(Received April 26, 1971; revision accepted for publication January 27, 1972.)
This work was supported by Federal-Provincial Health Grants, numbers 604-13-64 and 604-7-720. ADDRESS FOR REPRINTS: (P.M.F.) Montreal Children’s Hospital, 2300 Tupper Street, Montreal 108, Quebec, Canada.
50
THE
SMALL-FOR-DATE
INFANT.
II. NEUROLOGICAL
AND
INTELLECTUAL
SEQUELAE
P. M. Fitzhardinge, M.D., and E. M. Steven, M.B.B.S.
From the Department of Pediatrics, McGill University, Montreal, Canada
ABSTRACT. A prospective study has been done
on 96 full term small-for-date infants to determine the incidence and type of neurological and intellec-tual sequelae. Major neurological defects were un-common with an incidence of 1% for cerebral palsy and 6% for convulsions. Minimal cerebral dysfunction characterized by hyperactivity, a short attention span, learning difficulties, poor fine coor-dination and hyper-reflexia was diagnosed in 25%. EEG abnormalities predominantly of a diffuse mild nature were seen in 59% of the boys and 69% of
the girls (similar EEC tracings are reported in 27% of apparently normal children). Speech de-fects featuring immaturity of reception and expres-sion were present in 33% of the boys and 26% of the girls. Hearing and vision were not appreciably affected.
The average IQ was 95 (boys) and 101 (girls). However 50% of the boys and 36% of the girls had a poor school performance. Pediatrics, 49:50, 1972, SMALL-FOR-DATE INFANT, SPEED, EEC, I.Q.,
LEARNING.
I
N a previous paper1 we reported onlater growth patterns in 96 children
born at term with a severe degree of
intra-uterine growth retardation. This present
study is a report on the same children with
reference to their neurological and
intellec-tual development and is designed to answer
the following questions:
1.
What type of long-term neurologicalabnormalities are associated with
intra-uterine growth retardation?
2. Is intellectual functioning normal in
children who were severely stunted at
birth?
3. Is the degree and type of later
abnor-mality related to the degree of intra-uterine growth retardation?
4. Are neurological and intellectual
de-fects related to later growth retardation?
METHOD
Patients were selected on the basis of
birth weight and consisted of all those
in-fants born at the Royal Victoria Hospital,
Montreal, Canada, from the years 1960 to
1966 inclusive who met the following
crite-ria:
1. Singleton birth.
2. Gestation of 38 weeks or more.
Gesta-tional age was based on the mother’s dates
and was substantiated by the obstetrical
re-cords and the neonate’s apppearance2 and
neurological development. Marked
dis-crepancies were discarded from the study.
3.
Birth
weight at least 30% under theexpected normal weight as determined by
Streeter’s tables.4 This was equivalent to
more than two standard deviations below
the mean weight for this nursery5 and well
below the third percentile of the Boston
grid6 (Fig. 1).
4. No obvious cause for low birth weight,
i.e., major congenital anomalies, prenatal
infection (rubella ), or chromosomal
abnor-malities.
The reader is referred to Part 11 for
de-tails of case selection. Ninety-six children
(39 boys and 57 girls ) out of a possible 131
infants have been followed for a minimum of
5 years (Table I). Table II depicts the
so-cioeconomic distribution of the group.
Sev-enty-five percent of the mothers were
be-tween 20 and 35 years of age at the time of
delivery; 10% were less than 20 years, 15%
over 35 years. Forty-six infants were
primi-parous. Antenatal complications occurred in
ARTICLES
51
-3 S.D. .2 S.D. 2SD. 0 To D. 0 .2 S.D. S43
S.D. 2600 2400 2200 0 2000 5-I 1800 1600 1400 1200C
3SD. .2 S.D. S .3 S.D. S .2 S.D. S 0 .3 S.D. 0 #{149} S 038 39 40 41 42 43 WKS
GESTATIONAL AGE AT BIRTH
S FSmaIS 0 MOIS
FIG. 1. Birth weights of infants in the study plotted against the nursery stan-dards which are expressed as 2 and 3 standard deviations below the mean. The 3rd percentile line from the Stuart grids is added at 40 weeks for comparison.
0 S #{149}o 5.3 S.D. -,-.-8 S S 0 0
45 with an incidence of 64% in the male
and 35% in the female infants. One-third of
the complications were due to toxemia, the
remainder to antepartum bleeding,
pro-longed ruptured membranes, and
made-quate antenatal care.
All babies were cared for in the same
nursery under the same general plan of
early high calorie feeding supplemented by
intravenous glucose therapy when
mdi-cated. Early weight gain was excellent in
all but seven cases who took more than 1
week to regain birth weight.
