From Wessex Cardiothoracic Centre, Southampton General Hospital
(P.E.F.D., B.R.K., S.A.W.), Southampton, UK; Fetal Cardiology, Guy's
Hospital, (G.K.S., A.C.C.), London, UK; and the Department of Paediatrics,
Imperial College at the National Heart and Lung Institute, (R.H.A.), London,
UK. Correspondence to Dr S.A. Webber, Division of Cardiology, Children's
Hospital of Pittsburgh, 3705 Fifth Ave at De Soto St, Pittsburgh, PA 15213.
Methods and Results—From 1991 to 1995, all infants born with
PAIVS and all fetal diagnoses in the United Kingdom and Eire were
studied. There were 183 live births (incidence 4.5/100 000 live
births). The incidence was 4.1 cases per 100 000 live births in
England and Wales, 4.7 in Scotland, 6.8 in Eire, and 9.6 in Northern
Ireland (P=0.01). There were 86 fetal diagnoses made at
a mean of 22.0 weeks of gestation leading to 53 terminations of
pregnancy (61%), 4 intrauterine deaths (5%), and 29 live births
(34%). The incidence at birth would be 5.6 per 100 000 births in
England and Wales, 5.3 in Scotland, and unchanged in Eire and Northern
Ireland, if there were no terminations of pregnancy and assuming no
further spontaneous fetal deaths (P=0.28). An initial
diagnosis of critical pulmonary stenosis was made in 6
cases, at a mean of 22.3 weeks of gestation with progression to PAIVS
by 31.4 weeks. Probability of survival at 1 year was 65% and was the
same for live-born infants whether or not a fetal diagnosis had been
made.
Conclusions—PAIVS is rare, occurring in 1 in 22 000 live births
in the United Kingdom and Eire. Termination of pregnancy has resulted
in an important reduction in the live-born incidence in mainland
Britain.
Statistical Analysis
Morphological Features
PAIVS was associated with Down's syndrome in 3 cases. In 2 of these
cases, a fetal diagnosis of Down's syndrome and PAIVS was made and led
to termination of pregnancy. In 1, there was a severely hypoplastic and
hypertrophied right ventricle and in the other, PAIVS was associated
with a dilated right atrium and right ventricle with Ebstein's
malformation of the tricuspid valve with severe valvar
regurgitation. Both fetuses also had pericardial
effusions. In the third case, also with Ebstein's malformation and
dilated right heart, a prenatal diagnosis of Down's syndrome was not
made and the infant was live-born.
Prenatal Intervention
Outcome
Infants were born at comparable gestational age, irrespective of
whether fetal diagnosis had been made (mean [SD] 38.2 [2.3] weeks
vs 38.7 [2.3] for infants with or those without a fetal diagnosis,
respectively, P=0.307). Fetuses with prenatal diagnosis were
no more likely to be delivered by cesarean section than their
counterparts without fetal diagnosis (4/25, 16% vs 42/134, 31%,
respectively, P=0.12; mode of delivery unknown in 24 cases).
Twenty-one (72%) of the live-born infants with a prenatal diagnosis
were delivered in proximity to a center for pediatric
cardiology, and all were commenced on an infusion of
prostaglandin E1 (to maintain patency of the
arterial duct) in the first few hours of life. Among
infants without a fetal diagnosis, only 19% were born in, or nearby, a
center for pediatric cardiology (P<0.0001).
Of patients without prenatal diagnosis, recognition of cyanotic heart
disease was usually rapid (mean time to commencement of
prostaglandin infusion 0.9 days, range 0 to 32; mean time
to transfer to a cardiac unit 2.2 days, median 1 day, range 0 to 45).
However, 7 of the 154 infants (4.5%) without a fetal diagnosis of
PAIVS were discharged home from the hospital without a diagnosis of
heart disease. They were subsequently readmitted after development of
severe cyanosis or shock. All 7 infants were successfully resuscitated
and survived to undergo initial palliation. One infant had an
arterial pH of 6.9 secondary to severe hypoxemia but has no
neurological deficit at latest follow-up.
Survival comparison was made between the 29 live-born cases with
prenatal diagnosis of PAIVS and the remaining 154 live-born infants who
were not diagnosed prenatally. Probability of survival was 65% (95%
confidence interval [CI] 47% to 82%) at 1 year and 59% (95% CI
39% to 78%) at 2 years for infants with a prenatal diagnosis (Figure 2
The association of PAIVS and Down's syndrome is very rare but occurred
in 3 of 240 (1.3%) cases in this study. Van Praagh et
al14 list a single patient with Down's syndrome
and pulmonary atresia with intact ventricular
septum in the Cardiac Registry of the Children's Hospital of Boston
(among 100 cases of Down's syndrome with CHD).
