J. Paediatr.

Child Health (2004) 40, 2-7

Review Article

Fetal alcohol syndrome: Diagnosis, epidemiology, and

developmental outcomes

CM O'Leary
Child, Community and Primary Health Care Directorate, Department of Health, Perth, Western Austratia, Australia

Abstract: In Australia the issue of fetal alcohol syndrome (FAS) has not been the subject of policy development or of
extensive research. There is a lack of knowledge, both in the general community and by health professionals, of the nature
of the risks associated with heavy alcohol consumption during pregnancy and the factors that increase this risk. This paper
reviews the literature surrounding FAS with the aim of providing the reader an understanding of the diagnostic features and
epidemiology of FAS and of the developmental sequelae associated with this syndrome.

Key words: alcohol; child development; fetal alcohol effects (FAE); fetal alcohol syndrome (FAS); partial FAS; pregnancy.

Considerable research has been conducted into the teratogenic
effects of alcohol on the developing embryo since the first
descriptions of a pattern of physical malformations were
observed in children of alcoholic mothers,''^ It was Jones et al.
(1973) in the United States who first termed the pattern of
abnormal features as fetal alcohol syndrome (FAS),^ FAS has
since become recognized as the foremost preventable, non-
genetic cause of intellectual impairment,^-'*
Although the issue of FAS has been the subject of a large
body of research overseas, particularly in Canada and the
United States, there has been limited work in this area within
Australia, Recent data from Western Australia^ have identified
FAS as a particular issue of concern for some groups within the
community and there is growing interest in the topic across
Australia, However, there remains a lack of knowledge about
FAS, the level of alcohol consumption that is associated with
an increased risk of fetal harm*^ and of current screening
methods for measuring alcohol consumption in health settings,^
Health professionals need to have a clear understanding of
the literature concerning FAS so that they may provide sound
advice to women and their families, thereby increasing under-
standing and minimizing stress so panic does not occur. Accu-
rate information regarding the risks of alcohol consumption
during pregnancy is necessary for the implementation of health
promotion and prevention strategies.
This article provides a summary of the scientific literature
surrounding FAS, its diagnosis, epidemiology, and develop-
mental problems of children with FAS,
DIAGNOSIS
To date there is no objective laboratory test for diagnosing
FAS, Instead, the diagnosis relies on a pattern of abnormalities
that make up the syndrome and reports (generally self-reports)
of alcohol use/misuse by the mother during pregnancy and
around the time of conception. The emphasis is on the occur-
rence of a set of criteria, as each of the individual abnormalities
are often subtle, difficult to detect, and may occur in situations
where alcohol is not a factor.
Over the years a number of paradigms have been described
for diagnosing FAS, but each has retained the following key
features, which occur in a majority of cases:
Growth retardation
• Prenatal growth deficiency - decreased birthweight for ges-
tational age
• Postnatal growth deficiency - lack of catch-up growth in
spite of adequate nutrition
• Low weight to height ratio
Characteristic facial features
• Short palpebral fissures
• Maxiliary hypoplasia
• Epicanthal folds
• Thin upper lip
• Flattened philtrum (an absent or elongated groove between
the upper lip and nose)
Central nervous system (CNS) anomalies or dysfunction
• Microcephaly - or other structural brain abnormalities with
no significant catch-up through early childhood
• Developmental delay - social and motor performance
related to mental, not chronological age
• Intellectual disability
• Neonatal problems including irritability and feeding diffi-
culties
Abnormalities in each of the three main categories exclude
most other birth defect syndromes,^"" while confirmation of
diagnosis requires a history of harmful maternal alcohol use
during pregnancy,* However, where reliable information on
maternal drinking behaviour is not available a diagnosis of
FAS can be recorded providing abnormalities are consistent
with the syndrome and other possible diagnoses have been
excluded.