A
comparison group was obtained byse-lecting that sibling of the test patient who
was the same sex and nearest in age to the
patient and who had a normal birth weight
and birth history. Fourteen males and 22
females were paired with a normal sibling.
The remainder (60) had either no sibling
(25), no sibling of the same sex (28), or
no sibling with a normal birth history (7).
In most cases the children were seen at
regular yearly intervals at which time a full
developmental history was recorded and a
complete physical examination was
per-formed. Visual acuity and a fundoscopic
ex-amination were done by an ophthalmologist
at 4 years. Hearing was tested in the
new-born period and again at 4 years. Speech
was assessed by the clinicians and if
abnor-mal was further evaluated by a speech
ther-apist, usually at age 3 to 4 years of age.
Electroencephalograms were taken
be-tween the age of 4 to 6 years and were
in-terpreted without prior knowledge of the
patients. Abnormalities were classified as
(1) diffuse nonspecific changes (2)
local-ized disturbances and, (3) subcortical
pa-roxysmal disturbances.
A
team of psychologists tested thechit-dren at ages 4, 6, and 8 years, again without
prior knowledge of the case history. The
Stanford-Binet test and Vineland Social
Maturity Scale were used with the younger
children. From 5 years on, the Wechsler
Preschool and Primary Scales of
Intelli-gence, the Wechsler Intelligence Scale for
Children, and the Goodenough Draw-a.
Man tests were employed. Bender
Motor-Gestalt tests were given to all the older
children.
In addition to the formal testing an
TABLE I
INFANTS Fri-rING STUDY CRITERIA
Total Male Female
Total 147 56 91
Still births 14 6 8
Neonatal deaths 2 0
Nursery survivors 131 48 88
Adequate follow-up 96 39 57
Percent of survivors followed 78% 81% 69%
TABLE
II
SOCIOECONOMIC DISTRIBUTION OF STUDY GROUP
Upper Class 8% professional executives Middle Class 34% skilled labor clerical Lower Class 38% small business unemployed unskilled labor
TABLE III
INCIDENCE OF SPEECH DEFECTS
(ussuvrs FOR CONTROL SIBLINGS ARE IN PARENTHESES) M
Total
ale F
Total emale
No speech defect
S’ithspeecbdefect
With severe defect
Q6 (13)
18(1) I (0)
SS%(7) 81%(0)
4Q (II)
15(1)
10 (0)
6%(5%)
18% (0)
Type of defect TOtal
Number with IQ<80 Total Number with IQ<80
Delayed onset only Articulation defect Immature speech with
poor recepUve and
expressive ability Absentspeech 1 (1) I (0) 10 (0) 1(0) 0 0 6 1 5 (1) 1 (0) 8 (0) 1(0) 0 0 1 1
from the parents and the teachers after each year of schooling. Students were then
divided into groups as follows:
1.
Those attending a specialized school for retarded children.2. Those attending regular school but
as-signed to the slow or special problem
classes.
3.
Those attending routine classes inreg-ular school but failing more than two
sub-jects.
4.
Those with a satisfactory performance in regular classes.A
diagnosis of minimal brain dysfunction was based on the presence of hyperactivity,short attention span, learning problems
par-ticularly related to perceptive limitations,
poor fine co-ordination, hyper-refiexia, and
an abnormal EEG tracing.7’8 The diagnosis
was not applied to any child under the age
of 5 years because of the difficulties in
eval-uating perceptual and learning problems in
the younger children.
1. Speech
RESULTS
The incidence of speech defects in the
el-ementary school population (USA) is
ap-proximately 1.5%0,b0 with the boys being
affected 13 to 2 times as frequently as girls. Table III outlines the speech problems seen
in this study. Thirty-three percent of the
boys and 26% of the girls showed some
form of speech abberation. Six children
showed only a delayed onset of speech (
af-ter 2 years), but 12 boys (31%) and 10
girls (18%) had severe defects which
per-sisted into school age. Two of these
chil-dren had abnormalities limited to
articula-lion only. Two others (one boy and one
girl) had virtually no speech due to severe
cerebral palsy in one and severe mental
re-tardation in the other. The remainder (10
boys and eight girls) all had similar speech
problems, namely a persistence of
infantil-isms in articulation associated with an
im-mature vocabulary. Both receptive and
ex-pressive ability were poor for their age.
The control siblings had an incidence of
6 cases
5
4
3
2
in
average-average-study controls-106
children-95
nInnjni
1L
30 40 50 60 70 80 90 100 110 120 130
..average-study children 101
controls 102
Inn
2
I
In
50 60 70 10 90 100 110
120
130
140ARTICLES 53
U most s.v.r.Iy stunt.cI at birth
Fic. 2. Range of
IQ
for the boys under study. The average for the group was95. Shaded areas represent infants more than 49% under normal birth weight
and demonstrate the even distribution of those children who had the most severe intra-uterine growth retardation. For comparison the average IQ of the
control male siblings is marked at 106.
