DOI: 10.

1093/brain/awh034

Brain (2004), 127, 321329

Critical periods of brain growth and cognitive

function in children
Catharine R. Gale, Finbar J. O'Callaghan, Keith M. Godfrey, Catherine M. Law and
Christopher N. Martyn
MRC Environmental Epidemiology Unit, University of
Southampton, Southampton General Hospital,
Southampton, UK

Summary

There is evidence that IQ tends to be higher in those

who were heavier at birth or who grew taller in childhood and adolescence. Although these ndings imply
that growth in both foetal and postnatal life inuences
cognitive performance, little is known about the relative
importance of brain growth during different periods of
development. We investigated the relationship between
brain growth in different periods of pre- and postnatal
life and cognitive function in 221 9-year-old children
whose mothers had taken part in a study of nutrition in
pregnancy and whose head circumference had been
measured at 18 weeks gestation, birth and 9 months of
age. Cognitive function of the children and their
mothers was assessed with the Wechsler Abbreviated
Scale of Intelligence. Full-scale IQ at age 9 years rose

Correspondence to: Dr C. Martyn, MRC Environmental

Epidemiology Unit (University of Southampton),
Southampton General Hospital, Southampton SO16 6YD,
UK
E-mail: cnm@mrc.soton.ac.uk

by 1.98 points [95% condence interval (CI) 0.34 to

3.62] for each SD increase in head circumference at 9
months and by 2.87 points (95% CI 1.05 to 4.69) for
each SD increase in head circumference at 9 years of
age, after adjustment for sex, number of older siblings,
maternal IQ, age, education, social class, duration of
breastfeeding and history of low mood in the post-partum period. Postnatal head growth was signicantly
greater in children whose mothers were educated to
degree level or of higher socio-economic status. There
was no relation between IQ and measurements of head
size at 18 weeks gestation or at birth. These results suggest that brain growth during infancy and early childhood is more important than growth during foetal life
in determining cognitive function.

Keywords: children; cognitive function; foetal growth; head circumference; postnatal growth
Abbreviations: SDS = standard deviation scores
Received June 30, 2003. Revised September 16, 2003. Accepted September 18, 2003. Advanced Access publication November 25, 2003

Introduction

The development of the CNS in man begins in the embryo

and continues for several years of postnatal life. Critical early
events are the closure of the neural tube around day 22 of
embryonic life and neurogenesis, which is complete by 16
weeks. In later gestation there are overlapping phases of
neuronal migration, glial cell proliferation and dendritic
sprouting. Myelination of the cerebral commisures and long
tracts continues into late childhood. Synaptic density in both
cerebral and cerebellar cortex increases until early adult life.
Although severe degrees of intrauterine growth retardation
are associated with poorer cognitive performance in later life

(Strauss, 2000; Hack et al., 2002), it is less clear whether

variation in early growth within the normal range affects
higher mental function. Some studies have found that IQ
tends to be higher in those who were heavier at birth
(Sorensen et al., 1997; Matte et al., 2001; Richards et al.,
2001), which implies that brain growth during foetal life is
important. On the other hand, the nding that height and head
size are consistently related to IQ in adults suggests that
postnatal growth is also inuential (Cox et al., 1987;
Andreasen et al., 1993; Rushton and Ankney, 1996;
Tuvemo et al., 1999; Richards et al., 2002). Little is known

Brain Vol. 127 No. 2 Guarantors of Brain 2003; all rights reserved

322

C. R. Gale et al.
Table 1 Characteristics of the 221 study participants and their mothers recorded at around
18 weeks gestation, at birth, at 9 months and at 9 years of age
Characteristics
Child
Head circumference (cm)
Weight (kg)
Length/height (cm)
Premature [n (%)]
Female [n (%)]
No. of older siblings [n (%)]
0
1
2 or more
Mother
Social class [n (%)]
I/II
III
IV/V
Age (years)
Education
None or CSE
O level
A level
Degree or HND
Low mood post-partum [n (%)]
IQ
Breastfeeding duration
Never
<1 month
14 months
>4 months

18 weeks gestation

Birth

9 months

9 years

15.3 (1.1)

35.0 (1.4)
3.3 (0.6)
50.0 (2.4)
17 (7.7)
105 (47.5)

45.6 (1.4)
9.0 (1.2)
70.8 (3.0)

53.3 (1.6)
29.5 (5.6)
130.9 (6.1)

120 (54.8)
71 (32.4)
28 (12.8)

56 (25.6)
126 (57.5)
37 (16.9)
27.0 (4.8)