Correspondence: Ms Colleen O'Leary, Senior Policy Officer, Child, Community and Primary Health Care Directorate, Department of
Health, Western Australia, 8th Floor, East Point Plaza, 233 Adelaide Terrace, Perth, WA 6000, Australia, Fax: +61 8 9323 6699; email:
Colleen,O'Leary@health,wa,gov,au
Accepted for publication 29 July 2003,
Fetal alcohol syndrome
Fetal alcohol syndrome facial features and growth retarda-
tion often change with age'^"'* and vary between ethnic popu-
lations," Diagnosis is generally tnade on infants and young
children, as central nervous system dysfunction and facial
morphology may be difficult to assess prior to 2 years of
age,'"-"*
Longitudinal studies have found that in adolescence the
FAS facial morphology becomes less distinctive and weight
approaches the mean'^-'^ although a number of signs and
symptoms persist,"' These include microcephaly, short pal-
pebral fissures, indistinct philtrum, a thin upper lip and mild
micrognathia,'* The central nervous system abnormalities do
not attenuate but continue to be pervasive throughout the
lifespan'^''^ and a number of psychiatric disorders have been
identified to occur in adolescents who have FAS,'^ Children
with FAS generally have an tQ around 60-70, which is in the
mildly mentally handicapped range'^^'^ although there is a
wide range of IQ scores expressed from severely intellectually
handicapped to within the normal range,'^
FETAL ALCOHOL EFFECTS (FAE)/PARTIAL FAS
The teratogenic effects of alcohol produce a range of out-
comes,^ The spectrum of disorders extends from full FAS
through to a milder although often clinically significant form
affecting physical, learning, and behavioural outcomes. The
range of effects is collectively termed alcohol related neuro-
developmental disorders (ARND), fetal alcohol effects (FAE),
or more recently partial FAS,
Diagnosis requires confirmation of maternal alcohol con-
sumption, some components of the facial features of FAS,
and evidence of any of the following: CNS neurodevelop-
mental abnormalities (IQ frequently borderline around
70-85)'^''* growth deficiency, or behavioural and cognitive
dysfunction,'^
The teratogenic effects of alcohol can also result in Alcohol
Related Neurodevelopmental Disorders (ARND) characterized
by CNS anomalies alone or Alcohol Related Birth Defects
(ARBD) characterized by physical anomalies. Both of these
diagnostic categories require confirmation of maternal alcohol
exposure.
The Institute of Medicine's 1996 diagnostic criteria for
partial FAS/FAE identifies a complex pattem of behavioural or
cognitive dysfunction that is unrelated to developmental matu-
rity or to family or home environment, and includes;
• Difficulties in learning
• Poor school performance
• Poor impulse control
• Problems in relating to others
• Deficits in language (understanding and speaking)
• Poor ability for abstract thinking
• Poor arithmetic skills
• Problems in memory, attention, or judgement
Although a number of paradigms have been described over
the years, they have been criticized for allowing diagnosticians
to place subjective weights to the facial and other features
when making a diagnosis. The lack of an objective, quantitative
diagnostic tool has increased the risk of diagnostic misclassifi-
cation, Astley and Clarren (2000) have recently developed a
more comprehensive diagnostic code encompassing quantita-
tive, objective measurement scales, specific case-definitions
and a new nomenclature. The increased precision of diagnosis
