ARTICLE IN PRESS

Neuroscience and Biobehavioral Reviews 31 (2007) 192201

www.elsevier.com/locate/neubiorev

Review

Dening the behavioral phenotype in children with fetal alcohol

spectrum disorders: A review
P.W. Kodituwakku
Center for Development and Disability, University of New Mexico, 2300 Menaul NE Albuquerque NM 87107, USA

Abstract
While there exists a large body of literature on cognitive functions in children with prenatal alcohol exposure, it remains undetermined
if these children exhibit a unique prole of cognitive-behavioral functioning or a behavioral phenotype. Researchers have consistently
found that intellectual functioning, as assessed by IQ tests, of children with prenatal alcohol exposure is decient. There is increasing
evidence that prenatal alcohol exposure is associated with slow information processing and attentional problems, in particular
inattentiveness. Studies examining specic cognitive abilities such as language, visual perception, and memory in alcohol-affected
children have shown performance decrements associated with increased task complexity. Children with prenatal alcohol exposure have
also been found to exhibit signicant decits in daily functional skills or adaptive behavior, with decits in socialization becoming
pronounced during adolescence. The above ndings point to the conclusion that a generalized decit in complex information processing
constitutes the central cognitive-behavioral characteristic of children with prenatal alcohol exposure. Researchers have consistently
documented that specic brain regions are more affected by alcohol than other regions. The problem of mapping focal anomalies of the
brain with a generalized pattern of decits can be solved by taking developmental processes into consideration.
r 2006 Elsevier Ltd. All rights reserved.
Keywords: Prenatal alcohol exposure; Fetal alcohol spectrum disorders; Fetal alcohol syndrome; Behavioral phenotype; Residual normality

Contents
1.
2.

3.

4.
5.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1.1. Behavioral phenotype . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Cognitive functions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.1. Intellectual ability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.2. Attention and speed of information processing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.3. Executive functioning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.4. Language . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.5. Visual perception and visual construction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.6. Learning and memory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.7. Number processing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Behavioral dysfunction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.1. Academic performance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.2. Adaptive behavior. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.3. Emotional functioning. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Atypical brain development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Summary and conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Tel.: +1 505 272 1861; fax: +1 505 272 9014.

E-mail address: pkodituwakku@salud.unm.edu.

0149-7634/$ - see front matter r 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.neubiorev.2006.06.020

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Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199

1. Introduction
It is now established that prenatal exposure to alcohol
produces a range of morphological and cognitive-behavioral outcomes, commonly referred to as fetal alcohol
spectrum disorders (FASD), in the offspring. Severely
affected children on the spectrum display a pattern of
altered growth and morphogenesis, called fetal alcohol
syndrome (FAS), which is characterized by prenatal and
postnatal growth retardation, craniofacial anomalies, and
abnormal brain function reected by cognitive decits and
developmental delays. The majority of children with
substantial prenatal alcohol exposure (about 3 times as
many children as those with FAS), however, show only
some of the above features (Sampson et al., 1997) and used
to be referred to as having fetal alcohol effects (FAE).
Following the publication of the Institute of Medicine
report on FAS (Stratton et al., 1996), the term FAE has
been replaced with two new terms: alcohol-related birth
defects (ARBD) and alcohol-related neurodevelopmental
disorder (ARND). For convenience, I use the term fetal
alcohol spectrum disorders (FASD) in this paper to refer to
the full spectrum of morphological and cognitive-behavioral outcomes observed in children exposed to alcohol
prenatally.
The most noticeable and devastating of these outcomes
are cognitive-behavioral decits. Over the last three
decades, researchers have made considerable progress in
delineating cognitive-behavioral functioning in children
with FASD. Despite these advances, it remains unanswered
if there is a unique pattern of cognitive-behavioral
functioning or a behavioral phenotype associated with
FASD. The identication of a behavioral phenotype will
aid in identifying those alcohol- affected children without
discernable anomalies in morphogenesis and in planning
appropriate interventions for children with FASD.
1.1. Behavioral phenotype
A behavioral phenotype refers to a characteristic
pattern of motor, cognitive, linguistic and social observations that is consistently associated with a biological
disorder (OBrien and Yule, 1995, p. 2). The task of
dening a behavioral phenotype, therefore, involves
comparing the FASD group with other neurodevelopmental groups having similar characteristics on a battery of
tests assessing motor, cognitive, linguistic, and social
functioning. In terms of causal pathways, one can
conceptualize that the teratogenic effects of alcohol cause
anomalous brain development, which in turn produces
cognitive social, and motor dysfunction. As shown in
Fig. 1, neuropsychological decits contribute to a range of

