CONGENITAL
MALFORMATIONS
OF
THE
CARDIOVASCULAR
SYSTEM
IN A SERIES OF
6.053
INFANTS
By Mary R. Richards, M.D.,* Katharine K. Merritt, M.D., Mary H. Samuels, M.D., and
Alfred G. Langmann, M.D.
12
E
STIIATES of the frequency of congenitalmalformations of the heart and great
vessels which are generally quoted have
l)een based either upon clinical signs
elic-ited during physical examination of older
children, or upon autopsy data, with
hos-pita! deaths from all causes as the base
populatioll. The frequency of this group of
anomalies in all unselected newborn
popu-lation is unknown, and, in particular,
cor-relations with the events of pregnancy are
lacking.
The present report is based upon data
gathered during a comprehensive study of
the relationships between infections and other complications of pregnancy and the
outcome of pregnancy. This study was
car-iied out at the Columbia-Presbyterian
Medical Center by the departments of
obstetrics and pediatrics, with the aid of
consultants froln many other departments,
from October 1, 1946, to March 11, 1953.
The plan of this study, which involves
the outcome of 5,964 pregnancies, is
de-scribed in detail in another publication.!
Each infant was given a careful physical
examination during the first week of life,
and RGs of the skull and chest were taken;
follow-up physical examinations at the ages
From the Babies Flospital and the Department
of Pediatrics, Columbia University College of
Physicians and Surgeons, New York.
This research was supported by grants from
the Rockefeller Foundation, the Life Insurance
Medical Research Fund, the Snyder Ophthalmic
Fund, the New York State Department of Health,
and the Association for the Aid of Crippled
Chil-dren.
Presented in part at a meeting of the Pediatric
Section of the New York Academy of Medicine,
April 8, 1954.
(Received for publication July 13, 1954.)
#{176}ADDRESS: The Presbyterian Hospital, 622 W.
168th St., New York 32, N.Y.
of 6 and 12 months were performed by the
same examiners. In those infants in whom a
congenital anomaly of the heart or great
vessels was suspected but could not be
es-tablished with certainty or completely diag-nosed at the 1-year follow-up visit, one or more appointments to a special cardiac
clinic were arranged. At this time, the infants were examined by a cardiologist, and RGs or ECGs were ordered as
indi-cated.
The diagnostic criteria in the 23 non-proven instances of congenital heart disease were as follows:
1) The presence of a heart murmur, heard at all examinations after it was first detected
and having the characteristics of an organic murmur.
2) The presence of other symptoms, signs
or laboratory evidence indicative of con-genital heart disease (e.g., cyanosis, club-bing, dyspnea, thrills, or cardiac
enlarge-ment).
All of the 23 patients fulfilled the first of
these criteria, and the great majority had
one or more of the findings listed in the
second.
Autopsies were performed in almost all
cases of fetal or infant death.
INCIDENCE OF CARDIOVASCULAR
MALFORMATIONS
Of the 5,964 pregnancies studied, 86 were multiple births (83 pairs of twins, 1.4 per cent, and 3 sets of triplets, 0.05 per cent), resulting in the birth of 6,053 indi-viduals. The incidence of cardiovascular malformations by status at birth is shown in Table I.
The overall incidence was 50 of 6,053 in-fants, a rate of 0.83 per cent. The
Status at Birth
SingLe Births Multiple Births
Total CVM* %
-
Total-____________________________
(VM* %
500 gui. or less 806 1 ? 8 -
-Stillborn ‘298 1 ? 6 -
-Neonatal death S - - ‘2
501-2500 gin. 48/ 1.5 .?. / 116 .3 ‘2J
tiveborn f 364 5 1.4 99 l 3.0
Stillborn 66 4 6.1 7 -
-Neonatal death** 51 6 11 .8 10 -
-251i1 gui. or over 5091 31 0.6 51
-l.iveborn t 5017 5 0.5 50 -
-Stillborn 37 5.4 1 -
-Neonatal (ltatll** 37 4 10.8
lotal 5878 47 0.8 175 .3 1.7
TABLE I
INCIDENCE OF CONGENITAL CARDIOVASCULAR MALFORMATIONS BY STATUS AT BIRTH
* Infants with cardiovascular malformations.
t Excluding neonatal deaths.
** I)eaths under one month of age.
500 gm. was 5.4 per cent, in neonatal deaths
10.2 per cent, and in live-born infants who
survived 1 month or more 0.6 per cent. The
group weighing 500 gm. or less at birth is not a suitable population upon which to
TABLE II
(o%hI’uATIvE INCIDEN(E OF CARDIAC AND TOTAL MALFORMATIONS IN INFANTS \\EIGIIING OvEll
500 GRAMS AT BIRTH
CVJf
Status Total (‘if (‘Vi! -.
(‘-if
Stillborn 15 6 33.3
Neonatal death 29 10 35.5
I)ied 1-’2 months 12 4 33.3
Survived 12 months
or longer 37 29 7 .5
lotal population 433 49 11 .3
Total CM-Total infants with congenital malforma-tions, including those with cardiovascular
malforma-(‘\riI Number of infants with cardiovascular mal.
formations.
* This ratio indicates what percentage of the total
nialformat ions is composed of cardiovaseu!ar
malforma-tions in each group.
compute incidence rates, because even when the specimen was recovered (36.5
per cent), it was often unsuitable because of size or condition for adequate study.
Table II shows what proportion of the
total number of malformed infants had cardiovascular malformations. The ratio of infants with cardiovascular malformations
to infants with congenital malformations of all types among those dying prior to 1 year of age is both high and remarkably con-stant, but decreases rapidly after this age. The accuracy of these rates is of course open to several questions. Theoretically it
should be possible to correct some of the errors in the rates by basing them upon only those infants, stillborn or dying in the first month, who had autopsy examinations, and upon only those live-born infants who were followed until the age of 1 year or longer. Table III shows the corrected rates, and reveals that not more than three cardiovas-cular malformations would be expected#{176} to
Derived by applying the corrected
cardio-vascular malformation rates to the 15 stillborn
infants and the 16 neonatal deaths who did not
TABLE III
CORRECTED CARDIOVASCULAR MALFORMATION RATES-INFANTS Wiio WEIGHED OVER 500 GRAMS AT BIRTH
Total
Status Infants Number
(‘Vii CVM#{176}7
Correct#{128}d Total Infants5
Corrected Number
(‘Vii
(‘orrected
%
CVM
-Stillborn lii 6 5.4 96 6 6.3
.‘ceonatal death 98 10 10.2 82 9 10.9
Liveborn 5530 33 0.6 4515 26 0.6
CViI = Infants with cardiovasrular malformations.
* lotal infants who either had III autopsy examination (stillborn and imeomiatal (Ie8th groups), or who were seen
iii the clinic at 1)0th 6 and 12 iiioiiths of age.
have been present in the stillborn infants
and neonatal deaths who had no autopsy
as compared with the one actually found.
The expected number of cardiovascular
malformations in the live-born infants who
were not followed until 1 year, all made themselves manifest clinically or
patholo-gically before this time. The addition of 2
cases to the total of 50 increases the proba-ble overall incidence rate by only 0.03 per cent, a negligible difference.
Other more important sources of error exist here, however, which are inherent in the method of study, and cannot be even roughly evaluated. The first of these, and probably the more important, is the
inef-ficacy of case finding in the group weighing 500 gm. or less at birth. The work of Mall2
and Hertig3 has demonstrated a high
inci-dence of serious anomalies in cases of spontaneous abortion, and it seems likely that a cardiovascular malformation rate as
high or higher than that of the stillborn
infants might be expected. For the present
this interesting area of speculation is largely
academic, since diagnostic and therapeutic
efforts now available depend on viability.
