ARTICLES
Effects of stunting, diarrhoeal disease, and parasitic infection
during infancy on cognition in late childhood: a follow-up study
Douglas S Berkman, Andres G Lescano, Robert H Gilman, Sonia L Lopez, Maureen M Black
Summary
Background Chronic malnutrition during infancy, marked by
stunting, has been associated with poor cognitive function.
We assessed the effect of stunting, diarrhoeal disease, and
parasitic infections during infancy on cognitive function in
late childhood.
Methods We followed up from birth to 2 years, a cohort of
239 Peruvian children for anthropometrics, stool samples,
and diarrhoeal status. At 9 years of age, we assessed
cognitive function in 143 (69%) with the full-scale
intelligence quotient of the Wechsler intelligence scale for
children-revised (WISC-R).
Findings All findings were adjusted for socioeconomic status
and schooling; in addition, findings related to diarrhoea
prevalence, Giardia lamblia, and Cryptosporidium parvum
were adjusted for severe stunting. During the first 2 years of
life, 46 (32%) of 143 children were stunted. Children with
severe stunting in the second year of life scored 10 points
lower on the WISC-R test (95% CI 2·4–17·5) than children
without severe stunting. Children with more than one episode
of G lamblia per year scored 4·1 points (0·2–8·0) lower than
children with one episode or fewer per year. Neither diar-
rhoea prevalence nor C parvum infection was associated with
WISC-R scores.
Interpretation Malnutrition in early childhood, indexed by
stunting, and potentially G lamblia, are associated with poor
cognitive function at age 9 years. If the observed
associations are causal, then intervention programmes
designed to prevent malnutrition and G lamblia early in life
could lead to significant improvement in cognitive function of
children in similar lower-income communities throughout the
less-developed world.
Lancet 2002; 359: 564–71
See Commentary page 542
Departments of Epidemiology (D S Berkman ScM) and International
Health (A G Lescano MHS, Prof R H Gilman MD), The Johns Hopkins
School of Public Health, Baltimore, MD, USA; Proyectos de
Informática, Salud, Medicina y Agricultura (A B PRISMA), Lima,
Perú (D S Berkman, A G Lescano, R H Gilman,
S L Lopez RN); Department of Pediatrics, University of Maryland
School of Medicine, Baltimore (M M Black PhD); Universidad
Peruana Cayetano Heredia, Lima, Perú (A G Lescano, R H Gilman)
Correspondence to: Dr Robert H Gilman, Department of International
Health, John Hopkins School of Public Health, 615 North Wolfe
Street, Room W3503, Baltimore, MD 21205, USA
(e-mail: rgilman@jhsph.edu)
564
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Introduction
Cognitive function in children is affected by environ-
mental and health-related factors.1–3 Risk factors that
interfere with cognitive function are especially important
during infancy because the first 2 years of life are an
essential period of rapid growth and development.
Chronic malnutrition during infancy, marked by
stunting, has been related to poor cognitive function in
late childhood in the Philippines,4 and in Jamaica,5
although the mechanisms are not fully understood.
Diarrhoea is both a cause and an effect of malnutrition,
and can lead to linear growth retardation.6–8
Cryptosporidium parvum and Giardia lamblia, two
common enteric infections often associated with
diarrhoea, adversely affect growth and nutritional status,
especially during infancy.9–14 Research on the relation
between cognitive function in children and diarrhoeal
disease during infancy is limited. Guerrant and
colleagues15 noted that diarrhoea during infancy was
negatively correlated with three tests of cognitive function
in Brazilian children. However, in this study, neither
environmental nor health-related factors were
considered, thus raising the possibility that the
associations seen could be attributed to confounding.
The complex interrelations among malnutrition,
diarrhoeal disease, and environmental factors such as
socioeconomic status and education, make it difficult to
determine the unique contribution of either malnutrition
or diarrhoeal disease to cognitive development. For
instance, because diarrhoeal disease can result in
retarded growth,6,10,16 stunting becomes a potential
confounder in the relation between diarrhoea and
cognitive function.
We aimed to examine the associations between health-
related factors during infancy and cognitive function in
late childhood. First, we extended previous research that
has linked stunting during infancy with poor cognitive
function in late childhood by investigating multiple
classifications of stunting and using a comprehensive,
standardised, and widely accepted measure of cognitive
function. Second, we assessed the independent effects of
diarrhoeal disease, and C parvum and G lamblia
infections during infancy on cognitive test scores in late
childhood, after adjusting for stunting, schooling, and
socioeconomic factors. If diarrhoeal disease during
infancy is associated with cognitive function at 9-years-
old after controlling for nutritional and environmental
factors, our understanding of the long-term burden
associated with diarrhoea and the health-related
determinants of cognitive function will be greatly
improved.
Patients and methods
Study setting
This study is a follow-up assessment of a cohort of
children who were examined longitudinally from
1989–91. The study was done in Pampas de San Juan de
Miraflores, a periurban shanty town in the outskirts of
Lima, Peru. In 1989, most families in this community
lived in houses constructed from woven thatch supported
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by wooden poles. Less than a half of families had latrines
or sewage connections, and water was largely supplied by
municipal trucks and stored in cisterns or barrels that
often became contaminated with faecal matter.17 Previous
studies11,18,19 have described the community in more
detail. Over the past decade, the population has grown to
40 000 people and the emigration rate has decreased.
