1. Ultrasound Obstet Gynecol 2013; 41: 47–53
Published online 5 December 2012 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/uog.11196
Pulmonary outflow tract obstruction in fetuses with complex
congenital heart disease: predicting the need for neonatal
intervention
M. D. QUARTERMAIN, A. C. GLATZ, D. J. GOLDBERG, M. S. COHEN, M. D. ELIAS,
Z. TIAN and J. RYCHIK
Fetal Heart Program at the Cardiac Center, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
KEYWORDS: congenital heart disease; fetal echocardiography; pediatric cardiology
ABSTRACT
Objective To identify prenatal echocardiographic mark-
ers that could predict the need for neonatal intervention in
fetuses with right ventricular outflow tract obstruction.
Methods This was a retrospective study of 52 fetuses with
right ventricular outflow tract obstruction. Echocardio-
grams were evaluated for fetuses with either two-ventricle
anatomy with a large ventricular septal defect or single-
ventricle anatomy. Fetuses with pulmonary atresia were
excluded. Parameters were compared between groups that
did and did not require an intervention at age < 30 days.
Results Fifty-two fetuses were studied; 20 (38%) under-
went neonatal intervention and 32 (62%) did not. The
most common diagnosis was tetralogy of Fallot (n = 32).
Fetuses with two ventricles that required an intervention
had lower pulmonary valve diameter Z-score (PV-Z-
score) (−4.8 ± 2.1 vs −2.6 ± 1.1; P = 0.0002) and lower
pulmonary valve to aortic valve annular diameter ratio
(PV/AoV) (0.53 ± 0.15 vs 0.66 ± 0.1; P = 0.003). Using
a PV/AoV ratio of < 0.6 or a PV-Z-score of < −3 at
final echocardiographic examination was highly sensi-
tive (92%) but poorly specific (50%), whereas classify-
ing direction of flow in the ductus arteriosus as either
normal (all pulmonary-to-aorta) or abnormal (aorta-to-
pulmonary or bidirectional) was both highly sensitive
(100%) and specific (95%) for predicting the need for a
neonatal intervention. Parameters for the single-ventricle
cohort did not reach statistical significance.
Conclusions Analysis of the pulmonary outflow tract and
ductus arteriosus flow in the fetus with complex congenital
heart disease can aid in identifying those that will require
a neonatal intervention to augment pulmonary blood
Correspondence to: Dr M. Quartermain, Fetal Heart Program at Wake Forest University School of Medicine, Winston-Salem, NC 27006,
USA (e-mail: mquarter@wakehealth.edu)
Accepted: 2 May 2012
flow. This has important implications for the planning of
delivery strategies. Copyright  2012 ISUOG. Published
by John Wiley & Sons, Ltd.
INTRODUCTION
Accurate prenatal diagnosis has led to advances in
perinatal care for the fetus with complex congenital
heart disease (CHD). Several studies have demonstrated
that a prenatal diagnosis of critical CHD allows for
improved clinical status after birth1,2. Pulmonary outflow
tract obstruction is often present in the fetus with
both single and two-ventricle forms of complex CHD.
Fetuses with severe pulmonary outflow tract obstruction
may develop significant cyanosis after birth and require
urgent intervention. In these situations, an accurate
assessment of the adequacy of the outflow tract by fetal
echocardiography can help to determine whether there
will be a need for prostaglandin infusion after birth to
maintain ductal patency.
Previous studies have supported the role of fetal
echocardiographic markers such as reversed shunting
in the ductus arteriosus as predictive of severe right
heart obstructive lesions3–5
. The characteristics of two-
dimensional, pulsed-wave and color Doppler findings of
the ductus arteriosus in severe right heart lesions have
been described6
. Assessments of pulmonary artery growth
in utero with attempts at prediction of the severity of
postnatal outflow tract obstruction have been performed
in fetuses with tetralogy of Fallot (TOF)7,8
. Despite these
efforts, models for predicting critical pulmonary outflow
tract obstruction do not exist. The goal of this study
was to identify prenatal echocardiographic markers that
would allow accurate prediction of which fetuses with
Copyright  2012 ISUOG. Published by John Wiley & Sons, Ltd. ORIGINAL PAPER

2. 48 Quartermain et al.
complex CHD and pulmonary outflow tract obstruction
will have ductal-dependent physiology after birth and
require a neonatal intervention.