48
82
60
31

89 (40.3)

103.9 (13.2)

64
48
45
54

(21.7)
(37.1)
(27.1)
(14.0)

(30.3)
(22.7)
(21.3)
(25.6)

Values are means (SD) unless stated otherwise.

about the relative importance of brain growth during different

periods of pre- and postnatal development.
Head circumference is known to correlate closely with
brain volume (Cooke et al., 1977; Wickett et al., 2000) and
can therefore be used to measure brain growth, but a single
measurement cannot provide a complete insight into neurological development. Different patterns of early brain growth
may result in a similar head size. A child whose brain growth
both pre- and postnatally followed the 50th centile might
attain the same head size as a child whose brain growth was
retarded in gestation but who later experienced a period of
rapid growth. Different growth trajectories may reect
different experiences during sensitive periods of brain
development and have different implications for later cognitive function.
We have investigated whether brain growth during different periods of pre- and postnatal development inuences later
cognitive function in a group of children for whom serial
measurements of head growth through foetal life, infancy and
childhood were available.

Subjects and methods

Participants

The mothers of the children in this study had all taken part in an
earlier study of nutrition during pregnancy between April 1992 and

June 1993. The study consisted of singleton children born to

Caucasian women aged 16 years or older who registered under two
obstetric consultants and who attended the midwives' antenatal
booking clinic at the Princess Anne Maternity Hospital in
Southampton at <17 weeks gestation. Anthropometric information
was available at three time points: 18 weeks gestation (via foetal
ultrasound), birth and 9 months of age. There were routine obstetric
data about the pregnancy and delivery, parental social class, and
maternal education. At the 9-month postnatal visit, information on
infant feeding was collected and maternal psychological morbidity
since the infant's birth was assessed using the Edinburgh postnatal
depression scale (Cox et al., 1987). A score of >12 was taken to
indicate low mood in the post-partum period. In total, 559 children
were followed up to the age of 9 months.
When these 559 children approached their ninth birthday, we
asked the Community Paediatric Service in Southampton to write to
their parents with an invitation to take part in a further follow-up
study. All the children in the cohort had previously been agged on
the Service's child health computer. Letters were sent to all 461
families who were still living in the Southampton area; 226 (49%)
agreed to take part in the follow-up study. In total, 221 families
(48%) were willing to allow their child's cognitive function to be
measured. The children who took part in the 9-year follow-up did not
differ signicantly from the non-responders or from those who had
moved out of the area in terms of social class distribution (P =
0.142), mean birthweight (P = 0.10), or mean head circumference at
18 weeks gestation (P = 0.36), at birth (P = 0.17) or at 9 months of
age (P = 0.56).

Brain growth and cognitive function in children

323

Table 2 Results of multivariate linear regression analyses into the relation between measures of head growth during
foetal life and full-scale, verbal and performance IQ at age 9 years (each measure of head growth has been analysed
separately)
Regression coefcient
(95% CI), adjusted for
sex and gestation*
Full-scale IQ
Head circumference
Head circumference
Verbal IQ
Head circumference
Head circumference
Performance IQ
Head circumference
Head circumference

Regression coefcient
(95% CI), further
adjusted for other factors

at 18 weeks gestation SDS

at birth SDS

0.93 (3.09 to 4.94)

0.81 (1.60 to 3.23)

0.649
0.507

1.05 (2.84 to 4.93)

0.16 (2.00 to 2.33)

0.594
0.883

at 18 weeks gestation SDS

at birth SDS

1.98 (2.10 to 6.07)

1.72 (0.75 to 4.19)

0.339
0.171

1.27 (2.83 to 5.36)

1.20 (1.09 to 3.49)

0.541
0.303

at 18 weeks gestation SDS

at birth SDS

0.17 (4.48 to 4.14)

0.35 (2.87 to 2.18)

0.938
0.787

0.75 (3.50 to 4.99)

1.02 (3.45 to 1.41)

0.727
0.407

*Length of gestation at time of head measurement; maternal age, social class, education, IQ, duration of breastfeeding, history of low
mood in post-partum period and number of older siblings; based on 133 children whose mothers were condent of the date of their last
menstrual period and were not taking oral contraceptives immediately prior to conception.

