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JACC Vol. 25, No. 3
March 1, 1995:739-45
739
In Utero Pulmonary Artery and Aortic Growth and Potential
for Progression of Pulmonary Outflow Tract Obstruction in
Tetralogy of Fallot
LISA K. H O R N B E R G E R ,
MD, S T E P H E N P. S A N D E R S , MD,* D A V I D J. SAHN, MD, F A C C , ?
M A R Y JO RICE, MD, F A C C , t P H I L I P J. SPEVAK, MD, B E R Y L R. B E N A C E R R A F , MD,$
R O B E R T W. M c D O N A L D , RCVT, R D C S , ? S T E V E N D. C O L A N , MD, F A C C
Boston, Massachusetts; Portland, Oregon; and Genolier, Switzerland
Objectives. This study was designed to define patterns of
pulmonary artery and aortic growth in fetuses with tetralogy
of Fallot and to determine the potential for in utero progression of
right ventricular outflow tract obstruction.
Background. Despite an abundance of reports documenting the
prenatal diagnosis of tetralogy of Fallot, there is little information
about its course in utero.
Methods. Pulmonary artery and ascending aortic diameters
were measured from prenatal and postnatal echocardiograms of
16 fetuses with tetralogy of Faliot, initially studied at 23.6 -+ 6.0
(mean -+ SD) weeks of gestation. Fetuses were classified retrospectively as having mild and severe tetralogy of Faliot according
to whether the pulmonary artery circulation was (severe, n = 5) or
was not (mild, n = 11) ductus arteriosus dependent at birth.
Results. Initial main pulmonary artery diameter was small for
gestational age in 9 fetuses, large in 2 and normal in 5 compared
with data from 57 gestational age-adjusted normal fetal studies; it
was significantly smaller in the group with severe tetralogy of
Fallot (p = 0.05). The initial main pulmonary artery/aortic
diameter ratio was also smaller for the group with severe tetralogy of
Fallot (0.50 ± 0.15 vs. 0.73 -+ 0.14 in the group with mild tetralogy of
Fallot, p = 0.01). Initial aortic and branch pulmonary artery
diameters tended to be normal or near normal for age. In eight
fetuses serially studied, main and branch pulmonary artery growth
was normal or reduced during prenatal follow-up. Pulmonary artery
growth was most reduced in two fetuses in the group with severe
tetralogy of Fallot, resulting in pulmonary artery hypoplasia at birth.
Two fetuses with valvular pulmonary atresia at birth had previously
shown anterograde pulmonary outflow in midgestation, suggesting
progression of pulmonary outflow obstruction.
Conclusions. The postnatal spectrum of pulmonary artery size
in tetralogy of Fallot can be attributed to variable patterns of
growth in utero. Main pulmonary artery size, main pulmonary
artery/aortic diameter ratio and pattern of pulmonary artery
growth may be predictive of the severity of postnatal pulmonary
outflow obstruction. Pulmonary atresia can develop in utero in
some fetuses with tetralogy of Fallot.
The majority of structural heart defects are present by the end
of the first trimester, after embryogenesis is complete. However, some cardiovascular lesions may continue to evolve
through gestation. Left ventricular hypoplasia may develop or
become more severe in the presence of endoeardial fibroelastosis (1-3) or left heart obstructive lesions (3,4). Right ventricular outflow tract obstruction may progress as an isolated
lesion (5) or in the presence of tricuspid valve disease and
tricuspid insufficiency (6,7). Knowledge of the in utero natural
history and potential for progression of cardiac defects is
important not only for our understanding of the determinants
of postnatally encountered disease, but also for appropriate
counseling of families, planning of postnatal management and
designing effective and appropriate antenatal intervention.