METHODS
Study patients
A review of the echocardiographic database from The
Fetal Heart Program at The Children’s Hospital of
Philadelphia between July 2004 and January 2008 was
performed to identify all fetuses referred for evaluation
of pulmonary outflow tract obstruction in the setting of
single-ventricle anatomy or two-ventricle anatomy with a
large ventricular septal defect (e.g. TOF). Fetuses with at
least one fetal echocardiogram, a postnatal transthoracic
echocardiogram, survival to birth and documentation of
neonatal clinical outcome were included. In order to
isolate the degree of pulmonary outflow tract obstruction
and its effects on postnatal cyanosis, we excluded patients
with isolated valvar pulmonary stenosis with intact
ventricular septum and other forms of CHD that could
lead to postnatal cyanosis (e.g. transposition of the great
arteries). Fetuses with pulmonary atresia documented on
the first fetal echocardiogram were also excluded, as
neonatal intervention is always needed in these patients.
The study was approved by the Institutional Review Board
at The Children’s Hospital of Philadelphia (CHOP IRB #
09-007176).
All fetuses underwent examinations including two-
dimensional echocardiography with color flow and
spectral Doppler utilizing standard guidelines from the
American Society of Echocardiography9
. This included
the four-chamber view and long- and short-axis images
of the intracardiac anatomy and great vessels. Imaging
of the ductus arteriosus was enhanced by utilizing a low
Nyquist limit, and direction of flow was confirmed with
pulsed-wave and color Doppler techniques. Images were
obtained using a Siemens Acuson Sequoia ultrasound
system (Mountain View, CA, USA) with appropriate
transducers for the mother’s body habitus and fetal gesta-
tional age. Measurements were made offline using Siemens
Syngo Dynamics workstation (Ann Arbor, MI, USA) and
were performed by a single worker (M.Q.) blinded to
clinical outcome. Each parameter was measured three
times and an average value recorded. Gestational age
was determined from date of the last menstrual period.
Interobserver variability was assessed between two inde-
pendent investigators on 15 randomly selected datasets.
Two-dimensional echocardiographic measurements
included pulmonary valve (PV) and aortic valve (AoV)
annular diameters, subpulmonary valve (SubPV) region,
main pulmonary artery (MPA) and branch pulmonary
artery diameters. Measurements were made of the inter-
nal diameter of the identified structure in systole with the
semilunar valve open. Both short- and long-axis views
were utilized and measurements were made from the
view that provided the clearest internal diameter of the
structure based on fetal position. Z-score transformation
was performed for structures with published normal val-
ues as previously described10
. Color and pulsed-Doppler
echocardiography were used to assess the peak velocity at
the level of the pulmonary valve and the direction of flow
across the ductus arteriosus. Ductal flow was designated
as normal when all systolic and diastolic flow was from
pulmonary artery to aorta. Flow was considered abnor-
mal when there was either exclusive flow from aorta
to pulmonary artery or bidirectional flow with reversal
occurring in any phase of the cardiac cycle (Figures 1–3).
As a means of assessing the degree of great-vessel dis-
proportion, ratios of PV to AoV annular diameters were
calculated.
All postnatal diagnoses were confirmed by a com-
plete transthoracic echocardiographic examination. The
patients’ medical records were reviewed to confirm inter-
ventions and clinical outcomes. Neonatal intervention was
defined as transcatheter balloon dilation valvuloplasty
or a surgical procedure to augment pulmonary blood
Figure 1 (a) Short-axis echocardiographic image of the right
ventricular outflow tract in a fetus with tetralogy of Fallot showing
normal flow (blue) across ductus arteriosus (DA) from pulmonary
artery (PA) to aorta. (b) Pulsed-wave Doppler signal, showing
continuous antegrade flow with high systolic and low diastolic
velocity. DAo, descending aorta; R-L, right to left; RPA, right
pulmonary artery; Sp, spine.
Copyright  2012 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2013; 41: 47–53.