Measurements

At 18 weeks' gestation, foetal head circumference was measured

around the outer table of the skull using standard sonographic
landmarks (Campbell and Thoms, 1977). Occipito-frontal circumference was measured within 48 h of birth, at 9 months and at 9 years
of age by passing a tape measure around the head, placing it on the
most anterior protuberance of the forehead and the most posterior
protuberance of the back of the head. The tape measure was pulled
tight to compress the hair and measurements made to the nearest
0.1 cm. Weight was measured at birth, at 9 months and at 9 years
using digital scales. Crownheel length at birth and at 9 months was
measured using a neonatal stadiometer. Height at 9 years of age was
measured using a portable stadiometer. Inter-observer tests of
repeatability were conducted regularly during each phase of the
study to ensure that any discrepancies in measurements made by the
research nurses were very small.
As part of the 9-year follow-up study, the cognitive function of the
child and his/her mother was assessed by a member of the research
team who visited the family at home. Cognitive function was
measured using the Wechsler Abbreviated Intelligence Scale
(Wechsler, 1999) This provides age-adjusted IQ scores for fullscale, verbal and performance intelligence.
The protocol for this study was approved by the Southampton and
South West Hants Joint Local Research Ethics Committee. The
children and their mothers gave written informed consent.

Statistical analysis

Anthropometric measurements made at the 9-month and 9-year

examinations were adjusted for age at the time of examination. We
used the British 1990 growth reference data on weight, height and
head circumference (Freeman et al., 1995; Cole et al., 1998),
obtained from the Child Growth Foundation, in combination with
our measurements and data on gestation and sex to estimate for each
child what his or her weight, length and head circumference would
have been at exactly 9 months and 9 years of age. Comparisons of
means and proportions was performed using analysis of variance
(ANOVA), t-tests or c2-tests as appropriate. Linear regression was
used to examine the relation between anthropometric measurements,

expressed as standard deviation scores (SDS), and cognitive

function, taking account of other factors. Analysis of the relationship
between head circumference at 18 weeks gestation and cognitive
function was restricted to the 133 children whose mothers had been
condent of the date of their last menstrual period and were not
taking the oral contraceptive pill immediately prior to conception.
As girls tended to be lighter, shorter and to have a smaller head
circumference than boys at each time of measurement, all linear
regression models were adjusted for sex.

Results

Characteristics of the 221 study participants and their mothers

recorded at 18 weeks' gestation, at birth, at 9 months and 9
years of age are shown in Table 1.
At age 9 years, the children's mean full-scale IQ was 106.6
(SD 14.4). Mean performance IQ was 104.7 (SD 13.8) and
mean verbal IQ was 106.9 (SD 14.4). On average, boys
gained higher scores than girls for full-scale IQ (108.7
compared with 104.2; P = 0.022) and for performance IQ
(107.4 compared with 101.7; P = 0.005), although there was
no statistically signicant difference between the sexes in
verbal IQ. As might be expected, the children's IQ test
performance was strongly associated with maternal characteristics. In univariate analysis, full-scale IQ, performance IQ
and verbal IQ were signicantly greater in those whose
mothers were older, of higher social class, more educated,
had a higher IQ or had continued breastfeeding for >1 month.
Full-scale and performance IQ tended to be lower in those
whose mothers had scored >12 on the Edinburgh postnatal
depression scale at the 9-month visit, suggesting low mood in
the post-partum period. Verbal IQ tended to be lower in
children who had one or more older siblings.
We found no statistically signicant associations between
head circumference at 18 weeks' gestation or head circumference at birth SDS and IQ at the age of 9 years. Table 2
shows the relationships between these two measures of foetal

324

C. R. Gale et al.

Table 3 Results of multivariate linear regression analyses into the relation between measures of head growth during
postnatal life and full-scale IQ at age 9 years; model 1 includes head circumference at 9 months and model 2 includes
head circumference at 9 years
Model 1: regression
coefcient (95% CI),
adjusted for sex and
other variables in the table
Head circumference at 9 months SDS
Head circumference at 9 years SDS
Maternal IQ (per point)
Maternal age (per year)
Maternal education*
O level
A level
Degree or HND
Maternal social class*
III
IV/V
Duration of breastfeeding*
Up to 1 month
1 to 4 months
Over 4 months
Low mood post-partum
No. of older siblings*
1
2 or more

Model 2: regression
coefcient (95% CI),
adjusted for sex and
other variables in the table

1.98 (0.34 to 3.62)

0.24 (0.06 to 0.40)

0.18 (0.61 to 0.25)

0.018
0.007
0.419

2.87 (1.05 to 4.69)

0.24 (0.07 to 0.40)
0.21 (0.63 to 0.22)

0.002
0.006
0.342

4.04 (0.97 to 9.05)

6.12 (0.70 to 11.65)
11.73 (3.80 to 19.65)