Tetralogy of Fallot is one of the most common cardiac
lesions identified in utero (8-10). Despite an abundance of
published reports documenting the prenatal diagnosis of tetralogy of Fallot (8-13), there is little information available
about its course and potential for progression during the
second half of pregnancy. Abnormal pulmonary artery growth,
resulting in pulmonary artery hypoplasia at birth, has been
described previously in isolated cases of antenatally diagnosed
tetralogy of Fallot (14,15). The purpose of the present study
was to describe patterns of pulmonary artery and aortic growth
in fetuses with tetralogy of Fallot and to determine the
potential for in utero progression of pulmonic outflow obstruction.
From the Department of Cardiology, Children's Hospital, Harvard Medical
School, Boston, Massachusetts; *Aldo Castaneda Institute for Congenital Heart
Disease, Clinique de Genolier, Genolier, Switzerland; tDepartment of Cardiology, Clinical Care Center for Congenital Heart Disease, Oregon Health Sciences
University, Portland, Oregon; and :~Departments of Obstetrics and Gynecology
and Radiology, Brigham and Women's Hospital and Massachusetts General
Hospital, Harvard Medical School, Boston, Massachusetts. This work was
performed during the tenure of Physician-Investigator Fellowship Award 13-625934 to Dr. Hornberger from the American Heart Association, Massachusetts
AtIiliate, Inc., Framingham.
Manuscript received May 19, 1994; revised manuscript received August 25,
1994, accepted September 28, 1994.
Address for corresoondence: Dr. Lisa K. Hornberger, Department of
Cardiology, Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts
02115.
@1995 by the American College of Cardiology
(J Am Coll Cardiol I995;25:739-45)
0735-1097/95/$9.50
0735-1097(94)00422-M
740
H O R N B E R G E R ET AL.
IN U T E R O G R E A T ARTERY G R O W T H 1N T E T R A L O G Y OF FALLOT
Methods
AI
JACC Vol. 25, No. 3
March 1, 1995:739-45
B.
Study patients. We retrospectively reviewed the prenatal
and postnatal echocardiograms of 16 fetuses prenatally diagnosed with tetralogy of Fallot. The 16 fetuses represented all of
the cases of prenatally diagnosed tetralogy of Fallot in which
there was postnatal follow-up from the Children's Hospital,
Boston; Oregon Health Sciences University Medical Center,
Portland; and the University of California, San Diego, Medical
Center. Indications for fetal cardiac examination included a
screening ultrasound examination suggestive of a cardiac abnormality (n = 12), a family history of congenital heart disease
(n = 2), fetal hydrops (n = 1) and the presence of a DandyWalker cyst (n -- 1). None of the fetuses had a chromosomal
abnormality. Twin gestation was present in three fetuses.
Fetuses prenatally diagnosed with absent pulmonary valve
syndrome were not included. Nine additional fetuses with
prenatally detected tetralogy of Fallot were excluded from the
study: two with tetralogy of Fallot, long-segment pulmonary
atresia and multiple congenital anomalies; one with a restrictive ventricular septal defect and left ventricular hypoplasia
who died in utero; one with tetralogy of Fallot and pulmonary
atresia who also died in utero after the initial study; three with
termination of pregnancy; and two lost to follow-up.
The postnatal clinical outcomes of the fetuses were reviewed. The severity of right ventricular outflow tract obstruction found in the newborn period was used to classify the
fetuses into two groups. Fetuses were classified as having severe
disease if the pulmonary circulation was ductus arteriosus
dependent at birth and mild disease if the pulmonary circulation was not ductus-dependent.
Prenatal and postnatal echocardiograms. Fetal echocardiography was performed using an Acuson 128XP or HewlettPackard 1000 or 1500 ultrasound system with 3.5-, 5- and
7.5-MHz transducers. Biparietal diameter and femur length
measurements were used to determine gestational age. Longand short-axis images of the intracardiac anatomy and great
arteries were obtained. In all prenatal studies, color flow
mapping was used, and in 21 of the 31 prenatal studies, spectral
Doppler flow analysis had been performed. Tetralogy of Fallot
was diagnosed when there was anterior deviation of the
infundibular septum, a conoventricular septal defect and an
overriding aorta.