5% in the girls. All were of the delayed
on-set type and were normal by school age.
2. Hearing
Hearing was fully tested in 35 males and
52 females. A mild conductive loss was present in two boys and one girl. The only
evidence of 8th nerve damage was in a girl who had a degree of unilateral nerve
deaf-1 2 cu#{deaf-149}s
11 10
9
8
7
6
5
ness. Among the 36 control siblings there
were two cases of mild conductive hearing
loss. None of the children with speech
de-fects had any impairment of hearing.
3. Vision
Thirty-three boys and 56 girls had full
fundoscopic and orthometric evaluations.
Eighteen percent of the boys and 10% of
most severely stunted at birth
Fic. 3. Range of IQ for the girls. The average for the group was 101. Shaded areas represent infants more than 40% under normal birth weight as in Figure 2. For comparison, the average IQ of the control female siblings is
I..
II
n
IU
1
cases 4
3
0
satisfactory scholarfailing in regular class
#{149}special class or school
0”
6070
80
90
100 110120
130
Fic. 4. School performance of the boys showing the relationship with
IQ
scores. A good proportion of students are classed as failures even though IQ score is 100 or more.
the girls had ocular defects requiring
cor-rection. The commonest lesions found were
astigmatism and squint. Similar defects
were seen in 7% of the male and 10% of the female control siblings.
4. Central Nervous System
Major abnormalities were present in five
boys (12%) and two girls (4%). Only
one of the 96 children had signs of cerebral
palsy; a boy with severe spastic
quadriple-gia and mental retardation. Four boys and
two girls were subject to repeated
convul-sions. The remaining 89 children were free
of any major neurological defects.
How-ever, seven of the boys and nine of the girls
had sufficient minor abnormalities to
war-rant the diagnosis of minimal brain
dam-age.7’5 This gave an incidence of 7/32
(over 5 years) or 22% for the boys and 9/35
or 25% for the girls. Only one girl of the
24 control siblings who were over age 5
years had a similar diagnosis of minimal
brain damage. The difference between the
test and the control group for the
inci-dence of minor brain damage was significant
(x2
4.5, p < 0.05). There was nocorrela-tion between the degree of growth stunting
at birth and the incidence of major or minor
cerebral abnormalities (p > 0.2 in both
in-stances).
An EEG was done on 27 boys and 35
girls. Sixteen of the boys (59%) and 25 of
the girls (69%) were considered abnormal.
Twenty (49%) of the abnormal tracings
were type 1 (diffuse and nonspecific), four
(10%) were type 2 (localized), and 17
(41%) were type 3 (subcortical and
parox-ysmal). In another study at the Montreal
Children’s Hospital conducted by the same
electroencephalographer 28 of 103
appar-ently normal children (27%) had abnormal
EEG records. Eleven (39%) of these were
type 1 (diffuse and nonspecific), five (17%)
were type 2, and nine (32%) type 3#{149}11,12
5. Intellectual Functioning
Full scale intelligence quotients are
de-picted in Figures 2 and 3. The average I.Q.
was 95 for the boys and 101 for the girls.
The curve is skewed to the left for males,
with 25% scoring 80 or less. The
distribu-tion for the girls is that of a normal curve.
Values for the control siblings were 106
(male ) and 102 (female).
There was no significant correlation
be-tween the degree of intra-uterine growth
re-tardation and subsequent intelligence scores.
(Males r = 0.21 and p > 0.10. Females r
0.03 and p > 0.50. ) In addition there was no
correlation between the degree of later
growth retardation and the IQ in the girls
(r 0.06 and p 0.10), although the boys
did show a significant correlation (r = 0.42
and p<0.05).
Adequate assessments on school
perfor-mance were obtained on 22 boys and 25
girls. Only 11 (50%) of the boys and 16
(64%) of the girls were classed as satisfac-tory scholars. Seven of the 16 unsatisfactory
scholars had been assigned to either a
remain-0
satisfactory scholarfailing in regular class
I special class or school
I
In
50 “ 80 90 100 110 120
ARTICLES
55FIG. 5. School performance of the girls showing the relationship with IQ scores as in Figure 4.
der, although in a regular class, were failing subjects consistently. Figures 4 and 5 relate
the school performance with the IQ scores.
All those who required specialized classes scored less than 100, although the reverse was not always the case. Although none had been put in a slow stream, 9 of the 30
chil-dren scoring 100 or more on intelligence
tests were doing badly at school. About half
of these children showed specific learning
defects. There was no relationship between
school performance and the degree of
intra-uterine growth retardation. School
evalua-lion data was available on 21 of the control
siblings. None was assigned to either a
spe-cial class or special school. One boy had
failed his first year. The remaining 20 were
classed as generally satisfactory scholars.