negative life outcomes, including academic, social, and

emotional problems. Recognizing the direction of this
causal relationship, Streissguth et al. (1998, 2004) have
labeled cognitive decits, primary disabilities and
negative behavioral outcomes, secondary disabilities.
While neuropsychological decits are typically assessed
with specic tests designed to probe cognitive functioning,
negative life outcomes are usually assessed with parent and
teacher-rated questionnaires. In line with the OBrien and
Yules denition cited above, the term behavioral is used
in this paper to refer to neuropsychological functioning
and parent and teacher-assessed behavior in children with
FASD.
It is evident from Fig. 1 that the establishment of a
causal connection between prenatal alcohol exposure and
cognitive-behavioral problems is methodologically challenging as environmental and genetic factors interactively
introduce variability in cognitive-behavioral functioning.
The severity of the effects is also known to vary as a
function of exposure (e.g. quantity and frequency) and
maternal (e.g. age, body weight) variables (May, 1995;
Jacobson et al., 1998).
Notwithstanding the variability associated with genetic
and environmental factors, there are emerging patterns of
cognitive-behavioral functioning in children with FASD.
The main objectives of the current paper are: to delineate
these patterns and to propose a working hypothesis on the
behavioral phenotype associated with FASD. Part 1 of this
paper presents a review of the literature on the cognitive
functioning in children with FASD, in particular on
intellectual functioning, attention and information processing, executive function, language, visual-perception, number processing, and memory. Part 2 of the paper reviews
the literature on adaptive behavior and parent and/or
teacher-rated behavioral problems in children with FASD.
Part 3 summarizes the ndings from recent neuroimaging
studies of FASD. The nal section integrates the ndings
reviewed in the above sections and presents the working
hypothesis on the behavioral phenotype of FASD.
2. Cognitive functions
2.1. Intellectual ability
There exists an extensive literature on intellectual
functioning in children and adolescents with FASD, which
was previously reviewed by Mattson and Riley (1998).
Researchers have consistently found diminished intellectual performance in children with FASD (Streissguth et al.,
1990; Mattson et al., 1997), with average IQs of these
children ranging from mildly retarded to borderline range
(Mattson and Riley, 1998). Mattson et al. (1997) found

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P.W. Kodituwakku / Neuroscience and Biobehavioral Reviews 31 (2007) 192201

Prenatal
Alcohol
Exposure
Academic
Difficulties

Genetic
Factors

Atypical
Brain
Development

Neuropsychological
Deficits

Generalized?
Specific Neural Circuitry?

Adverse
Postnatal
Environment

Domain-General?
Domain-Specific?

Emotional
Dysfunction

Social
Dysfunction

Fig. 1. A neuropsychological model of cognitive and behavioural outcomes of prenatal alcohol exposure.

that children heavily exposed to alcohol prenatally

displayed signicant intellectual decits, irrespective of
the presence or absence of physical features of fetal alcohol
syndrome. Evidence from a prospective study of FASD
indicates a dose-dependent decrement of intellectual
ability, exposure to one ounce of absolute alcohol a day
(AA/day) being related a decrease in nearly 5 full-scale IQ
points (Streissguth et al., 1989).
Streissguth et al. (1978) reported that intellectual decits
in alcohol-exposed children remained relatively stable over
time, as reected by high test-retest correlations of IQ
scores. Using different methodologies, researchers have
obtained converging evidence that infants, young children,
adolescents and adults with prenatal alcohol exposure
display decient intellectual performance. Jacobson (1998)
found that infants with prenatal alcohol exposure showed
slower processing speed than comparison groups on the
Fagan Test of Infant Intelligence. There are numerous
studies reporting decient intellectual performance in
young children, as assessed by the Wechsler Preschool
and Primary Scale of Intelligence- Revised (Mattson et al.,
1997), the Bayley Scales of Infant Mental and Motor
Development (OConnor et al., 1986), the Kaufman
Assessment Battery for Children (Coles et al., 1991), and
the McCarthy Scales (Larroque and Kaminski, 1998).
Diminished intellectual performance in school age children
has been demonstrated with the Raven Progressive
Matrices (Kodituwakku et al., 1995), the Wechsler
Intelligence Scale for Children (Mattson et al., 1997), and
the Grifths Mental Developmental Scales (Adnams et al.,
2001).
The question of whether children with FASD are
selectively impaired in specic intellectual abilities has

