BRAIN INJURY, 2001, VOL. 15, NO.

12, 1029± 1039

Neuropsychological long-term sequelae of

perinatal asphyxia

CRISTINA MAN Ä ERUy , CARME

J U N Q U E y , F R A N C E S C B O T E T ‡ , M E R C EÂ
Â
TALLADA} and JOAN GUARDIA}
y Department of Psychiatry and Clinical Psychobiology; ‡ Hospital ClõÂ nic, Faculty of
Medicine; } Department of Methodology and Behavioural Sciences, University of
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Barcelona, Barcelona, Spain; } Services of Neurophysiology and Neurology, Vall

d’Hebron Children Hospital, Barcelona, Spain
(Received 9 October 2000; accepted 8 June 2001 )

Objective: To investigate the long-term neuropsychological consequences of perinatal asphyxia (PA).

Methods: A group of adolescents were assessed with antecedents of mild …n ˆ 8† and moderate
…n ˆ 20† PA, and a matched group of 28 healthy adolescents as a control group.
Neuropsychological assessment included tests of memory, perceptual-motor skills, and frontal lobe
functions, because these are areas of cognitive functioning susceptible to hypoxic conditions.
For personal use only.

Results: Subjects with moderate PA showed significant differences from the control group on tests
related to delayed recall for both verbal and visual information, perceptual-motor speed, and tests
assessing attention and executive functions. Conversely, subjects in the mild PA group exhibited scores
which were similar to those of the control group in all the assessed variables.
Conclusion: The present findings demonstrate that subtle but persistent neuropsychological deficits were
observed in adolescents with antecedents of moderate PA, but not in those classified with mild
asphyxia.

Introduction
The cognitive outcome of neonates with Perinatal Asphyxia (PA) has been a subject
of interest for investigators for the last century. In fact, the pioneer of the idea that
an association exists between perinatal events and subsequent development and
behaviour was Little in 1862 [1], but his hypotheses did not receive attention
until the 1950s. From the early 1950s to the late 1970s, different authors [2± 6]
studied the association between perinatal anoxia and intellectual development, but
their results were contradictory and inconclusive. In 1973, Gottfried [7] argued that
the cause of this controversy was that these studies differed primarily with respect to
the assessment of the anoxia, the experimental design and the control variables.
Gottfried [7], after a review of 24 studies carried out before the early 1970s, con-
cluded that cognitive impairment resulting from anoxia (i.e. significantly lower

Correspondence to: Dra Carme JunqueÂ, Departament de Psiquiatria i Psicobiologia ClõÂ nica,
Universitat de Barcelona, ‡ IDIBAPS Casanova 143, 08036 Barcelona, Spain. e-mail: cjunque@
psi.ub.es

Brain Injury ISSN 0269± 9052 print/ISSN 1362± 301X online # 2001 Taylor & Francis Ltd
http://www.tandf.co.uk/journals
DOI: 10.1080/02699050110074178
 1030 C. ManÄeru et al.

mean IQs) was more often found in infants and pre-schoolers than in older children
and adolescents.
Nowadays it is widely accepted that severe PA is a cause of poor cognitive and
motor development and is related to important neurological impairment such as
cerebral palsy, epilepsy or intellectual delay [8]. Conversely, neonates who have a
diagnosis of mild encephalopathy related to PA are believed to be free from neu-
rologic impairment and have school performance scores similar to those of their
peers [9± 12]. However, the prognosis is uncertain for those within the moderate
category or stage 2, according to Sarnat and Sarnat’s [13] stages of Hypoxic-
Ischemic Encephalopathy (HIE).
The prediction of outcome after perinatal hypoxic-ischemic injury has been the
concern of more recent studies that have used some neurodevelopmental tests to
assess the possible deficits of children with PA from the first months of life to pre-
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school age. These studies have usually included general scales to evaluate the cog-
nitive development of children (Bayley Developmental Scale, Uzgiris and Hunt
Scale, Griffiths Scales of Mental Development, McCarthy Scales of Children’s
Abilities) [14± 20], but few studies have examined children at school age or during
adolescence with tests that allow one to evaluate subtle cognitive changes [21± 23].
Long-term evaluation of the population with PA shows that a significant
percentage of survivors without neurologic sequelae may have school-related
dysfunction [12]. Few prospective studies have focused on the long-term outcome
of survivors of PA from a comprehensive neuropsychological approach. In general,
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previous studies have only assessed general intellectual and motor-perceptive

