This study aimed to identify prenatal echocardiographic features that predict the need for a Rashkind procedure within 24 hours of birth in fetuses with dextro-transposition of the great arteries (d-TGA). The study retrospectively analyzed 51 fetuses with d-TGA, comparing those who did (n=29) and did not (n=22) require the Rashkind procedure. While most parameters did not differ between groups, fetuses requiring the procedure had significantly higher pulmonary venous maximum velocities and were more likely to have a flattened foramen ovale valve seen on prenatal ultrasound. These findings may help predict which fetuses will need urgent postnatal intervention.

1. Ultrasound Obstet Gynecol 2018; 51: 531–536
Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/uog.17469
New method to predict need for Rashkind procedure in
fetuses with dextro-transposition of the great arteries
M. SŁODKI1,2
, R. AXT-FLIEDNER3
, K. ZYCH-KREKORA1
, A. WOLTER3
, A. KAWECKI3
,
C. ENZENSBERGER3
, E. GULCZY ´NSKA4
and M. RESPONDEK-LIBERSKA1,5
, on behalf of The
International Prenatal Cardiology Collaboration Group
1
Prenatal Cardiology, Polish Mother Memorial Hospital Research Institute, Lodz, Poland; 2
Faculty of Health Sciences, The State University
of Applied Sciences in Plock, Plock, Poland; 3
Obstetrics and Gynecology, Division of Prenatal Diagnosis and Therapy, Fetal Cardiac
Program, Justus-Liebig University Giessen, Giessen, Germany; 4
Neonatology, Polish Mother Memorial Hospital Research Institute, Lodz,
Poland; 5
Diagnosis and Prevention of Fetal Malformations, Medical University, Lodz, Poland
KEYWORDS: d-TGA; foramen ovale; Rashkind procedure; restrictive; transposition of great arteries
ABSTRACT
Objective Prenatal congenital heart disease classifica-
tion systems distinguish between critical dextro-trans-
position of the great arteries (d-TGA) with restriction
of the foramen ovale (FO) (which requires a Rashkind
procedure within the first 24 h following delivery) and
d-TGA for which surgery is planned (after prostaglandin
perfusion or Rashkind procedure later than 24 h after
delivery). However, current prenatal diagnostic criteria
for postnatal FO restriction in d-TGA are inadequate,
resulting in a high false-negative rate. We aimed to iden-
tify echocardiographic features to predict the urgent need
for Rashkind procedure.
Methods We identified retrospectively 98 patients with
singleton pregnancy diagnosed prenatally with fetal
d-TGA at two European centers from 2006 to 2013. Two
groups were compared: (1) those in whom the Rashkind
procedure was performed within the first 24 h postnatally;
and (2) those who did not undergo a Rashkind procedure
before cardiac surgery. Exclusion criteria were: (1) no
fetal echocardiography within 3 weeks prior to delivery
(n = 18); (2) delivery before 37 weeks of gestation (n = 6);
(3) improper or lack of measurement of pulmonary vein
maximum flow velocity (n = 10); (4) lack of neonatal
follow-up data (n = 9); (5) Rashkind procedure performed
more than 24 h after delivery (n = 4).
Results Fifty-one patients met the inclusion criteria: 29
who underwent the Rashkind procedure and 22 who did
not. There were no differences between these two study
groups in terms of maternal age, gestational age at time
of fetal echocardiography, fetal biometric measurements,
estimated fetal weight, rate of Cesarean delivery, newborn
Correspondence to: Dr M. Słodki, Department of Prenatal Cardiology, Polish Mother Memorial Hospital Research Institute, ul. Rzgowska
281/289; 93-338 Ł´od˙z, Poland (e-mail: maciejslodki@op.pl)
Accepted: 7 March 2017
weight or Apgar score at 1 min. There were also no
differences during prenatal life between the two groups
in terms of fetal cardiac size (heart area/chest area ratio),
rate of disproportion between left and right ventricle,
FO diameter and maximum velocity of flow through
the FO. However, the pulmonary vein maximum velocity
was significantly higher in the group requiring a Rashkind
procedure (47.62 ± 7.48 vs 32.21 ± 5.47 cm/s; P < 0.001).