Of greater practical importance is the number of malformations which have
prob-ably been overlooked because of failure to develop symptoms or signs before the end of the follow-up at 1 year of age. The emer-gence of cardiac catheterization as a prac-tical diagnostic tool has made it possible to show that defects of the atrial septum may produce no symptoms or signs until the age
of 3 or 4 years,’ or even much later.’ The
fact that only 1 example of this anomaly was discovered as an isolated lesion among our 50 cases, in combination with the high mci-dence of such defects in autopsies reported in the literature’ 8 further corroborates the supposition that some of these lesions re-main undiagnosed in this series. Taussig9 is of the opinion that these defects are prob-ably the most frequent congenital malfor-mations of the heart encountered in young adults, and are also the least frequently diagnosed correctly. It seems reasonable to suppose that the atrial septal defects may comprise the major portion of the lesions primarily affecting the heart which have been overlooked among surviving live-born infants, since the other common members of the acyanotic group (ventricular septal defects and patent ductus arteriosus) usti-ally produce murmurs during the first year, and the cyanotic group usually have cyano-sis and dyspnea, a murmur, or both before the age of 1 year.
The inclusion of any normal infants as instances of congenital malformation of the heart is unlikely because of the diagnostic
criteria used.
In summary, the probability is that the incidence figure of 0.83 per cent is more accurate than most available rates, but it is
almost certainly low because of cases missed in the abortion group and in the group who failed to develop symptoms or
signs before the age of 1 year.
the still-born infants and neonatal deaths
can be accounted for only in part by the
lethality of the defects found in these
groups; an additional factor is the discovery
of lesions at post-mortem examination in
infants dying of other causes which could
I10t be diagnosed by clinical means.
Effect of Birth Weight Upon Incidence
\Vhen stillborn infants and neonatal deaths are combined, and divided into pre-mature and full-term groups on the basis of
birth weight, practically identical incidence
rates of 8.5 and 8.1 per cent are obtained.
The factor of birth weight seems to operate mainly in the live-born infants, in whom
the incidence of cardiovascular
malforma-tions is over three times as large in the
pre-mature group s in those weighing over
2500 gm. at birth (8 of 463 prematures or
1.73 per cent, and 25 of 5,067 full-term in-fants or 0.49 per cent). This difference is
statistically significant (P = less than 0.01).
Whether the etiology of the prematurity is
related to that of the malformations, or whether the malformations cause or pre-dispose to prematurity is not known, but the association is more frequent than would be expected to occur by chance. Premature infants made up 11.6 per cent of the total group with malformations and 8.1 per cent of the total group without malformations,
an insignificant difference (P = .02 to .05).
However, Murphy,1” in a study based upon 1,476 death certificates bearing diagnoses of
gross congenital defects which were filed
during a 5-year period in Philadelphia, noted that malformed infants were born prematurely more than 4 times as often as
a control group composed of the normal
siblings of the affected individuals.
The only congenital heart lesions which
occurred in the multiple birth group
oc-curred in live-born infants of the lower weight classification. The overall incidence in the multiple birth group (3 of 175 or
1.7 per cent) is about twice that in the single birth group (47 of 5,878 or 0.8 per
cent), which may be explained by the higher incidence of prematurity on a weight basis in the multiple l)irth group, without invoking the reported preponderance of
malformations of all types in multiple birth
infants.U The incidence of malformations of all types was not significantly higher in
twins than it was among single infants in the present series (7.8 and 7.5 per cent respectively).
Effect of Sex and Color Upon Incidence
Sex and color had no statistically signifi-cant effect upon the overall incidence (Table IV). The highest incidence of cardio-vascular malformations occurred in white
females (1.1 per cent). Since we have shown that premature infants who survive 1 month or more have a significantly higher cardio-vascular malformation rate than do surviv-ing full-term infants, the possibility exists
that the preponderance of cardiovascular malformations in white females might be explained by a higher incidence of surviv-ing premature infants in this sex-color group. However, reference to the data con-tained in Table IV-A reveals that no such
higher incidence of surviving premature infants occurred in the white female group, and so their higher cardiovascular
malfor-‘FABLE IV
EN(’IDENCE OF CONGENITAL CARDIOVASCULAR MALFORMATIONS BY SEX AND COLOR IN INFANTS WHO WEIGHED OVER 600 GRAMS AT BIRTH
Total White
CM % Total
Non-White
(‘if % Total
Total
(‘ii %
Male 1620 9 0.6 1282 12 0.9 2902 ‘21 0.70
Female 1589 17 1.1 1248 11 0.9 2837 28 1.00
INCIDENCE OF SURVIVING PREMATURE INFANTS BY SEX AND COLOR
Total individuals Surviving
prematures5 Vo Surviving
prernatures
TABLE IV-A remaining 145 cases, in which the reliability
of the diagnosis was considered open to question. The rather marked difference be-tween this figure of 0.3 per cent and our rate of 0.83 per cent after only a 1-year
follow-up does not necessarily represent a real difference between the incidence of these malformations in the two countries.
Rather, the routine regular examination by a small team of observers with a specific interest in the detection of malformations,
plus the high rate of autopsy examination
of infants dying in the perinatal period may account for the difference, at least in part.
1620 1589 1282 1248
106 106 118 133
6.5 6.7 9.2 10.7
Non- Non-White White white
white
if ale Female
Male Female
* One month or more.
mation rate is unexplained.
Some interesting differences between
types of malformations and incidence of
associated malformations in the 4 sex-color groups are shown in Table IV-B. In this small series, it would appear that the
cyan-otic types of cardiovascular malformations
tend to be slightly more common among white than among non-white individuals (11 of 3,129 or .35 per cent and 5 of 2,443 or .20 per cent respectively), and that white
females, in addition to having the highest
incidence of cardiovascular malformations, are the most likely to have them in com-bination with malformations involving other systems (9 of 17). Neither of these trends is statistically significant, and larger numbers of cases would be required to prove or disprove them.
There has been thus far no comparison of these figures with those of other
inves-tigators because, as stated in the first para-graph, it is very difficult to find any data
even remotely comparable in derivation to those of this study. The most similar ap-proach has been that of MacMahon, Mc-Keown, and Record,’2 who have recently
published a report on 633 cases of con-genital heart disease among 199,418 births, an incidence of 0.3 per cent for a 10-year period in Birmingham, England. The cases of congenital heart disease were of varying ages up to 10 years, and were diagnosed by autopsy or operation in 255 cases, and by physical examination in schools or hospitals n 233 cases. Death register data yielded the
Etiologic Factors
No new etiologic factors were discovered in the analysis of the pregnancies which
resulted in these 50 infants. The main re-sults are given in detail below.
1) MATERNAL AGE AND Binm ORDER:
Table V shows the distribution of cardio-vascular mafformations in live-born single infants#{176} in comparison with the population
as a whole. The risk of having an affected
child appears to be lowest in the first preg-nancy, regardless of maternal age. For the second pregnancy, the risk is higher than in the first, but there is no marked upward trend with age. However, in the third preg-nancy, the average risk is considerably high-er than in the lower birth ranks, and
in-TABLE IV-B
INFLUENCE OF SEX AND COLOR UPON TYPES OF MALFORMATIONS IN INFANTS Wuo WEIGHED
OVER 500 GRAMS AT BIRTH
White
ii ale
White Female
Non-white Male
Non-u’hite Female
Total infants 9 17 12 11
Cyanotic type 4 7 ‘2 3
Non-cyanotic type 5 10 10 8
With other CVM 3 5 2 1
With CM, other
system ‘2 9 5 2
With single CVM
TABLE V
INCIDENCE OF CONGENITAL CARDIOVASCULAR MALFORMATIONS AMONG SINGLE
LIVEBORN INFANTS BY MATERNAL AGE AND PARITY
Birth Under .5 25-29 80-34 Orer 84 Toa1
Rank Tot. CM % Tot. CM % Tot. CM ‘ Tot. CM % Tot. CM
1 1103 4 .36 554 .36 e40 I .4 98
-
-
-- 1995 7 .33479 3 .63 63 6 .96 4S 4 .95 175 1.14 1700 13 .88
146 --
---
304 3 .99 93 .5 1.71 186 5 .69 99 13 1.401+ 49 - - 183
---
C69 .74 ss a .ss 853 .5 .591t1 1777 7 .39 1664 Ii .66 1215 11 .98 811 10 1.13 5477 40 .73
creases abruptly with age of the mother. In
the fourth and higher birth orders, the risk
appears to be lower than in the second and
third birth orders, but it shows an increase with advancing maternal age.