Measurements. From videocassette recordings of the prenatal and postnatal two-dimensional images, the following
measurements were made by one investigator (L.K.H.):
1) main pulmonary artery internal diameter midway between
the valve and the bifurcation; 2) proximal left and right
pulmonary artery diameters in the short-axis view of the right
ventricular outflow tract and great arteries; 3) diameter of the
ascending aorta in the long-axis view (Fig. 1). All measurements were made along the axial plane of the ultrasound beam
whenever possible. Pulmonary valve diameters and dimensions
of the infundibulum were not measured because of difficulties
in standardization of these measurements.
Doppler velocity tracings of blood flow obtained at the level
Figure 1. Diagrams demonstrating measurements of (A) ascending
aortic (Ao) diameter from the long-axisviewand (B) main and branch
pulmonary artery diameters from the short-axis view of the right
ventricular outflowtract and great arteries. LPA (MPA, RPA) = left
(main, right) pulmonary artery; LV (RV) = left (right) ventricle.
of the pulmonary and aortic outflow tracts (sample volume
near the pulmonary and aortic valves, respectively) were
reviewed.
Data analysis. Measurements made in the fetuses with
tetralogy of Fallot were compared with similar measurements
adjusted for gestational age from 57 studies in fetuses without
heart defects. The gestational age of the normal pregnancies
ranged from 17 to 39 weeks. Measurements from the fetuses
with tetralogy of Fallot were expressed as z scores based on the
normal data.
The z score is the number of standard deviations from the
mean value for the reference group. For example, a z score of
zero describes a value at the mean value for normal fetuses at
a particular gestational age. A z score of +2 indicates that the
value is 2 SD above the mean value for gestational age.
An unpaired t test was used to determine whether measurements from initial prenatal examinations were different for
fetuses with mild versus severe tetralogy of Fallot. Main
pulmonary artery and ascending aorta z scores from the initial
studies were compared using regression analysis.
The initial main pulmonary artery diameter/ascending aortic diameter ratio was calculated, and a comparison was made
between the severe and mild group ratios using a MannWhitney rank sum test.
Eight fetuses were serially studied in utero. To identify
patterns of main and branch pulmonary artery and aortic
growth, growth curves were developed from all of the measurements obtained in this group of fetuses using regression
analysis against gestational age. Regression coefficients were
calculated using all prenatal measurements and the initial
postnatal measurement.
Mann-Whitney rank sum test was used to compare pulmonary and aortic outflow velocities between the severe and mild
tetralogy of Fallot groups.
Results
Table 1 describes the postnatal diagnosis and clinical outcome of the 16 fetuses with tetralogy of Fallot. Mean gestational age at the initial prenatal study was (mean _+ SD) 23.6 ___
JACC Vol. 25, No. 3
March 1, 1995:739-45
HORNBERGER ET AL.
IN UTERO GREAT ARTERY GROWTH IN TETRALOGY OF FALLOT
741
Table 1. Postnatal Outcome
Group and Case No.
Postnatal
Diagnosis
Noncardiac
Abnormality
Mild TOF
1-I 1
TOF
None
RVT patch/VSD closure
(mean 0.48 yr)
Good (mean [_+SD]2.9 -+ 2.2 yr)
Severe TOF, duct dependent
12
PAtr
None
Good (3.2 yr)
13
Severe PS
Hydrops
14
15
Severe PS
Severe PS
None
None
16
PAtr
Dandy-Walker cyst
RV-PA conduit/VSD
closure (<0.1 yr)
RVOT patchNSD
closure (<0.1 yr)
LMBTS (<0.1 yr)
RVOT patch/VSD
closure (<0.1 yr)
RMBTS (<0.1 yr)
Operation
Outcome
Death (<0.1 yr)
Death (<0.1 yr)
Good (1,1 yr)
Death (0.5 yr)
LMBTS = left modified Blalock-Taussig shunt; PAtr = pulmonary atresia; PS - valvular pulmonic stenosis; RMBTS = right modified Blalock-Taussig shunt;
RVOT = right ventricular outflow tract; RV-PA = right ventricle to pulmonary artery; TOF = tetralogy of Fallot; VSD = ventricular septal defect.