been the focus of some investigations. Studies that

contrasted the performance of children with FASD on
Verbal and Performance IQs have yielded equivocal results
(Mattson and Riley, 1998). Variability in subject backgrounds (e.g. social-ethnic) and amounts of prenatal
alcohol exposure probably would account for these
equivocal results. Studies involving children with heavy
prenatal alcohol exposure show comparable decrement in
both Verbal and Performance IQs (Mattson et al., 1997). In
a pilot study, Kodituwakku et al. (1995) found that
children with FASD earned signicantly lower scores than
normal controls on the Raven Standard Progressive
Matrices (SPM), a test of uid intelligence, while the
performance of the two groups were comparable on the
Peabody Picture Vocabulary Test (PPVT), a test of
crystallized intelligence. Given that the PPVT is relatively
simpler than the SPM, the observed differential effect can
be explained in terms of differential complexity of the tests.
Adnams et al. (2001) also reported that children with
FASD were impaired at intellectual tests of the Grifths
Scales (e.g. Speech-Hearing, Practical Reasoning, Performance), but were unimpaired at intellectually less demanding tests such as Motor. Therefore, it is reasonable to
conclude that children with FASD display decient
performance on complex intellectual tasks across the
board.
2.2. Attention and speed of information processing
Attentional skills of children with FASD have been the
focus of numerous studies, because attentional decits are
considered to be a pronounced characteristic of this group
(Streissguth et al., 1986; Nanson and Hiscock, 1990).

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Streissguth et al. (1986) observed decient performance of

alcohol-exposed children on a test of Continuous Performance, suggesting impairments of vigilance. Exposure
variables such as the amount of alcohol consumed were
observed to be associated with measures of distractibility
and reaction times on this task. Using a battery of
attentional tests based on an experimental paradigm
proposed by Douglas (1983), Nanson and Hiscock (1990)
found that children with FASD, like those with attention
decit disorder (ADD), had difculty with the investment,
organization and maintenance of attention over time and
had difculty in response inhibition. In view of the
similarities in test performance of children with ADD
and FASD, Coles et al. (1997) compared these two groups
on a battery of test designed to assess the four factors of
attention delineated by Mirsky et al. (1991): Alert, Sustain,
Encode, and Shift. Results of this study revealed distinct
patterns of decits in the two groups, with the FASD
group showing greater decits in Encode and Shift
components and the ADD group displaying greater decits
in Alert and Sustain components.
Thus, the nding that the FASD group was unimpaired
in sustained attention compared to normal controls is at
variance with the ndings reported by Streissguth et al.
(1986) and Nanson and Hiscock (1990). It is probable that
a number of variables, such as differences in subject
selection (clinic-referred vs. non-referred) and differential
sensitivity of the tests that were employed, would partly
account for the above differences. In a subsequent study,
Coles et al. (2002) found that adolescents with FASD were
impaired in sustained attention, but that the effect was
more pronounced in the visual than the auditory modality.
Lee et al. (2004) also found that children with FASD
performed less well than controls on a visual test of
sustained attention (Test of Variable Attention). A logistic
regression analysis revealed, however, that two tests
involving the auditory modality (Digit Span and Arithmetic) distinguished alcohol-exposed children from controls better than the test of visual sustained attention.
Given that Digit Span and Arithmetic tests involve
intellectual ability, it is probable that more complex tests
of attention distinguish children with FASD from controls
better than simple tests.
As noted above, infants exposed to alcohol prenatally
have been observed to show slower processing speed on the
Fagan Test of Infant Intelligence and slower reaction time
on a test of visual expectancy (Jacobson, 1998). Consistent
with this nding, Burden et al. (2005) found that prenatal
alcohol exposure was associated with decient processing
efciency in school age children. These researchers also
reported that decient performance of alcohol-exposed
children was found on tasks involving effortful processing,
but not on those involving automatic processing. Simmons
et al. (2002) compared children with FASD and normal
controls on reaction time tasks designed to differentiate
peripheral motor-unit recruitment and central processing
of stimulus information. Results showed reduced efciency