functions.
In 1965, Corah et al. [5] studied the neuropsychological consequences of peri-
natal anoxia after 7 years in a sample of 235 subjects (101 children who were anoxic,
full-term new-borns and 134 children who were full-term, normal neonates). This
study included tests of general intelligence, perceptual-motor skills and personality
measures. Statistically significant differences between the groups in areas of verbal
abstract ability and perceptual-motor skills were observed. These authors pointed
out that many measures of cognitive and intellectual functioning at pre-school ages
are not highly predictive of later functioning. It is important to stress that some
minor cognitive dysfunction perhaps remains undetected at early ages, but emerges
later when greater cognitive demands are placed on the child, such as those needed
for the learning of reading, writing or arithmetic in school education.
Robertson and Finer [9± 12] investigated the cognitive outcome of 167 children
with different degrees of HIE (mild-to-severe) according to Sarnat and Sarnat’s [13]
criteria. Their prospective study evaluated these children subsequently at 3.5, 5.5
and 8 years of age and included tests of general intelligence, vocabulary, visual-
motor integration, expressive/receptive language, and tests for the evaluation of
school-readiness, specifically reading, spelling and arithmetic. They concluded
that children with mild HIE performed well, but those with moderate and severe
encephalopathies were at risk for reduced school performance, because they had
significantly lower scores for many tests when compared to the mild and peer
groups. According to these authors, most children with mild encephalopathy do
well at school, meaning that they perform as well as normal children, whereas more
than 40% of children without neurologic impairment (i.e. free of cerebral palsy,
mental retardation, visual or hearing loss, or seizure disorder) but with previous
moderate neonatal encephalopathy will have some difficulties in school learning,
 Long-term sequelae of perinatal asphyxia 1031

i.e. reading, spelling and arithmetic. These children had low scores particularly for
tests involving the auditory pathway, attention and short-term recall, although they
did not show the perceptual-motor delay reported in younger survivors [9± 12]. The
absence of cognitive impairment in children with mild perinatal asphyxia was also
reported by Handley-Derry et al. [22].
More recently, Gadian et al. [23] studied five young patients (aged 11± 16 years)
with severe impairments of episodic memory, resulting from perinatal hypoxic-
ischemic injury that had been previously unrecognized in early childhood. The
authors suggested that the degree of hypoxia-ischemia in these patients was suffi-
cient to produce selective damage to particularly vulnerable regions of the brain, but
was not sufficient to result in the more severe neurological and cognitive deficits
that can follow hypoxic-ischemic injury.
Neuropathologic and Magnetic Resonance Imaging (MRI) studies have con-
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sistently demonstrated that perinatal asphyxia produces lesions in the periventricular

white matter of premature babies (more often than in term neonates), as well as in
the basal ganglia, brain stem, thalamus and hippocampus [24± 29].
To the authors’ knowledge, no previous studies have examined prefrontal func-
tions in children with antecedents of PA. For its correct functioning, the frontal lobe
requires the maturation and integrity of the posterior cortical regions and the white
matter as well. This is the first study to assess the long-term consequences of
perinatal asphyxia once the Central Nervous System has reached a high enough
stage of maturation relative to frontal lobe development, that is, after the age of 12
For personal use only.

years [30]. This approach allows the neuropsychological evaluation of frontal lobe
functions and its possible impairment in subjects with antecedents of PA.

Methods

Participants
Subjects with antecedents of perinatal asphyxia (PA)
The study sample was drawn from a total population of 647 children with ante-
cedents of PA, born in two general hospitals of the city of Barcelona (Catalonia,
Spain) between 1978± 1986. Clinical files were retrospectively recruited in order to
obtain information about the characteristics of the diagnosed asphyxia and the
follow-up of each case. Only patients fulfilling at least two of the following criteria
were included in the definite sample:
(1) umbilical pH artery less than or equal to 7.15;
(2) Apgar score at 5 minutes less than or equal to 6;
(3) meconium stained amniotic fluid;
(4) presence of intrapartum bradycardia;
(5) presence of respiratory distress during the first 24 hours of life;
(6) need of oxygen supply after delivery; or
(7) presence of neurological anomalies during the first 48 hours of life (including
tone abnormalities, neurological depression, primitive reflexes anomalies,
seizures, etc.).
From the total group with these characteristics, only patients with a history of
neurological good outcome were considered, excluding from the study those with
a diagnosis of Cerebral Palsy, mental retardation or any neurosensorial deficit, as
 1032 C. ManÄeru et al.