The cut-off value of 41 cm/s provided maximum specificity
(100%) and positive predictive value (100%) at only a
slight cost of sensitivity (82%) and NPV (86%). The
prenatal appearance of the FO also differed between the
groups, the FO valve being flat in 52% of those requiring
a Rashkind procedure.
Conclusions In fetuses with d-TGA, prenatal sono-
graphic findings of increased pulmonary venous blood
flow and flattened FO valve were associated with the
need for a Rashkind procedure within the first 24 h post-
natally; these echocardiographic features could be used
to predict prenatally a need for the procedure following
delivery. Copyright © 2017 ISUOG. Published by John
Wiley & Sons Ltd.
INTRODUCTION
Discordant ventriculoarterial connection of the main
pulmonary artery and aorta, known as transposition of the
great arteries (TGA), is a severe congenital cardiac defect
(CHD) which requires surgical intervention. Dextro-TGA
(d-TGA) accounts for 5–7% of all CHD and has an
incidence of 2–3 per 10 000 live births. The Rashkind
procedure, first performed in 1966, was a milestone in
cardiology and neonatal cardiac surgery1
and there is
Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. ORIGINAL PAPER

2. 532 Słodki et al.
a large body of evidence describing the need for it to be
performed urgently in neonates after prenatal diagnosis of
d-TGA2–6
. Current prenatal CHD classification systems
distinguish between critical d-TGA, which requires a
Rashkind procedure to be performed within the first 24 h
of delivery and d-TGA that involves planned surgery after
prostaglandin perfusion or Rashkind procedure later than
24 h after birth2,4–7
. However, current prenatal diagnostic
criteria for post-delivery foramen ovale (FO) restriction in
d-TGA are inadequate, resulting in a high false-negative
rate2,3,5,8. This is important, because even a short delay
in performing the procedure (e.g. that incurred during
transfer to a tertiary cardiac center) can result in cyanosis,
acidosis, multiorgan failure and death, due to the failure
to restore normal hemodynamic conditions before cardiac
surgery can be attempted9,10. The objective, therefore, of
this study was to identify echocardiographic features to
predict the need for a Rashkind procedure.
METHODS
We identified retrospectively from two cardiac centers
(Department of Prenatal Cardiology, Polish Mother
Memorial Hospital Research Institute, Lodz, Poland and
Obstetrics and Gynecology, Division of Prenatal Diag-
nosis and Therapy, Fetal Cardiac Program, Justus-Liebig
University Giessen, Germany) 98 singleton pregnancies
with prenatal diagnosis of fetal d-TGA between 2006
and 2013.
The need for balloon atrial septostomy was determined
at postnatal echocardiography by the presence of a
restrictive FO, which was diagnosed as a result of the
findings of severe hypoxemia (PaO2, 25 mmHg) and aci-
dosis (pH 7.30) after birth. If there was normal saturation
despite reduced FO diameter a Rashkind procedure was
not performed on the first day following delivery.
Subjects were divided into two groups, those in whom
the Rashkind procedure was performed within the first
24 h postnatally and those who did not undergo a
Rashkind procedure before cardiac surgery, and the
groups were compared. Exclusion criteria were: (1) no
fetal echocardiography within 3 weeks prior to delivery
(n = 18); (2) delivery before 37 weeks of gestation (n = 6);
(3) improper or lack of measurement of pulmonary vein
maximum flow velocity (n = 10); (4) lack of neonatal
follow-up data (n = 9); (5) Rashkind procedure performed
more than 24 h after delivery (n = 4).
Maternal age and mode of delivery were noted, as
well as neonatal outcome (i.e. birth weight, Apgar score
at 1 min). Gestational age was determined by date of
last menstrual period and fetal biometry. Estimated fetal
weight and amniotic fluid index (AFI) were recorded.