0.114
0.027
0.004

4.15 (0.81 to 9.12)

6.51 (1.08 to 11.93)
11.18 (3.31 to 19.05)

0.100
0.019
0.006

0.36 (5.20 to 4.46)

0.12 (6.01 to 6.33)

0.882
0.970

0.09 (4.70 to 4.89)

0.48 (5.69 to 6.63)

0.969
0.879

0.001 (4.85 to 4.85)

5.12 (0.01 to 10.24)
6.66 (1.42 to 11.89)
2.59 (6.20 to 1.03)

0.999
0.049
0.013
0.160

0.07
4.82
6.73
2.58

(4.74 to 4.89)
(0.24 to 9.88)
(1.57 to 11.90)
(6.15 to 0.99)

0.976
0.062
0.011
0.157

1.49 (5.54 to 2.56)

1.30 (7.22 to 4.62)

0.470
0.665

1.02 (5.04 to 2.30)

0.72 (6.51 to 5.07)

0.617
0.805

*Comparison groups for categorical variables are as follows. maternal education: no qualications or CSE; maternal social class: classes I/
II; duration of breastfeeding: never breastfed; number of older siblings: none.

head growth and full-scale IQ, verbal IQ and performance IQ,

adjusted for sex and gestation, then with further adjustment
for number of older siblings, maternal age, social class,
education, IQ, duration of breastfeeding and history of low
mood post-partum. When we repeated our analysis excluding
the 17 children who had been born before 37 weeks'
completed gestation, the relationships between head circumference at birth SDS and IQ changed little. We examined
whether birthweight or length at birth were associated with IQ
at age 9 years, but these relationships were not statistically
signicant. After adjustment for sex and gestational age at
birth, full-scale IQ fell by 0.27 points [95% condence
interval (CI) 2.89 to 2.36] for each SD increase in
birthweight and rose by 0.51 points (95% CI 1.92 to 2.95)
for each SD increase in length. The relationships between
birthweight or length at birth and verbal or performance IQ
were very similar (data not shown).
In contrast, there were strong statistically signicant
associations between measures of postnatal head growth
and IQ. After adjustment for sex, full-scale IQ rose by 2.59
points (95% CI 0.87 to 4.32) for each SD increase in head
circumference at 9 months of age, and by 3.85 points (95% CI
1.96 to 5.73) points for each SD increase in head circumference at 9 years; verbal IQ rose by 2.66 points (95% CI 0.49 to
4.83) for each SD increase in head circumference at 9 months
of age, and by 3.76 points (95% CI 1.81 to 5.72) for each SD
increase in head circumference at 9 years; performance IQ
rose by 2.88 points (95% CI 0.659 to 5.11) for each SD

increase in head circumference at 9 months of age, and by

3.16 points (95% CI 1.16 to 5.16) for each SD increase in
head circumference at 9 years. We found no signicant
associations between IQ and weight or length at 9 months or
weight or height at 9 years.
We carried out multivariate analyses examining these
measures of postnatal head growth separately and including
in the models all the factors that had been signicantly
associated with IQ in univariate analysis. In these analyses,
head circumference SDS either at 9 months (model 1) or at 9
years (model 2) remained a statistically signicant predictor
of full-scale, verbal and performance IQ (Tables 35 ). After
adjustment for sex and other factors, full-scale IQ rose by
1.98 points (95% CI 0.34 to 3.62) for each SD increase in
head circumference at 9 months and by 2.87 points (95% CI
1.05 to 4.69) for each SD increase in head circumference at 9
years. Maternal IQ, maternal education and duration of
breastfeeding were the only other factors that remained
signicantly associated with full-scale IQ in multivariate
analysis (Table 3). In multivariate analyses of factors
associated with verbal IQ, verbal IQ rose by 1.92 points
(95% CI 0.19 to 3.64) for each SD increase in head
circumference at 9 months and by 2.82 points (95% CI 0.90
to 4.74) for each SD increase in head circumference at 9
years. Maternal IQ and education remained signicant
predictors of the child's verbal IQ, but there were no
associations between IQ score and maternal age, social
class, duration of breastfeeding, history of low mood

Brain growth and cognitive function in children

325

Table 4 Results of multivariate linear regression analyses into the relation between measures of head growth during
postnatal life and verbal IQ at age 9 years; model 1 includes head circumference at 9 months and model 2 includes head
circumference at 9 years
Model 1: regression
coefcient (95% CI),
adjusted for sex and
other variables in the table
Head circumference at 9 months SDS
Head circumference at 9 years SDS
Maternal IQ (per point)
Maternal age (per year)
Maternal education*
O level
A level
Degree or HND
Maternal social class*
III
IV/V
Duration of breastfeeding*
Up to 1 month
14 months
Over 4 months
Low mood post-partum
No. of older siblings*
1
2 or more