that is offered by this method may, in the future, help to reduce
misclassification bias,"
EPIDEMIOLOGY OF FAS
Alcohol is clearly the necessary factor for the development of
FAS and related disorders, but as not all children exposed to
heavy alcohol consumption during pregnancy are affected or
are affected to the same degree, expression of anomalies
appears to require component causes. Factors such as the
pattern and quantity of alcohol consumption, timing of intake,
the stage of development of the fetus at the time of exposure,
and socio-behavioural risk factors may act as permissive
A range of brain malformations and disorders have been
documented in the embryos of chronic alcoholic mothers that
were aborted within the first trimester, including microcephaly,
hydrocephaly, hydranencephaly and disorders in the migration
of cellular elements, A dose-response relationship between the
quanitity and frequency of alcohol exposure and brain dys-
morphogenesis was observed, with the initial 3-6 weeks of
brain development identified as a critical time for the tera-
togenic effects of heavy alcohol consumption to occur,^^
The embryo develops rapidly during the first 8-12 weeks
with a second growth spurt occurring in the final two months
of pregnancy,^"'^^ Studies have demonstrated an association
between prenatal growth delays and alcohol consumption both
in the first two months of pregnancy^'* and later in pregnancy,^^
However, it has been suggested that confounding factors
such as maternal age, smoking, and parity may influence this
association,^^ Post-natal growth and/or behavioural^^ and cog-
nitive disorders^^ may result from alcohol exposure later in
pregnancy.
The full FAS phenotype is seen only in patients whose
mothers had a history of chronic, daily, heavy alcohol use or
frequent, heavy, intermittent alcohol use,^'"'' Major risk to the
fetus is reported to require chronic, daily alcohol consumption
of six or more drinks per day' or at least five to six drinks per
occasion,'''" with a monthly intake of at least 45 drinks,'"
The quantity of alcohol required to produce partial FAS/
FAE has been difficult to establish and is surrounded in
controversy due to methodological issues and bias,
Jacobson and Jacobson reported in 1999^^ that the principal
determinant of functional deficit was dose and frequency of
alcohol consumption and that a maternal history of alcohol
related problems (positive MAST score) was not related to
functional deficit. Their results showed that 80% of the func-
tionally impaired infants had been exposed to a binge pattern
(five or more drinks per occasion) of alcohol consumption that
occurred at least once a week during pregnancy. Functional
impairment in the offspring of women who drank at least
4 days per week required an average of five drinks per occasion
for impairment to occur,
A recent meta-analysis of seven studies examined the
relationship between moderate alcohol consumption during
pregnancy and FAS, The authors did not identify any increase
in fetal malformations with moderate alcohol consumption
(two drinks per week to two drinks per day), during the first
3 months of pregnancy,^'
BIRTH PREVALENCE OF FAS AND FAE
Estimates of birth prevalence of FAS vary between countries,
between ethnic groups within countries, and over time (birth
prevalence is adopted here to cover both incident and prevalent
cases among all age groups as described by May et al).^°
In Australia, the recent linking of the Western Australia
Birth Defects Registry and the Rural Pediatric Services (RPS)