Today, most homes are constructed at least partly from
brick, and have piped water and basic plumbing. Families
in the community are similar in socioeconomic status,
housing quality, and access to public utilities.11 A survey
in 2000 reported a median income for heads of
households of US$2100 per year (range $850–$4600;
unpublished data).
Enrolment
Between September, 1989, and March, 1991, 253
mothers in their final trimester of pregnancy were
randomly selected from the censused community and
asked to participate in a study to describe the effect of
C parvum infection on nutritional status.12 13 mothers
declined, and one child died of pneumonia early in the
study.12 The remaining 239 children (94%) were followed
up prospectively from birth until November, 1991, for
anthropometry and diarrhoeal illness. Census
information was obtained by A B PRISMA, a Peruvian
non-governmental organisation working in the
community.
In June, 1999, we selected all children from the
original cohort who had complete longitudinal data for at
least 6 months from birth (210 [88%] of 239). This
criterion reduced the risk of misclassifying the exposures
of interest (stunting, diarrhoeal disease, and parasitic
infections), while maintaining as large a sample as
possible. 145 (69%) of the 210 selected children were
located in the community, all agreed to participate in a
cognitive assessment, which were completed in 143
(99%) children. There were no significant differences
between the 145 study participants and the 65 children
who were not located, when compared by stunting
prevalence (p=0·21), proportion of days with diarrhoea
(p=0·35), proportion of C parvum-positive stool samples
(p=0·45), or by socioeconomic factors, including total
weekly expenses (p=0·45), weekly food expenses
(p=0·44), water quality (p=0·87), or floor type (p=0·19).
The proportion of giardia-positive stool samples was
greater in the children enrolled in the study (14·1% vs
8·4%, p<0·01). However, study children were followed
up longer (17·6 months vs 13·2 months, p<0·001) and
therefore observed through periods of higher risk than
children who were not located. When the comparability
analysis was restricted to the first 6 months of life, for
which both study participants (145) and losses to follow-
up (65) had complete surveillance, the proportion of
giardia-positive stool samples between the two groups
was no longer significant (p=0·13).
The longitudinal surveillance and follow-up
assessment were separately approved by the Committee
of Human Research of the Johns Hopkins University
School of Hygiene and Public Health and by the ethics
committee of A B PRISMA.
Data collection
We followed up children from September, 1989, until
November, 1991, for anthropometry and diarrhoeal
illness. Field workers measured each child’s height and
weight about every 30 days. Weight was measured with
Salter scales (Salter Housewares Ltd, Tonbridge,
England). Length was measured with a locally made
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ARTICLES
wooden platform and sliding footboard. Diarrhoea was
surveyed twice weekly. Field workers obtained
information from the mother or primary caretaker of the
child for the day of the interview and the 3 previous days.
For each day they inquired about the number of liquid or
semi-liquid stools the child had passed.11 We collected
stool samples weekly and examined for C parvum and
G lamblia as previously described.11,20–22 Helminths and
bacterial and viral enteropathogens were not determined.
When the children were 9-years-old, cognitive function
was assessed with the Wechsler intelligence scale for
children-revised (WISC-R),23 translated to Spanish, and
used routinely in local hospitals. The WISC-R,
standardised on 2200 children, has excellent
psychometric properties. The full scale intelligence
quotient has a reliability coefficient of 0·96, an SE of
measurement of 3·19, and a test-retest stability
coefficient of 0·95.23 Validity studies with tests of
intelligence, receptive vocabulary, and achievement, as
well as school grades, yield concurrent validity
coefficients from the upper 0·30s to low 0·80s.23
Six psychology interns, trained and supervised by a
licensed psychologist from the Department of Psychology
of the Hospital Nacional Hipolito Unanue, Lima, Peru,
administered the WISC-R. We assigned children to a test
administrator using a random number table;
administrators were unaware of each child’s previous
diarrhoeal status and anthropometric assessment. One
interviewer had significantly higher scores (5·6, p=0·047)
and two interviewers had significantly lower scores (–5·1,
p=0·029) compared with the other three interviewers.
We therefore created a variable with three categories to
adjust for these differences. This variable remained
significant in all our models and explained about 8·5% of
the total variance.
Weight in late childhood was measured with a Soehnle
scale (Murrhardt, Germany). Height was measured with
a locally constructed wooden backboard and sliding
headboard. A socioeconomic survey was administered,
and information on schooling was obtained at the end of
the academic year. The children were offered free clinical
examinations that included vision and hearing screening.
None of these tests showed important deficiencies in
either hearing or vision.
Variables analysed
We defined grade level in school as the grade of the child
when the cognitive test was administered. Additional
information on school type (public or private), class size
(small class defined as <30 students), kindergarten and
daycare attendance, whether the child worked, age of
school entry, and grade retentions was obtained. Study
habits were described by inquiring whether the child
completed homework assignments on a regular and
consistent basis.