observed in the follow-up histories. Of the total group of patients screened, clinical
and outcome information was not obtained for 25% of patients, 246 cases did not
meet inclusion criteria, 34 children had died during the first months of life,
updated address and/or telephone number were not available in 138 cases, and
parents or adult patients declined enrolment in 36 cases. A group of 28 patients
born at term, with antecedents of perinatal asphyxia constitutes the definite sample
whose findings are reported in this article. Patients’ clinical data are shown in
table 1. All the patients needed oxygen supply after delivery, so this variable is
not included in table 1. Table 2 presents the demographic characteristics of the
groups.

Comparison group
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A group of 28 healthy adolescents matched by age, sex, educational level and socio-
economical status were recruited as a comparison group. All the subjects included in
this group were voluntary participants with a mother’s certified history of pregnancy
with no major complications, normal birth and the absence of respiratory, cardiac or
neurological disease at the present or during development, as well as no psychiatric
antecedents, nor an IQ equal to or below 85.

Procedures
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All patients were invited to participate in this study by means of a letter. Both the
patients and the control groups received a phone call in order to make an appoint-
ment for a first interview, in which the characteristics and duration of the study
were exposed by the investigator carrying out the neuropsychological assessment. In
this first interview, a signed informed consent was obtained from all the participants
or their parents.

Neuropsychological assessment
The neuropsychological battery selected included tests for the evaluation of three
areas of functioning with a clear susceptibility to be affected in the case of hypoxic-
ischemic damage: memory, perceptual-motor ability, and prefrontal functions. Tests
for the evaluation of memory included the Rey’s Auditory Verbal Learning Test
(RAVLT), the Visual Reproduction Test from the WMS-R and the Digit Span
subtest from the Wechsler Intelligence Scales (WISC-R/WAIS). A modified
version of the RAVLT was used, in which the number of words learned during
five consecutive presentations of a list of 15 words and the number of words recalled
after a 20-minute delay were recorded. Tests to assess perceptual-motor speed
included the Digit Symbol subtest from the WAIS/WISC-R. Motor performance
was evaluated with the Purdue Pegboard Test and the Luria’s hand sequencing
task (fist-edge-palm) [31], recording the number of correct sequences achieved in
1 minute. Tests for the evaluation of prefrontal functions included the Controlled
Oral Word Association Test (COWAT), in which subjects were asked to supply
as many words as they could beginning with the letters F, A and S during a
90-second period; the Stroop Test and the computerized version of the
Wisconsin Card Sorting Test [32]. As a test of attention, an adapted Continuous
Performance Test, identical-pairs version, was also included, in which 45 target
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Table 1. Patients’ data

Systemic/
Case Weight Apgar Apgar Arterial Meconium Resp. Neurol Metabolic HIE
no (g) 1’ 5’ pH Bradyc in AF Distress Incubator Depress Tone P.R. Seizures EEG Complic. grade

1 4050 6 10 7.08 No No No No No N N No Ab No 1
2 3100 4 5 7.26 No No No No No N Ab No N Yes 2
3 3100 8 10 7.14 No Yes No No No N N No N No 1
4 3620 9 10 7.11 No Yes Yes Yes No Hyper N No N Yes 2
5 3100 2 5 Ð No No No No Yes Ð Ab Yes Ab Yes 2
6 4370 8 9 7.06 No No No Yes No Hyper N No Ab Yes 2
7 2650 3 8 7.27 No Yes Yes Yes Yes N Ab No N Yes 2
8 2920 8 10 7.09 Yes No No No No Hypo N No N Yes 2
9 2740 4 8 7.14 Yes Yes No No Yes Ð Ab No Ab Yes 2
10 3900 2 6 Ð No Yes No Yes Yes Hyper Ab No N Yes 2
Long-term sequelae of perinatal asphyxia

