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OCR for page 99
Chapter VIll
ANALYSIS OF THE MALFORMATION DATA
DATA on major malformations were collected
at the examination shortly following birth, and
again at the 9-months examination. For the
reasons advanced in Section 2.6, it was deemed
advisable to consider the results of these ex-
aminations separately. Moreover, to permit pool-
ing the information from the two examinations,
if such pooling was warranted, all infants found
on the "at-birth" examination to have one or
more major malformations were excluded from
consideration in the analysis of the 9-months
data.
8.1 The trail. In any consideration of the
relation of parental irradiation history to the
occurrence of major congenital malformations
in the offspring, it is of course first necessary to
define major congenital malformation. Since
there is no absolute dividing line between "ma-
jor" and "minor" malformation, an attempt to
formulate an a pYiori definition encounters cer-
tain difficulties. In actual practice, the examining
physicians were required to record all abnormali-
ties, down to and including such variations as
minor haemangiomas (excluding the very com-
mon occipital-nuchal type) and auricular pits.
When the final report on each infant was coded,
a decision was made as to the presence of major
malformation. Any one type of malformation
was consistently coded as either major or minor.
Table 8.1 is a listing of the malformations
which in the course of this investigation were
coded as major. A discussion of the relative fre-
quencies of the various malformations, and the
various combinations in which they occurred,
will be presented elsewhere. For our present
purposes, then, we shall define major malforma-
tion simply as any condition found on that
list. Obviously there are many other major
congenital malformations which do not appear
on that list, simply because they either did not
occur in this series, or, if they did occur, were
not recognized at birth. This listing deals solely
99
with conditions recognizable at birth by the
usual physical examination. A later chapter will
deal with autopsy findings.
S.2 Reliability of diagnosis. A question
which arose repeatedly during the course of
this study and which will undoubtedly occur
to the reader concerned the completeness
with which the significant malformations oc-
curring in the populations under study were
recognized and reported. This question has
already been commented on briefly (Sec. 2.6~.
It should at the outset be made quite clear that
no study organized as this one was can be
expected to yield an accounting of all signifi-
cant congenital defects present in the newborn
population. Thus, the diagnosis of mental de-
fect, or severe visual or hearing loss, is notori-
ously unreliable during the first several months
of life. From the standpoint of the present
study, while for obvious reasons one should
strive for as high a level of diagnostic accuracy
as possible, the primary danger to be guarded
against is that different diagnostic standards
obtain for the various segments of the popula-
tion under study. There is no reason to believe
that diagnostic standards were not uniform with
respect to infants in one exposure subclass as
compared with infants in another. We have al-
ready commented briefly on some of the evi-
dence suggesting that no bias has been intro-
duced by differences in the degree to which
various groups cooperated in the study (Sec.
5.7~.
It is important to reiterate that each infant
recorded in this study, with the exception of a
certain number of stillbirths or neonatal deaths,
as recorded in Section 2.5, was examined by a
Japanese physician. It was recognized from the
outset that both the loyalties and training of the
midwife were such that she might at times fail
to record the obvious. This suspicion was well
justified by instances in which a child with
OCR for page 100
00
Genetic Effects of Atomic Bombs Chapter VIII
harelip has been reported as normal by the at- marily occasioned by the disposal of the body of
tending midwife. Beginning in early 1950, the an infant alleged to have a major defect before
mothers of all living infants found to have examination by an ABCC physician, every mal-
either a major or a minor malformation in the formation recognized at birth was verified be-
course of the home visit were invited to bring fore the defect was accepted. Prior to early
TABLE S.1 AN ALPHABETICAL LISTING OF THOSE MALFORMATIONS OBSERVED IN THIS STUDY WHICH
OCCURRING ALONE OR IN CoMs~NAT~oN WITH ONE ANOTHER WERE GRADED
As MAJoR CONGENITAL DEFECT
Achondroplasia
Albinism
Amputation, congenital
Anencephaly
Anonychia
Anophthalmos
Arthrogryposis
Atresia ant or rectum
Atresia of the external nares
Blepharophimosis
Brachydactyly
Cataracts
Central nervous system defect, severe
Claw hand
Cleft palate
Club foot
Coloboma iridis
Corneal defect
Cryptophthalmia
Cystic hygroma
Diaphragm, defect of
Diastasis recti, severe
Dislocations, multiple, congenital
Dysplasia of acetabulum, congenital
Ectodermal defect, congenital
Ehlers-Danlos syndrome
Encephalocele
Exostosis, severe, of bone
External ear, major malformation of
Facial cleft, oblique
Flexion deformity of Angers and toes
Foetus amorphous
Foetus papyraceous
Funnel chest
Gastroschisis
Harelip
Heart disease, congenital, cyanotic
Hemimelus
Hydrocephalus
their children to an ABCC "Verification Clinic"
at some convenient time shortly after the diag-
nosis. Transportation to and from the clinic
was supplied by the ABCC. There the child was
seen by another Japanese physician and an
American physician. Thus, with exceptions pri
Hypertelorism
Hypospadias, marked
Ichthyosis congenita
Inguinal hernia (females)
Intestinal obstruction, ? congenital defect
Lymphangioma
Macroglossia
Major bone, absence of
Malformation, complex and ill-defined
Microcephaly
Micropenis
Microphthalmus
Microtia
Mongolism
Neurofibromatosis (von Recklinghausen's dis-
ease)
Nystagmus, congenital
Oligodactyly
Omphalocele
Polydactyly
Polyostotic fibrous dysplasia
Polyoty
Ptosis of eyelids
Pupillary membrane, persistent
Radio-ulnar synostosis
Recto-vaginal fistula
Rhinencephaly
Situs inversus viscerum
Spina bifida with or without menir~gocele or
myelomeningocele
Status Bonnevie-Ullrich
Sympodia
Syndactyly
Synorchism
Teratoma
Thyroglossal duct, persistent
Tumor, type undetermined
1951, major malformations were usually veri-
fied by a second home visit on the part of either
one of the more experienced Japanese physicians
or an American pediatrician. An analysis of the
results of these home visits and Verification
Clinic indicate a high degree of accuracy of
OCR for page 101
Analysis of the Malformation Data
diagnosis for those defects recognized as
present.
The crucial question is, how many defects
which should have been diagnosed at birth went
101
our control material with roughly comparable
material collected by other investigators. The
most extensive and reliable Japanese series to
come to our attention is that compiled by Dr.
TABLE 8.2 THE TYPES AND FREQUENCY OF VARIOUS MAJOR CONGENITAL MALFORMATIONS OBSERVED AT
THE TOKYO RED CROSS MATERNITY HOSPITAL DURING THE YEARS 1922 THROUGH 1940
(The over-all frequency is 456 malformations among 49,645 births t0.92~o]. The table is based on data
made available by Drs. S. Mitani and V. Kuji.)