6.0 weeks, and the interval to postnatal follow-up was 14.8 _+
7.1 weeks.
Five infants with severe subvalvular and valvular pulmonary
stenosis (n = 3) or valvular pulmonary atresia (n = 2) had a
ductus a r t e r i o s u s - d e p e n d e n t pulmonary circulation and underwent surgical palliation or correction at <1 month of age.
Three of the five with severe right ventricular outflow obstruction died in early infancy. Eleven infants with mild or moderate
right ventricular outflow obstruction (maximal instantaneous
gradient 26 _+ 17 mm Hg) underwent elective surgical correction in later infancy at a mean age of 0.48 years (range 1 to 14
months). All 11 are alive and clinically well at 2.9 + 2.2 years
of age.
Figure 2 demonstrates the typical in utero echocardiographic appearance of tetralogy of Fallot in a four-chamber
Figure 2. In utero echocardiographic features of tetralogy of Fallot.
Right, Four-chamber view that demonstrates an overriding aorta (Ao)
and the large conoventricular septal defect (>). Left, short-axis view of
the right ventricular (RV) outflow tract, pulmonary valve (PV) and
great arteries demonstrating the malaligned infundibular septum
(Inf S) and the conoventricular septal defect (>).
view angled toward the aortic outflow and a short-axis view of
the right ventricular outflow tract and great arteries. In Figure
3 (top), the echocardiographic appearance of the main and
Figure 3. Echocardiographic images obtained in a 28-week gestational
age fetus with severe right ventricular outflow tract obstruction. Top,
Main pulmonary artery tapers toward right ventricle (RV), and branch
pulmonary arteries are visualized in continuity. Bottom, There is
retrograde ductal flow and anterograde aortic flow visualized by color
flow mapping. DA = ductus arteriosus; other abbreviations as in
Figure 1.
742
H O R N B E R G E R E T AL.
IN U T E R O G R E A T A R T E R Y G R O W T H
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J A C C V o l . 25, No. 3
M a r c h 1, 1 9 9 5 : 7 3 9 - 4 5
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antenatal study versus the z score of (A) the initial main pulmonary
artery (MPA), (B) ascending aorta (Ao) and (C) right (RPA) and (D)
left (LPA) pulmonary artery measurements.
branch pulmonary arteries in one fetus with severe right
ventricular outflow tract obstruction is shown. Retrograde
blood flow through the ductus arteriosus into the main pulmonary artery, demonstrated by color flow mapping, indicates
severe right ventricular outflow tract obstruction (Fig. 3,
bottom).
Dimensions from initial examinations. The individual z
scores for the diameters of the main and branch pulmonary
arteries and the ascending aorta measured at the initial
examination are shown in Figure 4. The median initial main
pulmonary artery z score was -1.96 (range -3.60 to + 2.86). In
nine fetuses with tetralogy of Fall•t, the initial main pulmonary
artery diameter z score was - 2 or less, including all five with
severe fight ventricular outflow obstruction postnatally. In two
others, the initial main pulmonary artery diameter was large
for age. The median z score for the initial ascending aorta
dimension was 0.74 (range -0.34 to 2.18). The ascending aorta
z score was -<2 in most of the fetuses with tetralogy of Fallot.
There was no significant correlation between the initial main
Mild
Severe
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20
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pulmonary artery and ascending aorta z score (r = 0.04, p =
0.89).
Initial branch pulmonary artery dimensions were normal
for many of the fetuses in both groups with severe and mild
tetralogy of Fallot. The median initial z score for the right
pulmonary artery was -0.58 (range -10.0 to +2.12), and that
for the left pulmonary artery was -0.25 (range -6.16 to
+1.80). By unpaired t test, only the initial main pulmonary
artery diameter measurements differed significantly between
severe and mild tetralogy of Fall•t, with a smaller main
pulmonary artery z score observed in the group with more
severe right ventricular outflow obstruction (p = 0.05).