When these data are analyzed by the chi square method, the following results are
ob-tained:
1. The probability that differences in
incidence greater than those observed
among the 4 birth ranks would occur by chance is between 1 and 2 per cent.
How-ever when parity is corrected#{176} for the factor of age, the probability is between 5 and 10 per cent.
2. The probability that the difference
between the incidence in the first and third birth ranks would occur by chance is less than 1 per cent, but again increases to between 5 and 10 per cent with the application of an age correction.
3. The probability that differences in incidence greater than those observed among the 4 age groups would occur by chance is about 10 per cent. However when age is correctedt for the factor of parity, the probability is between 10 and 20 per cent.
* In making this correction, the expected
nuns-hers were computed by multiplying the base numbers in each cell by the incidence in the cor-responding age range, rather than by the overall
rate of 0.73 per cent.
f In making this correction, the expected
nuns-bers were computed by multiplying the base
num-bers in each cell by the incidence in the
cor-responding birth rank, rather than by the overall
rate of 0.73 per cent.
4. The probability that the difference
between the incidence in the youngest and oldest age groups would occur by chance is about 2 per cent, but again in-creases to between 10 and 20 per cent
with the application of a parity correc-tion.
Therefore, it is apparent that the only mathematically significant difference to be found in Table V is that between the mci-dence in the first and third birth ranks when they are not corrected for the factor of age. Since this difference was not antici-pated (in fact, if increased age and parity were predisposing causes of cardiovascular malformations the highest incidence rate would be expected to occur in the birth rank of 4 and above), it should be accepted with caution.
It is of interest that none of the 4 infants with congenital malformations of the heart
who also had mongolism (a condition known to be related to advanced maternal age) was the result of a third pregnancy; therefore, the concentration of malforma-tions at this birth order in women over 30 cannot be explained in this way. However, the removal of the mongoloids has 2 other interesting effects.
First, it makes more striking the
the average increase (i.e., in all birth orders) in malformations with advancing maternal
age becomes more gradual; .39 per cent
under 25, .60 per cent at 25-29 years, .90 per cent at 30-34 years, and .99 per cent at
ages above 34 years.
Opinions in the literature about the effect of maternal age and parity on cardiac
mal-formations vary widely. Still’3 in a study of
250 cases of congenital heart disease, com-pared the place in family of these patients
with that of 900 cases of pneumonia, and
found that 34 per cent of the cardiovascular
malformations occurred in first-born
mdi-viduals whereas only 20 per cent of the
cases of pneumonia occurred in firstborn
individuals. ‘ stated that
“con-genital cardiac disease is one of the
condi-tions more frequent in later maternal age
groups.” However, this opinion was based
upon 2 infants who were born to women
46-50 years of age, in a series in which only
10 cases of congenital heart disease were discovered among almost 14,000 births. MacMahon15 concluded after a study of the
maternal age and parity of the mothers of
588 infants with cardiovascular
malforma-tions, and 1015 controls, that there was no consistent association between parity and nsalformations, and that the apparent effect of advanced age upon the incidence of mal-formations disappeared when the
mongol-oids were removed from the series. It should
be stated that only viable pregnancies were counted in determining parity in his report, whereas in the present series all previous pregnancies including abortions have been counted in assigning a birth rank.
2) INFECTIoNs: There was no higher inci-dence of infections of any type during preg-nancy in the mothers of these 50 malformed infants than in the group as a whole.
Spe-cifically, there was iso indication that con-tagious diseases or exposure to them played a role in the etiology of congenital malfor-mations of the heart in general or of patent
ductus arteriosus in particular. Four rea-sonably convincing cases of rubella oc-curred during the first trimester of preg-nancy in the entire series of 5,964
preg-nancies. Three of these women gave birth
to normal full-term infants. The fourth had a spontaneous abortion, and the specimen, after careful study, was found to be com-pletely normal.#{176} This result (one of the few prospective data available on this much-discussed problem) is in accord with retro-spective studies of patients with congenital heart disease,1621 which estimate maternal rubella to be an etiologic factor in from 0 to 5 per cent of children with congenital heart disease. Only 1 patient in the present series was clinically suggestive of the rubella picture described by the Australian
observers. She had a patent ductus
arterio-sus, congenital cataract with
microphthal-mus, and a dental anomaly, along with retardation of growth. Unfortunately, we
cannot be sure whether the mother of this child had any symptoms of rubella during the pregnancy; but even assuming that this was the case, the rubella risk would still be
only 1 in 5 or 20 per cent.
Three women among the mothers of these 50 infants had clinical herpes simplex
in-fections during the first trimester. Although this incidence (6 per cent) is not significantly higher than that of the base population (4.5 per cent), it is of interest that in each of the three cases, the cardiovascular lesion was the tetrad of Fallot. The other 266
women in the study group who had first trimester herpes produced offspring with about the expected incidence of congenital
defects (18 or 6.8 per cent as compared to 7.3 per cent for the group as a whole), and the malformations were of many different types. Much larger numbers of cases would be required to establish a relationship be-tween herpes simplex in the first trimester and tetrad of Fallot, and in addition, bio-logical or immunological identification of the virus would be essential.
3) MEDICAL AND OBSTETRICAL FACTORS:
There was no higher incidence of acute or chronic medical conditions (i.e., heart dis-ease,_syphilis, arthritis, etc.) in the mothers
O The study was carried out at the Department
of Embryology, Carnegie Institution of
of infants with congenital cardiac
malforma-tions than in the group as a whole.
Only 2 instances of polyhydramnios were noted, one in the mother of an anencephalic infant, the other in the mother of an infant
with tetrad of Fallot and diaphragmatic hernia. However, the quantity of amniotic
fluid is notoriously difficult to estimate, and
there may have been other instances in
which it was increased in amount.
The incidence of vaginal bleeding
dur-lug pregnancy was not significantly higher
in these 50 women than in the total
popu-lation. Similarly, neither pelvic tumors nor
toxemias were more common in these
women.
4) SEASON: There was no seasonal
con-centration of conceptions either by month or
year (as computed from the date of the last
menstrual period) of these 50 infants.
5) GENETIC FACTORS: The incidence of abortions and stillbirths among the previous pregnancies of these 50 women was similar
to the incidence in the group as a whole.
Unfortunately, similar comparison of
pre-vious infants with regard to incidence of congenital malformations could not be made because specific questions about pre-vious malformed infants were not asked.
Dogramaci and Green’9 reported that
among 680 patients with congenital heart disease in whom an adequate history could
be obtained, 67 other members of the fami-lies had congenital malformations of various types, and 27 of these occurred in siblings.
Unfortunately no control population is
quoted for comparison.
McKeown et al.,22 in a study of 352
sib-lings born after the birth of individuals having congenital heart defects, discovered 6 affected children, a number 6 times larger
than that expected on the basis of the inci-dence in the general population of their report (3.2/1,000). In addition, it is of inter-est that in 3 of the 5 fraternities in which the nature of the cardiac defect was known, the lesion was identical in both members of the pair.
In summary, the only suggestive
predis-posing etiologic factors uncovered by this
study are maternal age and parity. The
possibility of an association between the
occurrence of herpes simplex and the tetrad of Fallot requires corroboration.