All images and videos of the fetal echocardiographic
examinations were reviewed for the purposes of this
study. We recorded the following fetal echocardiographic
parameters: (1) cardiac size measured as heart area/chest
area ratio (HA/CA); (2) presence of disproportion between
left and right ventricles; (3) flow in the ductus arteriosus
(DA); (4) direction of blood flow through the FO; (5) FO
Figure 1 Ultrasound image showing flattened foramen ovale valve
in a 39.2-week fetus. Rashkind procedure was performed within
first 24 h following delivery.
diameter; (6) maximum velocity of flow through the FO;
and (7) pulmonary venous maximum velocity at entrance
to the left atrium.
Our prenatal sonographic assessment of the FO was
based upon the report by Wilson et al.11
. Specifically, the
atrial septal appearance was described as: (1) redundant,
if the aneurysmal septum primum bulged 50% of the way
to the left atrial free wall; (2) flat, if the angle between
the septum primum and the rest of the atrial septum was
< 30◦
(Figure 1); and (3) fixed, if the septum primum did
not demonstrate the typical swinging motion during the
cardiac cycle11
. The diameter of the DA was measured
as described by Tan et al.12
. Both spectral Doppler and
color flow mapping were used to record flow in the
DA, which was considered antegrade if directed from
the pulmonary artery towards the aorta, and retrograde
if the opposite was the case13
. Laminar antegrade flow
throughout systole and part (or all) of diastole, as assessed
by Doppler velocimetry, was considered to be normal DA
blood flow14
.
Normality of distribution of continuous variables was
verified using the Shapiro–Wilk test. Depending upon
the distribution, characteristics of continuous variables
were presented as arithmetic means and SD, or medians
and lower and upper quartiles. Statistical characteristics
of qualitative variables were presented in the form of
numerical and percentage distributions. Depending on
the distribution for intergroup comparisons, continuous
variables were analyzed using Student t-test for unpaired
variables or the Mann–Whitney U-test. For intergroup
comparisons of distributions of qualitative variables,
Fisher’s exact test was used. All calculations were
performed using Statistica software (StatSoft, Palo Alto,
CA, USA), with statistical significance set at P < 0.05.
RESULTS
A total of 51 patients met the inclusion criteria and were
included in this retrospective analysis. All 51 neonates
received prostaglandin, starting from a low dose of 0.01
μg/kg/min, which was sufficient for most patients; one
Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Ultrasound Obstet Gynecol 2018; 51: 531–536.

3. Prediction of Rashkind procedure in d-TGA 533
Table 1 Characteristics of patients with fetal dextro-transposition of the great arteries diagnosed prenatally, according to whether Rashkind
procedure was performed within first 24 h after delivery, prior to cardiac surgery
Parameter Rashkind (n = 29) No Rashkind (n = 22) P
Maternal age (years) 30.04 ± 5.16 29.36 ± 6.68 0.767
Gestational age at diagnosis (weeks) 35.6 ± 3.6 36.1 ± 2.6 0.694
Amniotic fluid index 11.25 ± 3.49 11.25 ± 2.75 > 0.999
Gestational age at delivery (weeks) 38.0 (35.6–38.5) 37.2 (36.0–38.0) 0.502
Estimated fetal weight (g) 2803.7 ± 738.0 2925.8 ± 735.0 0.672
Cesarean section 15 (51.7) 14 (63.6) 0.569
Birth weight (g) 3385.7 ± 414.8 3566.2 ± 620.1 0.274
Apgar score at 1 min 8 (8–9) 8.5 (8–9) 0.591
Data are given as mean ± SD, n (%) or median (interquartile range) in those deviating from normal distribution.