The decision to terminate a pregnancy will be influenced by a variety
of factors other than the anticipated prognosis. Paramount among these
will be the cultural and religious values of the family and community.
Even when termination of pregnancy is not a consideration, fetal
echocardiographic diagnosis has several other
implications for management of the pregnancy and the newborn infant.
Prenatal scanning has clearly affected the choice of hospital for
delivery, with most infants in the current study being born in, or
near, referral centers for pediatric cardiology.
Furthermore, those infants with a prenatal diagnosis received earlier
institution of prostaglandin E1 infusion before closure of
the arterial duct. Among infants without prenatal
diagnosis, almost 5% were discharged from their maternity unit without
a diagnosis of heart disease. Such infants are at risk for the
development of profound cyanosis before return to hospital and are at
risk for sudden infant death in the community. We are not aware of any
instances of sudden infant death secondary to ductal closure in
newborns with PAIVS during our period of study. It is possible,
however, that such cases might be missed, because inquires were made
only of regional pathology services specializing in pediatric
pathology. No attempt was made to survey all pathologists in the United
Kingdom and Eire who might perform a postmortem examination on an
infant dying unexpectedly at home. Although one might anticipate that
fetal diagnosis might improve neonatal outcome because of earlier
appropriate therapeutic intervention, we have failed to demonstrate an
advantage in terms of survival for live-born infants with a prenatal
diagnosis. The spectrum of severity of PAIVS was similar whether
prenatally diagnosed or not. This might account for the similar outcome
for the 2 groups. Other less tangible benefits of prenatal diagnosis
have been suggested. It may allow parents to "prepare" themselves
psychologically, thus allowing a more cognitive and less emotional
approach to the decisions to be made after birth. In addition, there is
the potential for fetal intervention. If antegrade flow across the
pulmonary valve could be achieved (and maintained) before the
development of severe hypoplasia of the right ventricle, then there may
be a greater chance of achieving successful biventricular
repair. Fetoscopic and open transumbilical cardiac
catheterization has been performed on fetal sheep with
successful balloon valvoplasty of surgically created supravalvar
pulmonary stenosis.15 Such
feasibility studies are in their infancy, and much more experimental
work will be required before such prenatal interventions can be
routinely recommended in clinical practice. In the only case in our
study in which fetal valvotomy was successfully achieved, virtual
atresia had recurred by the time of birth.
Received November 12, 1997;
revision received March 25, 1998;
accepted April 16, 1998.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Pulmonary Atresia With Intact Ventricular Septum
Impact of Fetal Echocardiography on Incidence at Birth and Postnatal Outcome
Abstract
Top
Abstract
Introduction
Methods
Results
Discussion
References
Background—Fetal
echocardiography is widely established in the
United Kingdom for prenatal diagnosis of congenital heart disease. This
may result in a substantial reduction in incidence at birth because of
selected termination of pregnancy. The objective of this
population-based study was to determine the incidence of
pulmonary atresia with intact ventricular septum
(PAIVS) at birth, the impact of fetal
echocardiography on this incidence, and to compare
the outcome of cases with and those without prenatal
diagnosis.
Key Words: pulmonary heart disease • pulmonary atresia • echocardiography • diagnosis • pediatrics
Introduction
Top
Abstract
Introduction
Methods
Results
Discussion
References
Prenatal
ultrasonography is widely established in the United Kingdom and is
performed in >90% of pregnancies. In many regions this includes a
detailed fetal anomaly scan performed between 16 and 20 weeks of
gestation.1 2 3 Abnormalities in cardiac size,
structure, and function are sought by imaging the cardiac 4-chamber
view. It has been estimated that 15% to 25% of all cases of
congenital heart disease (CHD) are detectable from this
view,1 4 including nearly 60% of cases of
complex CHD.4 When cardiac abnormalities are
detected on the screening examination, a referral is made to a regional
pediatric cardiologist for a detailed cardiac scan (fetal
echocardiogram).3 4 5 Fetal
echocardiography has been shown to be an accurate
technique for the diagnosis of CHD, including pulmonary atresia
with intact ventricular septum
(PAIVS).6 7 Allan et al6
reported an incorrect or unconfirmed diagnosis in 96 of 1006 cases
(7%), and most incorrect diagnoses were considered not to affect
prognosis significantly. It has been suggested that prenatal
echocardiography may, in time, cause a substantial
reduction in the incidence of complex CHD seen at birth because of
selected termination of pregnancies.6 The aims of
this study were to ascertain, in a population-based review, the
incidence of PAIVS at birth, the impact of fetal
echocardiography on this incidence, and to assess
the outcome for the fetus including a comparison of outcome for
live-born infants with and those without a fetal diagnosis.