3. Pulmonary outflow tract obstruction in the fetus 49
Figure 2 (a) Aortic arch (Ao Arch) echocardiographic image in a
fetus with severe tetralogy of Fallot showing abnormal flow (blue)
across the ductus arteriosus (DA) from aorta to pulmonary artery.
(b) Pulsed-wave Doppler signal, showing continuous flow with high
systolic and very low diastolic velocity. DAo, descending aorta;
L-R, left to right.
flow performed within 30 days of birth. Management of
patients with pulmonary outflow tract obstruction at our
institution includes a review of the postnatal echocar-
diogram and assessment of the patient’s clinical status
without a trial of prostaglandin if deemed possible. If
adequate oxygen saturation is maintained after ductal
closure then patients are discharged and followed closely
in the outpatient setting until they are electively referred
for intervention.
Data analysis
Data collected and analyzed included echocardiographic
measurements, postnatal diagnostic groupings and pri-
mary clinical outcome (need for neonatal interven-
tion). All analysis was done separately based on
diagnostic group (single- vs two-ventricle circulation).
Descriptive statistics were used to summarize the data,
Figure 3 Pulsed-wave Doppler signal in a fetus with complex
single-ventricle anatomy and pulmonary stenosis, showing
bidirectional flow with high systolic and diastolic velocities. Above
baseline is pulmonary artery-to-aorta flow in diastole; below
baseline is reversal of flow in systole. DA, ductus arteriosus; R-L,
right to left.
using mean ± SD for normally distributed continuous
variables, median (range) for skewed continuous vari-
ables and frequency (percentage of total) for categorical
or dichotomous variables. Comparisons of variables based
on the primary clinical outcome status were made using
the independent t-test for normally distributed continuous
variables, Wilcoxon rank-sum test for skewed continu-
ous variables and Fisher’s exact test or the chi-square
test for categorical variables. Changes in fetal echocar-
diographic measurements over time were assessed by
measuring the change in PV annular dimension between
the first and last fetal echocardiograms and dividing by
the time between studies to generate a rate of growth
of the PV annulus in mm/week. Comparison of annular
growth based on clinical outcome status was made using
an independent t-test. STATA v10.0 (STATA Corp., Col-
lege Station, TX, USA) software was used for statistical
analysis, and P < 0.05 was considered to be statistically
significant.
To assess the predictive accuracy of prenatal indices,
sensitivity and specificity were calculated for ductal flow
pattern, PV annulus Z-score and the ratio of PV annulus
diameter to AoV annulus diameter (PV/AoV ratio).
Using receiver–operating characteristics curve analysis,
optimum cut-off points in the predictor variables were
obtained by selecting a cut-off point that produced
a minimum sensitivity of 90% in discriminating the
observed resulting classifications. This standard was
established a priori in order to define a prediction
rule that would minimize the very high cost of a
false negative (incorrectly predicting that a neonatal
intervention would not be needed in a newborn with
ductal-dependent pulmonary blood flow). Because no
cut-off point for PV annulus Z-score or PV/AoV ratio
individually performed with a sensitivity of more than
90%, these two variables were combined in an either/or
fashion to increase sensitivity.
Copyright  2012 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2013; 41: 47–53.

4. 50 Quartermain et al.
RESULTS
Study population and clinical outcomes
A total of 65 fetuses were identified from the database
during the study period. Eight pregnancies associated with
heterotaxy (n = 4), trisomy 21 (n = 2), Dandy–Walker
malformation (n = 1) and multicystic kidney disease
(n = 1) were electively terminated. Fetal demise occurred
in four cases and was associated with 22q11 microdeletion
(n = 2), cystic hygroma (n = 1) and multiple congenital
anomalies (n = 1). One fetus with TOF with restriction
of the ventricular septal defect was excluded, thus 52
fetuses were included in the final cohort. Forty-seven
had serial imaging performed and a total of 144 studies
were reviewed. The mean gestational age at the time of
diagnosis was 25 ± 4.0 weeks. There were four sets of
twin pregnancies and the remaining 48 were singleton.
Diagnoses are shown in Table 1 and divided into two
cohorts: two-ventricle defects (n = 39) and single-ventricle
defects (n = 13).