11 3340 9 10 7.16 No Yes No No No N N No N No 0

12 3660 9 10 7.12 No No No No Yes N N No Ab Yes 2
13 3500 8 9 7.17 No No No No No N N No N No 0
14 2560 3 5 Ð No Yes No Yes Yes Hypo Ab Yes Ð No 2
15 3350 1 6 6.98 Yes Yes No No Yes Hypo Ab No N Yes 2
16 4580 4 6 7.24 No No No No No N N No N No 1
17 3850 5 7 Ð No Yes No No No N Ab No N Yes 1
18 2260 0 3 6.99 No Yes No Yes Yes Hyper Ab No Ab Yes 2
19 3270 4 10 Ð No Yes No No No Hypo N No N No 1
20 3020 5 7 7.28 No Yes Yes No No Hypo Ð No N Yes 2
21 2720 4 8 7.22 No Yes No Yes No N N No N No 1
22 3530 1 3 7.39 No Yes No No Yes Hypo Ab No N Yes 2
23 3220 3 8 Ð Yes No No Yes Yes Hypo Ab Yes Ab No 2
24 4330 9 10 7.04 No No Yes No Yes Ð Ab No N No 2
25 3250 3 7 7.30 Yes Yes Yes Yes Ð Hypo Ð No Ab Yes 2
26 2980 3 5 Ð No No No No Ð Hypo Ab Yes Ab Yes 2
27 3280 ?7? Ð 7.21 No No No No Yes N Ab No N Yes 2
28 3300 1 3 7.30 No Yes Yes No Yes Hypo Ab Yes Ð Yes 2
Bradyc: Bradycardia; AF: Amniotic fluid; Resp. Distress: Respiratory distress; Neurol. Depress: Neurologically depressed; Tone: N, normal; Hypo, hypotonia; Hyper, hypertonia; P.R.:
Primitive Reflexes: N, normal; Ab, abnormal; EEG: N, normal; Ab, abnormal; HIE: Hypoxic-Ischemic Encephalopathy, graded by Sarnat and Sarnat [13]: 0, no encephalopathy; 1, mild;
2, moderate; Ð : missing value.
1033
 1034 C. ManÄeru et al.

Table 2. Demographic characteristics of the groups

Subjects with antecedents of PA

Control group
Mild …n ˆ 8† Moderate …n ˆ 20† …n ˆ 28†
Variable n M SD n M SD n M SD

Age (years) 15.62 3.02 15.65 3.03 16.82 2.96

Education (years) 9.62 2.45 9.65 2.43 11.21 2.71
Gender (male/female) 3/5 14/6 15/13
Handedness (right/left) 8/0 17/3 25/3

stimuli were presented among a total of 340, with a duration of 10 minutes, an

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interstimulus interval of 1500 ms and an exposure time

of 500 ms.
In order to estimate general intellectual ability, Similarities and Vocabulary
subtests of the WAIS/WISC-R were administered in all the cases. The whole
scale was not administered to avoid an excessively long evaluation. These subtests
were chosen because they are not directly related to the cerebral structures most
importantly affected by the asphyxia, as has been shown in studies of anoxic adults
[33± 35]. Furthermore, both are tests with a slight `load’ of the target cognitive
functions, (i.e. attention, memory and visual-motor speed).
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Statistical analysis
Statistical analysis was performed with the Statistical Package for the Social Sciences
(SPSSWin, v. 9.0). One-way analysis of variance (ANOVA) with Scheffe multiple
comparisons were used to examine the significance of the differences in the neuro-
psychological performance of the subgroups mild PA, moderate PA and control.

Results
All subjects were considered as having normal intelligence according to an estima-
tion of their general intellectual abilities from the subtests Vocabulary and
Similarities (WAIS/WISC-R). There were no differences for these subtests
among the groups (Similarities, F ˆ 0:73, p ˆ 0:49; Vocabulary, F ˆ 2:83,
p ˆ 0:07).