No. of
Description of abnormality cases
Acrania or hemicrania (anencephaly) .... 32
Hydrocephalus .............
Congenital ascites ..........
Spina bifida with club foot....
Sacral teratoma ..........
Umbilical cord hernia (omphalocele) ....
Spina Linda .........................
Club foot (T. varus, T. equino-varus)..
Harelip with cleft palate..............
Polydactyly ( fingers ) ................
Cleft palate ........................
Club foot (T. valgus) ...............
Hemangioma or lymphan,gioma.........
Congenital teeth ....................
Malformation of ear lobe..............
Micromelus .........................
Atresia ant et vaginalis (including imper-
forate anus) .......................
Syndactyly of toes ...................
Microphthalmia (and others)..........
Luxation of knee joint................
Polydactyly (toes) ...................
Microcephaly .......................
Pseudohermaphroditism
......... 14
2
3
. 3
9
8
63
53
38
30
18
16
13
13
11
10
10
7
6
6
4
4
Hydrocephalus, cleft palate, gastroschisis 1
Atresia and, umbilical hernia 1
Atresia and, malformation of external au
ditory canal 1
Atresia and, cleft palate (mild degree?.. 1
Atresia and, sympodia 1
Atresia and, cleft palate 1
Cleft palate, oblique facial cleft 1
1
1
Cleft palate, malformation of fingers.....
Cleft palate, malformation of ear.......
Harelip, pseudohermaphroditism .......
Harelip, oblique facial cleft, absent nose,
syndactyly (fingers) ...............
Harelip, Polydactyly (fingers), syndactyly
(toes ) ...........................
Fissured palate, club foot.............
Fissured palate, microphthalmia.........
Club hand, club foot, small thumb, miss
ing right labium 1
Elbow contraction, club foot, luxation of
knee joint 1
1
l
No. of
Description of abnormality cases
Inguinal hernia, micromelus, hydrocepha
lus 1
Gigantism of feet and arms 1
Polydactyly ( toes ), harelip 1
Polydactyly (fingers), syndactyly (fin
gers ) 1
Syndactyly (fingers), harelip 1
Torticollis, abdominal hernia 1
Torticollis, club foot, facial asymmetry. ..
Monophthalmia, Polydactyly (toes).....
Monophthalmia, Polydactyly ( fingers ) . . .
Hydrocele ..........................
Cleft hand (lobster claw).............
Polydactyly ( toes ) with syndactyly (toes ~
l
4
4
Ankylo-glossum (tongue-tie) 3
Club foot (T. calcaneus) 3
Abnormal elbow joint 3
Malformation of external auditory canal. . 3
Amelus (arm or arms missing) 3
Inguinal and scrotal hernia
Meningocele (cranium)
Club hand
Brachydactyly ( 2 fingers ~
Contraction of the knee joint
Polydactyly (toes) with syndactyly (fin
gers )
Malformation of fingers
Absence of nose
Club foot (T. equinus)
Parasitic teratoma of jaw
Tumor of "waist"
Bind uvula
Hypospadias or epispadias
Cleft sternum (lower portion)
Phimosis (extreme)
White hair (partial albinism)
Tumor (small) of vagina
Anencephaly, Polydactyly (fingers)
Club foot, syndactyly (toes)
Club foot, malformation of fingers
Malformation of face
Monster (amorphous)
Polydactyly (fingers and toes) 1
Missing fingers, syndactyly (toes) 1
2
2
2
2
l
l
unrecognized? There are three general ap- V. Kuji (personalcommunication) et the Tokyo
preaches to the evaluation of this question
which we shall now consider.
(A) The first approach involves a compari-
son of the frequency of major malformation in
Red (gross Maternity Hospital. the Endings are
shown in Table 8.2. The over-all frequency of
malformed individuals in this series (0.92 per
cent) and in the children of the non-irradiated
OCR for page 102
102 Genetic Efects of Atomic Bombs Chapter VIII
parents included in this study (0.85 per cent)
is quite comparable. The agreement is all the
more striking in view of two facts: (1) certain
of the "malformations" on the Kuji list, such
as congenital teeth, hydrocoele, and partial
albinism, would be considered minor in our
terminology, and (2) a hospital series in Japan
cannot be considered random, but probably in-
cludes a disproportionate representation of the
complications of pregnancy. In view of the
tendency of gross malformations to be associated
with such complications as hydramnios (Prindle,
Ingalls, and Kirkwood, 1955), this should bias
the Red Cross Hospital series in an upward di-
rection. There is no evidence from this compari-
son that any considerable number of congenital
defects diagnosable at birth are being over-
looked in Hiroshima and Nagasaki.
(B) A second approach to the question of
missed diagnoses of significant defect consists
of checking the ABCC findings against those
of another medical group in Hiroshima or
Nagasaki. Such a spot check was carried out for
the last three months of 1951 in Nagasaki. Out
of twelve major "malformations" seen at the
two largest hospitals in the city (the Nagasaki
recur in the remainder of the study. It might
be noted, however, that, as can be seen in Sec-
tion 2.6, most of the errors were ones which
would overestimate the number of those diag-
noses which were made at birth and not subse-
quently verified at nine months. We may now
compare the final figures for major malforma-
tions present in those infants examined at age
9 months with the findings recorded for these
same infants at birth. Such a comparison, repro-
duced in Table 8.3, provides the best means
available for reaching an opinion concerning
the confidence to be placed in the "at-birth"
data on congenital malformation. Perusal of
the table brings out a number of Points of
interest. Out of a total of 563 infants with one
or more major defects diagnosed either at the
examination shortly after birth or at the ex-
amination at an age of approximately 9 months,
or on both occasions, only 112 were clearly
verifications at age 9 months of an "at-birth"
diagnosis. However, there were altogether 130
infants with one or more major defects in whom
the diagnosis could not be verified at 9 months
because of the death of the child in question; it
seems likely that the great majority of these
children did indeed suffer from a major mal-
formation. The 2 cases of defect at birth which
were not verified at age 9 months were both
cases of polydactyly which we assume to have
undergone surgery. Of the total number of de-
fective infants detected by these two approaches,
then, the figures taken at face value indicate that
only 43 per cent of them were observed at
birth. However, it is clear that in many of the
319 infants with one or more defects not
diagnosed shortly following birth, the defects
are of such a nature that their certain detection
at that time would have been difficult if not
impossible. This is especially true of the two
diagnoses which contribute most to this list
. .