Main pulmonary artery/aortic diameter ratio. The main
pulmonary artery diameter/ascending aortic diameter ratio
measured at the time of the initial examination was significantly smaller in the group with severe (mean 0.50 -+ 0.15) than
in the group with mild tetralogy of Fallot (mean 0.73 + 0.14,
p = 0.01).
Aortic and pulmonary artery growth. As shown in Figure 5,
growth of the main and branch pulmonary arteries and aorta
was linear in all eight of the serially studied fetuses. The linear
regression coefficients for all analyses were ->0.97.
There was considerable variation in the rate of main
pulmonary artery growth in the fetuses with tetralogy of Fallot.
For some, there was little growth from the initial prenatal
JACC Vol. 25, No. 3
March 1, 1995:739-45
H O R N B E R G E R ET AL.
IN U T E R O G R E A T A R T E R Y G R O W T H IN T E T R A L O G Y OF F A L L O T
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examination to the postnatal examination, resulting in severe
pulmonary artery hypoplasia. Two serially studied fetuses with
severe right ventricular outflow obstruction postnatally demonstrated this pattern of main pulmonary artery growth. For
other fetuses with tetralogy of Fallot, growth paralleled the
normal curves.
Growth of the branch pulmonary arteries for most of the
fetuses with mild tetralogy of Fallot paralleled the normal
range. In contrast, there was little or no growth of the branch
pulmonary arteries in two fetuses of the severe group, resulting
in branch pulmonary artery hypoplasia despite normal or only
mildly hypoplastic branch pulmonary arteries at the initial
examination.
Growth of the ascending aorta was accelerated in most of
the fetuses with tetralogy of Fallot, resulting in an aortic
diameter that was larger than normal at birth. This was most
apparent in two fetuses with severe tetralogy of Fallot.
Doppler analysis. By color flow mapping and spectral
Doppler, one fetus had retrograde flow in the main pulmonary
artery from the ductus arteriosus and no detectable anterograde right ventricular outflow at the time of the initial
examination. Severe tetralogy of Fallot with a ductusdependent pulmonary circulation was confirmed postnatally.
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Figure 5. Growth curves for (A) the main pulmonary artery (MPA),
(B) ascending aorta (Ao), (C) right pulmonary artery (RPA) proximal
diameter and (D) left pulmonary artery (LPA) proximal diameter in
fetuses with tetralogy of Fallot. Individual measurements and the
slopes developed by regression analysis are shown. Closed circles and
solid line = mild tetralogy of Fallot group; Open circles and dashed
line = severe tetralogy of Fallot group. The gray area includes the 5th
through the 95th percentiles for gestational age measured in normal
fetuses.
In two fetuses with severe right ventricular outflow obstruction
at birth, Doppler interrogation was not performed.
Spectral Doppler tracings of anterograde flow across the
pulmonary outflow tract were available in 21 of the prenatal
studies (mean gestational age at the time of study 26 weeks),
and for the aortic outflow tract in 11 (mean gestational age 25
weeks). The peak flow velocity across the pulmonary outflow
tract was normal or mildly elevated for most of the fetuses
compared with normal values established by Reed et al. (16),
with a mean peak velocity of 1.25 _ 0.30 m/s in the group with
severe and 0.90 _+ 0.20 m/s in the group with mild tetralogy of
Fallot. Although there was a trend toward higher peak velocities in the fetuses with more severe tetralogy of Fallot (range
744
H O R N B E R G E R ET AL.
IN U T E R O G R E A T A R T E R Y G R O W T H IN T E T R A L O G Y OF FALLOT
0.80 to 1.5 m/s), the difference was not statistically significant.
Aortic outflow velocities were also not statistically different
between the group with mild (0.80 _+ 0.10 m/s) and that with
severe (1.0 _+ 0.50 m/s) tetralogy of Fallot, although the
velocities again tended to be higher in the group with severe
tetralogy of Fallot.