database resulted in a cotnprehensive estimate of the birth
prevalence of FAS in Western Australia, The estimate from
these combined data sets is 0,02/1000 births for non-Aboriginal
children and 2,76/1000 for Aboriginal children,^ A similar
prevalence has been estimated for the Northern Territory (NT)
through a retrospective review of medical records and out-
patient correspondence of children born between 1990 and
2000, The estimate for the NT was 0,68/1,000 live births
and between 1,87 and 4,7/1,000 live births for indigenous
children,^' Although these are the most reliable Australian
statistics currently available the authors suggest that under-
diagnosis, under-ascertainment, or both may have resulted in an
underestimate of the true birth prevalence.
The estimated birth prevalence of FAS in Australia presents
a similar pattern to that which is reported overseas. Reviews
critiquing population-based studies have reported the US inci-
dence of FAS, 1973-1992, as 1,95/1000 births; 0,26/1000
when restricted to middle/upper class Caucasians, 2,29/1000
births for African/Native Americans, and the European inci-
dence as 0,8/1000 births,'' Sampson etal. (1997) in their
review of the literature reported the prevalence of both FAS
and FAE combined to be 9,1/1000 births based on data from
Seattle,'^
Estimates of the birth prevalence of FAS in indigenous
communities are higher than that reported for the wider com-
munity. This difference is thought to reflect socio-cultural
variables such as socio-economic status and drinking patterns
rather than racial characteristics. Estimates vary considerably
across indigenous communities from 0,585/1000 births in a
retrospective study of Canadian indigenous people,^-' 3,0/1000
births among Alaska Natives (1977-1992)^'* through to
the highest documented prevalence of 39,2/1000 births in
the Western Cape Province of South Africa,'^
Variation in the birth prevalence of FAS has been demon-
strated to occur between cultural groups and over time, A study
by May (1991)^* reported rates of FAS in three major Indian
cultural groups (Navajo, Pueblo, and SW Plains) for two
periods in time, 1969-1977 and 1978-1982, The results were
1,0, 1,3, and 17,5/1000 births (respectively) with an increase in
the birth prevalence over time, most notably in the two groups
with the initial low rates, to 5,2, 5,7, and 20,5/1000 births,
respectively (Fig, 1),
I mental pollutants such as lead, which can directly affect central
I contribute to the impact of alcohol on the fetus. Studies of
i to FAS indicating a genetic basis. There is no clear evidence
Navajo Pueblo SW Plains Combined
Maternal Rate
Fig. 1 Birth prevalence of fetal alcohol syndrome (FAS) and alcohol
related neurodevelopmental disorders (ARND) per 1000 births.
• , 1969-77; D, 1978-82; 0 , Maternal rate* 1982, Adapted from May
(1991), *Maternal rate: proportion of women, 15-44 years of age,
giving birth to children with FAS and ARND,
CM O'Leary
The SW Plains Indians had a high rate of abusive drinking in
the earlier time period that was not found in the other two
groups. The increase in the birth prevalence in FAS over time
in the other two groups reflects the increased prevalence of
harmful drinking in these communities over time.
The authors noted that only a small proportion of women
gave birth to children with FAS and ARND, This maternal rate
varied from 4,6/1000 births in the Pueblo cultural group
through to 30,5/1000 in the SW Plains group, with a combined
matemal rate for all three groups of 6,1/1000 births (Fig, 1),
Following the birth of a child with FAS, unless the mother
totally abstained from alcohol during subsequent pregnancies,
all their subsequent offspring were also afflicted with FAS or
FAE, This pattern of recurrence has also been demonstrated in
Australia, Four mothers in the recently published NT study
were identified as having more than one child with FAS or
partial FAS while one mother had three children with complete
3'
SOCIO-BEHAVIOURAL COMPONENT CAUSES
Maternat age
The risk of functional impairment in the offspring of women
drinking five or more drinks per occasion at least weekly, is
increased by 2-5 times when the mother is 30 years of age or
older. Duration of drinking or physiological changes, including
increased maternal body fat-to-water ratio and an increased rate
of alcohol metabolism with a chronic pattern of drinking, may
be related to the increased risk,''--*^
Race, genetic factors and socio-economic status
Low socio-economic status was identified as being associated
with FAS in the early study by Jones et at. (1973),^
In a study of lower socio-economic and upper-middle class
women who were chronic alcoholics, the incidence of FAS was
increased in the offspring of lower SES alcoholic mothers
compared with the children of upper-middle class alcoholic
mothers. The authors proposed that the socio-economic differ-
ences in the incidence of FAS and FAE were due to an
interaction of poor nutrition, genetic, and social factors along
with the cumulative effect of intergenerational maternal
alcoholism in the impoverished group,-''
Other factors associated with low SES include environ-
nervous system damage, psychological stress or physical
abuse'' and smoking, all of which are thought to combine to
elicit an increased susceptibility to the teratogenic effects of
Differences in individual sensitivity to alcohol are thought to
twins have found a high correlation for FAS among monozy-
gotic twins, while dizygotic twins show differential sensitivity
however, to suggest that the increased prevalence of FAS/FAE
seen in some racial groups is due to genetic factors,"*
The importance of race as a contributing factor to the risk of
FAS/FAE is confounded by socio-economic status since the
two are highly linked, Abel and Hannigan in their review of