195

in information processing in alcohol-affected children, as

indexed by reduced speed of information processing and
peripheral delays in responding. Roebuck et al. (2002)
found that children with FASD made more errors than
normal controls on a test of nger localization, in
particular on those trials that involved interhemispheric
transfer of information. These researchers also noted a
performance decline in children with FASD with increased
complexity of the task.
2.3. Executive functioning
Executive functioning is an umbrella term, referring to a
range of abilities involved in conscious, goal-oriented
behavior, including planning, set shifting, inhibition of
goal-irrelevant responses, and holding goals in working
memory (Kodituwakku et al., 2001b). Evidence from both
animal and human research justies drawing a distinction
between cognition-based and emotion-related aspects of
executive functioning (Damasio, 1994). The tasks that
involve holding and manipulating complex, non-emotional
information, such as the Tower of London and the
Wisconsin Card Sorting Test, require cognition-based
executive functioning. In contrast, advantageous decision
making and alteration of behavior in response to the
changes in reinforcement (e.g. visual discrimination
reversal) involve emotion-related executive functioning.
There is converging evidence from animal and human
studies that the dorsolateral prefrontal cortex is primarily
involved in cognition-based executive tasks (Robbins,
1996), and that the orbitofrontal cortex is critically
involved in emotion-related learning (Rolls et al.,
1994) and advantageous decision making (Bechara et al.,
1994).
Given that the tasks assessing executive abilities demand
effort, it is reasonable to hypothesize that children with
FASD are impaired in both cognition-based and emotionrelated tasks (Rasmussen, 2005). Numerous researchers
have obtained evidence supporting this hypothesis. Children with FASD perform less well than controls on tests
assessing cognitive planning, such as the Progressive
Planning Test (Kodituwakku et al., 1995) and the
California Tower Task (Mattson et al., 1998). Researchers
have obtained evidence that prenatal alcohol exposure is
associated with decient cognitive set shifting, reected by
increased perseverative errors on tests such as the
Wisconsin Card Sorting Test (Coles et al., 1997; Carmichael Olson et al., 1998). There is evidence that children
with FASD employ ineffective strategies during problem
solving (Mattson et al., 1999). Children with FASD have
also been found to be decient in non-verbal and verbal
uency (Schoenfeld et al., 2001), particularly in letter
uency (generation of words beginning with certain letters
under specic constraints; Kodituwakku et al., 1995;
Mattson and Riley, 1999; Kodituwakku et al., 2006).
Noland et al. (2003) reported that children exposed to
alcohol performed less well than controls on a tapping

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inhibition task. Adults with FASD also display decient