Progression of disease. Two fetuses examined initially at
21 and 27 weeks, respectively, had anterograde flow in the
main pulmonary artery with a thickened but mobile pulmonary
valve. In one, only retrograde ductal flow was observed on a
subsequent antenatal study. After birth, both infants were
found to have valvular pulmonary atresia by echocardiography,
at catheterization and at surgical intervention.
Discussion
In the present study, we described patterns of in utero main
and branch pulmonary artery and aortic growth in the presence
of tetralogy of Fallot. Furthermore, we identified prenatal
features of severe postnatal right ventricular outflow tract
obstruction. Main pulmonary artery hypoplasia at the initial
examination was a consistent feature in fetuses with more
severe postnatal disease. The main pulmonary artery to ascending aortic diameter ratio on the initial antenatal examination was significantly smaller in fetuses with more severe
postnatal disease. During prenatal follow-up, little or no
growth of the main and branch pulmonary arteries was observed also in fetuses with a ductus arteriosus-dependent
pulmonary circulation at birth. Finally, by color flow mapping
or spectral Doppler, retrograde ductus arteriosus flow in utero
was associated with severe obstruction to pulmonary outflow,
as previously described (17).
Direct antenatal assessment of the severity of right ventricular outflow tract obstruction associated with tetralogy of
Fallot is limited. The diminutive right ventricular outflow tract
and pulmonary valve are frequently difficult to visualize by
imaging, and a Doppler gradient is typically not present. Use of
secondary indicators, including main pulmonary hypoplasia at
the initial examination, reduced main and branch pulmonary
artery growth on serial follow-up and retrograde ductal flow
should facilitate antenatal recognition of more severe disease.
It has been suggested in published obstetric reports that the
presence of a dilated aorta is a useful marker for tetralogy of
Fallot in the fetus (11). At the time of the initial examination,
we found a normal aortic diameter in 87% of the fetuses in the
present series. This would suggest that a large for gestational
age aortic diameter may not be a reliable feature of fetal
tetralogy of Fallot, particularly through the midtrimester.
Great artery growth in tetralogy of Fallot. The postnatal
spectrum of pulmonary artery size observed in tetralogy of
Fallot (18) can be attributed to variable patterns of pulmonary
artery growth in utero. The main pulmonary artery diameter in
midgestation ranged from very hypoplastic to large for gestational age in our fetuses, suggesting that earlier in gestation
pulmonary artery growth is variable. In contrast, branch pulmonary artery size was normal or near normal in most of our
JACC Vol. 25, No. 3
March 1, 1995:739-45
patients at midgestation, even in fetuses with severe tetralogy
of Fallot at birth. Through the second half of pregnancy,
growth of both main and branch pulmonary arteries in tetralogy of Fallot was normal or reduced, the latter resulting in
pulmonary hypoplasia at birth.
The determinants of in utero great artery growth in the
presence of congenital heart disease remain unknown. Our
observations and postnatal observations made in patients with
tetralogy of Fallot (18) could be explained by the theory that
blood flow influences cardiovascular growth (19,20). Initial
main pulmonary artery size was significantly smaller in fetuses
with severe right ventricular outflow tract obstruction at birth,
in whom anterograde pulmonary flow was probably most
reduced in utero. Main pulmonary artery growth was markedly
slower in two of the fetuses with severe right ventricular
outflow tract obstruction after birth compared to other fetuses
with less severe disease. With diminished right ventricular
outflow and redistribution of flow through the large ventricular
septal defect toward the aorta, increased blood flow could have
resulted in accelerated growth of the ascending aorta through
the second half of pregnancy.
The lack of correlation between the initial main pulmonary
artery and aortic z scores may in part reflect limitations in the
measurement of these small structures in normal and affected
fetuses. It may also suggest that the great arteries do not grow
equally in response to changes in flow and that other factors,
including intrinsic characteristics of the vessels and retrograde
ductal flow (the latter in more severe disease), play a role in
great artery growth.