Housing conditions were defined according to floor
type (cement vs soil), water source (direct pipe
connection, a neighbour, or other), and stool disposal
method (bathroom with plumbing, hole in the ground
(silo), or other). Information was gathered about
maternal birthplace (coast, highlands, or jungle), whether
either parent had completed some college education
(college or less), the language spoken (Spanish or
Quechua), the mother’s parity at the birth of this child,
and the profession of the main source of income
(technical employee, construction worker, skilled worker,
street seller, chauffeur, small business owner, or
independent). Regarding the primary caregiver, we
questioned the mother or guardian about who cared for
565
ARTICLES
the child on a daily basis during infancy (mother, father,
sibling, grandparent, or other relative) and whether the
father lived in the home during this period.
Standardised height-for-age and weight-for-height Z
scores were calculated with the EPINUT program in
EpiInfo (version 6.04b). We defined stunting as an
height-for-age Z score of less than –2; wasting was
defined as weight-for-height Z score of less than –2, on
the basis of WHO reference data.
We assessed age of the first stunting event by 6-month
intervals (0–5, 6–11, 12–17, 18–24 months). Severity of
stunting was classified as moderate (–3⭐ height-for-age
<–2) and severe (height-for-age <–3). Persistence of
stunting was defined as persistent (stunted at least once
during infancy and also in late childhood), catch-up
(stunted at least once during infancy but not in late
childhood), late incident (stunted for the first time in late
childhood), and never stunted. We calculated stunting
prevalence as the number of anthropometric
measurements classified as stunted divided by the total
number of measurements. This prevalence rate can be
interpreted as the number of months stunted per year.
Wasting was analysed as both a continuous and
dichotomous variable. Age at first wasting and wasting
prevalence were also calculated. These expressions were
then analysed by age intervals, but no associations with
WISC-R scores were recorded.
A day of diarrhoea was defined as one in which a child
passed three or more liquid or semi-liquid stools.
Diarrhoea episodes were defined as at least 1 day of
diarrhoea followed by 2 or more diarrhoea-free days.16
Diarrhoea incidence rates were calculated by dividing the
number of diarrhoea episodes by the total number of
diarrhoea-free days. We calculated a diarrhoea
prevalence rate by dividing the number of diarrhoea-
positive days by the total number of days under
surveillance for diarrhoea. Episodes of C parvum and
G lamblia were defined as having one positive stool
sample followed by at least three consecutive negative
samples.16–17 Incidence rates for C parvum and G lamblia
were calculated as the number of episodes divided by the
number of stool samples at risk of a new episode (ie, total
episode-free samples). We multiplied incidence by 52 to
express it in episodes per year at risk, given that the
number of stool samples assessed per year was 52 due to
weekly collections. C parvum and G lamblia prevalence
rates were calculated by dividing the number of positive
weekly stool samples by the total number of stool
samples. Episodes of C parvum and G lamblia were
judged symptomatic if the child had at least one
diarrhoea-positive day in the period 2 weeks before the
beginning and 2 weeks after the end of the episode. Since
giardia infections are commonly symptomless and can
last for several weeks or even months,24 we also defined
giardia-positive stools as symptomatic if the child had
diarrhoea on any one of the 3 days surrounding or
including the day the sample was collected. Thus,
giardia-positive stools were also defined as symptomless
in the absence of diarrhoea. We then calculated incidence
and prevalence rates for symptomatic C parvum and both
definitions of G lamblia infection by the same methods
described previously. We estimated the median age at
onset of first infection with the Kaplan-Meier statistic.25
Statistical analysis
We used Stata (version 6.0) for all analyses, and one-way
analysis of variance (ANOVA) for univariate analysis of
the WISC-R scores. Sequential multivariate ANOVA was
applied to identify factors independently associated with
566
For personal use. Only reproduce with permission from The Lancet Publishing Group.
cognitive test scores; significance of the contribution of
each variable was assessed with the F test after
adjustment for the effects of variables already included in
the model. We used the Wald test for the comparison of
WISC-R scores for categorical variables with more than
two categories. Regression coefficients were used to
estimate the change in WISC-R scores between levels for
categorical variables and for a one unit increase in
continuous variables. We constructed multivariate
models to adjust for the effects of socioeconomic status
and education on cognitive test scores. Adjustment
variables were selected by sequentially adding significant
predictors from the univariate analysis into the model.
We manually rotated the order of the variables to identify
interactions and collinearity.
Continuous variables were truncated into fixed-size
intervals and analysed as categorical variables to identify
non-linear associations. If a monotonic trend or U-
shaped relation was recorded between WISC-R scores
and a particular covariate, an attempt was then made to
combine categories that had similar WISC-R average
scores.
Several variables were highly correlated and
represented similar domains relating to cognitive
function (eg, maternal and paternal education; school
type and class size). In these cases, we chose the variable
that explained the largest percentage of the variance and
enhanced the strength of associations of the other
variables in the model.