TYPES OF MALFORMATIONS
Table VI lists the principal malformation
in the 27 proven cases, and whether it occurred alone or with other cardiovascular anomalies. (The reader is referred to the
appendix for a detailed table containing the
complete diagnosis of cardiovascular and
associated malformations in the 50 infants.) Patent ductus arteriosus and patent fora-men ovale were not included as
malforma-tions in infants dying under the age of 6
months regardless of their size, since these
fetal channels have been known to remain
anatomically patent in many normal infants
for the first few months.23 The one case
listed as an aneurysm of the ductus
arterio-sus occurred in a neonatal death, but was
included because the pathologist con-sidered the aneurysm per se to be an anomaly.
Twenty-five of the twenty-seven diag-noses in Table VI have been verified either
by
autopsy2#{176}or operation,5 and the other 2 are considered so well-established on clinical grounds that surgery is anticipated in the near future (1 case of patent ductusarteriosus and 1 case of tetrad of Fallot). The provisional clinical diagnoses in the remaining 23 cases are as follows:
1) Septal defects-16;
2) Tetrad of Fallot-3;
3) Unclassified cyanotic lesions-2 (1
death), and
4) “Idiopathic hypertrophy” group#{176}-2
(2 deaths).
Twenty of these twenty-three infants are still alive and are being followed in a con-tinuing effort to elucidate the diagnosis.
Autopsies were not performed in the 3 in-fants who died.
Symptoms and signs associated with the
Sole CV Principal Lesion Total Anomaly
With Other CV Anomaly
5 1 4
5 5 (1
9
‘2 ‘2 0
‘2 ‘2
2 0
0
‘4
1 1 0
1 1 0
TABLE VI
TYPES OF CARDIOVASCULAR MALFORMATIONS IN THE PROVEN CASES 27
‘I’etrad of Fallot Patent (luctus arteriosus Anomalies of great vessels
Coaretation of aorta Aortic hypoplasia
“(orrected transposition Amiomnalous subclaviamm Ahseit hypogastric artery
8(ptZ1l defects
Atrial
\entricular
( ()1111fl0I1 atrioven tricular orifice
l’ulniomiary lesions Valvular atresia Bicuspid valve Fibroelastosis
Aneurvsms of the (luctus arteriosus
commoner operable lesions are of interest.
Of the 7 patients with confirmed or
sus-pected tetrad of Fallot who survived the immediate postnatal period, all developed sustained cyanosis within the first year, 5 within the first month. Five had a murmur at birth, 1 at 2 months, and 1 with no mur-mur at birth was found to have a murmur when next examined at 15 months of age. Four of the five infants who survived more
than 2 years developed clubbing of the fingers between 2 and 3 years of age. Six of the seven patients developed exercise intolerance, squatting, or syncopal attacks, 4 during the first year of life, and 2 during the second.
Of the 5 infants with patent ductus arteriosus, none had a murmur during the first week of life, which confirms the
experi-ence of Owens and Kingsbury24 and casts doubt upon the contention that transitory murmurs in the newborn infant are due to the flow of blood through this channel. A murmur was heard for the first time before the end of the first year in 4 of the 5 cases,
but not until the age of 20 months in the fifth. The typical machinery murmur was first heard at 6 months of age in 2 cases, 9 months in 1, 3 years in 1, and 4 years in 1
I.
‘)
0 0
0
3
‘4
1 0
1 0
(I
(1
case. This experience is in agreement with
that of Gibson,25 and Keith,2#{176}but in dis-agreement with the experience reported by Ziegler,27 who found a murmur to be
pres-ent in all 8 of the infants less than 1 year of age in his series, and stated that the typical continuous murmur appeared prior to 18 months of age in all patients except those who had pulmonary hypertension. Current opinion about the mechanism of the ductus murmur is well-summarized in a recent paper28 which emphasizes the atypical find-ings in patients with pulmonary hyperten-sion.
No other symptoms or signs were
con-sistently seen in the 5 patients with patent
ductus arteriosus. Two of these infants were premature, weighing 1180 and 2500 gm. at birth, and both remained signifi-cantly below average weight and height during the first 2 years of life. The other 3, of normal birth weight, grew at a rate which kept their weight and height meas-urements within 1.5 standard deviations of normal mean levels throughout the first 24
months.
The age of the mother and the sex of the infants in these two groups of cases are
TABLE VIII
RESULTS OF NEONATAL CHEST RG
Average age tetrad of Fallot mothers-34.6 years. Average age patent duetus mothers-26.2 years.
Average age for total population (5.964 mothers)-‘28.5 years.
21
between the average age of mothers of
in-fants with these two anomalies is
interest-ing. The probability that a sample having the age distribution of the 5 tetrad mothers would be drawn at random from the
uni-verse of 5,964 mothers is between 1 and 2 per cent, whereas the corresponding prob-ability for the age distribution of the 5
patent ductus mothers is 39 per cent. It
may be that the advanced age of the tetrad mothers tends to imply a genetic back-ground for this malformation in contrast with patent ductus arteriosus. The fact that 3 of 5 cases of tetrad of Fallot had associ-ated malformations involving other systems, and 4 of the 5 had other cardiovascular mal-formations, whereas only 1 case of patent ductus arteriosus had associated malforma-tions involving other systems, and none had
associated cardiovascular malformations (as far as could be determined at operation),
may be construed as additional support for
a genetic factor in tetrad of Fallot.
Vith regard to the birth order and sex in these two types of cases, our numbers are too small to reach valid conclusions. How-ever, 3 of the 5 infants with patent ductus
TABLE VII
MATERNAL AGE AND PARITY AND INFANT SEX IN PROVEN CASES OF PATENT DUcTUS ARTERIOSUS
AND TETRAD OF FALLOT
Age
Birth Order
Sex of Infant
letrad.s
1 32 2 M
2 43 3 F
3 37 3 M
1 34 3 M
.5 27 3 F
PD.1
1 24 1 F
2 22 1 F
3 27 3 M
4 26 1 M
.5 32 3 F
Abnormal
RG
Normal
RG Total
Malformed heart 5 30 35
Normal heart 45 5286 5331
total 50 531 (; 5366
arteriosus were the result of first
pregnan-cies, which conforms well with the figure of
53.9 per cent first-born found by Record
et al.29 among 166 cases of this defect (as compared with a control of 39.8 per cent).
None of the 5 cases of tetrad of Fallot
was in a first-born. It must always be kept in mind that the effects of age and parity
are interrelated, and difficult to assess mdi-vidually; for example, the birth order of infants with patent ductus arteriosus is
closely related to maternal age, the 2
in-fants who occupied the third birth rank
being born to the oldest 2 mothers of the
series of 5; and since none of the mothers
of infants with the tetrad of Fallot was under 27 years of age, it is perhaps not
sur-prising that none of the infants occupied the
first birth rank (see Table V), and much
larger numbers would be necessary to assess the effect of parity independent of age.
Routine RGs for cardiac size and
con-tour in the newborn infant proved to be ineffective as a screening procedure for
cardiac malformations (Table VIII). Thirty-five infants whose malformations directly affected the heart had RGs in the first week of life, and in only 5 or 14 per cent was the
cardiac size or contour abnormal. On the other hand 45 infants or 0.8 per cent of the total population with presumably normal hearts were suspected of congenital
M(,ItTALITY ExeERIENF: AMONG TilE 43 LIVE-BORN INFANTS \ITIi (‘iwiu MALFORMATIONS
Number Number
Age Period
.1lire (ii
Begin-aing
of Age Period
tf A\07t
cardiac Deaf/tx in Age Period
Cardiac Deaths
‘s’umber %
Birth-i day Iday-i month I111(111th-i year
1-2 years
43
38
33
2$)
diagnosis of congenital heart disease in only
5 of 50 RGs so interpreted (10 per cent). The inefficacy of neonatal chest RGs in
providing a lead to the diagnosis of con-genital heart disease is not surprising
be-cause normal cardiac size and contour are
often present in affected infants during the
neonatal period, but it serves to emphasize
the futility of using routine neonatal RGs in the hope of ruling out congenital heart
dis-ease. The high rate of disagreement (90 per cent) between the roentgen evidence of
ab-normal cardiac size or contour (even in the
hands of an experienced radiologist6) and the subsequent clinical and roentgen find-ings at follow-up examination emphasizes
the wide variability of the heart shadow in newborns, and the difficulty of interpreting the significance of apparent cardiac enlarge-ment in the RG at this age. The shadow of the thymus gland is in all probability the major factor which produces this temporary
variability.