Neuropsychological test results

As shown in table 3, subjects with antecedents of perinatal asphyxia generally had a
lower performance than the control group in several neuropsychological variables.
These differences reached statistical significance for tests related to delayed recall for
both verbal and visual information, perceptual-motor speed and tests assessing
attention and executive functions. Post-hoc analyses revealed that the group with
antecedents of moderate PA performed more poorly than the control group. The
mild PA group had scores which were not statistically different from those of the
comparison group in any of the evaluated variables.
 Long-term sequelae of perinatal asphyxia 1035

Table 3. Neuropsychological performance of the groups

Mild PA Moderate PA Controls

Tests …n ˆ 8† …n ˆ 20† …n ˆ 28† F p

Memory
RAVLTÐ Sum of words 52.1 2.8 52.0 7.6 55.9 5.9 3.70 0.03y
RAVLTÐ Delayed recall 12.0 1.6 11.5 1.9 12.9 1.5 4.00 0.02y
VR WMS-RÐ Immediate 37.1 2.8 37.3 2.3 38.2 1.8 1.53 0.22
VR WMS-RÐ Delayed 37.3 2.1 32.4 5.6 36.9 3.6 7.68 0.001y‡
Digit SpanÐ Forward 5.8 0.7 5.5 1.0 6.4 1.2 6.00 0.004y
Digit SpanÐ Backward 4.6 0.9 4.9 0.8 5.1 1.1 1.29 0.28
Perceptual/motor
Digit Symbol WAIS/WISC-R 12.0 3.1 11.2 2.9 13.3 2.0 4.54 0.01y
Luria’s hand sequencing task 41.0 4.5 39.9 8.6 45.9 9.8 2.97 0.06
Purdue Pegboard-Assembly 32.6 2.1 31.9 4.4 36.3 5.5 4.89 0.01y
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Prefrontal
COWAT 34.3 10.4 34.4 12.9 42.7 10.2 3.57 0.03
Stroop TestÐ Word 98.1 10.4 92.0 19.3 101.8 13.3 2.22 0.11
Stroop TestÐ Colour 68.4 12.0 62.4 35.1 69.4 13.3 1.65 0.20
Stroop TestÐ Colour-Word 40.8 7.5 35.1 10.3 44.4 9.6 5.19 0.008y
CPTÐ Median RT (ms) 653.8 153.0 589.4 152.9 554.3 114.9 1.78 0.18
CPTÐ Total no errors 3.7 1.8 3.9 3.8 2.3 2.1 2.16 0.13
WCSTÐ Categories achieved 5.3 1.1 5.2 1.2 5.7 0.9 1.31 0.28
WCSTÐ Perseverative errors 13.8 5.9 15.0 10.5 11.4 8.7 1.03 0.36
VR WMS-R: Visual Reproduction, Wechsler Memory Scale-Revised.
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y Denotes differences between groups control and moderate PA.

‡ Denotes differences between mild and moderate PA groups.
None of these differences were statistically significant between the mild PA and the control groups.

Memory
Subjects in the moderate PA group differed from controls in the long-term reten-
tion trial of the RAVLT and the total amount of words recalled in this test. The
delayed recall condition of the Visual Reproduction Test (WMS-R) was also sta-
tistically different: subjects with moderate PA showed a lower performance than
either the mild PA or the control groups. The moderate PA group also performed
poorer than controls in the forward Digit Span subtest, although they performed at
the normal level in the backward condition.

Prefrontal functions
Differences between the groups were observed for the colour± word interference
condition of the Stroop Test, which is the subtest most directly related to frontal
lobe damage. The one-way ANOVA analysis for the COWAT showed differences
among the groups, although the Scheffe comparisons test did not reveal any specific
group difference in this task of phonemic verbal fluency.
No significant differences were found either in the number of categories
achieved or in the number of perseverative errors committed in the WCST. All
three groups had similar scores in the RT and the number of errors committed in a
sustained attention task (CPT).
 1036 C. ManÄeru et al.

Perceptual/motor functions
Subjects with moderate PA performed below controls in the Digit Symbol subtest
of the WAIS/WISC-R. The Purdue Pegboard Test showed statistical differences
between the groups in the assembly condition, which requires high dexterity and
fine co-ordination of both hands and visuo-motor speed. Again, the group with
moderate PA showed the poorest performance, while the mild PA group did not
differ from controls. Post-hoc comparisons revealed a tendency toward statistical
significance … p ˆ 0:08† between the moderate PA and the control group in the
Luria’s hand sequencing task, a test considered to evaluate pre-motor functions [32].
The results showed that general performance of subjects with antecedents of PA
was poorer than that of the control group, although the means and SD from both
groups of PA were within the normal range. However, taken individually, 15 of the
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28 youths with PA had low scores according to published normative data in at least
one of the measured variables [36]. Thirteen of these subjects were in the moderate
PA category, and seven of them had low scores in two or more tests.