Medical School Hospital and the Mitsubishi
Hospital), five were already known to the
ABCC. The remaining seven were the follow-
ing: congenital dislocation of the hip 3
cases; congenital heart disease 2 cases; idiocy
with funnel chest - 1 case; hydrocephalus - 1
case. In view of the frequent delayed appear-
ance of congenital dislocation of the hip and
hydrocephalus, these cases are not thought to
constitute "missed" diagnoses. As noted earlier
(Sec. 2.6) congenital heart disease was not in-
cluded in the "at-birth" series of the ABCC.
Only the funnel chest perhaps should have been
detected in the ABCC series. Again, then, there
is no evidence that any substantial proportion O -
of major defect diagnosable at birth by the (dysplasia of the acetabulum- 133 cases; and
techniques of physical examination was missed. inguinal hernia in females 56 cases; total-
(C) A third approach to the question of 189 cases, 33.6 per cent of the grand total of
accuracy of diagnosis comes from a comparison 563 infants or 59.3 per cent of the additional
of the "at-birth" with the "9-months" series. infants diagnosed at 9 months). The relatively
In Section 2.6 we have recorded the results of high frequency of acetabular dysplasia may re-
a "spot check" in Hiroshima in 1952 concerning fleet a particular interest in this condition on
the clerical and medical problems which can the part of several of the American pediatri-
arise in a program concerned with congenital clans associated with the project. We have at-
malformations such as this, and the steps taken tempted to indicate in the table by a single
to meet some of these problems. Every effort asterisk those diagnoses which should in all
was made to insure that these errors did not probability have been made at the time of the
OCR for page 103
Analysis of the M alformation Data
TABLE 8.3 A COMPARISON, FOR HIROSHIMA AND NAGASAKI, OF THE FINDINGS AS REGARDS MAJOR
CONGENITAL MALFORMATION IN INFANTS EXAMINED AT APPROXIMATELY AGE 9 MONTHS, AND
IN THOSE SAME INFANTS WHEN EXAMINED SHORTLY AFTER BIRTH
103
(The figures are obtained from 14,768 infants in Hiroshima and 12,324 infants in Nagasaki. Infants born
of consanguineous marriages have not been excluded from this comparison. Since no diagnoses of congenital
heart disease were accepted on the "at-birth" examination, this diagnosis does not appear in the comparison.
There were 50 such diagnoses made in Hiroshima in the "9-months" examination and 55 in Nagasaki. Ex-
planation of asterisks in text.)
Comparison
1. Total number of infants in whom a diagnosis of one or more
major malformations was made on the "at-birth" and the
"9-months" examination...............................
Total number of infants in whom a diagnosis of one or more
major malformations was made on the "at-birth" examination,
but who could not be re-examined at age 9 months because of
Hiro
shima Nagasaki Total
57
55 112
the Heath of the child 74 56 130
3. Total number of infants in whom a diagnosis of one or more
major malformations was made in the "at-birth" examination,
but in whom no major defect was detected at age 9 months.. . 2
4. Total number of infants in whom no diagnosis of major mal
formation was made at birth, but in whom one or more major
defects were detected in the "9-months" examination a 165
o
154
Achondroplasia ~ 1 2
Anterior synechiae 0 1
Branchial cyst 0 1 1
Cataracts ~ ~ , 1 0
Club foot ** 2 2
Coloboma of eyelids ~ 1 1
Coloboma of iris ~2 0
Cyst, thyroglossal 1 0
Complex and ill-defined condition ! 0 1
Cryptorchism 0 2
Deformity of bone O
Dextrocardia * O
Dysplasia of acetabulum 76
Ectodermal defect, congenital O
2
319
3
1
4
2
l2
1
2
1
133
1
Funnel chest ~ * 8 5 13
Hammer toe 0 1
Harelip and cleft palate * 1 2
Hernia, inguinal, in females 35 21
Hydrocephalus 4 1
Hypertelorism ** 0 1
Hypoplasia of bone 0 1
Ichthyosis (congenital type)** 3
o
Laryngeal strider, congenital O
Lymphangioma O
Maldevelopment of central nervous system 0 1
18
2
o
o
Mental defect, severe
Microcephaly .......
Micrognathia * .....
Micropenis ~ .......
Microphthalmus ~ ......................................
Microtia ~ . . .
Mongolism ~ ~
Nystagmus, congenital 0 6
Polydactyly *
Ptosis 1
.......................................... 1 0
3
3
1
1
6
1
1
2
6
1
OCR for page 104
104 Genetic Ejects of Atomic Bombs Chapter VIII
TABLE 8.3-Continued
C.
omparlson
Hiro-
shima
1
4
1
5
1
Situs inversus viscerum
Spastic infantile paralysis
Spina bifida *
Strabismus
Syndactyly *
Teeth, malformation of
Tumor, cutaneous O
Nagasaki
3
o
o
3
1
Wilm's tumor 0 1
Xeroderma pigmentosum 0 ~
165 154
- A Defective infant regardless of number of major defects. is entered under Item 4 in the
Total
4
4
1
8
2
l
1
1
319
563
~ table only
once. In case two or more major defects were detected for the first time at the 9-months examination, only the
most severe of the defects is listed under Item 4.
"at-birth" examination, and by a double aster-
isk those diagnoses which as a rule are more
difficult to make in newborn infants but which
might well have been made at that time. (How-
ever, each infant was entered into Table 8.3
but once, and the numbers entered opposite
specific diagnoses under item 4 refer to the
number of infants in whom that diagnosis was
considered the most severe one). There are 35
diagnoses in the first category, and 22 in the
second. All of the remaining defects may either
not have been diagnosable at birth or are of
such a nature that uncertainty might surround
them.
In Section 2.6 the possibility was raised that
such relatively common diagnoses as acetabular
dysplasia and pilonidal sinus "unbalance" the
9-months data. These are both Endings which
border on being normal variations, in their less
extreme forms. Ideally, in an analysis of this
type one would introduce a weighting constant
to take into account the genetic component in
the etiology of the various malformations under
study, but in view of the obvious impossibility
of this, there seemed no alternative to giving
each diagnosis, including the common ones,
equal weight.
Despite the many observations which have
been published on congenital malformation in
man, it is a surprising fact that to our knowl-
edge there exists only one series comparable to
this one, in terms of re-examination at some
later date of a series of infants examined shortly
after birth. McIntosh et al. (1954), in a study
of 5,739 products of conception weighing over
500 grams who were followed, unless death
intervened, until 12 months of age, and some
even longer, found that only 43.2 per cent of
all malformations detected in the course of the
study were observable at birth. Although for a
number of reasons, to be dealt with elsewhere,
these figures are not directly comparable to our
own, the general agreement between the two
series is striking.