Model 2: regression
coefcient (95% CI),
adjusted for sex and
other variables in the table

1.92 (0.19 to 3.64)

0.25 (0.07 to 0.43)

0.06 (0.51 to 0.39)

0.030
0.006
0.790

2.82 (0.90 to 4.74)

0.25 (0.08 to 0.43)
0.09 (0.54 to 0.36)

0.004
0.005
0.694

4.54 (0.74 to 9.82)

6.68 (0.92 to 12.44)
11.91 (3.57 to 20.26)

0.091
0.023
0.005

4.66 (0.56 to 9.89)

7.01 (1.29 to 12.72)
11.37 (3.08 to 19.66)

0.080
0.017
0.007

0.13 (5.22 to 4.95)

2.05 (4.48 to 8.60)

0.959
0.536

0.32 (4.74 to 5.37)

2.42 (4.08 to 8.91)

0.901
0.464

1.16
3.09
4.83
1.59

6.27)
8.47)
10.33)
2.21)

0.656
0.259
0.085
0.410

1.23
2.79
4.91
1.58

6.29)
8.13)
10.35)
2.19)

0.633
0.304
0.077
0.410

3.34 (7.60 to 0.92)

4.58 (10.81 to 1.65)

0.124
0.149

2.89 (7.12 to 1.34)

4.03 (10.13 to 2.07)

0.180
0.194

(3.95
(2.29
(0.68
(5.40

to
to
to
to

(3.84
(2.54
(0.53
(5.34

to
to
to
to

*Comparison groups for categorical variables are as follows: maternal education: no qualications or CSE; maternal social class: classes I/
II; duration of breastfeeding: never breastfed; number of older siblings: none.

post-partum or number of older siblings (Table 4). In

multivariate analyses of factors associated with performance
IQ, performance IQ rose by 1.85 points (95% CI 0.09 to 3.61)
for each SD increase in head circumference at 9 months and
by 2.39 points (95% CI 0.35 to 4.43) for each SD increase in
head circumference at 9 years. Duration of breastfeeding and
maternal education were the only other factors that remained
signicantly associated with performance IQ in multivariate
analysis (Table 5).
Children who had a larger head at 9 months of age tended
to have a larger head at 9 years (r = 0.77, P < 0.001). In order
to examine whether the relation between postnatal head size
and intelligence differed according to period of growth, we
derived standardized residuals from a linear regression rst of
head circumference at 9 months on head circumference at
birth and secondly of head circumference at 9 years on head
circumference at 9 months. These residuals provided measures of head growth during the periods between birth and 9
months and between 9 months and 9 years that took account
of head size at the start of each period. The residuals were also
independent of each other (r = 0.03, P = 0.66) and so could
be used simultaneously in linear regression (Table 6). Head
growth during both periods was associated with full-scale IQ,
after adjustment for sex and other factors. Full-scale IQ rose
by 2.30 points (95% CI 0.56 to 4.03) for each SD increase in
head growth between birth and 9 months, and by 2.12 points
(95% CI 0.39 to 3.86) for each SD increase in head growth
between 9 months and 9 years. Thus the highest full-scale IQs
were seen in children who had experienced a large increase in

head circumference between birth and 9 months of age and a

further large increase in head circumference between the ages
of 9 months and 9 years. There was some evidence that the
two periods of head growth differed in importance as regards
verbal and performance IQ. Verbal IQ was associated with
head growth between 9 months and 9 years of age, while
performance IQ was more strongly associated with head
growth in the rst 9 months of life.
Finally, we examined whether factors in the child's home
environment might inuence IQ test performance through an
effect on head growth. Table 7 shows the relationships
between the extent of head growth during these two periods of
postnatal life, as measured by the standardized residuals
described above, and maternal and family characteristics. We
found no statistically signicant associations between head
growth in either period and maternal IQ, age, duration of
breastfeeding, or history of low mood post-partum. There
were also no signicant associations between head growth
and number of older siblings. However, children whose
mothers were educated to degree level experienced a
signicantly greater increase in head circumference both
between birth and 9 months, and between 9 months and 9
years, than those whose mothers were less educated or who
had no qualications. There was also evidence to link social
class and head growth. Between birth and 9 months of age,
head growth tended to be poorer in children whose mothers
came from social classes III, IV or V than in those whose
mothers came from social classes I or II, although this trend
was not statistically signicant. But during the period from 9