The presence of interactions in the final model was
tested for by introducing products of the variables by
pairs into the model. The internal validity of our results
was assessed by repeating the analyses on children who
had more than 12 months of prospective surveillance
from birth (ie, children who were followed up into the
second year of life). The three exposure variables were
also analysed by age categories in 6-month intervals (0–5,
6–11, 12–17, 18–24 months). This analytical strategy
enabled us to identify effects that acted only during
specific periods in infancy, and to further reduce the risk
of misclassification that could arise when comparing
children who were followed up prospectively for different
lengths of time.
Role of the funding source
The study sponsors had no role in study design, data
collection, data analysis, data interpretation, or writing of
the report.
Results
Description of the sample
Table 1 shows the characteristics of the children. All
children were enrolled in school from grade 2 to 5.
25 (18%) of 141 children had been held back in school
once and required to repeat a grade; nine (6%) had been
held back at least twice (table 2).
46 (32%) of 143 children were stunted at least once
during infancy. Of these, ten (22%) were severely
stunted. Most stunted children became stunted between
6 and 17 months of age. Nearly half of children who were
stunted during infancy had persistent stunting into late
childhood; the remaining stunted children had catch-up
growth and were not stunted at 9 years of age. Several
expressions of stunting were correlated with each other.
18 (95%) of 19 persistently stunted children were stunted
for the first time between 6 and 17 months of age
whereas only 18 (68%) of 27 catch-up children were
stunted for the first time during this period (p=0·02, ␹2
test). Catch-up children were nearly seven times as likely
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 ARTICLES

Children (n=143) n ␤ [95% CI) p†

Demographic characteristics Grade
Age (years)* 9·36 (0·46) Fifth 31 .. <0·001
Male sex 76 (53%) Second 7 –23·5 (–32·9 to –14·2) <0·001‡
WISC-R test scores* 88·9 (12·53) Third 29 –11·7 (–17·5 to –6·0) <0·001‡
Fourth 76 –3·9 (–8·6 to 0·9) 0·110‡
Stunting severity
Severe (HAZ <–3) 10 (7%) School type
Moderate (–3 ⭐HAZ <–2) 36 (25%) Public 115 .. <0·001
Never stunted 97 (68%) Private 26 10·3 (5·2 to 15·4) ..
Diarrhoea episodes (total) Class size
0–2 29 (20%) ⭓30 119 .. 0·033
3–4 35 (25%) <30 22 6·2 (0·5 to 11·8) ..
5–6 35 (25%)
Held back
7–8 23 (16%)
No 107 ..
⭓9 21 (14%)
Yes 34 –12·4 (–16·8 to –8·0) <0·001
Diarrhoea prevalence (days/month) by age (months)*
Homework habits
0–5 3·60 (3·70)
Always or almost always 124 .. 0·001
6–11 2·06 (3·24)
Sometimes or never 17 –10·2 (–16·4 to –4·1) ..
12–17 1·67 (1·90)
18–24 1·70 (1·90) Maternal education
0–11 2·93 (2·73) No college-level education 135 .. 0·026
⭓12 1·67 (1·95) Some college schooling 6 11·5 (1·37 to 21·7) ..
Giardia episodes (total) Paternal education
0 20 (14%) No college-level education 133 .. <0·001
1 37 (26%) Some college schooling 8 15·4 (6·8 to 24·1) ..
2 37 (26%)
Parity
3 28 (20%)
⭓4 40 ..
4 12 (8%)
1–3 101 5·1 (0·6 to 9·7) 0·027
5–7 9 (6%)
Income source
Cryptosporidium episodes (total)
Other 5 .. 0·013
0 66 (46%)
Father or mother 136 14·0 (3·0 to 25·1) ..
1 47 (33%)
Career
2 20 (14%)
Other§ 125 .. 0·036
3 10 (7%)
Technical employee 13 7·7 (0·5 to 14·8) ..
Cryptosporidium incidence (episodes per year at risk)* 0·56 (0·61)
Floor type
Follow-up time (months) Cement 119 .. ..
6–11 28 (20%) Soil 24 –8·6 (–14·0 to –3·2) 0·002
12–17 50 (35%)
*Socioeconomic and education variables except for grade level and floor type,
18–23 43 (30%) were determined from survey, which was completed in 141 children. †From
⭓24 22 (15%) ANOVA F test. ‡Wald test. §Three patients did not report a main source of
HAZ=height-for-age z score. *Values are mean (SD). household income. Factors not significantly associated with WISC-R scores:
toilet and water connection, language spoken at home during the first 5 years
Table 1: Children’s characteristics of life, mother’s origin, primary caregiver, father living in the household during
infancy, attended day-care or kindergarten before school, began school late,
and worked while in school.
(33%, nine of 27 vs 5%, one of 19) to be stunted for the Table 2: Association between education and socioeconomic
first time before age 6 months and after 17 months factors and WISC-R test scores*
compared with children with persistent stunting.