Table 8.3 also serves another purpose, in that
it permits a partial comparison of the diagnoses
being made in Hiroshima and Nagasaki. With
one possible exception, the findings in the two
cities appear as uniform as might be hoped for
under these circumstances. It will be noted that
severe mental defect is listed 18 times for Naga-
saki, but only twice for Hiroshima. It seems
quite likely that this reflects a difference in ap-
proach in the two cities, rather than a real
difference.
8.3 The genetic argz~mer;t for radia~ion-ir'-
duced changes. Within the spectrum of mu-
tations induced by the irradiation of experi-
mental animals, the most dramatic, but least
common, group of mutations are the so-called
"visibles." These mutations produce, as the
name implies, visible alterations in the pheno-
type. Although direct evidence is lacking, it
seems probable that in man a certain fraction of
these mutations would lead to gross physical
departures from the norm readily detectable at
birth. Accordingly, one measure of genetic
damage consequent to atomic bombing would
entail determining whether differences in the
frequency of congenital malformation arose
OCR for page 105
Analysis of the Malformation Data
consistent with parental exposure. On an a
priori basis, we might expect that the frequency
of malformation would increase with increasing
parental exposure.
The extent to which the frequency of mal-
formation would be altered by parental exposure
would, naturally, be a function of the com-
ponent in the etiology of such malformations
attributable to genetic factors. While this com-
ponent cannot be exactly specified, that it is not
inappreciable is indicated by (1) the number of
specific malformations known to be inherited,
and (2) the finding that the total malformation
rate within the Japanese data increases with
increasing parental relatedness (Schull, un-
published) .
f3.4 Concomitant variations inf Arcing the ir;-
dicator.-Among the numerous agents for
which there exists some evidence regarding a
role in the etiology of congenital malformations
in man, and which may prove important in the
analysis of these data, are such diverse factors
as maternal age, parity, nutrition, and viral in-
fections in the first trimester of pregnancy. No
really complete review of the literature on the
etiology of human malformations has been
published. Certain aspects of the etiology have
been treated by Warkany (1947), Gruenwald
(1947), and Landtman (1948~.
Within the data here presented, there appear
to exist only two sources of concomitant varia-
tion which require comment. These are: (a)
known differences between exposure categories
in maternal age and parity, and (b) possible
nutritional differences between the exposure
categories.
Of these concomitant variables maternal age
and parity are undoubtedly the most important.
An extensive literature exists describing the
effects of these variables on pregnancy outcome.
In the main, however, this literature is con-
cerned with the effect of maternal age and/or
parity on specific malformations rather than on
the total malformation rate. Two exceptions are
the work of Carter and McCarthy (1951) and
Coffey and Jessop (1955), who find a positive
association between maternal age and total
malformation rate.
The relationship of maternal age and parity
to malformation rate in the present data is sum-
marized in Tables 8.4 and 8.5 and Figures 8.1
and 8.2. Table 8.4 presents the effect of age for
specific parities. The data have been analyzed
105
according to the method of Krooth (1955~. In
the column headed "A.D." have been entered
by parity class, the absolute differences between
the proportion of all normal infants born at a
specific age interval and the proportion of all
malformed infants born at the same age interval.
A X2 test has been applied to the significance of
the findings for each parity class, with the usual
convention of indicating significance at the 5
per cent level with one asterisk, and at the 1
per cent level with two asterisks.
For each parity, an index of absolute differ-
ence (`IAD) has been calculated as suggested by
Krooth (1955 ), namely,
IAD=~di~
where do corresponds to the individual entries
in the column headed "A.D." For each parity
the proportion of the total number of births
which occurred at this parity {\PT) has been
calculated. The IAD for maternal age, all parities
considered, is simply the weighted mean of the
IAD'] for the individual parities. The same ma-
terial is presented graphically in Figure 8.1. In
the entire data, there is a highly significant age
effect, although only two of the individual parity
classes show effects at the level of significance.
It is noteworthy that by inspection, age effects
seem to be limited to the four highest parity
classes, suggesting an age-parity interaction. A
much more detailed analysis of these data will
be presented elsewhere.
Table 8.5 presents a similar analysis with
respect to parity effects. There is a highly signifi-
cant relationship between parity and the fre-
quency of malformation in the data as a whole,
consistent in all six age classes, although reach-
ing the level of significance in just one of these
six classes. The findings are shown graphically
in Figure 8.2. These results, like the age effects,
will be discussed in detail elsewhere. Suffice it
to say for the present that the effects of age and
parity appear to follow different patterns, the
age effect, as noted previously, emerging
strongly at the higher ages, the parity effects
being more uniformly distributed.
Carter and McCarthy (1951) were inclined
to attribute the positive association between ma-
ternal age and total malformation rate almost
entirely to the known association of mongolism
with increasing maternal age. This interpreta-
tion would not be valid for the Japanese data,
since there are included only three children with
OCR for page 106
106
Genetic EfJec~s of Atom~c Bom bs Chapter VIII
TABLE 8.4 THE EFFECT OF MATERNAL AGE AT FIXED PARITY ON THE FREQUENCY OF MALFORMED INFANTS
(Detai1ed eXP1anatiOn in teXt.)
TOta1 NOrma1 Ma1fOrmed Per Cent
birthS birthS infantS ma1fOrmed AD
ParitY 1
< 21 .........................1,9291,91316 0.83 .02982
21-25 .........................8,6978,63661 0.70 .02119
26-30 .........................3,1683,15117 0.54 .04538
31-35 .........................6216174 0.64 .00211
36-40 180: 198 1: 0.50 .00354
1 +
TOta1 14,614 14,515 99 - .10204
X 4 - 1.771 IAD = 0.0510
PT = 0.2664
ParitY 2
< 21 ......................... 424 421 3 0.71 .00541
21-25 ......................... 6,392 6,334 58 0.91 .01817
26-30 ............ ' 6,156 6,101 55 0.89 .01079
31-35 ......................... 1,431 1,420 11 0.77 .01145
36-40 ......................... 357\ 405 2} 0.49 .01209
41 + 50J -
TOta1 14,810 14,681 129 .05791
X 4 = 1.117 IAD = 0.0290
PT = 0.2700
ParitY 3
~37 36 1 2.70 .00577
~1
21-25 2,016 1,99917 0.84 .02999
26-30 '. 5,869 5,810 59 1.01 .00001
31-35 2,422 2,396 26 1.07 .01517
36-40 531 l 525 6l 1 17 .00609
41 + 67! 66 1; .00300
~_ _
TOta1 .......................10,94210,832 110 .06003
X23 = 0.618 I&V = 0.0300
PT = 0.1995
ParitY 4
21-25 487} 484 8} 1.63 .08157
26-30 ......................... 2,872 2,853 19 0.66 .05963
31-35 ......................... 2,537 2,523 14 0.55 .10750
36-40 ......................... 761 752 9 1.18 .06080
41 + 87 85 2 2.30 .02577
.