326

C. R. Gale et al.

Table 5 Results of multivariate linear regression analyses into the relation between measures of head growth during
postnatal life and performance IQ at age 9 years; model 1 includes head circumference at 9 months and model 2 includes
head circumference at 9 years
Model 1: regression
coefcient (95% CI),
adjusted for sex and other
variables in the table
Head circumference at 9 months SDS
Head circumference at 9 years SDS
Maternal IQ (per point)
Maternal age (per year)
Maternal education*
O level
A level
Degree or HND
Maternal social class*
III
IV/V
Duration of breastfeeding*
Up to 1 month
14 months
Over 4 months
Low mood post-partum
No of older siblings*
1
2 or more

Model 2: regression
coefcient (95% CI),
adjusted for sex and
other variables in the table

1.85 (0.09 to 3.61)

0.17 (0.01 to 0.35)

0.26 (0.73 to 0.20)

0.040

3.01 (2.47 to 0.86)

3.91 (2.14 to 9.96)
9.05 (0.36 to 17.73)

0.275
0.204
0.041

0.56 (5.89 to 4.77)

1.08 (7.80 to 5.65)

0.836
0.753

0.06 (5.31 to 5.43)

1.12 (8.03 to 5.77)

0.982
0.748

0.57
6.90
7.60
3.30

(5.90 to 4.76)
(1.30 to 12.51)
(1.95 to 13.26)
(7.33 to 0.73)

0.834
0.016
0.009
0.108

0.60
6.58
7.57
3.30

(5.98 to 4.78)
(0.91 to 12.25)
(1.78 to 13.36)
(7.30 to 0.70)

0.827
0.023
0.011
0.105

1.87 (2.47 to 6.22)

3.16 (3.31 to 9.63)

0.396
0.336

1.75 (2.75 to 6.25)

3.46 (3.03 to 9.94)

0.443
0.294

2.39 (0.35 to 4.43)

0.16 (0.24 to 0.35)
0.30 (0.78 to 0.17)

0.063
0.271

2.90 (2.66 to 8.45)

4.70 (1.37 to 10.78)
8.67 (0.15 to 17.48)

0.022
0.088
0.210
0.305
0.129
0.054

*Comparison groups for categorical variables are as follows: maternal education: no qualications or CSE; maternal social class: classes I/
II; duration of breastfeeding: never breastfed; number of older siblings: none.

Table 6 Results of simultaneous multivariate linear regression analyses into the relation between head growth during two
periods of postnatal life and full-scale, verbal and performance IQ at age 9 years
Full-scale IQ
Regression coefcient
(95% CI), adjusted for
sex and other factors*
Head growth between
birth and 9 months
Head growth between
9 months and 9 years

Verbal IQ
Regression coefcient
(95% CI), adjusted for
sex and other factors*

Performance IQ
Regression coefcient
(95% CI), adjusted for
sex and other factors*

2.30 (0.56 to 4.03)

0.010

1.72 (0.16 to 3.60)

0.072

2.49 (0.57 to 4.40)

0.011

2.12 (0.39 to 3.86)

0.017

2.08 (0.21 to 3.95)

0.030

1.76 (0.15 to 3.67)

0.070

*Maternal age, social class, education, IQ, duration of breastfeeding, history of low mood in post-partum period and number of older
siblings. Expressed as standardized residuals of regression of head size at 9 months on head size at birth. Expressed as standardized
residuals of regression of head size at 9 years on head size at 9 months.

months to 9 years of age, there was a signicant difference in

head growth between the classes. Children whose mothers
came from social classes III, IV or V experienced markedly
poorer head growth than children whose mothers came from
social classes I or II.

Discussion

In this study of 9-year-old children, performance on a test of

cognitive function was related to current head size and head
size at 9 months of age but not to head size at birth or at 18
weeks gestation, after adjustment for sex, number of older
siblings, duration of breastfeeding, and maternal age, IQ,
education, social class and history of low mood in the post-

partum period. As head circumference is a close correlate of

brain volume (Cooke et al., 1977; Wickett et al., 2000), we
interpret these ndings as evidence that postnatal brain
growth is more important than prenatal brain growth in
determining higher mental function. This interpretation is
supported by the nding that head growth in the rst 9 months
of life and head growth between 9 months and 9 years of age
are also related to cognitive function, regardless of head size
at the beginning of these periods. Postnatal head growth was
signicantly greater in children whose mothers were educated
to degree level or of higher socio-economic status.
In common with many other studies, we found that children
who had been breastfed for longer periods gained higher
scores on the test of cognitive function (Anderson et al., 1999;