The reason that branch pulmonary artery growth in utero is
abnormal in some fetuses with severe tetralogy of Fallot,
despite blood flow from the ductus arteriosus, is not clear.
Perhaps branch pulmonary arteries in more severe tetralogy of
Fallot respond abnormally to factors that influence vascular
growth. Retrograde ductal flow in this disease may be insufficient for branch pulmonary artery growth. Abnormal growth
could also result from changes in pulmonary vascular resistance during fetal life, which could reduce the blood flow
traversing the branch pulmonary arteries.
Blood flow velocity observations. Although pulmonary artery blood flow velocities are increased in many fetuses with
tetralogy of Fallot, the absence of a significant gradient
through the right ventricular outflow tract is a consistent
feature in fetuses with tetralogy of Fallot (12,13). By contrast,
a gradient is more frequently observed in fetuses with valvular
pulmonary or aortic stenosis and intact ventricular septum. In
the fetus with tetralogy of Fallot, the nonrestrictive ventricular
septal defect allows for a redistribution of the right ventricular
output toward the aorta, and the ductus arteriosus allows for
the equalization of pressures in the aorta and pulmonary
artery. If a significant right ventricular outflow tract gradient is
encountered antenatally in the fetus with tetralogy of Fallot,
the presence of a restrictive ventricular septal defect, which
may be associated with a worse prognosis (21), or a restrictive
ductus arteriosus should be suspected.
JACC Vol. 25, No. 3
March 1, 1995:739-45
HORNBERGER ET AL.
IN UTERO GREAT ARTERY GROWTH IN TETRALOGY OF FALLOT
Development of pulmonary atresia. Although the basic
features of tetralogy of Fallot, including anterior deviation of
infundibular septum, a conoventricular septal defect and overriding aorta, develop during embryogenesis and are present by
7 to 8 weeks of gestation, our observations indicate that this
lesion may continue to evolve through the subsequent 7
months of fetal life. In addition to the development of pulmonary artery hypoplasia secondary to abnormal antenatal pulmonary artery growth (14,15), valvular pulmonary atresia may
develop in some fetuses in the second half of gestation.
The postnatal natural history of tetralogy of Fallot is
characterized by progressive obstruction at the level of the
infundibulum and the pulmonary valve (22,23) and decreased
pulmonary artery growth (22,24). In childhood right ventricular outflow obstruction may even progress to atresia of the
infundibulum or pulmonary valve. To our knowledge this is the
first description of the in utero development of pulmonary
atresia in the presence of tetralogy of Fallot.
Clinical implications. Many infants with tetralogy of Fallot
are asymptomatic or have mild cyanosis in the neonatal period.
However, some affected infants present with severe cyanosis
immediately after birth and improve with prostaglandin E~.
Early antenatal recognition of severe right ventricular outflow
tract obstruction, in addition to the detection of noncardiac
abnormalities that are commonly associated with tetralogy of
Fallot (25-27), would improve counseling of families concerning postnatal outcome. Identification of fetuses with more
severe disease in utero would also provide time for planning of
postnatal management. Furthermore, if growth of the pulmonary arteries is dependent on the quantity of anterograde flow
in utero, perhaps early detection and subsequent intervention
could prevent the development of main and branch pulmonary
artery hypoplasia.
Because of the potential for progression of right ventricular
outflow tract obstruction, serial study of fetuses with tetralogy
of Fallot should be considered. Serial study is warranted
particularly in fetuses with hypoplastic pulmonary arteries at
midgestation who appear most likely to present with severe
pulmonary stenosis or valular pulmonary atresia at birth.
Prospective serial echocardiographic study of a larger group
of fetuses with tetralogy of Fallot would be useful to substantiate the findings of our retrospective study. Furthermore,
advances in ultrasound technology may ultimately permit
investigation of the hemodynamic consequence and subsequent evolution of tetralogy of Fallot or other forms of
congenital heart disease from the first trimester.
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