Clinical outcomes including birth weight and ges-
tational age at delivery by group are presented in
Table 2. Twenty of 52 subjects (38%) had critical
pulmonary outflow tract obstruction and required a
Table 1 Diagnoses of congenital heart disease grouped according
to type of defect present in the fetus
Type of defect n
Two-ventricle group
TOF 33
DORV/PS 6
Single-ventricle group
Unbalanced AVC, DORV, PS 3
Unbalanced AVC, TOF 2
Unbalanced AVC, DORV, TAPVC 4
DILV, PS 2
DORV, MS, PS 2
AVC, atrioventricular canal; DILV, double-inlet left ventricle;
DORV, double-outlet right ventricle; MS, mitral stenosis; PS,
pulmonary stenosis; TAPVC, total anomalous pulmonary venous
connection; TOF, tetralogy of Fallot.
neonatal intervention at a median of 12 (range, 1–30)
days of age to increase pulmonary blood flow. Of
the two-ventricle cohort, 13 of 39 (33%) required
a neonatal intervention, comprising complete surgical
repair (n = 8), transcatheter balloon dilation valvuloplasty
(n = 3) or placement of a surgical shunt (n = 2). Of
the single-ventricle cohort, seven of 13 (54%) required
a neonatal intervention, which included transcatheter
balloon dilation valvuloplasty (n = 3) and placement of
a surgical shunt (n = 4). Compared with two-ventricle
patients, the single-ventricle cohort demonstrated an
increased risk of requiring neonatal intervention, with
an odds ratio of 2.3 (95% CI, 0.7–8.1), although this
difference did not reach statistical significance (P = 0.2).
Two-dimensional echocardiographic measurements
Measurements of the PV, AoV, SubPV region, MPA and
proximal branch pulmonary arteries are presented by
group in Table 3. These measurements were obtained
from the final fetal echocardiogram performed at a mean
gestational age of 34 ± 2.7 weeks. In the two-ventricle
cohort, all measurements of the pulmonary outflow tract
were significantly smaller in fetuses that went on to
require a neonatal intervention than in those that did not.
In the single-ventricle cohort, there were trends towards
smaller measurements in PV-Z-score and PV/AoV ratio,
but statistical significance was not reached. In both
groups, accurate measurements of the SubPV region
and MPA were not obtainable in a significant number
of subjects. Interobserver variability was assessed with
the intraclass correlation coefficient, which was 0.98
for the AoV and 0.96 for the PV, suggesting excellent
reproducibility of measurements.
For the two-ventricle cohort sensitivities and speci-
ficities were obtained for the presence of a PV-Z-
score of < −3 or a PV/AoV ratio of < 0.6 for their
ability to predict the need for neonatal interven-
tion (Table 4). Using either threshold produced > 90%
sensitivity, which was consistent among various
gestational ages. As demonstrated in Figures 4–6, the
PV-Z-scores and PV/AoV ratios were significantly smaller
Table 2 Clinical outcomes in fetuses grouped by type of defect and time of intervention
Intervention at:
Outcome > 30 days < 30 days P
Two-ventricle group (n = 39)
n (%) 26 (66.7) 13 (33.3)
Gestational age at delivery (weeks, mean ± SD) 37.7 ± 2.5 37.6 ± 2.7 0.9
Birth weight (g, mean ± SD) 2974 ± 832 2625 ± 868 0.25
Prostaglandin use (n (%)) 4 (15.4) 11 (84.6) 0.0001
Age at intervention (median (range)) 2.9 (1.6–5.2)* 8 (1–30)†
Single-ventricle group (n = 13)
n (%) 6 (46.2) 7 (53.8)
Gestational age at delivery (weeks, mean ± SD) 38.8 ± 1.8 38.5 ± 1.2 0.7
Birth weight (g, mean ± SD) 3357 ± 931 3190 ± 545 0.7
Prostaglandin use (n (%)) 3 (50.0) 6 (85.7) 0.3
Age at intervention (median (range)) 4.2 (2.8–10)* 14 (3–30)†
*In months. †In days.
Copyright  2012 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2013; 41: 47–53.