Median age at onset of first diarrhoea episode was
0·9 months. The total number of diarrhoea episodes scored higher than children of less educated parents.
during infancy ranged from 0 to 29, with a mean of 5·5. Children who were born before the fourth child, or who
122 (85%) of 143 children had eight or fewer episodes. had parents who were the primary source of income in
The estimated median age at onset of first G lamblia the home or who were technical employees had higher
infection was 7·2 months. 123 (86%) of 143 children had scores. Children who lived in homes with soil floors
at least one G lamblia episode during the first 2 years of scored lower than children who lived in homes with
life. G lamblia incidence ranged from 0 to 4·8 episodes cement floors. We saw no association between primary
per year at risk during infancy. caregiver and WISC-R scores.
267 (3%) of 9959 stool samples tested positive for Stunting prevalence rates were negatively correlated
C parvum. 77 (54%) of 143 children had at least one with cognitive test scores. An increase in prevalence of
episode of C parvum. The estimated median age at onset stunting corresponded to a decrease in WISC-R score
of first C parvum infection was 16·1 months. (table 3). Children with 2 months or more of stunting per
year had lower scores than those with little or no
Univariate analysis stunting. Children stunted for the first time between ages
Children in grades 2 and 3 scored lower on the WISC-R 6 and 11 months, and 12 and 17 months, achieved lower
test than children in grade 5 (table 2). Children in grade WISC-R scores than children never stunted during
4 had similiar scores to those in grade 5. Private school infancy (table 3). WISC-R scores of children stunted for
attendees and smaller class size were asssociated with the first time before age 6 months and after 17 months
higher scores. Children who were held back in school at did not differ from those of children who were never
least once and who completed homework assignments stunted in the first 2 years.
infrequently had lower scores. Persistent stunting into late childhood was also
Table 2 shows socioeconomic covariates that were associated with cognitive test scores—children who
significantly associated with WISC-R scores. Children of suffered persistent stunting scored lower on the
mothers and fathers who had had a college education WISC-R than children who were never stunted. Catch-

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ARTICLES

Children Unadjusted Multivariate adjusted*

(n=143)
␤ (95% CI) p† ␤ (95% CI) p†
Stunting prevalence (months per year) 143 –1·2 (–2·0 to –0·4) 0·005 –0·6 (–1·3 to 0·1) 0·162
<2 38 Reference .. .. ..
⭓2 105 –7·4 (–12·0 to –2·9) 0·002 –4·2 (–8·0 to –0·4) 0·032
Age at first stunting event (months)
Never stunted 97 Reference 0·011 .. 0·173
0–5 6 1·4 (-8·7 to 11·5) 0·779‡ –0·1 (–9·5 to 9·3) 0·983‡
6–11 18 –6·0 (–12·2 to 0·1) 0·055‡ –2·0 (-7·3 to 3·3) 0·458‡
12–17 18 –9·1 (–15·3 to –3·0) 0·004‡ –6·5 (–11·6 to –1·4) 0·014‡
⭓18 4 7·4 (–4·8 to 19·7) 0·232‡ 0·8 (–9·4 to 10·9) 0·882‡
Never or stunted other age 107 Reference .. .. ..
6–17 36 –7·9 (–12·5 to –3·3) 0·001 –4·3 (–8·3 to –0·5) 0·031
Stunting persistence, infancy until late childhood
Never stunted 91 Reference 0·010 .. 0·129
Persistent 19 –8·4 (–14·5 to –2·4) 0·009‡ –4·6 (–9·7 to 0·5) 0·077‡
Catch-up 27 –1·8 (–7·1 to 3·5) 0·503‡ –2·1 (–6·5 to 2·3) 0·347‡
Late incident 6 9·0 (–1·1 to 19·1) 0·081‡ 5·4 (–2·9 to 13·7) 0·200‡
Stunting severity§
None or not severe 133 Reference .. .. ..
Severe 10 –9·1 (–17·1 to –1·1) 0·027 –5·4 (–12·4 to 1·6) 0·129
0–11 months (none or not severe) 138 Reference
Severe 5 –10·1 (–21·3 to 1·1) 0·077 0·1 (–10·7 to 10·9) 0·989
⭓12 months (none or not severe)㛳 107 Reference
Severe 10 –13·2 (–21·5 to –4·8) 0·002 –10·0 (–17·5 to –2·4) 0·011
Diarrhoea prevalence by age-groups (days/month)
0–5 months 143㛳 0·0 (–0·6 to 0·6) 0·953 –0·2 (–0·8 to 0·4) 0·530
6–11 months 142㛳 0·4 (-0·3 to 1·0) 0·272 0·3 (–0·5 to 1·1) 0·508
12–17 months 116 –1·5 (–2·7 to –0·2) 0·026 –0·1 (–1·2 to 1·1) 0·888
⭓18 months 72 –1·5 (–1·6 to 0·5) 0·293 0·1 (–1·0 to 1·1) 0·918
0–11 months 143㛳 0·2 (–0·6 to 1·0) 0·606 0·0 (–0·9 to 0·8) 0·951
⭓12 months 116 –1·7 (–2·9 to -0·4) 0·008 –0·2 (–1·4 to 0·9) 0·670
Giardia incidence
⭐1 episode 66 Reference .. .. ..