Discussion
In the present study, subjects with antecedents of moderate perinatal asphyxia
performed more poorly than a well-matched control group on measures of verbal
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and visual memory, perceptual-motor skills and executive functions. Twenty-five

per cent of the subjects with moderate PA had scores below normative data in two
or more neuropsychological variables. Those subjects with antecedents of mild
perinatal asphyxia did not differ from the control group in any of the assessed
variables.
Cognitive deficits were found that are in line with those previously described in
both human and animal studies of asphyxia. Deficits of memory, both verbal and
non-verbal, have been consistently described in adult survivors of hypoxic con-
ditions, such as CO poisoning, cardiac arrest, drowning or hangings, as well as
hippocampal atrophy related to these memory impairments [30, 37± 43]. In addi-
tion, experimental studies have reported learning and memory deficits in guinea pigs
and rats submitted to a period of asphyxia during birth [44± 47]. Spatial learning
deficits and spatial memory disturbances can persist into adult life [46, 47].
The present study has demonstrated what some authors had previously suggested
based on isolated cases. Gadian et al. [23] reported the severe memory impairment
associated with bilateral hippocampal atrophy, observed in five cases of young
patients with antecedents of hypoxic-ischemic injury. The most striking result
was that their memory impairments had been unrecognized during childhood.
Apart from Gadian et al.’s [23] investigation, few studies of the consequences of
PA in humans have included tests of memory as part of their cognitive evaluation
[22, 48].
These results agree with those from Robertson and Finer [9± 12], who docu-
mented academic underachievement as well as long-term deficits in specific tests of
attention and short-term recall in children with antecedents of moderate perinatal
asphyxia. However, in their studies, Robertson and Finer [9± 12] did not include
cognitive tests sensitive to more subtle damage, such as those related to the acquisi-
tion of new learning, long-term memory, or executive functions.
 Long-term sequelae of perinatal asphyxia 1037

The authors are in agreement with the previous literature regarding speed of
mental processing, and perceptual-motor skills in subjects with PA [5, 9± 12].
Particularly, the results showed that the moderate PA subjects had some difficulties
dealing with tasks related to motor speed and perceptual-motor co-ordination.
As had been hypothesized, subjects with moderate PA performed significantly
worse than a control group in tasks related to executive functioning, such as verbal
fluency and the Stroop test. Differences were not found between the groups on the
WCST, either in the number of categories achieved or in the number of perse-
verative errors committed, although the moderate PA group showed the highest
number of errors. Fronto-striatal circuitry may be responsible for executive disfunc-
tioning [49]. Neuropathologic and MRI studies have consistently demonstrated that
perinatal asphyxia produces lesions in the basal ganglia of term neonates [26± 29].
On the other hand, frontal lobe functioning requires the maturity of white
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matter and posterior cortical regions, which does not occur until the age of 12
years [30]. Previous studies of the cognitive consequences of PA [5, 9± 12, 21, 22]
have focused primarily on the evaluation of infants and school-age survivors of PA.
The authors think this could possibly be the reason why these studies did not
include frontal lobe tests in the selected cognitive batteries.
Corah et al. [5] pointed out the importance of the age at which the children are
tested, since some differences between brain-damaged and normal children could
not be apparent in early childhood but could be demonstrated in later childhood or
adolescence. The present investigation was performed with a sample of adolescents
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older than 12 years of age, which allowed the assessment of cognitive functions
related to the frontal lobe.
In summary, the present study provides evidence of subtle but persistent neuro-
psychological deficits in adolescents with antecedents of moderate perinatal
asphyxia. These deficits can be observed particularly in tests of visual memory,
verbal memory, perceptive-motor skills and prefrontal functions. However, those
children with antecedents of asphyxia who did not present neurological anomalies
during the first hours of life showed a neuropsychological performance similar to
their peers from the normal population.
Some limitations of this study should be mentioned. First, the use of multiple
statistical tests may introduce a greater likelihood of error in the analysis, so the
significance of those p values near 0.05 should be considered with caution.
Secondly, due to the relatively small size of the sample studied, new data from a
larger and prospective sample should be obtained to generalize the results.

Acknowledgements
This work was supported by Grant PM 98-0192 from the Spanish Ministry of
Education and Culture, and Grant 99SGR00081 from the Generalitat of
Catalonia. Cristina ManÄeru holds a Research Grant from the University of
Barcelona.

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