was performed in
81/100 (81%) of cases, and a combined transabdominal
and transvaginal approach was used in 19/100 (19%) of
cases.
The four-chamber view was visualized in all fetuses in
early gestation. In 94 fetuses heart anatomy was normal.
The CAx value in this group of normal fetuses ranged
from 34.5 to 56.8◦
(mean (SD) 47.6 ± 5.6◦
). Based on
our results, a CAx of < 35◦
and > 60◦
represents 2 SD
outside our mean measurement and should be considered
abnormal. The relationship between CAx and gestational
age is shown in Figure 3. The CAx showed a tendency to
be significantly higher (levorotation) at a gestational age
of 11 + 0 to 11 + 6 weeks compared with a gestational
age of between 12 + 0 and 14 + 6 weeks (Table 2).
Copyright  2010 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2010; 36: 676–681.

3. 678 Sinkovskaya et al.
Figure 2 Assessment of the cardiac axis using high-definition power Doppler in a normal fetus at 12 + 6 weeks’ gestation. (a) Right and left
ventricles are colored bright red and separated by a dark line, which represents the interventricular septum (arrows). (b) Cardiac axis
measurement is shown. LV, left ventricle; RV, right ventricle; S, spine.
Table 1 Demographics, gestational age and nuchal translucency
(NT) measurements at first presentation (n = 100)
Parameter Value
Maternal age (years) 31.1 ± 6.4
Race
Caucasian 59
African–American 31
Asian 8
Hispanic 2
Gravidity 3 (1–13)
Parity 1 (0–4)
Body mass index (kg/m2) 24.2 ± 3.5
Gestational age (weeks)
11 + 0 to 11 + 6 18
12 + 0 to 12 + 6 40
13 + 0 to 13 + 6 26
14 + 0 to 14 + 6 16
NT* (mm) 1.5 (0.9–4.6)
Values given as mean ± SD, median (range) or %. *n = 72.
Repeated-measures ANOVA showed no significant
differences in the three separate measurements of CAx
made by the same observer (P = 0.3). Figure 4 presents
a Bland–Altman plot of interobserver reproducibility.
The mean difference in CAx measurements performed by
Observer 1 (E.S.) and Observer 2 (S.H.) was close to zero,
and no significant difference was obtained. Based on the
CV, the interobserver variation for CAx measurements
was 2.8%.
CHDs were diagnosed prenatally in six out of 100
fetuses and were confirmed postnatally or by autopsy. In
four cases the CHDs were found during the initial scan
at the first trimester and included heterotaxy syndrome
with complex CHD, hypoplastic left heart syndrome,
40
35
40
45
50
55
50 60
CRL (mm)
CAx(°)
70 80 90
Figure 3 Scatter plot presenting cardiac axis (CAx) measurement
plotted against crown–rump length (CRL). Individual values for
the CAx of normal fetuses and the reference range (mean, 5th and
95th centiles) are shown.
tetralogy of Fallot and atrioventricular septal defect.
All fetuses had abnormal CAx measurements. In three
of these cases left deviation of the CAx (74, 97 and
68◦
) was noted, and one fetus had mesocardia with
the CAx = 0◦
(Table 3). Figures 5 and 6 show CAx
measurements in two fetuses with left axis deviations
in early gestation (12 + 2 and 13 weeks, respectively). In
addition, two fetuses were first diagnosed with CHDs
during fetal echocardiography in the second and third
trimesters of pregnancy. In these two fetuses, CAx
measurements in the first trimester were within the normal
range.
Copyright  2010 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2010; 36: 676–681.