performance on tests assessing executive control functioning, including tests of working memory, response inhibition, set shifting (Connor et al., 2000) and uency (Kerns
et al., 1997).
Kodituwakku et al. (2001) examined the ability of
children with FASD to alter behavior in response to the
changes in reinforcement contingencies using a visual
discrimination reversal learning task. Results showed that
the FASD group was impaired in the ability to make
reward-response reversals and that decient reversal
learning was associated with parent-rated behavioral
problems in these children.
2.4. Language
While there are many reports on the intellectual aspects
of verbal functioning in children with FASD (Mattson and
Riley, 1998), there exist only limited data on the effects of
prenatal alcohol exposure on specic linguistic processes.
Researchers have documented that prenatal alcohol
exposure is associated with decits in naming (Mattson
et al., 1998), word comprehension (Conry, 1990), grammatical and semantic abilities (Becker et al., 1990), and
pragmatics (Abkarian, 1992). Streissguth et al. (1994)
reported a relationship between prenatal alcohol exposure
and decreased performance on the Word Attack subtest of
the Woodcock Reading Mastery Tests, which required
subjects pronounce unfamiliar words. Consistent with this
nding, our research team has obtained evidence that
children with FASD are impaired in phonological working
memory, as measured by repetition of non-words (unpublished data). A comparison of children with FASD and
controls on the Grifths Mental Development Test
revealed that the Hearing and Speech subscale accounted
for the most variance in the multivariate group effect
(Adnams et al., 2001). A recent population-based study
conducted in Italy showed that decient grammar comprehension discriminated a non-referred sample of children
with FASD from normal age peers (Kodituwakku et al., in
press). Using the Dichotic Competing Sentence Test and a
test of word recognition with ipsilateral competing noise,
Church and Kaltenbach (1997) have obtained evidence that
children with FASD are decient in central processing of
language, which they labeled, central hearing impairment. As mentioned above (see executive functions),
children with prenatal alcohol exposure displayed decient
performance on tests of verbal uency (Schoenfeld et al.,
2001; Mattson and Riley, 1999), particularly in letter
uency.
Some researchers have failed, however, to nd an
association between prenatal alcohol exposure and language development. For example, Greene et al. (1990) did
not nd statistically signicant relationships between
indices of language development and maternal drinking
in a large of cohort children at ages 1, 2, and 3. At 5-year
follow-up of children prenatally exposed to marijuana,

cigarettes, and alcohol in a Canadian prospective

study, researchers failed to nd an association between
alcohol exposure and language development (Fried et al.,
1992).
Two explanations can be offered to account for the
discrepancies in ndings on the effects of prenatal alcohol
exposure on language. First, the studies reporting negative
results included children, on average, with lower levels of
exposure than those studies reporting positive results.
While only one child in the Greene et al study had
signicant morphological anomalies consistent with FAS,
the studies reported by Mattson et al. (1998) and Adnams
et al. (2001) included children with heavy exposure.
Second, the studies that obtained positive results employed
relatively complex tests of language involving working
memory. For example, the Word Attack Test (Streissguth
et al., 1994) the Grammar Comprehension test (Kodituwakku et al., in press), and verbal uency tasks all involved
phonological working memory, in addition to the processing of linguistic information per se.
2.5. Visual perception and visual construction
Despite reports documenting ocular anomalies in children with prenatal alcohol exposure, there exist only a few
published studies on visual perceptual skills of children
with FASD. Uecker and Nadel (1996) reported that
children with FASD were relatively unimpaired in visual
perception as assessed by a test of facial recognition, but
were markedly impaired at tests assessing visual construction such as the Beery Visual Motor Integration and Clock
Drawing. Mattson et al. (1996b) investigated whether
children with FASD differentially processed global and
local features of visual stimuli. There is increasing evidence
that the right hemisphere is preferentially involved in the
processing of global features and the left hemisphere, in the
processing of local features. Results showed that the FASD
group was impaired in copying and recalling local features
of hierarchical stimuli, e.g. a large letter D (global) made
up of small letters y (local features).
The above ndings suggest that children with FASD are
impaired at visual perceptual tasks that demand integration of information. Uecker and Nadels (1996) results
demonstrate that children with FASD performed as
competently as controls on a task of visual matching, but
experienced signicant difculty with drawing designs that
required planning and visual-motor integration. The
basis of the differential effect in processing global
and local features needs to be further investigated. As
Mattson et al. (1996a, b) suggest, an alternative interpretation of the data is that children with FASD have difculty
shifting attention from global to local features when
processing complex, hierarchical stimuli. The performance
of the FASD group was correlated with their intellectual
ability suggesting that higher-order cognitive skills are
involved in the efciency of integrating global and local
features.