In the same group of 35 infants, 15 had
either a murmur or cyanosis or both in the
first week of life, and among these 15 were
the 5 patients whose RGs were interpreted as suspicious. From this it may be inferred that during the first week of life physical examination offers a somewhat more reli-able index of the existence of congenital heart disease than does roentgenography, although the chances of detecting a cardiac
* All RGs were interpreted b Dr. John Caffey.
TABLE IX malformation with both of these means
remain low-probably less than 50 per cent.
It should be stated in this connection that
of the 4,986 normal, full-term, live-boni,
single infants who were examined at birth,
77 (1.5 per cent) had a systolic murmur
dur-ing the neonatal period but later, at subse-quent follow-up examinations, seemed to
have normal hearts. Thus only 8.3 per cent of the neonatal heart murmurs were finally
3
:
considered to be due to cardiac defects._± 4 12 The number of deaths among the 43
- ‘2 7 live-born infants shown to have a congenital malformation of the heart is given in Table
Ix.
The overall mortality rate for this group was 16 out of 43 (37.2 per cent) for the first 2 years, and that which was apparently due to the cardiovascular lesion per se was 12 out of 43 (27.9 per cent). None of the 12 infants who died of cardiac causes came to operation, but 5 had lesions which were presumably amenable to surgical correc-tion (Numbers 1, 2, 3, 23, and 27-see Appendix). However, all5
had other serious malformations of the heart or other systems,and all died before the age of 15 months (3 under the age of 3 months). Thus it
ap-pears that the mortality from cardiac mal-formations in this series was irreducible.
In the present series, 29 of the 50 infants with cardiovascular malformations were still alive at 1 year of age, an incidence rate of 0.5 per cent in the total study popula-tion who survived until 1 year. This figure approaches but still exceeds the reported incidence of congenital heart disease among school children, namely 0.15 per cent,3#{176} 0.19 per cent3’ and 0.21 per cent.32 Longer
follow-up will make it possible to deter-mine how many of the 29 1-year survivors will be alive at school age, but unfortu-nately the number of cases missed because
they produced no signs during the first year will probably never be known. In this con-nection, Rauh3#{176}reported that of 95 patients
with congenital heart disease in whom the
time of diagnosis was known, only 52 had been recognized prior to 2 years of age, another 20 between 2 and 5 years, and 23
TABLE X
ASSOCIATE!) MALFORMATIONS AFFECTING
OTHER SYSTEMS
A. By Length of Surt’iral:
Stillborn
l)ied under 1month
l)ied 1month-I year
I)ied 1-2 years
Survived over’2 years
Total
B. By Tissue Invol red:
23
In summary, if our experience is
trans-posed to a hypothetical group of 100
live-born infants with congenital cardiovascular
malformations diagnosable prior to 1 year
of age, 27 would be expected to die of
cardiac causes during the first year (15
tinder 1 month), and another 7 during the
second year, and 66 would be expected to
survive for more than 2 years.
ASSOCIATED MALFORMATIONS
1. Cardiovascular
Eleven of the fifty patients had a total of
20 malformations of the cardiovascular
sys-tem other than the principal listed lesion.
Ten of these were found by autopsy exam-ination, and 1 was found at operation.
Prob-ably there are others present in surviving
patients which have remained undiagnosed. The most frequently diagnosed lesion was right-sided aorta, which occurred in 3 of the 5 proven cases of tetrad of Fallot, and in no other patient in the study group, as
far as could be determined. No other com-mo pattern of association emerged from
this analysis. (See Appendix for the detailed
1is.)
2. Other Systems
Table X summarizes the data on the 18 patients (36 per cent) who had 1 or more
malformations involving systems other than the cardiovascular (44 malformations in all). In contrast to the situation in the case of associated vascular malformations, the
diagnosis of associated malformations
in-volving systems other than the cardiovascu-lar was made in 13 of the 18 children
dur-ing life. (Four of these thirteen patients died subsequently.)
The distinction between the number of
patients affected and the number of malfor-mations is made in order to emphasize 2
facts: first, that just as many surviving in-fants had malformations affecting other sys-tems as did infants who died before the
age of 2 years; and second, that the average
number of malformations in the fatal cases
.‘%‘umber S,’un,ber
of of Ma!-Patients formations
‘2 8
4 17
1 2
‘2 2
9 15
18 44
Germ Layer of Origin #
Organ or System #
Central nervous
Eye Skin
6
(i
tJ
Genitourinarv Skeletal
81
4J
(;&istroiiittstiiial Respiratory
3 41
Extremities . Miscellaneous
& ( I
.
Mixed i
lotal 44 44
was higher for 2 reasons: the increased
chance of a lethal defect being present when there are multiple defects, and the completeness of diagnosis in the autopsied cases as opposed to the survivors, some of
whom may have clinically silent
malforma-tions.
The genitourinary system was most com-monly involved, and all of these anomalies occurred in infants who died before the age of 2 weeks. This may indicate that many genitourinary lesions have been undiag-nosed in surviving infants, a hypothesis which is supported by the high incidence
of such anomalies in autopsies at all ages. When the associated malformations are classified by germ layer of origin, the ecto-dermal derivatives, namely central nervous system, eye, and skin were most frequently affected.
The most common associated malforma-Fctodern, I(;
Mesoderm 12
tion in the 50 cases was mongolism (4 cases
or 8 per cent). The comparable figure was
5.8 per cent in the 720 cases of Dogramaci and Green’9 and only 1.7 per cent among the autopsy series of Maude Abbott7 which included many adults.
The incidence of congenital heart disease among the 11 mongoloids in the entire
series was 4 cases (36 per cent). Benda,33 in discussing mongoloids, states that “-the heart is found abnormal in 75 per cent of the infants who die in the first 2 years of
life. In those who survive, about 35 per cent show congenital heart malformations.” Our experience is in accord with thelafter
esti-mate (2 cases of congenital heart disease
among 5 surviving mongoloids), but only 2 of the 6 mongoloids who died in the first 2
years of life are known to have had cardiac
malformations. However, none of the other 4 infants had an autopsy examination, and so we cannot be sure their hearts were nor-mal in spite of the absence of convincing clinical evidence of congenital heart dis-ease. Engler34 claims that 60 per cent of mongoloids dying at all ages have heart
disease, and emphasizes the frequency with which lesions are found at autopsy in pa-tients who presented no clinical evidence of
congenital heart disease during life. Among
100 adult mongoloids examined by him, 19 were found to have definite evidence and 9 inconclusive evidence of congenital heart disease.
The cardiac diagnosis in our 4 infants with mongolism is of interest. In 1 infant who died at the age of 11 months, autopsy
showed coarctation of the aorta, patent due-tus arteriosus, and a ventricular septal de-fect. Another died at 19 months of age of cyanotic heart disease, but no autopsy was
performed. The other 2 patients are still living, 1 with severe cyanosis, clubbing, and dyspnea, and the other with convincing clinical evidence of an atrial septal defect.