Brain growth and cognitive function in children

327

Table 7 Results of separate linear regression analyses into the relation between maternal and family characteristics and
head growth during two periods of postnatal life
Head growth between
birth and 9 months*
Regression coefcient
(95% CI)
Maternal IQ (per point)
Maternal age (per year)
Maternal education
O level
A level
Degree or HND
Maternal social class
III
IV/V
Duration of breastfeeding
Up to 1 month
1 to 4 months
Over 4 months
Low mood post-partum
No of older siblings
1
2 or more

Head growth between

9 months and 9 years
Regression coefcient
(95% CI)

0.01 (0.002 to 0.02)

0.01 (0.02 to 0.04)

0.136
0.474

0.01 (0.002 to 0.08)

0.02 (0.01 to 0.05)

0.138
0.534

0.12 (0.25 to 0.47)

0.29 (0.10 to 0.68)
0.45 (0.002 to 0.91)

0.556
0.140
0.049

0.03 (0.32 to 0.38)

0.01 (0.36 to 0.39)
0.56 (0.11 to 1.02)

0.870
0.943
0.014

0.23 (0.55 to 0.09)

0.35 (0.78 to 0.08)

0.151
0.107

0.45 (0.76 to 0.14)

0.46 (0.87 to 0.06)

0.005
0.026

0.03
0.01
0.07
0.01

0.41)
0.50)
0.29)
0.28)

0.900
0.623
0.699
0.964

0.27 (0.57 to 0.03)

0.14 (0.29 to 0.56)

0.076
0.520

(0.36
(0.30
(0.44
(0.27

to
to
to
to

0.15
0.44
0.23
0.09

(0.23 to 0.52)
(0.06 to 0.82)
(0.13 to 0.60)
(0.18 to 0.35)

0.444
0.025
0.207
0.534

0.22 (0.51 to 0.07)

0.37 (0.78 to 0.04)

0.139
0.079

*Expressed as standardized residuals of regression of head size at 9 months on head size at birth. Expressed as standardized residuals of
regression of head size at 9 years on head size at 9 months. Comparison groups for categorical variables are as follows: maternal
education: no qualications or CSE; maternal social class: classes I/II; duration of breastfeeding: never breastfed; number of older
siblings: none.

Jain et al., 2002). Interpretation of such ndings has been

complicated by the failure of most studies to control
adequately for social and environmental confounding factors,
such as maternal intelligence and quality of parenting
(Anderson et al., 1999; Jacobson and Jacobson, 2002; Jain
et al, 2002). The association found in our study between
duration of breastfeeding and IQ at age 9 years persisted after
adjustment for mother's intelligence, age, education, social
class and history of low mood in the post-partum period, but
we had no data on quality of parenting in early life. Several
previous studies have shown lower IQs in children of mothers
who were depressed postnatally (Cogill et al., 1986; Sharp
et al., 1995; Hay et al., 2001). In our study, maternal low
mood in the rst few months of life was associated with lower
IQ in univariate analysis, but this relation was no longer
statistically signicant after adjustment for other risk factors.
One of the limitations of this study was our inability to
follow up all children in the original cohort. This was partly
because some had moved away from the area in which the
original study took place and it was not possible to trace them,
and partly because some declined to participate. Mean head
size at birth and at 9 months of age, however, was similar in
the groups who did and who did not take part in the current
phase of the study, and we think that it is unlikely that nonresponse or our inability to follow up children who had
moved away will have introduced bias. Another limitation is
that data on head circumference at 18 weeks gestation was
only available for a proportion of the children in the study
those whose mothers could be sure of the gestational age of

their baby from the dates of their last menstrual period.