TOta1 ....................... 6,749 6,697 52 .33527
X24 11.091* I,5D = 0.1676
PT = 0.1230
ParitY S
21-25 ......................... 77T - ~1.20 .02400
26-30 ......................... 1,005 J 1,069 13J
31-35 ......................... 1,783 1,758 25 1.40 .0329S
36-40 ......................... 847 839 8 0.94 .06290
41 + ......................... 102 98 4 3.92 .05396
TOta1 3,814 3,764 50 .17381
X 3 = 6.466 IAD = 0.0869
PT-0.0695
OCR for page 107
Analysis of the Malformation Data
TABLE 8.4 Continued
Total Normal
births births
107
Malformed Per cent
infants malformed AD
Parity 6
21-25 .........................11 ~-l 1.59 .00587
2~30 .........................241 ~2484J
31-35 .........................989 97910 1.01 .15231
36~0 .........................794 78014 1.76 .06145
41 ~.........................147 1425 3.40 .08548
Total 2,182 2,149 33 .30511
X23 = 5.535 IAl) = 0.1526
PT = 0.0398
Parities 7 +
21-25 ......................... 4T - l 3.57 .04849
26-30 ......................... 52 ~54 2J
31-35 ......................... 455 449 6 1.32 .02196
36-40 ......................... 935 928 7 0.75 .26142
41 + ......................... 293 283 10 3.41 .23489
TOta1 1,739 1,714 25 .56676
X23 = 13.0464 * IAD = 0.2834
PT-0.0317
All Parities
< 21 ......................... 2,395 2,375 20 0.84 .00354
21-25 ......................... 17,684 17,540 144 0.81 .03355
26-30 ......................... 19,363 19,194 169 0.87 .01378
31-35 ........................ 10,238 10,142 96 0.94 .00617
36~0 ......................... 4,405 4,358 47 1.07 .01420
41 ~......................... 765 743 22 2.88 .03051
TOta1 ....................... 54,850 54,352 498
X25=36.39S' I'AD (for mOtherS age)=IPTIAD=0.0691
40T
3st
3.0t
MALFORMATION
(PER CENT)
42.st
2.0
1.5 .
1 n. .
. .
0.s- _
15
PARITY
- 7-8
· 6
1
lo.'` ~' .',}?
it. ~
// /
, . /
// I ,
/ ~
/ ll ,,
. / ,
.1 //
, ~
1
i
/ .1
/l
. 1
MOTHER S AGE
FIGURE 8.1 The distribution of the frequency of infants with major malformation by maternal age for
SPeCified parities.
OCR for page 108
108
Mother's age: ~ 21
Mother's age: 21-25
Genetic Efects of Atomic Bombs Chapter VIII
4.0
3.5
3.0
2.5
MALFORMATION
(PER CENT)
2.0
1 .5
1.0
0.5
MATERNAL AGE
36 -40
31-35
26 -30
21 -25
..~`'~~'~
-
. -.: ,/ · ~ `~S,. .ii \
_~ /
~\,
1 1 1 1 1 1 1 1 1
1 2 3 4 5 6 7 8
PARITY
FIGURE 8.2 The distribution of the frequency of grossly malformed infants by parity for specified
maternal ages.
TABLE 8.5 THE EFFECT OF MATERNAL PA Rib AT FIXED AGE ON THE FREQUEN CY OF
MALFORMED INFANTS
(Detailed explanation in text.)
Total Normal Malformed Percent
births births infants malformed AD
1 1,9291,91316 0.82 .00547
2 4244213 0.71 .02726
3 37}41_ } 2.38 .03274
. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Total 2,3952,37520 .06547
X2O = 1.296 IAD = 0.0327
PT = 0 0437
1 8,697 8,636 61 0.70 .06875
2 6,392 6,334 58 0.91 .04166
3 2,016 1,999 17 0.84 .00409
4 487: 81
5 77 ~571 l 1.38 .02301
6 111
7 + 4J - J
Total 17,684 17,540 144 .13751
X23 = 4.387 IAD = 0.0688
OCR for page 109
Mother's age: 26-30
Analysis of the Malformation Data
TABLE 8.5- Continned
109
Total Normal Malformed Per merit
births births infants malformed AD
1 3,1683,151 17 O.S4 .06358
2 6,1566,101 55 0.89 .00758
3 5,8695,810 59 1.01 .04641
4 2,8722,853 19 0.66 .03621
5 1,005992 13 1.29 .02524
6 241237 4 1.66 .01132
7 ~ 5250 2 3.85 .00923
Total 19,363 19,194 169 .19957
X20 = 15.935~. IAD = 0.0998 PT - 0~3530
Mother's age: 31-35
1 621 617 4 0.64 .01917
2 1,431 1,420 11 0.77 .02543
3 2,422 2,396 26 1.07 .03458
4 2,537 2,523 14 0.55 .10294
5 1,783 1,758 25 1.40 .08707
6 989 979 10 1.01 .00763
7 ~ . . ......... 455 449 6 1.32 .01823
Total 10,238 10,142 96 .29505
X 6 = 10.472 IAD = 0.1475 PT = 0.1867
Mother's age: 36-40
1 180 179 1 0.56 .01979
2 357 355 2 0.56 .03891
3 531 525 6 1.13 .00719
4 761 752 9 1.18 .01893
5 847 839 8 0.94 .02231
6 794 780 14 1.76 .11889
7 + 935 928 7 0.75 .06400
~_ _
Total 4,405 4,358 47 .29002
X26 = 6.095 I.\D = 0.1450 PT = 0.0803
Mother's age: 41 +
1 191 ~
2 ....... 50L 135 ~ 0.74 .13625
. . . . . . . . . . . . . . . . . . . . . .
3 67J 1J
4 87 85 2 2.30 .02349
. . . . . . . . . . . . . . . . . . . . . .
5 102 98 4 3.92 .04992
6 ....... 147 142 5 3.40 .03615
. . . . . . . . . . . . . . . . . . . . . .
7-- 293 283 103.41 .07366
Total 765 743 22- .31947
X24 = 3.184 IAD = 0.1597 PT = 0.0139
All ages:
1 14,614 14,515 99 0.68 .06826
2 14,810 14,681 129 0.87 .01107
3 10,942 10,832 110 1.01 .02159
4 6,749 6,697 52 0.77 .01880
5 3 814 3 764 50 1.31 .03115
. . . . . . . . . . . . . . . . . . . . . . . . . .