>1 episode per year at risk㛳 77 –5·3 (–9·4 to –1·3) 0·011 –4·1 (–8·0 to –0·2) 0·039
*Multivariate models for stunting variables have been adjusted for intertester variability, paternal education, school type, ever held back, and grade level (grades 3, 4,
and 5, combined as reference category). Models for diarrhoea and Giardia included these variables as well as severe stunting in the second year of life. †p-values from
ANOVA F test. ‡Wald test. §Severe stunting is defined as height-for-age Z score below –3 SDs of the NCHS median. Analysis of severity was done by year of life
because too few children had severe stunting in each of the first two semesters of life. ||Multivariate adjusted model has 117 children or less as indicated due to
inclusion of stunting severity in the second year of life. For continuous variables, regression coefficient (␤) is the change in WISC-R for a one unit increase in the
variable.
Table 3: Relations of stunting, diarrhoeal disease and G lamblia infection to WISC-R test scores

up and late incident children did not significantly differ
from those who were never stunted. Children who were
severely stunted had lower WISC-R scores compared
with moderately stunted and non-stunted children (table
3). Children who were severely stunted in the second
year of life scored much lower on the WISC-R test than
children moderately stunted and non-stunted during that
period.
Diarrhoea prevalence in the second year of life was
significantly associated with cognitive test scores at age 9
(table 3). Between 12 and 24 months, a 1-day increase in
diarrhoea per month was associated with a decrease in
WISC-R scores.
G lamblia incidence was significantly associated with
cognitive test scores (table 3). Children with more than
1 episode per year at risk had lower WISC-R test scores
than children with one or fewer G lamblia episodes per
year at risk. Neither symptomatic nor symptomless
episodes and stool samples were associated with WISC-R
scores. No associations were recorded between C parvum
infection and cognitive test scores according to the
number of episodes, incidence and prevalence, and
symptomatic infections.
Multivariate-adjusted models
Class size and homework habits were no longer
significant predictors of cognitive test scores after
adjustment for school type, grade repetition, and grade
level. In addition, maternal birthplace, level of education,
parity, main source of income, career type, floor type,
and language spoken at home while the child was
learning to speak, were all accounted for by paternal
education. We believe that paternal education had a
stronger association with cognitive test scores because it
is the most comprehensive indicator of household
socioeconomic status in this community. Fathers were
more likely to achieve higher educational levels than their
wives or partners and were generally the main source of
income in the household. These patriarchal patterns are
common in Peru and many less-developed countries.
Although conceptually each variable may have a specific
effect, statistically they are all highly correlated. Paternal
education was the only predictor that was independently
associated with cognitive test scores after adjustment for
maternal education and birthplace, parity, principal
source of income and career type, floor type, and
language spoken at home while the child was learning to
speak.
Multivariate models for stunting were adjusted for four
significant covariates: paternal education, school type,
grade retention, and grade level. The models for
diarrhoea prevalence and G lamblia incidence were also
adjusted for severity of stunting in the second year of life.
After multivariate adjustment, stunting prevalence and
age at first stunting event were still significant predictors
of cognitive test score, whereas persistent stunting was no
longer significant in multivariate analysis. Adjustment
only modified slightly the effect of severe stunting in the

568 THE LANCET • Vol 359 • February 16, 2002 • www.thelancet.com

For personal use. Only reproduce with permission from The Lancet Publishing Group.

= ␤ coefficient = 95% CI
Parental
education
School type
School
retention
School grade
Severe
stunting
Giardia
incidence
⫺20 ⫺15 ⫺10 ⫺5 0 5 10 15
␤ (95% CI)
Factors associated with WISC-R test scores
CIs are the change in mean WISC-R test scores associated with the
presence of each variable. Values at the right of the graph are the
percentage of the variance explained by each factor.
second year of life on WISC-R scores. This analysis was
repeated with data from 117 children who had at least
12 months of follow-up from birth. The effects of the
four adjustment covariates were unchanged compared
with the models that included all 143 children.
Diarrhoea prevalence in the second year of life was not
significantly associated with WISC-R scores after adjusting
for paternal education, school type, grade retention, grade
level, and severe stunting in the second year of life.
However, children with higher diarrhoea prevalence rates
were more likely to be severely stunted in the second year
of life and have parents who were not college educated
(p<0·001 and p=0·008, likelihood-ratio test).
G lamblia incidence remained significantly associated
with WISC-R scores in the multivariate adjusted model
after controlling for socioeconomic status, schooling, and
severe stunting.
We were able to explain 40% of the variability in
WISC-R scores in a model including both severe stunting
in the second year of life and giardia incidence, as well as
socioeconomic and schooling variables (figure). No
significant interactions were seen between any variables
in our multivariate-adjusted models.
Discussion
We have shown that stunting during infancy has a strong
adverse effect on cognitive function in late childhood.