Taussig3’ states that when a mongolian idiot presents marked cyanosis or clubbing, the diagnosis of persistent atrioventricular
orifice should not be entertained. Therefore this lesion, which is considered by Potter36
to be the most frequent malformation
among mongoloids, is definitely absent in the 1 autopsied case, and may be absent in the 2 cyanotic cases. Furthermore, neither of the 2 infants in this series who had this defect was a mongoloid. Rogers and
Ed-wards37 in a review of 55 reported cases of this cardiac anomaly found a diagnosis of mongolism in 17 cases, mention of its ab-sence in 8, and no statement regarding mongolism in 30 cases.
Abbott38 reported that 13 of the 17 mon-goloids in her series of 1,000 autopsies had either persistent ostium atrio-ventriculare commune or persistent ostium primum alone. Silvy39 stated that defects of the ventricular septum were the most common cardiac lesion in mongoloids, and Gibson8
reported a variety of lesions among the 7
mongoloids of his autopsy series. Mac-Mahon et al.12 reported septal defects in 14 of 18 mongoloids in whom the diagnosis was known, but did not classify the type of defect. Since common atrioventricular ori-fice is not included by this name or its usual variations in the classification of these authors, some cases may be included among
the group with septal defects.
The next most common associated mal-formations were cataract, cleft palate, and
diaphragmatic hernia, each of which oc-curred in 3 cases. The latter 2 malforma-tions are of interest in that there were only 4 cases of each of these 2 anomalies among the entire population, an incidence which is probably quite accurate because of the external nature of the cleft palate and the opportunity for diagnosis of the diaphrag-matic hernia afforded by routine neonatal
chest RGs.
In order to test the validity of these
TABLE XI
INCIDENCE OF ASSOCIATED MALFORMATIONS OF OTHER SYSTEMS IN INDIVIDUALS
HAVING CARDIOVASCULAR MALFORMATIONS
Clinical Autopsy
Clinical
Autopsy
24 multiple Many adults
Total Investigator Number of
Individuals
Individuals with Associated CSIs
--Type of
Population Miscellaneous
\umber %
Vierordt’ 700 80 11 .0
Irvine-Jones43 100 54* ?
Ah)1)0tt38 1000 188 18.8
Brumhik4’ ? 6.0
‘23.0
Gibson8 105 28 27.0 Autopsy
-MacMahon’2 488 101 20.7 Mixed Children to 11 years
Present series .50 18 36.0 Mixed Infants under 1year
* At least 7 of the 54 malformations listed by this observer are conditions not counted in the present series as congenital anomalies, e.g., thymic enlargement, highly arched palate, asymmetry of the head, and suppression of
the incisor teeth. In addition itis not clear whether the number 54 refers to individuals or malformations.
other patients had functional murmurs at
some examination, and the remaining 41 (21
of whom had been followed more than 2 years) had no evidence of any cardiac ab-normality. The majority of these 50 patients were hospitalized for plastic surgery, and
so they undoubtedly represent a group
selected
by
virtue of survival and goodhealth, but among 19 infants with cleft palate who died and had autopsy examina-tions in this hospital, only 2 had congenital heart defects, and both of these were tetrads of Fallot.
In the case of diaphragmatic hernia, the records of 21 hospitalized patients revealed 1 infant with cyanotic congenital heart
dis-ease who died but did not have an autopsy examination, 1 infant with a functional murmur, and 1 infant with an abnormal
cardiac contour in RG and an abnormal ECG but without clinical evidence of
congenital heart disease. The remaining 18
infants showed no signs of cardiac
abnor-mality, but only 2 of them have been
fol-lowed past the age of 2 years. In 22 autopsy records of patients with congenital dia-phragmatic hernia, 10 had definite cardio-vascular malformations, and 4 others had
questionable ones. These lesions were of
many different types, and no particular
pat-tern was apparent.
Thus it appears possible: 1) that there is
not a strikingly frequent association
be-tween cleft palate and congenital heart dis-ease in general, but that when the
associa-tion does occur, the lesion is frequently a tetrad of Fallot (definitely Case #2 and
probably Case #31 of the present series, 1 of 2 cardiac anomalies in the 50 hospital-ized patients, and both cardiac defects in the 19 autopsies in the Babies Hospital
records), and 2) that a high proportion of infants with diaphragmatic hernia who die in early life have associated cardiovascular
malformations.
There were 12 cases of cataract in the
series as a whole, so there is apparently no consistent association with congenital heart disease. Congenital cataract occurred in 1 infant with mongolism. This condition has
recently been found to be present in 8 per cent of 165 mongoloids who were examined
by slit lamp.4#{176} These observers and others4’
emphasize that true congenital cataracts should be distinguished from the acquired lenticular opacities which appear in almost all mongols at 6 to 17 years of age.
malforma-tions involving other systems which has been reported in the literature varies a
great deal with the type of population
tinder consideration, e.g., autopsy, clinical,
or mixed, and is summarized in Table
XI.
In our experience, the specific associa-tions between : 1) congenital heart diseaseand accessory nipples;’7 2) congenital heart disease and spinabifida and anencephaly,’
and 3) patent ductus arteriosus and
aber-rant right subclavian artery4’ which have
been reported were found in only 1 of 25,
1 of 8, and none of 4 cases respectively.
SUMMARY
The incidence of cardiovascular
malfor-nations has been studied in a large series of unselected infants. The overall rate was 0.83 per cent, and it varied from 7.7 per
cent in infants who were either stillborn
or died within the first month (16 of 209), to 0.6 per cent in infants who survived for more than 1 month (see Table I).
The accuracy of these incidence rates is
discussed, and it is concluded that they are
probably somewhat low.
Live-born infants weighing less than 2500 gm. at birth who survived for a month or
more have a higher incidence of cardio-vascular malformations than do those
weighing more than 2500 gm. at birth. This difference is of statistical significance.
A careful evaluation of etiologic factors in this group of 50 cases revealed the fol-lowing:
a) Maternal age and parity are of some
importance as predisposing factors in the
causation of cardiovascular malformations. The risk of having an infant with a
con-genital malformation of the heart or great
vessels is greater in the third pregnancy than in the first, especially in women over 30.
b) No association between maternal
infec-tions early in pregnancy and the occurrence of cardiovascular malformations in the off-spring was noted, except for a suggestive l)lt of evidence that herpes simplex in the
first 3 months may be related to the tetrad
of Fallot. However, the number of cases of
first trimester maternal herpes in this group
of 50 cases was not significantly greater
than in the entire population, and in all
probability the observed association is
coin-cidental.
c) Obstetric and medical complications dence of vascular anomalies.
failed to show any correlation with the mci-d) Genetic factors could not be
satisfac-torily evaluated.
The types of malformations encountered
are listed, and the methods of diagnosis are discussed. Twenty-three of the fifty cases
are still not completely diagnosed, and of these, 20 are alive, and are still under
observation.
The development of the symptoms in the tetrad of Fallot and in patent ductus
arteri-osus is discussed. A rather marked differ-ence in maternal age and parity in the two conditions is apparent, but unexplained.
Routine RG of the chest in newborn infants was considerably less valuable than clinical evidence in the diagnosis of
con-genital heart disease.
The mortality rates for the group of 50
cases are discussed. Twenty-seven of the fifty patients survived more than 2 years.
Associated malformations, involving sys-tems other than the cardiovascular system, occurred in 18 of the 50 cases (36 per cent), and organs derived from the embryonic ectoderm were most frequently affected. Mongolism (4), and cleft palate, cataract,
diaphragmatic hernia (3 each) were the most frequently noted anomalies, and the association was thought to be of definite significance in the case of mongolism, and in fatal cases of diaphragmatic hernia.
ACKNOWLEDGM ENT
Credit is due Miss Marjorie Bellows, Statistician for the American Heart Associa-tion, for her many valuable criticisms and
suggestions.
REFERENCES
mci-ORIGINAL ARTICLES
deuce of congenital malformations: a
study of 5,964 pregnancies. PEDIATRICS,
14:505, 1954.