6 2,182 2,149 33 1.51 .02673
7-- 1,739 1,714 25 1.44 .01867
....................... 54,850 54,352 498 -
X26 = 32.594** I" AD (parity) = 0.1002
OCR for page 110
110 Genetic Efects of Atomic Bombs Chapter VIII
diagnoses of mongolism, and of these three,
one was born at a maternal age of 25 and the
other two at 34 and 40 years of age. The diag-
nosis of mongolism, while not particularly un-
common at 9 months of age (1 out of 1,580
children), was singularly infrequent in the at-
birth data. This is not surprising in view of the
not-uncommon failure to diagnose mongolism
at birth in Caucasian infants, and the added
diagnostic difficulties among Japanese.
In view of the greater average age and parity
of the mother as parental exposure increases, a
spurious irradiation effect could arise if the data
were unadjusted for this fact. It might also be
pointed out, however, that if no differences are
demonstrable without age-parity adjustments,
it is unlikely that differences will be detected
following adjustment because of the direction of
the bias.
It was felt that while some adjustment for
age-parity effects was indicated, any attempt to
subdivide the present data in such a manner as
to take into consideration both age and parity
effects would jeopardize the validity of the
statistical tests employed. Somewhat arbitrarily
the decision was reached to take into considera-
tion age but not parity effects. Accordingly,
for this analysis the terminations have been
classified not only with respect to sex, city, and
parental exposure, but also maternal age. Five
age categories were recognized, namely, 15-20,
21-35, 3~38, 39~1, and 42 and over. Since
the selection of the age intervals is purely arbi-
trary, the intervals were so selected as to be of
the shortest span consistent with significant
numbers in those areas where maternal age
appears to be most important. It must be borne
in mind, however, that the "age effects" which
emerge from this analysis are also in part
"parity effects." Some bias may be introduced
as a consequence of ignoring parity but this bias
would again appear to favor a higher rate of
malformation among the exposed population.
The necessity for accounting for possible
differences between exposure cells in maternal
nutrition is more difficult to appraise. Warkany's
(1947) extensive studies on the effect of severe
dietary stresses on pregnancy outcome in gravid
rats and mice would lead to the conclusion that
diet is of considerable importance. In these
animals, the degree of dietary stress needed to
induce malformation is, however, far more
severe than could have obtained even in the war
torn cities of Japan. Moreover, neither Smith
(1947) nor Antonov (1947), in their studies
of the populations of Rotterdam and Leningrad
following severe dietary stress during World
War II, could demonstrate an increase in the
frequency of congenital malformations. What-
ever dietary stresses may have existed in the
populations of Hiroshima and Nagasaki during
the earlier stages of this study were very prob-
ably not so severe as those which obtained in
Rotterdam and Leningrad. With respect to
possible differences in nutritional status between
exposure categories, detailed dietary histories
on random samples of the population are not
available. However, in a marginal economy such
as existed in post-war Japan, there is undoubt-
edly a high correlation between economic status
and nutritional level; we have already seen
(Sec. 5.3) that in neither city is there a demon-
strable relationship between economic level and
exposure history. It will be assumed in this
analysis that there are no important differences
in maternal nutrition with respect to the various
exposure subclasses.
Lastly, by way of completing a discussion of
the concomitants, it might be mentioned that
during the course of this study no exceptional
epidemics of German measles or other viral
infections were known to have occurred in
Hiroshima or Nagasaki.
S.5 The "~-birth" data. In Tables 8.6
and 8.7 are presented the "at-birth" frequencies
of major malformation by parental exposure,
sex of infant, and city, with and without classi-
dcation of the termination by maternal age.
Inspection of these tables reveals no striking,
general differences in the frequency of infants
with at least one major malformation by sex,
city or parental exposure. The results of the
analysis of these two tables are given in Tables
8.8 and 8.9. From Table 8.8 (a and b) we note
no demonstrable differences when age is ig-
noted, among the cities, sexes, or parental ex-
posures. It is worth noting at this point that the
frequency of malformation in the unexposed
groups in Hiroshima and Nagasaki is very simi-
lar to the frequency of malformation in Kure
where during the years control studies were in
effect there 57 malformed infants were reported
in 7,544 registered terminations (0.76~o).
In Table 8.9, with the data further parti-
tioned to take into account age differences
among the parents, the only "main effect"
OCR for page 111
Analysis of the Malformation Data
TABLE 8.6 FREQUENCY OF AlALFORMED INFANTS BY PARENTAL EXPO
SURE, SEX OF INFANT, AND CITY
(Unrelated parents)
Male infants
Hiroshima
: -
cat
in
1] m
UP
in
2/ m
UP
En
3/ m
UP
Mothers
1234-5Total
En9,0052,8321,11457113,522
15 m733046113
tp.0081.0106.0036.0105.0084
En7729412201092,042
2] m1114-126
(p.0142.0149-.0092.0127
En31319726854832
3/m42129
tp.0128.0102.0037.0370.0108
En2091228056467
4-5gm11 2
l P.0048.0082 .0043
En10,299 4,0921,68279016,863
Total: m89 4759150
tp.0086 .0115.0030.0114.0089
Male infants
Nagasaki
r ~
Mothers
3
360
4-5
279
4 3
.0111 .0108
1,120
7
.0063
12
7,6084,849
6839
.0089.0080
2,112
23
.0109
129
4
.0310
140
Total
13,096
114
.0087
134 563,422
2 -32
.0149 -.0094
51 18
1
-.0196
338
.0148
( n751031415207
4-54m2 --2
tP.0267- _.0097
En8,9327,20455936817,063
Totals m816273153
tp.0091.0086.0125.0082.0090
111
OCR for page 112
112 Genetic EJects of Atomic Bombs Chapter VIII
TABLE 8.~Continaed
Female infants
Hiroshima
1<
2 :1
cow
cat
Mothers
1234-5Total
n8,2892,5361,07154612,442
m8721107125
p.0105.0083.0093.0128.0100
rn728909204931,934
) m6122222
(p.0082.0132.0098.0215.0114
rn28318825356780
3g m324110
tp.0106.0106.0158.0179.0128
in1861227761446
4-5]m31116
tp.0161.0082.0130.0164.0135
En9,4863,7551,60575615,602
Total: m99361711163
p.0104.0096.0106.0146.0104
Female infants
Nagasaki
Mothers
~ ~34
cc
In
13 m
IMP
| n
24 m
IMP
En
' m
IMP
| n
4~54 m
IMP
1 in 8,230
I Total] m
7,002
66
.0094
4,467
31
.0069
1,0502,032
13
.0064
.0038
114
1
.0088
64
2 3 4-5Total
28012,136
105
.0087
603,287
20
.0061
307
1
.0033
387
.0129 .0107
145
.0207
133
43
17
75 21 13
.0267
173
2
- .0116
6,707596
71468
.0086.0069.0134
37015,903
3128
.0081.0080
OCR for page 113
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OCR for page 114
14
Genetic Effects of
emerging at the level of significance is the al-
ready discussed effect of maternal age on the
frequency of congenital malformation. Among
the first order interactions none is significant
save mother's exposure-mother's age. However,
since the effect of mother's exposure is not inde-
pendent of age no generalizations can be made
with respect to the effect of maternal irradiation
TABLE 8.8 CHI SQUARE ANALYSIS OF THE FRE
QUENCY OF CONGENITALLY MALFORMED INFANTS
BY SEX, CITY, AND PARENTAL EXPOSURE
(Unrelated parents)
a. All exposure cells (4 X 4)
Atomic Bombs Chapter VIII
age levels. For these five age levels mother's
exposure seems to exert an effect only in the
15-20 year age interval. From inspection of
Table 8.10 we note that the frequency of mal
TABLE 8.9 CHI-SQUARE ANALYSIS OF THE FRE
QUENCY OF CONGENITALLY MALFORMED
INFANTS BY CITY, MATERNAL AGE,
AND PARENTAL EXPOSURE
(Unrelated parer~ts)
All exposure cells
Total ...............