Methods
Top
Abstract
Introduction
Methods
Results
Discussion
References
The United Kingdom and Eire Collaborative study of PAIVS is a
multicenter, population-based study of all children born with PAIVS in
the United Kingdom and Eire over a 5-year time period from January 1,
1991, to December 31, 1995. All fetal diagnoses of PAIVS, whose
estimated date of delivery lay within that time frame, were also
included. Data collection was retrospective from 1991 to 1993 and
prospective from 1994 to 1995. Completeness of data collection was
accomplished by a single investigator (P.E.F.D.) visiting on several
occasions from 1993 to 1996 all the 17 centers for pediatric
cardiology in the United Kingdom, and the single center
in Eire (see Acknowledgments for Participating Institutions). Live-born
infants with PAIVS were enrolled by direct inspection of local
databases, admission records, and
echocardiography log books. Fetal diagnoses were
obtained by direct inspection of fetal
echocardiography databases and log books. Regional
pathologists were contacted to identify unrecognized cases of PAIVS
among stillbirths and unexplained postnatal deaths. Cases were included
when they had PAIVS without other complex cardiac abnormalities, though
cases of tricuspid valvar dysplasia or Ebstein's malformation
coexisting with PAIVS were included. Cases were excluded if they were
born outside the United Kingdom and Eire. Fetal diagnoses of critical
pulmonary stenosis were only included when there was
documentation of progression to PAIVS. The outcome for each fetal
diagnosis was ascertained and recorded. All data were stored on a
relational database in coded fashion (Filemaker Pro 3.0, Claris Corp).
This was an observational study, and no attempt was made to influence
management of individual cases.
Categorical data were compared with the use of Pearson's
2 test with Yates' correction as appropriate
when expected values were small. The Mann-Whitney U test was
used to compare nonparametric data. Probability of survival
was calculated according to the method of Kaplan and Meier, and
survival curves were compared with the use of the log-rank test
(Statview 4.1, Abacus Concepts). Values of P<0.05 were
considered statistically significant.
Results
Top
Abstract
Introduction
Methods
Results
Discussion
References
Incidence
There were 183 live births with PAIVS for the 5-year period of
1991 to 1995. The total number of births during this time in the United
Kingdom and Eire was 4 068 145,8 9 giving an
incidence of 4.5 per 100 000 live births. The incidence of PAIVS at
birth was 4.1 cases per 100 000 live births in England and Wales, 4.7
in Scotland, 6.8 in Eire, and significantly higher at 9.6 in Northern
Ireland (P=0.01) (Table 1
).
There were 86 diagnoses made in fetal life at a mean of 22.0 weeks of
gestation (SD 4.6, range 15 to 37). The proportion of total cases of
PAIVS that were diagnosed in fetal life was 43% in England and Wales,
18% in Scotland, and 0% in Northern Ireland and Eire. Outcome for the
fetuses with antenatal diagnosis of PAIVS comprised 53 terminations of
pregnancy (61%), 4 intrauterine deaths (5%), and 29 live births
(34%) (Table 2). Had there been no
terminations of pregnancy (and assuming that no further intrauterine
deaths would have occurred in the pregnancies that were terminated),
the incidence of PAIVS at birth would be 5.6 per 100 000 births in
England and Wales, 5.3 in Scotland, and unchanged in Eire and Northern
Ireland, where there were no terminations of pregnancy (Table 1). The
difference in incidence between England and Wales and Northern Ireland
then narrows and no longer reaches statistical significance
(P=0.28). Table 3 shows the
trend in terminations of pregnancy over the period of study for
England, Wales, and Scotland only. The number of terminations as a
proportion of the number of fetal diagnoses made was fairly constant
over the period of study. The decrease in incidence at birth that
occurred as the result of terminations of pregnancy (again assuming no
further fetal losses) ranged from 12.5% in 1991 (when there were
fewest fetal diagnoses) to a peak of 37% in 1993.