5. Pulmonary outflow tract obstruction in the fetus 51
Table 3 Fetal echocardiographic measurements in fetuses with pulmonary outflow tract obstruction and congenital heart defect grouped by
type of defect and whether or not neonatal intervention was required
Parameter n No intervention Intervention P
Two-ventricle group
PV (mm) 39 5.3 ± 1.0 4.1 ± 1.1 0.0035
PV Z-score 39 −2.6 ± 1.1 −4.8 ± 2.1 0.0002
AoV (mm) 39 8.0 ± 1.2 7.9 ± 0.9 0.7
AoV Z-score 39 2.6 ± 0.8 2.5 ± 1.0 0.7
SubPV region (mm) 19 5.0 ± 1.1 3.8 ± 1.1 0.032
MPA (mm) 24 5.7 ± 0.8 4.2 ± 0.8 0.0005
LPA (mm) 33 3.6 ± 0.5 2.8 ± 0.55 0.0006
RPA (mm) 35 3.7 ± 0.5 3.1 ± 0.4 0.0007
PV/AoV ratio 39 0.66 ± 0.1 0.53 ± 0.15 0.003
Single-ventricle group
PV (mm) 13 5.0 ± 0.8 4.5 ± 1.1 0.38
PV Z-score 13 −3.4 ± 1.0 −4.1 ± 2.4 0.5
AoV (mm) 13 7.7 ± 0.9 8.0 ± 0.4 0.4
AoV Z-score 13 2.0 ± 1.1 2.6 ± 0.4 0.23
SubPV region (mm) 4 4.2 ± 0.98 — —
MPA (mm) 9 5.3 ± 1.0 5.1 ± 0.6 0.8
LPA (mm) 12 3.45 ± 0.15 3.9 ± 0.9 0.29
RPA (mm) 12 3.6 ± 0.4 3.9 ± 0.8 0.4
PV/AoV ratio 13 0.65 ± 0.1 0.57 ± 0.15 0.27
Data are given as mean ± SD. AoV, aortic valve; LPA, left pulmonary artery; MPA, main pulmonary artery; PV, pulmonary valve; RPA,
right pulmonary artery; SubPV, subpulmonary valve.
Table 4 Sensitivity and specificity for a pulmonary valve diameter
(PV) Z-score of < −3 or a PV to aortic valve annular diameter
(PV/AoV) ratio of < 0.6 and ductal flow patterns in the prediction
of need for neonatal intervention in fetuses that had two-ventricle
defects
Parameter
Sensitivity
(%)
Specificity
(%)
PV-Z-score < −3 or PV/AoV ratio < 0.6
Early-gestation (< 24 weeks) 100 50
Mid-gestation (24–32 weeks) 100 48
Final echo (mean age, 34 weeks) 92 50
Ductal flow pattern
Early-gestation (< 24 weeks) 75 100
Mid-gestation (24–32 weeks) 88 94
Final echo (mean age, 34 weeks) 100 95
echo, echocardiographic examination.
in fetuses that required a neonatal intervention over vari-
ous gestational ages. The AoV-Z-scores were larger than
normal in both groups in the majority of cases.
Ductal flow patterns
In 30 of 39 (77%) of the two-ventricle fetuses an
assessment of the ductal flow pattern was made on the
final echocardiogram. An abnormal ductal pattern was
observed in all nine that required a neonatal intervention,
providing a sensitivity of 100%. Of the 21 remaining
fetuses that did not require a neonatal intervention, the
ductal flow pattern was normal in all but one, providing
a specificity of 95% (Table 4). Ductal flow patterns were
obtained in 11 of 13 (85%) of the single-ventricle fetuses.