Interactions, first order
DF %2
164.205
156
p
.50-.60
Source DF %' P CM 3 9.657 .02-.05
Total 63 63.077 .50-.60 CF 3 2 053 50- 70
Interactions, first order AM 12 23.786 .02-.05
CS 1 1.039 .30-.50 AF 12 7.907 .70-.80
CM 3 9.427 .02-.05 MF .............. 9 6.107 .70-.80
CF 3 2.054 .50-.70
SM 3 5.210 .10-.20 Main effects
SF 3 3.057 .30-.50 Age (A) 4 18.057 .001-.01
MF 9 6.107 .70-.80 City (C)&
Age intervals
Main effects 15-20 ......... 1 0.438 .50-.70
City (C) 1 2.269 .10-.20 21-35 ......... 1 2.720 .05-.10
Sex (S) 1 0.169 .50-.70 36-38 ......... 1 0.032 .80-.90
Mothers (M) 3 1.907 .50-.70 39~1 ......... 1 0.062 .80-.90
Fathers (F) 3 1.232 .70-.80 42 + ......... 1 1.863 .10-.20
b. Excluding parents in Category 1 (3 X 3) Sum 5 5.115 .30-.SO
Source DF %2 p Mothers (M)a' b
Total 35 28.806 .80-.90 Age integrals
15-20 ......... 3 14.581 .001-.01
Interactions, first order 1 1 027 30 50 21-35 ......... 3 4.463 .20-.30
CS . ~ 36-38 3 2277 50-70
CM . 2 6411 O0-05 39_41 3 3 111 30_50
SM 2 3 052 20- 30 42 + ......... 3 1.462 .50-.70
5F 2 2 364 30-50
MF 4 4 080 30- 50 Slam ........ 15 25.894 .02-.05
Main effects
City (C) 1
Sex (S) 1
Mothers (M) 2
Fathers ~ F ) 2
based on the main effects test alone.
2.406 .10-.20
0.015 .90-.95
0.222 .80-.90
0.480 .80-.90
In order
to interpret the effect of maternal exposure, we
must consider separately the maternal age classi-
fications. Table S.10 presents the distribution
of the frequency of malformation by mother's
age and exposure. For purposes of comparison
and its bearing on a possible somatic maternal
effect, a comparable table (Table 8.13) is given
for father's exposure. In Table 8.11 are given
the results of analyzing the effect of mother's
exposure at each of the five different maternal
Fathers (F)&
Age intervals
15-20 .........
21-35 .........
36-38 .........
39~! .........
42 + .........
3
3
3
0.411
2.619
3.555
1.303
1.400
15 9.288
a Adj usted for age ( see Sec. 6.5) .
bseeTable8.ll.
.90-.95
.30-.50
.30-.50
.70-.80
.70-.80
.80-.90
formation tends to increase with increasing ma-
ternal exposure with an eight-fold difference
between mother's "1" and mother's "~5," or
a two-fold difference between mother's "2" and
mother's "~5." This difference ceases to be
significant, however, when consideration is
OCR for page 115
Analysis of the Malformation' Data
limited to only those cells in which both parents
are exposed. Moreover, it is not significant if
only mothers who were unexposed are excluded
from consideration (X2 = 1.062; DF = 2 ~ . The
significance of the difference seems to be largely
a function of the inordinately low frequency of
malformation observed among the unexposed
mothers in the 15-20-year age interval. In
TABLE 8.10 THE DISTRIBUTION OF FREQUENCY OF
MAEFORMED INFANTS CLASSIFIED BY MOTHER S
AGE AND EXPOSURE ONLY
Age 1
rn 1,492
15-204 m 5
tp .0034
On 32,256
21-35/ m 294
up .0091
(n 2,007
36-38\ m 23
tp .0115
On 901
39-41] m 10
up .0111
On 291
42-t~m 8
(P .0275
On 36,947
Total: m 340
(p .0092
Mothers
~ _
23
1,013221
163
.0158.0136
17,9173,685
13830
.0077.0081
1,569324
141
.0089.0031
920152
172
.0185.0132
33960
61
.0177.0167
21,7584,442
19137
.0088.0083
4-5
106
3
.0283
1,933
22
.0114
129
1
.0078
87
2,284
26
.0114
Total
2,832
27
.0095
55,791
484
.0087
4,029
39
.0097
2,060
29
.0141
719
15
.0209
-
65,431
594
.0091
TABLE 8.11 CHI-SQUARE ANALYSIS OF THE EFFECT
OF MOTHER S EXPOSURE ON THE FREQUENCYin
OF MAEFORMED INFANTS AT EACH OF36 - 38] m
THE FIVE DIFFERENT AGE LEVELSLP
115
amination necessitated two departures from the
usual analytical approach. Firstly, parental ex-
posure categories 3, 4, and 5 were pooled. Sec-
ondly, all extraneous variation was ignored.
TABLE 8.12 THE DISTRIBUTION BY MATERNAL
EXPOSURE AND PARITY OF MAEFORMED INFANTS
BORN TO MOTHERS OF AGES 15 - 20
Parity
Jn
TOta11 m
UP
Mothers
~_
123
1,204805168
3131
.0025.0161.0060
26618550
132
.0038.0162.0400
-
4-5 Total
772,254
320
.0390.0089
24525
.0114
22 23 3
1 - 1
.0455
553
1
.0189
1,4921,013221
5163
.0034.0158.0136
1062,832
327
.0283.0095
TABLE 8.13 THE DISTRIBUTION OF FREQUENCY OF
MAEFORMED INFANTS CLASSIFIED AT BIRTH BY
MOTHER S AGE AND FATHER S EXPOSURE ONLY
Age1
On2,233
15-204 m22
up .0099
rn44,764
21-35\ m379
tp .0085
2
458
4
.0087
8,201
74
.0090
2,6551,074
297
.0109.0065
Fathers
3 4-5 Total
104372,832
1 27
.0096 .0095
1,7531,073
2110
.0120.0093
21090
12
.0048.0222
55,791
484
.0087
4,029
39
.0097
Age group DF %2 pOn1,203672122 632,060
15-20 3 14.581 .001-.01 39-415 m 18 10 1 29
21-35 3 4.463 .20-.30 (P .0150 .0149 .0082 .0141
36-38 3 2.276 .50~.70 rn 341 280 68 30 719
39~1 2a 2.421 .20-.30 42 +1 m 9 5 1 15
42 + . . . . . . . . . . . . 2 a 1.196 .50~.70 (p .0264 .0179 .0147 .0209
a Groups 3, 4, and 5 have been pooled.