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2.6. Learning and memory

There is converging evidence from several lines of
research that learning and memory are specically vulnerable to the effect of prenatal alcohol exposure. In early
studies of infants exposed to alcohol prenatally, Streissguth
et al. (1983) reported that alcohol exposure was associated
with diminished conditioning and habituation. Animal
research has provided consistent evidence that the hippocampus, a region subserving learning and memory, is
specically vulnerable to the toxic effects of alcohol during
brain development (Berman and Hannigan, 2000). Using
various learning paradigms (e.g. spatial navigation),
researchers have now established the association between
hippocampal damage resulting from prenatal alcohol
exposure and learning and memory decits in animals
(Sutherland et al., 2000).
A number of researchers have sought to extend the
ndings in animal research to humans by using tests that
have been found to be sensitive to hippocampal functioning. Uecker and Nadel (1996) compared the performance
of 15 children with FASD with that of 15 normal controls
on the Smith and Milner Memory for 16 objects task,
which has previously been shown to be sensitive to
hippocampal functioning. Results showed that children
with FASD had difculty with delayed, but not with
immediate, object recall, a pattern of performance observed in patients with right hippocampal damage. Uecker
and Nadel (1996) also found that the FASD group was
impaired at nonhippocamapal visual tasks such as the Test
of Visual Motor Integration, suggesting generalized visual
decits. Hamilton et al. (2003) investigated spatial navigation in children with FASD using a computerized (virtual)
version of a classic test of hippocampal functioning, the
Morris Water Maze. Participants were required to nd a
hidden platform in a xed location relative to 4 extramaze
cues. Performance on these place learning trials was
contrasted with that on cued-navigation trials, in which
participants were required to navigate to a visible platform.
Children with FASD were impaired at place learning, but
not at cued-navigation. It should be noted, however, that
the FASD group also displayed decient performance on a
range of nonhippocampal tasks.
Most studies of learning and memory in children with
FASD have utilized standardized neuropsychological tests.
Mattson et al. (1996a) investigated verbal learning in
children with FASD using the California Verbal Learning
Test- Childrens Version (CVLT-C). Results showed that
the FASD group was signicantly decient in verbal
learning, as indexed by difculty in free recall of word
lists and an increased number of perseverative and
intrusion errors. A number of researchers have since
obtained supporting evidence for verbal learning decits
in children with FASD. Willford et al. (2004) reported that
children with prenatal alcohol exposure during the rst
trimester predicted verbal learning decits. These investigators found that prenatal alcohol exposure was associated

197

with delayed free recall, but not with delayed recognition.

Mattson and Roebuck (2002) examined verbal and nonverbal learning in children with FASD using two tasks with
a comparable structure (both involving free recall of items
over multiple trials): CVLT-C and the Biber Figure
Learning Test. This study revealed that the FASD group
was impaired in both verbal and visual memory. Kaemingk
et al. (2003) also found that children with FASD were
decient in both verbal and visual learning as assessed by
the Wide Range Assessment of Learning and Memory
(WRAML). Despite decient initial learning, the FASD
group was successful in retaining the newly learned
information. Mattson and Riley (1999) obtained evidence
that children with FASD are impaired in explicit memory,
but are unimpaired in implicit memory.
Accordingly, the extant literature on learning and
memory in FASD leads to the conclusion that prenatal
alcohol exposure is associated with decits in both visual
and verbal learning and memory. There is also consistent
evidence that children with FASD are more impaired in
free recall than in recognition memory. Consistent with this
pattern, explicit memory in alcohol-affected children
appears to be more compromised than implicit memory.
2.7. Number processing
There is increasing evidence that children with FASD
experience relatively more difculty with number processing than with other academic subjects. On standardized
test batteries of academic achievement, alcohol-exposed
children obtain relatively lower arithmetic scores (Streissguth et al., 1994). Kopera-Frye et al. (1996) investigated
number processing in children with FASD using a test
battery based on recent developments in cognitive neuroscience (Dehaene, 1997). This study revealed that
children with prenatal alcohol exposure performed without
difculty on relatively simple tasks of number processing
such as number reading and number writing, but displayed
decits on relatively complex tasks such as calculation and
cognitive estimation.
In a recent investigation into information processing in
FASD, Burden et al. (2005) found a specic decit in
number comparison in children with prenatal alcohol
exposure. This nding raises the question of whether
number processing is differentially affected in children with
FASD. The demonstration of a differential effect requires
comparing number processing tasks with non-number
processing tasks of equal complexity. The existing data
suggest, however, that only complex number processing
tasks discriminate alcohol-exposed children and controls.
3. Behavioral dysfunction
As Fig. 1 shows, the above cognitive decits contribute
to a range of behavioral outcomes, including academic
difculties, social skills decits, and emotional problems.
Streissguth et al. (2004) assessed life outcomes of the