2 Mall, F. : On the frequency of localized
anomalies in human embryos and
in-fants at birth. Am.
J.
Anat., 22:49,1917.
3. Hertig, A., and Rock,
J.
: A series of po-tentially abortive ova recovered from fertile women prior to the first missedmenstrual period. Am.
J.
Obst. &Gynec., 58:968, 1949.
4. Nadas, A. : Atrial septal defect. Am.
J.
Dis. Child., 86:456, 1953.
5. Chapman, C., and Fraser, R. : Clinical and
hemodynamic features of uncomplicated
interatrial defect in adults. Am. Heart
J.,
46:352, 1953.6. Keith,
J.,
and Forsyth, Constance C.: Auricular septal defects in children.J.
Pediat., 38:172, 1951.7. Abbott, Maude E., Atlas of Congenital
Heart Disease. New York, American Heart Association, 1936, p. 60-61. 8. Gibson, S., and Clifton, Willie Mae.:
Con-genital heart disease: a clinical and post mortem study of one hundred and five cases. Am.
J.
Dis. Child., 55:761, 1938.9. Taussig, Helen B.: Congenital Malforma-tions of the Heart. New York, The Com-monwealth Fund, 1947, p. 354. 10. Murphy, D.: Congenital Malformations,
2nd Ed. Philadelphia, Lippincott, 1947,
p. 27.
11. Worcester, Jane, Stevenson, S., and Rice,
R.: 677 congenitally malformed infants
and associated gestational characteris-tics, II. Parental factors. PEDIATRICS, 6:
208, 1950.
12. MacMahon, B., McKeown, T., and Rec-ord, R.: The incidence and life expecta-tion of children with congenital heart disease. Brit. Heart
J.,
15:121, 1953. 13. Still, C.: Place-in-family as a factor indisease. Lancet, 2:795, 1927.
14. Malpas, P.: The incidence of human mal-formations and the significance of changes in the maternal environment in
their causation. J. Obst. & Gynaec. Brit.
Emp., 44:434, 1937.
15. MacMahon, B.: Association of congenital malformation of the heart with birth rank and maternal age. Brit.
J.
Soc.Med., 6:178, 1952.
16. Gibson, S., and Lewis, Katherine C.: Con-genital heart disease following maternal
rubella during pregnancy. Am. j. Dis.
Child., 83:317, 1952.
17. Brown,
J.
: Congenital Heart Disease, 2nd Ed. London, Staples, 1950, p. 26.18. Lamy, M., and Schweisguth, 0. : Enqu#{234}te #{233}tiologique sur 304 malformations
car-diaques cong#{233}nitales. Ann. paediat.,
174:65, 1950.
19. Dogramaci, I., and Green, H. : Factors in
the etiology of congenital heart
anoma-lies.
J.
Pediat., 30:295, 1947.20. Campbell, M. : Genetic and environmental
factors in congenital heart disease.
Quart.
J.
Med., 18:379, 1949.21. Lvnxwiler, C., and Wells, C.: Patent
duc-tus arteriosus: a report of 180
opera-tions. South M.
J,
43:61, 1950.22. McKeown, T., MacMahon, B., and
Par-sons, C. : The familial incidence of
con-genital malformation of the heart. Brit. Heart
J.,
15:273, 1953.23. Christie, A. : Normal closing time of the foramen ovale and the ductus arteriosus.
Am.
J.
Dis. Child., 40:323, 1930.24. Owen, S., and Kingsbury, A. : The
diagno-sis of congenital heart disease in the
newborn including a record of cases of
foetal endocarditis and maldevelop-ment. Brit.
J.
Child. Dis., 21:161, 1924. 25. Gibson, S.: Symposium on CardiovascularDiseases. Pediatric Clinics of North America. Philadelphia, Saunders, 1954, p. 11.
26. Keith,
J.,
and Forsyth, Constance: Aortog-raphy in infants. Circulation, 2:907, 1950.27. Ziegler, R.: The importance of patent ductus arteriosus in infants. Am. Heart
J.,
43:553, 1952.28. Dammann,
J.
Jr., and Sell, C.: Patent duc-tus arteriosus in the absence of a con-tinuous murmur. Circulation, 6:110, 1952.29. Record, R., and McKeown, T.:
Observa-tions relating to the aetiology of patent
ductus arteriosus. Brit. Heart
J.,
15:376,1953.
30. Rauh, Louise W.: The incidence of organic
heart disease in Cincinnati school
chil-dren. Am. Heart
J.,
18:705, 1939. 31. Robinson, S., Aggeler, Dorothy M., andDaniloff, Gladys T.: Heart disease in
San Francisco school children.
J.
Pediat., 33:49, 1948.
32. Cardiner,
J.,
and Keith,J.:
Prevalence ofheart disease in Toronto children. Pi-DIATRICS, 7:713, 1951.
33. Benda, C.: Mongolism and Cretinism, 2nd Ed. New York, Crune and Stratton,
34. Engler, M. : Mongolism. Baltimore,
Wil-hams and Wilkins, 1949, p. 49-50.
35. Taussig, Helen B. : Congenital
Malforma-tions of the Heart. New York, The
Commonwealth Fund, 1947, p. 385.
36. Potter, Edith L. : Pathology of the Fetus
and the Newborn. Chicago, Yr.Bk. Pub.,
1952, p. 225.
37. Rogers, H., and Edwards,
J.
: Incompletedivision of the atrioventricular canal
with patent interatrial foramen primum
(
persistent common atrioventricular os-tium). Am. HeartJ.,
36:28, 1948.38. Abbott, Maude E. : Congenital Heart
Dis-ease, in : Nelson’s Loose-leaf Medicine,
Vol. 4. New York, Nelson, 1932, p. 307.
39. Silvy, M. : Mongolisme et malformations
cardiaques. Paris Thesis, 1934.
40. Igersheimer,
J.,
and Mautner, H. : Aboutthe significance of lenticular changes in
mongolism. Ann. paediat., 181 :34, 1953.
41. Engler, NI.: Mongolism. Baltimore,
Wil-hams and Wilkins, 1949, p. 26.
42. Vierordt, H. : Die angeborenen
Herzkrank-heiten: in Nothnagel’s Spez. Path. u.
Ther., 15:244, 1898.
43. Irvine-Jones, Edith I. M. : A clinical study
of congenital heart disease in childhood.
Am. Heart
J.,
2:121, 1926.44. Brumlik,
J.:
quoted by Brown ,j.: Con-genital Heart Disease, 2nd Ed. London,Staples, 1950, p. 23.
45. Brean, H., and Neuhauser, E.: Syndrome
of aberrant right subclavian artery with
patent ductus arteriosus. Am.
J.
Roent-genol., 58:708, 1947.
SPANISH ABSTRACT
Malformaciones Cong#{233}nitas
Cardiovas-culares en 6053 Lactantes
La autora estudi#{243} Ia incidencia de las
mal-formaciones cardiovasculares en una gran serie
de lactantes no seleccionados, siendo
global-mente de 0.83%, con variaciones de 7.7% en
los nacidos muertos y fallecidos dentro del
primer mes (16 de 209) a 0.6% para los
sobre-vivientes de m#{225}sde un mes. La exactitud de estos datos naturalmente presenta algunas
ob-jeciones; te#{243}ricamente podrIan corregirse los
errores de Ia tabulaci#{243}nbas#{225}ndosesolo en los
estudios post mortem de los fallecidos al nacer
o en el primer mes o bien sOlo en los ni#{241}os
mayores de un a#{241}ode edad; otro factor de
error puede achacarse al m#{233}todo de estudio,
como por ejemplo, aceptar datos poco veraces
en el grupo de niflos con peso menor de 500
gramos al nacer 6 de malformaciones que
pasaron desapercibidas por no presentar
sInto-mas o signos antes del a#{241}ode edad (la
comuni-caciOn interauricular puede manifestarse clmni-camente sOlo hasta los 3 o cuatro a#{241}osde edad); Ia autora acepta que la frecuencia de 0.83% quiz#{225}sea un poco baja pero bastante aproximada.