Severe stunting in the second year of life was associated
with a 10-point reduction in intelligence quotient scores
after adjustment for socioeconomic, schooling, and other
significant factors. Previous studies have been limited by
use of shorter, less comprehensive cognitive tests that are
restricted to specific domains of intellectual ability and
have relatively weak internal validity. Mendez and Adair4
reported a similar association between severe stunting
and cognitive function in Filipino children using a local
test of non-verbal intelligence. However, because the
construct validity of this test was not described, the
correspondence of the reported differences in test scores
(1·4–3·3 points) with actual intelligence deficits cannot
be established. Our use of the full-scale WISC-R, a
widely used, comprehensive, and reliable test of cognitive
ability, greatly increases the internal validity of our results
and extends our conclusions to a wider range of
intellectual skills than those examined in other reports.
In our analysis, severe stunting in the second year of
life explained 4% of the variance in cognitive test scores.
This figure is similar to the results reported by Mendez
and Adair (3%–6%),4 despite the striking difference
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For personal use. Only reproduce with permission from The Lancet Publishing Group.
ARTICLES
between Peruvian and Filipino children in the proportion
of children who were severely stunted (22% vs 43%).
8·8
This finding shows that the negative effect of linear
6·9 growth retardation on cognitive function is not restricted
to settings with a high proportion of severely stunted
children.
14·4
Our results also show that prevalence and timing of the
3·2 first stunting event are related to a decrease in
intelligence quotient after adjustment for other significant
4·0 covariates. Sample size prevented us from examining the
independence of these effects from those of severe
2·5 stunting. However, if independent effects of stunting
severity, timing, and persistence on cognitive ability are
20 shown, then the burden of growth retardation will reach
even greater levels.
We did not assess iron status in this study. Surveillance
studies26 in this community and other shanty towns in
Lima have reported that about 25% of children under
4 years of age were anaemic. Since iron deficiency is a
risk factor for cognitive deficits in school-aged children,27
we cannot rule out the possible effects of iron deficiency
on WISC-R scores.
In univariate analysis, diarrhoea prevalence in the
second year of life was associated with lower cognitive
test scores. Although children with higher diarrhoea
prevalence rates were more likely to be severely stunted
in the second year of life and have parents who were not
college educated, when children with high and low
diarrhoeal burden were assessed separately, children who
were severely stunted scored worse than those who had
never been stunted. These results suggest that the effect
of severe stunting is present even in children with low
diarrhoeal burdens, and supports the hypothesis that the
effect of stunting is independent of the action of
diarrhoeal disease. In addition, the effect of diarrhoea
disappeared after adjustment for paternal education,
whereas the effect of stunting remained significant.
Because stunting and paternal education are both
significantly associated with WISC-R scores, and
stunting is not a unique consequence of diarrhoea, they
act as confounders by artificially creating the association
between diarrhoeal disease and cognitive test scores. The
effect of diarrhoeal disease on WISC-R was not found
after modelling the relation between stunting and
socioeconomic factors, and WISC-R.
Guerrant and colleagues15 have reported an association
between diarrhoeal disease and poorer cognitive test
scores, after adjustment for socioeconomic status and
maternal education. However, it is unlikely that with a
sample of only 25 children, appropriate adjustment for
multiple confounding factors could have been done. In
our study, a larger sample allowed us to model the
association of multiple factors with cognitive function,
even for variables with prevalence rates that were lower
than 8%. Although parents in general are better educated
in the Peruvian Pampas than in the Brazilian Favela, our
larger sample size allowed us to adjust for paternal
education while taking into account other significant
covariates, namely schooling and stunting. In addition,
the effect of stunting on cognitive function described in
our results was not assessed in the Brazil study25 and
might also explain their finding.
C parvum infections were not related to decreased
cognitive function, despite the reported effect of
cryptosporidiosis on linear growth faltering.11,12 The
absence of a detectable effect might stem in part from the
low incidence and the late age of onset of C parvum in
these children. Similarly, Guerrant and colleagues15 in
Brazil recorded no correlation between C parvum and
569
ARTICLES
cognitive dysfunction. Other studies28–30 have recorded an
association between cognitive function and helminth
infections such as hookworm and Trichuris trichiura.
However, the dry desert conditions present in the
Pampas surrounding Lima are not conducive to survival
or transmission of geohelminths. Current data suggest
a low prevalence from 0 to 0·8% of geohelminths such
as Ascaris lumbricoides, T trichiura, hookworm, and
Strongyloides stercoralis in the Pampas, and that when
infections do arise, severity is minimum.
We have reported a small effect of incident giardia
episodes on WISC-R test scores. The effect of giardiasis
on WISC-R scores remained significant after adjustment
for paternal education, schooling factors, and severe
stunting, reducing the chance that residual confounding
could explain these findings. Giardia infections reflect the
occurrence of only a few specific events of faecal-
oral contamination, making diarrhoeal disease a
more comprehensive indicator of environmental
contamination. However, in this study, WISC-R scores
were associated with giardiasis and not with diarrhoeal
disease, suggesting that G lamblia infection could be a
better indicator of those aspects of environmental
contamination that are associated with deficits in
cognitive function. There is no evidence or rationale for a
specific aspect of the pathogenesis of G lamblia infection
to have deleterious effects on cognitive development.