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Seattle cohort during adolescence and adulthood using a

Life History Interview with knowledgeable informants.
These investigators found that prevalence rates of life-term
adverse outcomes in this cohort were high, with 61%
having had disrupted school experiences, 60% trouble with
the law, 50% connement, 49% inappropriate sexual
behaviors, and 35% alcohol and drug problems. Two
variables, receiving the diagnosis of FAS or FAE (fetal
alcohol effects) at an earlier age and living in a stable and
good home environment, were associated with better life
outcomes. Thus, these results suggest that postnatal
environment directly and indirectly (through decient
cognitive functioning) inuence behavioral outcomes. In
view of the increased variability in behavioral outcomes
associated with environmental conditions, can one identify
a phenotype?

psychiatric outpatient clinic on the VAB. The two groups

did not signicantly differ on any of the domains of
adaptive functioning. However, with age, alcohol-exposed
children exhibited lower scores in socialization than nonexposed controls.
Social decits in children with FASD become pronounced during their adolescence because social demands
at this age are complex. Effective social interactions involve
coordinating a wide range of skills such as comprehension
of facial and vocal affective expressions, reading body
language and understanding the pragmatic aspects of
language. Therefore, it is reasonable to conclude that
children with FASD experience greater difculty with
relatively complex adaptive tasks than with simple ones.

3.1. Academic performance

A number of researchers have documented emotional

disturbances in children and adults with FASD (Spohr and
Steinhausen, 1987; Streissguth et al., 2004). In a sample of
23 children referred to a fetal alcohol diagnostic clinic,
87% met the criteria for a psychiatric disorder, with a
majority exhibiting symptoms of mood disorder (61%).
(OConnor et al., 2002). Streissguth et al. (2004) reported
that a signicant number of adolescents and adults from
the Seattle cohort developed emotional problems (Streissguth et al., 2004). Emotional difculties in this population
have been hypothesized to result from an interaction of
multiple variables, including CNS damage, familial genetic
factors, and adverse postnatal experiences (Streissguth and
OMalley, 2000; Auti-Ramo, 2000).

Carmichael Olson et al. (1992, 1997) assessed the

classroom behavior of children with FASD using teacherrated questionnaires. These questionnaires assessed classroom behaviors such as attention and activity level,
classroom conduct, ne motor skills, and school achievement. Results showed that maternal binge drinking and
drinking during very early pregnancy were associated with
poor classroom behaviors. Teachers identied a number of
problem behaviors in the classroom, including distractibility, lack of persistence, and restlessness. The alcoholaffected children were also rated as having difculty in
information processing and reasoning.
As noted above, in a recent population-based study
conducted in Italy, teachers rated children with FASD as
being hyperactive and inattentive. However, inattentive
behaviors, but not hyperactivity, distinguished the FASD
group from normal controls (Kodituwakku et al., in press).
Inattentiveness can be considered to be associated with
slow information processing and diminished intellectual
functioning.
3.2. Adaptive behavior
Several studies show that children with FASD are
decient in adaptive behavior, particularly in social skills.
LaDue et al. (1992) reported that adolescents and adults
with prenatal alcohol exposure were assessed as having
signicantly low adaptive skills. A comparison of subscale
scores showed relatively higher scores on Daily Living and
lower scores on Socialization. Thomas et al. (1998)
compared children with FASD, those with low verbal
IQs, and normal controls on the Vineland Adaptive
Behavior Scales (VAB). Results showed that all groups
differed with respect to social ability, with the FASD group
earning the lowest scores. In particular, the FASD group
was rated as having most difculties in interpersonal
relationships. Whaley et al. (2001) compared alcoholexposed children with a group of children referred to a