Incompleteness of these data will have reduced the statistical
power of the study and our ability to detect associations
between early head growth and later cognitive function. A
further weakness is that we had no information on the nature
and quality of the child's home environment, so were unable
to take account of parenting style or level of cognitive
stimulation, both of which are known to affect intellectual
development (Guo and Harris, 2000).
The strengths of the study are the longitudinal measures of
head size and therefore the ability to estimate the inuence of
brain growth during different periods of pre- and postnatal
development. A further advantage was that we had information on other potentially confounding factors that are known
to inuence intelligence, including the mother's IQ, educational level and social class, whether she had suffered from
low mood in the post-partum period, duration of breastfeeding, and the child's birth order.
A number of other investigators have examined associations between foetal or childhood head growth and subsequent cognitive function. Results of studies into the inuence
of head size at birth have been conicting. In a follow-up
study of over 14 000 children born at term whose head
circumference at birth had been above the 10th percentile for
gestational age, there were no differences in IQ at age 4 or 7
years between those whose head circumference had been
small relative to their birthweight and the rest of the
population (Brennan et al., 1985). But in a study of around
248 000 young men, risk of poor performance on a test of

328

C. R. Gale et al.

cognitive function was signicantly higher in those whose

head circumference at birth had been more than 2 SDs below
the mean (Lundgren et al., 2001). Although a statistically
signicant association was found in this very large study, the
size of the effect exerted by head size at birth was small; the
difference in mean cognitive function test scores between
those whose head circumference at birth had been more than
2 SDs below the mean and those whose head circumference
had been more than 2 SDs above the mean was only 0.5 of a
point.
Evidence that postnatal head growth may inuence cognitive function has been more consistent. In a cohort of 249
children who weighed <1.5 kg at birth, those whose head
circumference was >2 SD below the mean at 8 months of age
had poorer cognitive function at the age of 8 years than those
whose head size was normal (Hack et al., 1991). Among 365
children aged 7 years, larger head circumference was
associated with higher scores on measures of verbal ability
and practical reasoning (Ounsted et al., 1988). A similar
relationship was found between head circumference and IQ in
334 boys aged 8 to 9 years (Weinberg et al., 1974). Only one
previous study has examined how head growth at various
stages during postnatal development relates to cognitive
performance. In a cohort of 2023 children followed up from
birth, those who had an IQ in the superior range (>120) at the
age of 7 years had a larger head circumference at age 1 year
than children whose IQs were average (80119) or low
(<79), and this difference in head size persisted at 4 and 7
years of age (Fisch et al., 1976).
Findings in our study that the extent of postnatal head
growth was greater in the children of women who were
educated to degree level or who were of higher social class
suggest that part of the inuence of maternal education and
socio-economic status on a child's intellectual development
may be due to their effect on brain growth. It may be that the
extent and quality of cognitive stimulation and the style of
parenting provided by such mothers help promote brain
growth, and with it, intellectual development. Several studies
have demonstrated that provision of a cognitively enriched
environment in early life can lead to improvements in
intellectual performance (Anderson et al., 2003; Eickmann
et al., 2003; Hill et al., 2003), but whether this is partly
mediated by increases in head growth is unclear.
In contrast to some recent studies, we found no signicant
association between cognitive function and birthweight in
these 9-year-old children. Lower birthweight has been linked
to poorer cognitive test performance in childhood and
adolescence in the 1946 and 1958 British birth cohorts
(Richards et al., 2001; Jefferis et al., 2002) in 4300 Danish
conscripts (Sorensen et al., 1997), in 3484 children aged 7
years enrolled in the US National Collaborative Perinatal
Project (Matte et al., 2001) and in 449 Scottish 11 year olds
(Shenkin et al., 2001). The effect size in all these studies was
small; in the US study, for example, a 1 kg increase in
birthweight was associated with an increase in IQ of 4.6
points in boys and 2.8 points in girls (Matte et al., 2001). The

lack of such an association in our data may be due to the

smaller size of our study.
Findings in our study linking full-scale, performance and
verbal IQ in 9-year-old children to measurements of head
circumference made currently and at 9 months of age, but not
those made at 18 weeks gestation or at birth, suggest that
postnatal brain growth is more important than foetal growth
in determining cognitive function. Intelligence in children of
this age tends to remain stable into adulthood, so the fact that
head growth in the rst 9 months of life and between 9 months
and 9 years were both associated with IQ, regardless of head
size at the start of each period, suggests that maximizing
growth during both infancy and childhood is critical for the
attainment of peak cognitive capacity in adult life. Work is
now needed to investigate the mechanisms whereby maternal
education and socio-economic status inuence postnatal head
growth and to explore which other factors in the child's
environment help to determine eventual brain size.

Acknowledgements

We wish to thank the children and their families for their help
with this study, the research nurses, Tracey Tudball, Anne
Abel and Glynis Bouseld, for collecting data for the 9-year
follow-up, Chris Newsome for helping to organize the study,
Susan Knight for advice on IQ testing and Vanessa Cox and
Patsy Coakley for computing assistance. The study was
funded by the Medical Research Council, the Dunhill
Medical Trust and Children Nationwide.
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