Table 8.12 is presented the distribution of mal-
formed infants among mothers in the 15-20-
year age interval by parity and maternal ex-
posure. We note that unexposed mothers (in
the 15-20 year age interval) having their first
or second pregnancies experienced an extremely
low malformation rate. An explanation for this
extremely low rate is not immediately apparent.
S.6 The "9-mon~hs" data. The sparcity of
the material available from the 9-months ex
Cn
Total] m
lP
5 1,19610,685
457100
.0089.0094
2,2571,293
2512
.011 1.0093
65,431
594
.0091
These considerations must be borne in mind in
appraising Tables 8.14 and 8.15.1 In Table 8.14
iThe discrepancy in terms of total number of in-
fants recorded in Tables 8.3 and 8.13 is due to the
fact that in the former any child seen in the "9-
months follow-up" is scored (these infants will vary
in age from 7{ to 17 months), whereas in the latter
only those infants whose ages were 8-10 months in
OCR for page 116
116
Genetic Ejects of Atomic Bombs Chapter VIII
TABLE 8.14 THE FREQUENCY OF MALFORMED INFANTS AMONG Are INFANTS RE-EXAMINED AT 9 MONTHS
OF AGE, BY CITY AND PARENTAL EXPOSURE
(Malformed infants are defined here as being those infants found to have one or more major defects at
9 months of age not diagnosed at birth.)
Hiroshima Nagasaki
- ~ , ~
Mothers Mothers
, ~, ^
12 3-5 Total 12 3-5Total
En 5,424 1,718 1,0168,158 rn 4,016 2,474 371 6,861
14 m 116 25 13154 1: m 97 45 5 147
(p .0214 .0146 .0128.0189 ~ p .0242 .0182 .0135 .0214
rn 458 501 1801,139 rn 563 990 115 1,668
24m 5 12 219 2/m 16 22 4 42
-~tp .0109 .0239 .0111.0167 =~up .0284 .0222 .0348 .0252
=-(n303178250731 ~En11614261319
3-5gm52310 ~3-5gm1236
tp.0165.0112.0120.0137 ~ p.0086.0141.0492.0188
En6,1852,3971,44610,028
Totals m1263918183
tp.0204.0163.0124.0182
are presented the frequencies of malformed
infants, diagnosed at 9 months but not so dial
nosed at birth, distributed by city and parental
exposure. The analysis of these data is presented
in Table 8.15. Inspection of the analysis reveals
no significant differences between cities or
father's exposure categories, but an effect of
mother's exposure significant at the 5 per cent
level. This effect, however, is contrary to what
one might expect from radiation, since there are
elusive are scored. The purpose of the more rigid
definition in the latter table was to minimize another
source of extraneous variation, namely, age of infant.
En 4,695 3,606 547 8,848
Totalism 114 69 12 195
tp .0243 .0191 .0219 .0220
TABLE 8.15 CHI-SQUARE ANALYSIS OF THE FRE
QUENCY OF MALFORMED INFANTS AT 9 MONTHS
OF AGE BY CITY AND PARENTAL EXPOSURE
(Unrelated parents)
Source
DF
Total 17
Interactions, first order
CM .............
CF ..............
ME ..............
Main effects
City (C) .........
Mothers (M) .....
Fathers (F) ......
2
2
4
1 3.441
2 6.070
2 1.643
TABLE 8.16 THE DISTRIBUTION BY MATERNAL EXPOSURE OF THE SEVEN MOST COMMON MAJOR
CONGENITAL MALFORMATIONS IN THE JAPANE SE, EXCLUSIVE OF CONGENITAL HEART DISEASE
(The incidences of the malformations are given in terms of number of malformations per 1,000 births.)
Anencephaly .............
Cleft palate, single........
Club foot ...............
Harelip with cleft palate...
Harelip without cleft palate.
Polydactyly ..............
Syndactyly ..............
%2
p
22.543 .10-.20
1.062 .50-.70
1.011 .50-.70
3.942 .30-.50
.05-.10
.02-.05
.30-.50
No./1,000
No. births
26
32
52
55
37
37
23
-
0.70 17
0.87 7
1.41 28
1.49 34
1.00 18
1.00 28
0.62 10
0.78
0.32
1.29
1.56
0.83
1.29
0.46
Mothers
2 3
No./l,Ooo No./l,Ooo
No. births No. births
4
0.90
0.68
1.13
0.68
1.13
0.68
0.68
4-5
e
No./l,Ooo
No. births Total
2 0.88
3 1.31
6 2.63
2 0.88
2 0.88
49
42
88
98
62
70
36
Sum of malformations 262 7.09 142 6.53 26 5.85 15 6.57445
Total Births 36,947 21,758 4,442 2,28465,431
OCR for page 117
Analysis of the Malformation Data
relatively more malformations among the chil-
dren of category 1 mothers, and this despite
the fact that age-parity effects, which should
introduce a bias in the direction of hypothesis,
have not been allowed for.
117
an analysis of this possibility has been under-
taken. The results, with respect to the seven
most common malformation types, are given in
Table 8.16. When the data are partitioned in
this manner there are relatively few malforma
S.7 Arlalysis by specific malformation type. lions of any specific type. For this reason, the
The genetic basis of most of the common classification according to radiation history is by
mother's exposure only. Inspection of Table
8.16 reveals no noteworthy trends.
S.~3 Summary. Analysis of the frequency
of malformed infants by city and parental ex-
posure reveals no significant, consistent effect of
parental exposure. The small departures from
expectation which are observed cannot be said
to be in the direction of genetic hypothesis.
=_A
types of malformations is poorly understood.
Accordingly, the remote possibility had to be
considered that the frequency of children with
certain kinds of malformations was affected in
a rather specific way by parental radiation.
Despite the improbability of the existence of
such an effect in the absence of an effect of
radiation exposure in the material as a whole,
Representative terms from entire chapter:
maternal age