Table 2 Echocardiographic parameters of patients with fetal dextro-transposition of the great arteries diagnosed prenatally, according to
whether Rashkind procedure was performed within first 24 h after delivery, prior to cardiac surgery
Parameter Rashkind (n = 29) No Rashkind (n = 22) P
HA/CA 0.37 ± 0.07 0.36 ± 0.06 0.710
Disproportion between left and right sides of heart 7 (24.1) 1 (4.5) 0.117
Abnormal DA flow 1 (3.4) 0 (0.0) > 0.999
Bidirectional flow in FO 5 (17.2) 0 (0.0) 0.062
FO valve flat 15 (51.7) 0 (0.0) < 0.001
FO diameter (mm) 4.89 ± 1.78 5.92 ± 2.07 0.157
FO-Vmax (cm/s) 66.80 ± 22.30 76.13 ± 25.67 0.469
PV-Vmax (cm/s) 47.62 ± 7.48 32.21 ± 5.47 < 0.001
Days between fetal echo and delivery 11 (3–17) 3 (1–21) 0.531
Data are given as mean ± SD, n (%) or median (interquartile range) in those deviating from normal distribution. DA, ductus arteriosus;
echo, echocardiography; FO, foramen ovale; HA/CA, heart area/chest area; PV, pulmonary vein; Vmax, maximum flow velocity.
neonate required a dosage increase to 0.05 μg/kg/min.
However, despite prostaglandin infusion, 29 neonates
developed hypoxemia and acidosis and subsequently had
an urgent Rashkind procedure performed within the first
24 h after birth, while 22 did not undergo this procedure
before cardiac surgery; these formed the two study groups.
No immediate postpartum access to cardiac therapy
(IMPACT procedure) was performed. There were no
catheter/surgical interventions within the first few minutes
following separation from the placental circulation. Nine
(31%) neonates from the Rashkind group were intubated
due to low oxygen saturation (< 60%), severe hypoxemia
(PaO2 < 25mmHg) or metabolic acidosis (pH < 7.30) and
one (3%) neonate from the Rashkind group required
catecholamine administration.
There were no statistically significant differences
between the two study groups with respect to maternal
age, gestational age, fetal biometric measurements or
estimated fetal weight, AFI, rate of Cesarean delivery,
newborn weight or Apgar score at 1 min (Table 1). Only
one patient from the Rashkind group demonstrated
prenatally signs of DA constriction (increased systolic and
diastolic velocities and decreased pulsatility index). A flat
FO valve (n = 15; 51.7% (P < 0.001)) and bidirectional
FO flow (n = 5) occurred more often in the Rashkind
group, though the latter difference was not statistically
significant. There were no statistically significant differ-
ences during prenatal life between the two study groups
in terms of cardiac size (HA/CA), rate of disproportion
between left and right ventricles, FO diameter and FO
maximum velocity.
The variable which differed significantly between
the two groups was pulmonary venous maximum
velocity at entrance into the left atrium. This value
(47.62 ± 7.48 cm/s) was significantly higher in the group
requiring a Rashkind procedure than it was in those not
requiring the procedure (32.21 ± 5.47 cm/s; P < 0.001)
(Table 2, Figures 2 and 3). Both arbitrarily selected
cut-off values for maximum velocity (35 cm/s and 40 cm/s)
provided the same sensitivity in the identification of
patients who required an urgent Rashkind procedure,
but 40 cm/s turned out to be superior in terms of
the specificity, and positive (PPV) and negative (NPV)
predictive values. However, markedly better accuracy was
obtained with the cut-off value read automatically from
the receiver–operating characteristics curve (41 cm/s).
This cut-off value provided maximum specificity and PPV
at only a slight cost of sensitivity and NPV. Its superiority
was also confirmed by a markedly greater area under the
curve than those for cut-offs of 35 cm/s and 40 cm/s
(Table 3, Figure 4).
DISCUSSION
Current prenatal CHD classification systems specify
critical d-TGA which requires a Rashkind procedure
to be performed in the first hours following delivery
and d-TGA requiring planned surgery2–7
. A newborn
with d-TGA may present in good general condition
immediately after birth but may develop declining oxygen
saturation and cyanosis within the next few hours. Despite
Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Ultrasound Obstet Gynecol 2018; 51: 531–536.