Of the six that required a neonatal intervention, flow
was abnormal in all, providing a sensitivity of 100%. Of
Table 5 Echocardiographic measurements in fetuses with normal
vs abnormal ductus arteriosus (DA) flow patterns in those in which
DA flow could be measured (n = 41)
Parameter
Normal
DA flow
(n = 24)
Abnormal
DA flow
(n = 17) P
PV (mm) 5.2 ± 0.98 4.3 ± 1.1 0.012
PV-Z-score −2.4 ± 1.6 −4.4 ± 2.0 0.0001
AoV (mm) 7.7 ± 1.0 8.3 ± 0.56 0.037
PV/AoV ratio 0.67 ± 0.1 0.52 ± 0.13 0.0001
Data are given as mean ± SD. AoV, aortic valve annular diameter;
PV, pulmonary valve annular diameter.
the remaining five fetuses that did not require a neonatal
intervention ductal flow was normal in four, giving a
specificity of 80%. In those fetuses in which ductal flow
direction could be measured (n = 41), comparison was
made of the echocardiographic measurements between
those with normal ductal flow and those with abnormal
ductal flow patterns (Table 5). Pulmonary valve size and
PV/AoV ratios were significantly smaller and AoV size was
larger in the group with an abnormal ductal flow pattern.
Pulmonary valve Doppler velocities
Velocities were obtained across the pulmonary outflow
tract in all but two fetuses. In general, velocities were only
minimally above published norms. In addition, there were
no significant differences between the group that required
a neonatal intervention (1.32 ± 0.37 m/s) and the group
that did not (1.16 ± 0.28 m/s), P = 0.112.
Copyright  2012 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2013; 41: 47–53.

6. 52 Quartermain et al.
18
−10
−8
−6
−4
−2
0
2
20 22 24 26 28 30
Gestational age (weeks)
PulmonaryvalveannulusZ-score
32 34 36 38 40
(a)
18
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
20 22 24 26 28 30
Gestational age (weeks)
PV/AVannulusratio
32 34 36 38 40
(b)
18
0
1
2
3
4
5
20 22 24 26 28 30
Gestational age (weeks)
AorticvalveannulusZ-score
32 34 36 38 40
(c)
Figure 4 Echocardiographic parameters in fetuses that did (blue)
and did not (red) require neonatal intervention plotted against
gestational age: (a) pulmonary valve annular diameter Z-score
(dashed black line represents Z-score of −3); (b) ratio of
pulmonary valve to aortic valve annular diameter (dashed black
line represents ratio of 0.6); and (c) aortic valve annular diameter
Z-score (dashed black line represents Z-score of +2).
Progression of pulmonary outflow tract obstruction
with gestational age
Serial fetal echocardiography was available for 47 of
52 fetuses. One fetus with antegrade flow on an
early fetal echocardiogram developed pulmonary atresia
on subsequent imaging. Fetuses that required a new-
born intervention demonstrated diminished growth of
the pulmonary valve from early-gestation echocardio-
gram (< 24 weeks) to late-gestation echocardiogram
(> 32 weeks). When all fetuses with both an early and
a late study were included (n = 20), growth rates for the
intervention and non-intervention groups were 0.6 and
0.9 mm/month, respectively (P = 0.05).
DISCUSSION
We reviewed our experience with a cohort of fetuses
with outflow tract obstruction to determine prenatal
echocardiographic markers that could identify those that
required a neonatal intervention to augment pulmonary
blood flow. We found that fetuses with two ventricles, a
large ventricular septal defect and pulmonary outflow
tract obstruction (e.g. TOF) that require a neonatal
intervention had significantly smaller measurements of
the pulmonary outflow tract on echocardiography. In
addition, PV/AoV ratio was significantly smaller in the
neonatal intervention group. When using a PV/AoV ratio
of < 0.6 or a PV-Z-score of < −3 there was a greater than
90% sensitivity across gestational age for predicting the
need for a neonatal intervention. The weaker specificity
values are acceptable in this clinical setting where the cost
of a false negative is high.
Ductal flow pattern as a single marker provided the
best sensitivity and specificity for predicting the need
for a neonatal intervention; all fetuses with abnormal
ductal flow required a neonatal intervention. Nonetheless,
there will always be some patients where reliable ductal
flow patterns cannot be obtained owing to fetal position
or maternal body habitus. In our series, when ductal
flow could not be obtained, measurements of the PV-
Z-score and PV/AoV ratio allowed for discrimination
between those fetuses that did and those that did not
require a neonatal intervention. These measurements
could therefore act as surrogate markers for abnormal
ductal flow and need for neonatal intervention. In
addition, valvar annular measurements have the added
benefit of being more readily obtainable, which allows for
their use by a variety of medical care providers.