View this table:
[in a new window]
Table 1. Regional Incidence of PAIVS and `Corrected
Incidence' Expected Assuming No Terminations of Pregnancy and No
Additional Spontaneous Intrauterine Deaths
View this table:
[in a new window]
Table 2. Outcome After Fetal Diagnosis of PAIVS With and
Without Ebstein's Malformation
View this table:
[in a new window]
Table 3. Impact of Termination of Pregnancy on Number of Live
Births With PAIVS for Each Year of Study in England, Wales, and
Scotland Only
Ebstein's malformation coexisting with PAIVS was diagnosed
prenatally in 9 of 86 (10%) cases. An additional 11 of 86 cases were
labeled prenatally as having severe tricuspid
regurgitation caused by "tricuspid valvar
dysplasia" without Ebstein's malformation in addition to PAIVS
(Figure 1). An initial diagnosis of
critical pulmonary stenosis had been made in 6 of 86
(7%) cases, at a mean gestation of 22.3 weeks (range 19 to 28).
Progression to PAIVS was documented at a mean of 31.4 weeks of
gestation (range 24 to 40). All 6 infants were live-born, and absence
of antegrade flow across the atretic valve was confirmed in all cases.
Five infants were diagnosed prenatally as having small muscular
ventricular septal defects. Only 1 case was confirmed by
postnatal echocardiography (a tiny apical defect).
In 3 of the 4 remaining cases, postnatal
echocardiography and angiography demonstrated
fistulous communications from the right ventricle to the
coronary arteries, which may have been the cause of the
disturbance in color flow seen in the region of the muscular
ventricular septum on the prenatal echocardiogram.
Insufficient data were recorded from fetal echocardiograms to allow
reporting of tricuspid valvar diameters or right
ventricular cavity size or to allow distinction (in most
cases) of membranous from muscular atresia. Among the cases resulting
in termination of pregnancy or spontaneous intrauterine death (n=57),
autopsy examination of the fetal heart was performed in 41 (72%). This
confirmed the diagnosis of PAIVS in all cases.
View larger version (104K):
[in a new window]
Figure 1. Characteristic fetal
echocardiographic findings from 4-chamber view. A,
Severe hypoplasia of right ventricular cavity caused by
marked muscular overgrowth (arrowed). B, Severe right atrial and right
ventricular dilatation associated with tricuspid valvar
dysplasia (arrowed) with severe tricuspid
regurgitation. LV indicates left ventricle; RA, right
atrium; and RV, right ventricle.
Two patients had prenatal cardiac interventions. One of these
cases has been previously described.7 This
involved a cardiocentesis by direct transventricular
puncture at 31 weeks of gestation, which revealed a ratio of pressure
between the right and left ventricles of 1.4:1. Injection of saline
failed to demonstrate forward flow across the pulmonary valve
and, with an unfavorable position of the fetus, attempted valvar
perforation and dilation was not performed. The second prenatal
cardiac intervention was an attempted radiofrequency perforation of the
pulmonary valve at 23 weeks of gestation, unsuccessful because
of inadequate positioning of the wire in the right
ventricular outflow tract. This was repeated at 26 weeks,
and the valve was successfully perforated and this was followed by
balloon angioplasty. This resulted in antegrade pulmonary blood
flow. After birth, the valve had become almost atretic again, though a
0.025-inch guide wire could be passed into the pulmonary
artery. It was not possible, however, to pass a catheter across the
valve, and surgical intervention was carried out (personal
communication, Dr J. Wright, Birmingham Children's Hospital).
The 4 intrauterine deaths occurred at 31, 32, 32, and 32 weeks of
gestation. The causes for these are unknown. Among the 53 pregnancies
undergoing termination, 2 had abnormal fetal karyotypes (both trisomy
21) (see above). No other chromosomal abnormalities were documented
before birth. ). This was similar to the group without
prenatal diagnosis (1-year survival, 65% [95% CI 58% to 73%] and
2-year survival, 64% [95% CI 56% to 72%], log-rank,
P=0.576). The morphological features of these 2 groups, as
determined at birth, were also compared. No differences were found in
the proportion of infants with the following features: membranous
versus muscular atresia (P=0.230); obliteration by muscular
overgrowth of either the apical and outlet components, the apical
component alone, or the presence of 3 well-developed
ventricular components (often described as so-called
unipartite, bipartite, or tripartite ventricles) (P=0.796);
and the presence or absence of Ebstein's malformation
(P=0.271), coronary-right ventricular
fistulas (P=0.792), or coronary arterial
stenoses (P=0.190). There were also no differences
between the 2 groups for the following continuous variables
measured by cross-sectional echocardiography in the
apical 4-chamber view: z-score for tricuspid valvar
diameter, P=0.896, and z-score for right
ventricular inflow dimension (mid annulus to apex),
P=0.630.