3.3. Emotional functioning

4. Atypical brain development

There exists a growing body of literature indicating
specic alterations of the brain as a result of prenatal
alcohol exposure. Using voxel-based morphometry, Sowell
et al. (2001a, b) found signicant anomalies in the
perisylvian cortices of the parietal and temporal lobes in
children and adolescents with prenatal alcohol exposure.
Compared to controls, alcohol-exposed participants had
relative increases in gray matter and decreases in white
matter in the perisylvian cortices of the temporal and
parietal lobes. Sowell et al. (2002a) have also reported
shape abnormalities in the same regions of the brain in
alcohol-exposed adolescents. These investigators also
found signicant reduced brain growth in the ventral
regions of the frontal lobes, particularly in the left
hemisphere. Sowell et al. (2002a, b) observed a gray matter
surface asymmetry in the temporal lobes of control
subjects, with the right hemisphere being greater than the
left. This asymmetry was reduced in alcohol-exposed
adolescents (Sowell et al., 2002b).
Abnormalities in the corpus callosum of alcohol-exposed
individuals have been the focus of a number of studies. In a
series of papers, Bookstein et al. (2001, 2002a, b) have
documented that adults with prenatal alcohol exposure

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(FAS and FAE) signicantly differed from controls on

morphometric indices of the corpus callosum. These
investigators also reported that callosal form correlated
with neuropsychological functioning of these individuals.
Using surface-based image analytic methods, Sowell et al.
(2001a, b) also examined the association between callosal
morphology and cognitive functioning in a group of
subjects with FASD. Results showed a signicant association between verbal learning and corpus callosum displacement.
There is some evidence indicating that the basal ganglia
is vulnerable to the effects of prenatal alcohol exposure.
Mattson et al. (1992) found that, compared with controls,
basal ganglia volume was reduced in children with FASD,
even after controlling for overall brain size. Recent data
show that only the volumetric differences in the caudate
remained signicant after controlling for brain size.
Reductions in cerebellar volume in individuals with FASD
have also been reported (Archibald et al., 2001). Examination of regional volumetric differences in the cerebellum
has revealed greater reduction in size in the anterior than in
the posterior vermis (Sowell et al., 1996).
5. Summary and conclusions
Researchers and clinicians have consistently found
diminished intellectual abilities in children and adults with
FASD. The growing consensus is that verbal and nonverbal skills in individuals with FASD are equally affected.
There is consistent evidence that individuals with FASD
are slower in information processing than controls.
Numerous studies have documented that prenatal alcohol
exposure is associated with decient performance on tests
assessing executive control functioning, including planning,
conceptual set shifting, affective set shifting, response
inhibition, and uency. Results from numerous studies
designed to investigate specic cognitive abilities (e.g.
language, memory, visual perception) show impaired
performance on relatively complex tasks, but unimpaired
performance on simple tasks. On tests of memory, children
with FASD show impaired performance on free recall, but
unimpaired performance on recognition. The FASD group
tend to perform in the normal range on tests of simple
visual perception, but in the impaired range on tests of
visual construction. Investigators have obtained consistent
evidence that the FASD group exhibit increased behavioral
problems and decits in adaptive behavior.
Evidence from teacher and parent-rated questionnaires
seem to indicate that children with FASD are inattentive
and have short-term memory problems. There is also an
increased prevalence of negative life outcomes among
teenagers and adults with FASD, including psychiatric
illness and legal problems. It should be underscored,
however, individuals with FASD experience greater difculty with inherently complex adaptive behaviors (e.g.
social) than with less complex adaptive skills (e.g. daily
living).

199

Accordingly, the essence of the cognitive-behavioral

phenotype associated with FASD can be dened as a
generalized deficit in processing complex information.
Diminished intellectual functioning, slow information
processing, and relative difculty with complex tasks are
all consistent with a generalized decit model. Successful
completion of complex tasks require recruiting multiple
regions of the brain. It is reasonable to hypothesize that
children and adults with FASD are decient in the ability
to integrate information. Even though specic regions of
brain have been affected by prenatal alcohol exposure, one
can not assume that other regions of the brain are
functioning normally. Thomas and Karmiloff-Smith
(2002) have forcefully argued that the assumption that
atypical development can produce selective decits while
the rest of the system develops normally, which they
dubbed the assumption of residual normality, is untenable
in developmental neuroscience.
Acknowledgments
Preparation of this manuscript was supported by a
fellowship awarded to the author by the University of
Rome, La Sapienza, Italy. The author would like to thank
professor Mauro Ceccanti of La Sapienza and the Center
for Development and Disability, University of New
Mexico for support.
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