Se obtuvieron incidencias pr#{225}cticamente
similares de 8.5 a 8.1% para el grupo de
pre-maturos y de ninos a t#{233}rminofallecidos, en tanto que en los vivos fueron de 1.73 y 0.49%, es decir, el peso al nacer parece ser un factor que actha prmncipalmente en la sobrevida, pues
las malformaciones cardiovasculares fueron
tres veces mayores en el grupo prematuro que en los normales, con diferencia de significaciOn estadistica. El sexo y el color no tuvieron sig-nificaciOn estadIstica en la incidencia total.
La valoraciOn cuidadosa de los factores eti-ol#{243}gicos en el grupo de los 50 casos con mal-formaciones mostrO que Ia edad materna y el niimero de embarazos previos tienen cierta importancia predisponente a las
malforma-ciones cardiovasculares. El riesgo de tener UR
nmno con malformaci#{243}n cong#{233}nita del coraz#{243}n
0 grandes vasos es mayor en el tercero que en el primer embarazo, en particular si Ia madre tiene mOs de 30 a#{241}osde edad. No hubo mayor incidencia de infecciones durante
el embarazo de las madres de estos ni#{241}osque
en las madres del grupo en total; no se
en-contrO papel especIfico de enfermedades o
exposiciOn a ellas en Ia etiologIa de
padeci-mientos cardiocos en general o persistencia del conducto arteriovenoso en particular; sin embargo, tres madres sugieren Ia posibilidad de que el herpes simple que sufrieron durante
el primer trimestre del embarazo se puede
relacionar a Ia tetralogia de Fallot; el niimero de madres que lo padecieron no fu#{233} signifi-cativamente mayor que en Ia poblaciOn
ma-terna global por lo que tal posibilidad, dice Ia doctora Richards, puede ser simple
coinciden-cia. No mostraron acci#{243}n aparente sobre el
curso del embarazo o la incidencia de las anormalidades cardiovasculares, factores ob-st#{233}tricoscomo padecimientos cardiacos, smfihis, artritis, hemorragia vaginal, tumores p#{233}lvicos o toxemia.
29
hacen preparativos para el tratamiento
quir(ir-gico. Los otros 23 casos no se han
diagnosti-cado completamente, tres han fallecido y 20
ann viven; los diagn#{243}sticos provisionales son:
16 con comunicaciones de tabique, 3 con
tetralogIa de Fallot, 2 con cianosis no definias
y dos con “hipertrofia idiop#{225}tica.”
Se presentan algunos sintomas y signos de
inter#{233}s para la tetralogia de Fallot y Ia
persi-stencia del conducto arteriovenoso; siete fli#{241}OS
COil el primer diagnOstico que sobrevivieron al perlodo neonatal, desarrollaron cianosis
per-manente dentro del primer aflo de edad, 5 tuvieron soplo ar nacimiento, uno de ellos a los dos meses y el Oltimo a los cinco meses
(Ic edad; 4 de 5 niflos mayores ya de dos
anos desarrollaron dedos en palillos de tambor
entre los 2 a 3 aflos de edad; 6 de los 7 casos presentaron disnea, cianosis o ataques sincopales en los dos primeros aflos de la vida.
Ninguno de los 5 ni#{241}oscon persistencia del
conducto arteriovenoso presentO soplo durante
Ia primera semana de la vida 4 de ellos lo
presentaron por primera vez a los doce meses
de edad q 5 de ellos a los veinte; en este grupo
de ni#{241}osno se observaron signos o sintomas
constantes con la anomalla. La autora encontr#{243}
notables diferencias en las edades maternas y
m’imero de embarazos de estos dos grupos de enfermos, mucho mayor para las madres de
los ni#{241}oscon tetralogIa; datos que hacen
su-ponerle un factor gen#{233}tico, reforzado por el hecho de haber encontrado en ellos otras
mal-formaciones.
La radiografIa de tOrax de los reci#{233}nnacidos se consideraron considerablemente menos
vali-osas que el examen clinico para hacer un
diagnOstico de la cardiopatia cong#{233}nita, lo que
no es de sorprender ya que Ia silueta y
con-tomb cardiacos son frecuentemente normales en los reci#{233}nnacidos con tales anomallas; las observaciones realizadas en esta serie sirven
para recalcar Ia inutilidad de hacer rutinarias
con el fin de eliminar padecimientos cong#{233}nitos cardiacos, las radiograflas de tOrax a esta edad.
El timo fu#{233}un factor de importancia en
de-terminar amplias variaciones de Ia sombra
cardiaca.
La mortalidad global del grupo que
sobre-viviO el periodo neonatal ha sido de 37.2% a
los dos aflos, debi#{233}ndose en eI 27.9% a Ia lesiOn
cardiovascular en si. 27 de los 50 casos han sobrevivido m#{225}sde dos aflos.
En 18 de los 50 pacientes hubo un 36% de malformaciones asociadas, siendo m#{225}s
afecta-dos los Organos derivados del ectodermo
APPENDIX
Last J)rjjpj .lasocialsd Auodate4 Miscellaneou3
# (]VM #{163}‘VM CMother Dab
I ‘I’etxad of Fallot Bicuspid aortic valve. Diaphragmatic hernia. Died at 1 hour.
,e Tetrad of Fallot Persistent left superior vena Microphthalmo*. Murmur, cyanosis at birth.
cava. Cleft palate & hare lip. l)yspnea at 7 days.
Right-sided aorta. Polycystic kidneyu Died at IS days.
Fistula between left pulmonary Hydroureter.
artery & left bronchial ar- Anomalies of toes & fingers.
tery. Syndactylism.
Malformation of the uterus.
a ‘Fetra(l of Failt Right-sided aorta. Diaphragmatic hernia. local- Cyanosis 1 month.
Sub-endocardial fibrosis, left ized to anteriomedial por- Syncoal attacks, 4 months.
auricle. tion. No murmur through 6 months.
Anomalous origin left subclav- I)ied at 15 months.
ian artery. Patent foramen ovale. Common coronary artery trunk.
lttrad of l:illot Itiglit-sided aorta. a Murmur at birth.
Cyanosis at 7 months.
Dyspnea at 15 months. Clubbing at 3 years.
Operated at age 3 years, 4 months.
5 Tetrad of Fallot 0 Murmur, cyanosis at birth.
Squatting, clubbing at 25 months.
II Patent ductus arteriotu 0 Cataract. Murmur at 71 months.
Microphthalmos. Continuous at 3 years.
l)ental anomaly. Growth retarded.
7 Patent (luctus arteriosus I) Murmur at 6 weeks.
Continuous at 9 months. Operated at 3 years.
8 Patent (luctus arteriosus 0 Murmur at 4 months.
Continuous at 6 months.
Operated at 2j years.
9 Patent ductus arteriosus 0 Continuous murmur at 6
months.
Operated at 3 years, 10 months.
10 Patent ductus arteriosus 0 0 Murmur at 20 months.
Continuous 3 years, 10 months.
Operated at 1 years.
Ii Anomalous origin right sub 0 Sacrococcygeal teratoma. Stillborn
clavian artery
1 Absence right hypogastric ar- 0 0 Stillborn
tery
i:b Anomalous origin right sUb)- 0 0 Stillborn
clavian artery
14 Anomalous origin right sub- 0 Tracheo-esopbageal fistula. Died at 4 days.
clavian artery
15 Absence right hypogastric ar- 0 Craniostenosis. Died at Q4hours.
tery Polydactylism.
Syndactylism.
Diaphragmatic hernia.
Horseshoe kidney.