View larger version (17K):
[in a new window]
Figure 2. Kaplan-Meier curve showing probability of survival
for live-born infants with PAIVS with and those without a fetal
diagnosis.
Discussion
Top
Abstract
Introduction
Methods
Results
Discussion
References
We have demonstrated that the incidence of PAIVS in the United
Kingdom and Eire for the 5-year period 1991 to 1995 was 4.5 cases per
100 000 live births. In the New England Infant Cardiac Program, the
incidence was 7.1 cases per 100 000 live
births.10 The Baltimore-Washington Infant study
reported an incidence of 8.1 per 100 000 live births for the period
1981 to 1989.11 We have also demonstrated
regional variation, with an incidence twice as high in Northern
Ireland. CHD has previously been reported as being more common in
Northern Ireland.12 At least some of the
difference in the current study, however, is explained by the high rate
of termination of pregnancy in mainland Britain after fetal
echocardiographic diagnosis. Indeed, almost two thirds
of women elected to terminate their pregnancy after prenatal diagnosis
of this serious congenital cardiac malformation. This proportion is
similar for other complex lesions reported in the United
Kingdom.1 5 For the 5 years of the study,
termination of pregnancy in mainland Britain resulted in a decrease in
incidence at birth of 26%. This calculation assumes that all
pregnancies terminated would have progressed to term. In reality, this
assumption is unlikely to be valid. We speculate that termination of
pregnancy would be most likely to be carried out for fetuses showing
the greatest hemodynamic compromise (such as those with
severe tricuspid regurgitation and fetal hydrops). The
study was not able to provide the cause of the 4 intrauterine deaths.
Furthermore, the calculation also assumes that any pregnancies with
fetal critical pulmonary stenosis that may have been
terminated would not have progressed to PAIVS. Even allowing for these
assumptions, it appears that fetal echocardiography
is having an important impact on birth incidence of PAIVS. Abu-Harb and
colleagues4 estimated that fetal
echocardiographic screening with the 4-chamber view
will decrease the overall incidence of CHD at birth by only 2%. This
reduction assumes that only 15% of CHD is readily detectable from the
4-chamber view, that the detection rate is 20%, and that the
termination rate is 67%. The authors did comment that reductions could
be higher for complex lesions. The overall detection rate in our study
was considerably higher, at 41% (86/211) for mainland Britain or 36%
(86/240) for the United Kingdom and Eire combined. This may be because
this lesion is more readily detectable on a 4-chamber view than other
lesions.13 Increasing experience with fetal
cardiac scanning by obstetric ultrasonographers may increase the
frequency of antenatal diagnosis. The observation that this disease may
evolve from critical pulmonary stenosis, and the
potential for late growth failure of the right ventricle in the latter
half of pregnancy, suggest that a single scan at 16 to 20 weeks of
gestation may not be adequate to identify all cases of this
condition.
Acknowledgments
Dr Piers Daubeney and the project were supported by the
Wessex Cardiac Trust. We wish to thank the cardiologists, cardiac
surgeons, and staff of the following institutions in the United Kingdom
and Eire for their cooperation and help during this study: Alder Hey
Children's, Liverpool; Birmingham Children's, Birmingham; Bristol
Children's, Bristol; Freeman, Newcastle; Glenfield, Leicester; Guys
and St. Thomas', London; Harefield, Middlesex; Hospital for Sick
Children, Great Ormond Street, London; John Radcliffe, Oxford;
Killingbeck, Leeds; Our Lady Hospital for Sick Children, Dublin; Royal
Belfast Hospital for Sick Children, Belfast; Royal Brompton and
National Heart, London; Royal Hospital for Sick Children, Edinburgh;
Royal Hospital for Sick Children, Yorkhill, Glasgow; Royal Manchester
Children's, Manchester; University Hospital of Wales, Cardiff; and
Wessex Cardiothoracic Center, Southampton.
References
Top
Abstract
Introduction
Methods
Results
Discussion
References
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