4. 534 Słodki et al.
the use of prostaglandin, the condition will not improve
without intervention and in these cases it is necessary to
perform an emergency Rashkind procedure1
, which takes
the form of cardiac catheterization of the newborn in
the first 24 hours after delivery2–5,8
. Prenatal prediction
of a requirement for the procedure allows appropriate
60
65
50
55
40
45
30
35
PV-Vmax(cm/s)
20
Rashkind No Rashkind
25
Figure 2 Box-and-whiskers plot of maximum velocity (Vmax) of
pulmonary venous (PV) flow in fetuses requiring and those not
requiring Rashkind procedure in first 24 h following delivery
(47.62 ± 7.48 vs 32.21 ± 5.47cm/s; P < 0.001). Boxes with internal
squares represent mean and SD, and whiskers are range.
planning; however, current prenatal diagnostic criteria
are inadequate, resulting in a high false-negative rate. In
the current study, therefore, two groups with fetal d-TGA
were studied retrospectively in an attempt to identify
prenatal sonographic parameters associated with neonatal
clinical status and an urgent need for the Rashkind
procedure.
The indication to perform the Rashkind procedure in
neonates with d-TGA is a decrease in oxygen saturation,
caused by closure of the FO. However, studies have
Figure 3 Doppler image showing pulmonary venous flow in fetus
with urgent need for Rashkind procedure after delivery.
Table 3 Sensitivity, specificity and positive (PPV) and negative (NPV) predictive values for cut-off values of maximum velocity of flow
through pulmonary veins (Vmax)
Vmax cut-off
Sensitivity
(%)
Specificity
(%)
PPV
(%)
NPV
(%) AUC (95% CI)
35 cm/s 94.1 63.2 69.6 92.3 0.786 (0.632–0.941)
40 cm/s 94.1 78.9 80.0 93.8 0.865 (0.736–0.994)
41 cm/s 82.4 100 100 86.4 0.955 (0.886–1.000)
AUC, area under the receiver–operating characteristics curve.
1.0(a)
0.6
0.8
0.4
Sensitivity
0
1.0
1 – Specificity
0.2
0.80.60.40.20
1.0(b)
0.6
0.8
0.4
Sensitivity
0
1.0
1 – Specificity
0.2
0.80.60.40.20
1.0(c)
0.6
0.8
0.4
Sensitivity
0
1.0
1 – Specificity
0.2
0.80.60.40.20
Figure 4 Receiver–operating characteristics (ROC) curves for different cut-off values of maximum velocity (Vmax) of pulmonary venous
(PV) flow: (a) 35 cm/s; (b) 40 cm/s and (c) 41 cm/s. PV-Vmax cut-off value of 41cm/s, read automatically from ROC curve, provided
maximum specificity and positive predictive value at only slight cost of sensitivity and negative predictive value (Table 3).
Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Ultrasound Obstet Gynecol 2018; 51: 531–536.

5. Prediction of Rashkind procedure in d-TGA 535
reported that sonographic evaluation of the fetal FO is one
of the most difficult tasks of prenatal echocardiography.
Furthermore, its restriction may occur in both normal and
abnormal hearts15–18
. A restrictive FO can originate in
two different ways. Primary restriction occurs when there
is an abnormal FO, with either abnormal septum primum
angle, abnormal motility of the septum primum or an
aneurysmal septum primum16
. Secondary restriction is
the result of hemodynamic alteration, i.e. abnormal DA
or pulmonary venous flow16–18
. In fetuses with d-TGA,
highly oxygenated blood in the left ventricle is pumped
to the pulmonary artery. This blood then returns to the
pulmonary veins and may cause the oxygen saturation
in the left ventricle to be even higher than that in the
normal heart. In the fetal lamb, Konduri et al.19
found
that a 13% increase in oxygen saturation was associated
with a three-fold increase in pulmonary blood flow and
an increase in left atrial pressure from 4 to 8 mmHg. In
our study population, the restriction of the FO seems to
be secondary, in association with high pulmonary venous
flow velocity. If pulmonary venous flow is observed to
increase early in gestation, then FO restriction can be
suspected and confirmed by imaging in utero; however,
if this occurs late in pregnancy, for example just prior
to delivery, the restriction will be detected only if late
prenatal echocardiography is performed.