Nevertheless, giardiasis can lead to zinc and other
micronutrient deficiencies that have been associated with
deficits in cognitive development.31 Nash and Mowatt32
reported that G lamblia variant specific surface proteins
bind zinc and other heavy metals in the intestine. Giardia
can also cause malabsorption of fats.24
To keep the risks of confounding to a minimum, we
modelled the effects of each variable significantly
associated with WISC-R scores. Analysis of multiple
expressions of each variable, excluding those that were
colinear or redundant in their relation with cognitive test
scores in univariate analyses, were made. This analytical
strategy enabled us to obtain a highly parsimonious
ANOVA model that explained 40% of the variance in
WISC-R scores. Mendez and Adair4 reported very similar
results using at least ten more variables and a sample size
15 times greater than ours. Our results show that a
reduced set of carefully selected variables can
appropriately describe the sources of variability in
cognitive test scores and represent the most relevant
domains affecting intelligence.
The combined effects of stunting and giardia infections
account for an intelligence quotient deficit of almost 15
points. These results are important for re-evaluating the
current estimates of the burden imposed by symptomatic
and symptomless infections and malnutrition during
infancy. Our finding of an association between giardia
infections and decreased WISC-R scores is interesting
and deserves further attention in a more rigorous study
designed to account for multiple parasitic, bacterial, and
viral enteric infections. Because of the high prevalence of
stunting in children living in less-developed countries,
estimated to be as high as 40% in children younger than
5 years of age,33 our results can be used in design of
intervention programmes seeking to have the greatest
effect on the adverse effects of stunting.
In our study, children who were severely stunted in the
second year of life had the most substantial impairments
in cognitive function. We also showed that children who
had persistent stunting into late childhood were
considerably more likely to be stunted for the first time
after age 6 months and before 17 months compared with
570
For personal use. Only reproduce with permission from The Lancet Publishing Group.
children who experienced catch-up growth. Children
who either recovered early or became stunted late in
infancy were relatively unaffected. Our results suggest
that strategies to promote the cognitive function of school
age children in less-developed countries should focus on
securing the nutrition and wellbeing of children early in
life.
Contributors
D Berkman designed the research methods, gathered data, managed data
entry, devised the analytical framework for the study, did the statistical
analysis, and wrote and edited the paper. A Lescano assisted in devising
the analytical framework for the study and doing the statistical analysis,
wrote most of the statistical analysis, and edited the paper. R Gilman
participated in study design, advised in data collection, guided the
scientific process, contributed to writing and editing of the paper,
provided advice on the epidemiology of diarroheal diseases and
G lamblia infection, and assisted with funding. S Lopez organised,
managed, and did most of the data collection. M Black participated in
study design, guided the scientific process, contributed to writing and
editing of the paper, and provided advice on anthropometrics, and the
assessment and interpretation of cognitive performance in children.
Conflict of interest statement
None declared.
Acknowledgments
This study was funded in part by ITREID and the RG-ER fund for the
advancement of research in tropical medicine, and by the SSB fund.
We thank Richard L Guerrant for his stimulating lecture and
comments which provoked this study, Elissa Malkin for her support, and
J B Phu and D Sara for technical assistance.
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Uses of error
Assumptions
Martin Barratt
A Commentary on our trial comparing medical or
surgical treatment for children with vesicoureteric reflux
(VUR) and nephropathy picked up on a statement which
was not strictly accurate. “We have shown that there are
no differences in the outcome of children with severe
VUR using medical or surgical management strategies”.
It would have been more correct to say that we failed to
demonstrate a significant difference in outcome between
the two groups, but that if there were a benefit from
surgery, we could be 95% confident that it was not more
than 20% at 4 years, and 30% at 10 years of follow-up.
We could well have missed a benefit from surgery,
apparent with more cases, longer follow-up, better
selection of patients, or less than ideal medical
management (the trial effect). We could have
prematurely closed the book on surgery, discouraging
others from embarking on long-term clinical studies, or
research foundations from funding them, and dissuading
purchasers from approving the procedure.
If this was a mistake, it was not my biggest one.
I supported the use of short-course high-dose prednisolone
Institute of Child Health, University College, London WC1N 1EH, UK (Prof M Barratt FRCP)
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25 Brookmeyer R, Crowley J. A confidence interval for the median
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for the treatment of the first episode of nephrotic
syndrome in childhood. Corticosteroids were introduced
in 1950, and by the time I entered paediatric nephrology
in 1967, it had become sufficiently obvious that they
induced remission in most children with minimal change
nephropathy, such that a prospective controlled trial was
thought to be unethical. There was uncertainty about
how long treatment with high dose steroids should
continue after remission. I wanted to minimise steroid
toxicity and advocated withdrawal as soon as the urine
was free of protein. This policy was the basis of our local
management protocol, and was repeated in lectures,
reviews, textbooks and consensus statements. However,
others believed that longer courses of steroids were
needed to prevent relapse, and in the end, several
controlled trials proved them to be correct. Our desire to
protect children from the side effects of prolonged
treatment resulted in a higher relapse rate and more
steroids in the long run. The mistake was not to have
recognised earlier that a controlled trial would have
resolved this dilemma.
571