4. Fetal cardiac axis 679
Table 2 Cardiac axis (CAx) measurements in fetuses with normal
heart anatomy
CAx (◦)
GA (weeks) n Mean ± SD 95% CI
11 + 0 to 11 + 6* 17 52.0 ± 2.9 46.2–57.8
12 + 0 to 12 + 6 38 47.3 ± 2.4 42.4–52.2
13 + 0 to 13 + 6 24 48.8 ± 3.0 39.9–51.8
14 + 0 to 14 + 6 15 45.6 ± 5.0 35.6–55.7
*Multiple comparison using the Tukey test showed a significant
(P < 0.05) difference between the 11 + 0 to 11 + 6 group compared
with the three other groups (i.e. between 12 + 0 and 14 + 6 weeks’
gestation). GA, gestational age.
DISCUSSION
CHD is the most common congenital abnormality in the
human fetus, and it accounts for more than half of the
deaths from congenital abnormalities in childhood12
. Sev-
eral risk factors for CHD, including maternal and fetal
factors, have been reported13
. Most neonates born with
CHD, however, have no preidentified risk factors14
. In
fact, of all pregnancies referred for fetal echocardio-
graphy, the highest rate of CHD (50%) is found in
pregnancies with a suspected CHD on a routine ultra-
sound examination15
.
The four-chamber view of the heart is included in the
basic obstetric ultrasound examination and has been pro-
posed as a screen for CHD in the second trimester of
pregnancy5
. Specialized ultrasound skills are not required
because the heart is easily imaged in a transverse view of
the fetal chest. Detection of an abnormal four-chamber
view, axis or position of the fetal heart should be con-
sidered as an indication for fetal echocardiography in the
second trimester7,16.
In recent years, fetal heart evaluation has become
feasible in the first and early second trimesters of
pregnancy because of improvements in the resolution of
transvaginal and transabdominal probes. Measurement of
NT is offered routinely in many countries and thickened
30
DifferenceinCAx(°)
−3
−1
1
3
40
Mean CAx (°)
50 60
+2SD
Mean
−2SD
Figure 4 Bland–Altman plot of interobserver variation (mean ±
SD, 0.4 ± 1.1) in measurements of the fetal cardiac axis (CAx).
NT is associated with cardiac anomalies. Recently-
published data show that, in comparison to other views,
the four-chamber view has the highest visualization rate at
each gestational age and can be obtained in 85–100% of
first-trimester ultrasound examinations17,18
. Based on our
experience, a combined transabdominal and transvaginal
approach allows visualization of the four-chamber view
in all cases between 11 + 0 and 14 + 6 weeks of gestation.
The normal CAx does not change significantly between
16 and 40 weeks of gestation and lies at a 45◦
angle to the
left of the midline6. The present study shows the CAx to
be significantly higher at 11 + 0 to 11 + 6 weeks of gesta-
tion than later in pregnancy. The reason for a levorotated
CAx in early gestation is currently unclear.
Defining left axis deviation as > 75◦
, one study noted
fetal anomalies in 76% of fetuses9
in the second trimester.
In left CAx deviation, tetralogy of Fallot, coarctation of
the aorta and Ebstein anomaly are the most common
cardiac lesions, whereas double-outlet right ventricle,
atrioventricular septal defect and common atrium are the
most common cardiac lesions in right axis deviation8,10,19
.
Our findings in early gestation were similar. Three
Table 3 Cardiac axis (CAx) values in six fetuses diagnosed with congenital heart defect (CHD)
First-trimester scan
CAx at
Case
CAx
(◦)
NT
(mm)
second/third-trimester
scan (◦) GA at diagnosis (weeks) Type of congenital heart defect
1 74 2.2 67 12 + 2 Tetralogy of Fallot
2 97 3.7 92 12 + 6 Hypoplastic left heart syndrome
3 68 4.6 79 13 + 0 AVSD, dominant RV
4 0 1.3 2 13 + 6 Heterotaxy syndrome, mesocardia,
complex CHD (AVSD, common
atrium, infracardiac TAPVC to the
portal vein)
5 44 1.1 45 23 + 4 Muscular VSD
6 48 NM 68 33 + 2 Coarctation of the aorta, small VSD
AVSD, atrioventricular septal defect; GA, gestational age; NM, not measured; RV, right ventricle; TAPVC, total anomalous pulmonary
venous connection; VSD, ventricular septal defect.
Copyright  2010 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2010; 36: 676–681.

5. 680 Sinkovskaya et al.
Figure 5 Cardiac axis measurement in a fetus with tetralogy of
Fallot at 12 + 2 weeks’ gestation. The angle shown in this case is
74◦ (left axis deviation). RV, right ventricle; S, spine.
Figure 6 Cardiac axis measurement in a fetus with an unbalanced
atrioventricular septal defect at 13 + 0 weeks’ gestation. Left axis
deviation, with an angle of 68◦, is present. RV, right ventricle;
S, spine.
fetuses with left axis deviations had hypoplastic left
heart syndrome, tetralogy of Fallot and unbalanced
atrioventricular septal defect in our small series. Right
deviation of CAx was found in the fetus with heterotaxy
syndrome. Of note, two of four fetuses in our study which
had CAx deviation in the first trimester and CHD had
a normal NT measurement and thus CHD could have
escaped detection by NT screening alone. In one case of
coarctation of the aorta in our series, CAx was normal in
the first trimester and left deviated in the third trimester.
Isolated ventricular septal defect did not affect the CAx
significantly.
The interobserver reproducibility for measuring the
CAx in our study was similar to that previously reported
by Crane et al.7
in fetuses in the second and third
trimesters (CV: 2.8% vs. 3%). Intraobserver agreement
in measurement of the CAx was also noted in our study.
Currently there are no approved indications for patient
referral for early fetal echocardiography. Based upon our
experience and that of others, an enlarged NT, the pres-
ence of a major extracardiac malformation, the presence
of reversed flow in the ductus venosus and the detection
of tricuspid and/or mitral regurgitation or an abnor-
mal CAx can be considered indications for early fetal
echocardiography20–22.
Limitations of the study
Maternal body habitus and in utero fetal position play a
critical role in the image obtained during the ultrasound
examination in early pregnancy. The ability to perform an
evaluation of the fetal CAx in difficult-to-image patients
(BMI > 30) is challenging and remains to be determined.
To our knowledge this is the first study to evaluate
prospectively the CAx during the first and early second
trimesters of pregnancy. The value of the CAx in early
gestations for the prenatal diagnosis of CHD remains
to be established in larger studies. However, our initial
results are promising. In this study, we demonstrated the
feasibility of CAx assessment in the first and early second
trimesters of pregnancy and its potential clinical applica-
bility. Further prospective studies in a clinical setting are
needed to confirm the value of CAx measurement as a
screening test for CHD in early gestation.
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