The prenatal features of restrictive FO in d-TGA have
been described rarely. In 1999, Maeno and colleagues18
reported FO restriction and/or premature closure of the
DA in 16 fetuses with d-TGA. No emergency Rashkind
procedures were required when there was normal appear-
ance of the FO, but the last prenatal echocardiogram was
performed at a mean gestational age of 30.5 weeks and
they did not follow up fetuses with d-TGA and apparently
normal FO. They assessed only FO and DA flow, with the
pulmonary venous flow not being part of their analysis,
although they noted a redundant septum primum causing
occlusion of the FO orifice after birth and large pulmonary
veins with a prominent color flow signal18. Jouannic
et al.8
determined the sensitivity and specificity of prenatal
features of physiological shunts to predict neonatal clinical
status in d-TGA. Prenatal restriction was detected in only
10% of cases, and the preoperative mortality rate was 4%.
They concluded that the sensitivity of FO and DA restric-
tion to detect fetuses at high risk of needing a Rashkind
procedure was too low; however, they did not measure
the pulmonary venous flow before delivery. Jouannic et al.
also highlighted the need for performing late echocardio-
graphic evaluation in fetuses with DA- and FO-dependent
CHD in order to determine whether the malformation is
critical8
.
In most cardiac surgery centers worldwide, the results
of surgical treatment for infants with d-TGA are very
good, with a typical mortality rate not exceeding 5%8,20
.
Some preoperative deaths would be preventable by
determination of the need for an emergency Rashkind
procedure using perinatal echocardiography. More than
a decade ago, Donofrio et al. pointed out the need
to monitor the FO in fetuses with CHD21
. In 2011,
Punn and Silverman noted that FO restriction in the
neonate can mean hypermobility of the FO septum and
retrograde flow in the DA22
. In the current study, we
also observed and recorded cases with retrograde flow
in the DA but these all resolved within minutes after
observation. Punn and Silverman hypothesized that the
mechanism of the hypermobile atrial septum and reversed
diastolic ductal flow is related to decreased pulmonary
vascular resistance, which increases pulmonary blood
flow from both the pulmonary artery and the DA. The left
atrium subsequently has more venous return than normal,
given the increased amount of pulmonary blood flow22
.
This increase in left atrial blood volume explains our
results and supports our theory that emergency Rashkind
procedure is associated with increased blood flow velocity
in the pulmonary veins, regardless of the size of the FO.
It is possible that such an increased velocity of pulmonary
venous blood flow prenatally could be the first sign, which
might be present 2–3 weeks before delivery, indicating
a need for emergency Rashkind procedure postnatally.
Requiring further research is the possibility that FO
closure, occurring just before or even after delivery,
is another sign indicating the need for an emergency
Rashkind procedure.
Another question that needs to be addressed is whether
prenatal administration of corticosteroids to accelerate
fetal lung maturity in gestations at risk of preterm
delivery could be associated with the growing number of
emergency Rashkind procedures in neonates with d-TGA
in our obstetric-cardiology centers. Steroid therapy, by
increasing congestion of the lungs, may increase the blood
flow in the pulmonary veins to the left atrium and may
be responsible for an antepartum increase in left atrial
pressure and decrease in right-to-left flow through the FO.
Studies to investigate this hypothesis are underway in our
centers.
A strength of this study is the ease of assessment of
pulmonary flow, much more so than that of the FO
flow. Another strength is our analysis of data from two
independent centers. Limitations include the retrospective
nature of the study and the small number of fetuses,
since echocardiographic examinations are not performed
commonly after 37 gestational weeks.
In conclusion, in fetuses with d-TGA, prenatal
sonographic findings of increased pulmonary venous
blood flow and flattened FO valve were associated with
the need for a Rashkind procedure within the first
24 h postnatally; these echocardiographic features could
potentially be used to predict prenatally a need for the
procedure following delivery.
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