There is a paucity of data describing perinatal outcomes
of fetuses with complex single ventricles with pulmonary
outflow tract obstruction with respect to the timing of
the intervention. Therefore we studied a second, smaller
group of complex single-ventricle patients. Fetuses in this
group that required a neonatal intervention also had
smaller PV and lower PV/AoV ratio, although statistical
significance was not obtained – a result that is possibly
related to the smaller numbers in this cohort. Similarly
to the two-ventricle cohort, an abnormal ductal flow
pattern produced excellent sensitivities and specificities
for predicting the need for neonatal intervention.
Progression of pulmonary outflow tract obstruction was
observed in our cohort. This finding supports previous
reports that focused on pulmonary artery growth in
CHD7. In our cohort, we also demonstrated diminished
growth velocity of the PV in fetuses that went on to require
a neonatal intervention. These differences in growth
velocity can aid in the identification of fetuses at risk
for critical obstruction after birth, which highlights the
need for serial imaging throughout pregnancy.
Copyright  2012 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2013; 41: 47–53.

7. Pulmonary outflow tract obstruction in the fetus 53
Previous studies attempting to predict the need for
neonatal intervention were limited by sample size. A
review of 25 fetuses with TOF was unable to correlate
echocardiographic findings with timing of surgery8
. A
separate review of 47 fetuses with TOF-type anatomy
demonstrated that lower PV-Z-scores were associated
with the use of prostaglandin, but it was not clear
how many actually had critical CHD and required
a neonatal intervention11
. The importance of reversed
ductal shunting in critical right-sided obstructive lesions
was initially reported by Berning et al.3
. In this series,
15 fetuses survived to term and only three survived the
neonatal period, leading the authors to conclude that
reversed ductal shunting predicts severe disease and poor
outcome. Our study expands on this literature with a
larger cohort, more perinatal management details and
outcome data in the current era. Our findings further
highlight the importance of abnormal ductal shunting as
a strong marker of the need for neonatal intervention,
even when pulmonary atresia and more severe CHD are
not present.
Prenatal identification of pulmonary outflow tract
obstruction is clinically relevant. It allows for more
accurate prenatal counseling and enables the development
of a perinatal plan for delivery in a tertiary center
when appropriate. Moreover, our measurements and
ratios are relatively easy for physicians who are not fetal
cardiologists to utilize, making them excellent screening
tools for those who often perform initial prenatal
evaluations.
Our study is limited in that it is a retrospective review
with selection bias of fetuses evaluated at a large referral
center. In addition, there were patients in whom we were
unable to accurately measure subpulmonary regions and
therefore we could have missed important obstruction. We
chose not to assess valvar pulmonary stenosis alone, as our
goal was to isolate a dimension of the pulmonary outflow
tract that would correlate with postnatal cyanosis and
ductal dependency. Newborns with critical pulmonary
stenosis may be cyanotic for various reasons, including
significant right ventricular hypertrophy with a smaller
than normal cavity and poor compliance leading to
right-to-left atrial-level shunting, thus making them a
different cohort of patients when predicting postnatal
physiology. Finally, owing to small numbers our study
was not powered to draw significant conclusions in the
single-ventricle cohort.
In conclusion, in fetuses with pulmonary outflow tract
obstruction in the setting of two ventricles with a large
ventricular septal defect (e.g. TOF), assessment of the
outflow tract allows for good discrimination between
those that will and those that will not require a neonatal
intervention to augment pulmonary blood flow. The
presence of reversed ductal shunting is both highly
sensitive and specific for critical obstruction, and is the
strongest single fetal echocardiographic marker to predict
the need for a neonatal intervention. When the ductus
arteriosus cannot be identified, measurements of the PV
and PV/AoV ratio are highly sensitive markers of the
need for neonatal intervention. Fetuses that required a
neonatal intervention had diminished growth of the PV
from early to late gestation, highlighting the importance
of serial echocardiography in determining critical CHD.
Single-ventricle fetuses are more complex, but ductal
patterns also appear to be sensitive and specific for
predicting the need for an intervention. These findings
have important implications for family counseling, the
planning of delivery strategies and immediate postnatal
care for these patients.
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