The difference in school performance be-tween the study and the comparison groups
was highly signfficant (y2 8.30, p <
0.01).
DISCUSSION OF RESULTS
In a prospective study such as this one it
is difficult to relate cause and effect in
re-gard to all the data accumulated. As
men-tioned previously,1 it is not the purpose of
this paper to examine the multiple causes of
intra-uterine growth retardation and we
recognize that, even after eliminating
chro-mosomal defects, congenital anomalies,
twinning, and prematurity, we probably are
still not dealing with a homogeneous group.
After discharge in the hospital each child
enters a different environment.
Undoubt-edly the intelligence, anxiety, and interest
of the parents play an important role in
whether the child reaches his full
intellec-tual potential. Even siblings are subject to a
different environment by
virtue
of theirrank in the family and by the fact that an
affected child may receive more attention
and care or conversely may be rejected by
the family. Nevertheless siblings have a
more similar environment and heredity
than do children from different homes and
families, regardless of how careful the
matching has been.
There was a remarkably low incidence of
cerebral palsy in our study group. The one
child so affected had a very severe form of
spastic quadriplegia and mental
retarda-tion. There was not even a suggestion in the
other children of the spastic diplegia
de-scribed commonly in premature infants 13,14
Six percent of the group were prone to
seizures, although all were easily
con-trolled. Neither the spastic boy nor the
chil-dren with convulsions were extremely
small-for-dates at birth, but all had
sus-tained severe neonatal asphyxia.
In contrast to the low incidence of major
neurological defects was the significantly
high incidence (25%) of minimal cerebral
dysfunction and of EEG abnormalities. Also
of interest is the common occurrence of
speech defects in the small-for-date infants.
Although classed generally as immaturity of
speech development, these defects, like
cases 6
5
those of the EEG tracings, may reflect a
diffuse type of mild brain damage. These
results would concur with Gruenwald’s
sug-gestion’5 that, apart from increased
neona-tal morneona-tality, the problem of greatest
medi-cal significance in the small-for-date
infant
is
that of permanent cerebral damage andretardation of postnatal growth. He noted
spotty areas of maturation defects in the brains at autopsies on small-for-date infants
dying at birth and postulated that such
de-fects might have led to later abnormalities
in
the inter-relationship of parts of the brain had the infants survived. The delay inspeech development seen in this study may
be an example of such a maturation defect. The average IQ results of 95 and 101 for the study children would at first indicate
that intellectual functioning was not
af-fected by intra-uterine growth retardation. However the high incidence of school
fail-ures emphasizes the fallacy of assessing
in-tellectual potential by the IQ scoring alone.
An individual may achieve an acceptable
full scale IQ even though he may have
seri-ous visuomotor and perceptual defects that
can interfere with his performance at
school and elsewhere. Additional tutoring and use of teaching methods adopted to
compensate for the individual’s particular
learning defect can result in a better
over-all school performance. Early recognition of
such learning defects is important before
the child develops a defeatist attitude at
school and becomes another “drop-out.”
Al-though we have been unable to
demon-strate any early fool proof method for
pre-dicting which of the small-for-date infants
will have later learning defects, an
aware-ness of the possibility and adequate
pre-school testing should point out potential problems before the age of 6 years.
SUMMARY
Ninety-six children with a severe degree
of intra-uterine growth retardation were
followed for a minimum of 5 years.
Major neurological defects were
uncom-mon. Cerebral palsy occurred in 1%,
con-vulsions in 6% with males more affected
than females. Evidence of minimal cerebral
dysfunction was present
in 25%. EEG
ab-normalities, predominantly of a diffuse mild
nature, were seen in 59% (males) and 69%
(females). Speech defects featuring
imma-turity of reception and expression were
present in 33% of the boys and 26% of the
girls. Hearing and vision were not
ap-preciably affected.
The average full scale intelligence score
was 95 for the boys (control 105) and 101
for the girls (control 102). However 50%
of the boys and 36% of the girls were doing
poorly in school. One-third of the children
with IQ results over 100 were failing
consis-tently at school.
No relationship could be drawn between
neurological and intellectual defects and
the degree of intra-uterine growth
retarda-tion.
No relationship could be drawn between
later growth retardation and intellectual
defects except in cases of severe mental
retardation. There was a greater proportion
of severe mental retardation in the boys
than in the girls and their later growth
re-tardation did correlate with their IQ level.
The importance of assessing a child by
virtue of his total performance rather than
IQ
level has been stressed.REFERENCES
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Acknowledgment
We are grateful to Dr. R. Usher, Director of