the literature, found no evidence to suggest that biological
factors were responsible for the increased risk of FAS in
African and Native-American alcoholic women. The authors
Fetal alcohol syndrome
concluded that cultural factors such as drinking patterns,
amount consumed per occasion, low socio-economic status and
differences in diet contribute to the racial differences seen in
the incidence of FAS,''
'Other' factors
There is evidence that tobacco, cannabis, and cocaine individu-
ally reduce fetal oxygenation through effects on uterine blood
flow, resulting in hypoxia and increased free radical formation,
while smoking and caffeine are also thought to reduce the
levels of certain nutrients,*' These effects may enhance
the teratogenic effects of alcohol.
The literature reports on the use of alcohol in combination
with other substances during pregnancy including cannabis,
tobacco, other illicit drugs and inhalants are conflicting,'*'*^"^''
Overall there are too few studies analyzing the interactive
effects of antenatal polydrug exposure to draw a conclusion.
Certain antiepileptic drugs taken during pregnancy have
been demonstrated to have a teratogenic effect on the develop-
ing fetus, which may exhibit features similar to FAS,'*'"''*
Furthermore, numerous viral infections during pregnancy,
including toxoplasmosis'''-'" and herpes simplex''-'^ may also
result in features similar to FAS,
BEHAVIOUR AND DEVELOPMENTAL
ABNORMALITIES
There is a wide range of behaviour and developmental abnor-
malities that are demonstrated by children exposed to high
levels of alcohol during the antenatal period. These abnormali-
ties can be exacerbated by a number of negative environmental
factors. Children with FAS are highly likely to live in homes
with family instability, dysfunction, and multiple foster-home
placements, all of which have been found to exacerbate the
intellectual and social delays,'-'
Infants with FAE may show mood and state regulation and
self-soothing problems, hypersensitivity to sensory stimuli,
irritability, and hyperactivity,''' They may be difficult to settle
or have a slow-to-warm temperament. Antenatal alcohol expo-
sure is highly related to attachment insecurity and has also been
found to predict the expression of negative emotions in chil-
dren, however high levels of maternal support of these children
are reported to be associated with better coping skills and more
secure attachment,''
Young children with FAS tend to be impulsive, uninhibited,
overly friendly, inquisitive, excessively demanding for affec-
tion and physical contact, intrusive, insensitive to social cues
and lacking in social judgment,-'-' A link between FAS, FAE,
and attention-deficit hyperactivity disorder (ADHD) has been
suggested in the literature"' however, there are reports that the
neurocognitive and behavioural characteristics differ between
children with FAS or FAE and those with a primary diagnosis
of ADHD,'^
Children with both FAE and ADHD are reported to fre-
quently be misdiagnosed as having oppositional defiant dis-
order as they are talkative but lack cognitive understanding,
give inappropriate answers and often do not link cause and
effect, or react positively to standard behavioural-management
techniques,'*
Approximately one-third of children exposed in the ante-
natal period to moderate or heavy levels of alcohol have been
found to exhibit significant aggressive behaviour compared
with 4-5% of the general population,^** Other studies have
reported a significant association between maternal binge
drinking during pregnancy and antisocial behaviour, school
problems, and self-perceived learning difficulties at 14 years of
age,'8
Other documented behaviour problems associated with
prenatal alcohol exposure include inattention, impulsivity, and
problems with social interaction and attention,'^
Results of longitudinal studies have shown that there is an
increased risk of learning problems and attention/memory defi-
cits in children when examined at age 7 years and as adolescents
at 14 years of age, which were found to be associated with
high levels of alcohol consumption during pregnancy. These
problems include self-perceived learning difficulties, school
problems, and deficits in reading, spelling, and arithmetic,''''
Impairments in cognitive development in adolescents and
young adults with FAS or FAE are prominent in the areas of
mathematics, particularly in calculation and estimation tests
and higher order processes,*' Estimation of cognitive deficits in
young adults with FAS who have an IQ within the normal
range has demonstrated deficits in attention, verbal learning,
and executive function that are more severe than suggested by
the IQ '^2
FINE AND GROSS MOTOR DEVELOPMENT
By 12-13 months of age, fine and gross motor difficulties may
be apparent in those affected with FAS, Jacobsen etal. found
that a high quantity and frequent antenatal alcohol consumption
was related to abnormal walking and balance, and fine motor
and prehensile coordination at I year of age,*^ Fine and gross
motor development at 3 years of age is reported to be poorly
developed in children where maternal binge drinking occurred
during pregnancy,*''
COMMUNICATION
Children with FAS or FAE also experience speech and
language difficulties,'^''*-*''* with receptive and expressive
language delays that effect communication and also social
development,'*
HEARING DISORDERS
Three types of hearing disorders are associated with FAS
including delays in auditory maturation, sensorineural hearing
loss, and intermittent conductive hearing loss due to recurrent
serous otitis media that is frequently associated with FAS,*'
The presence of a hearing disorder has the potential to exacer-
bate the behaviour and intellectual problems that are character-
istic of children with FAS,
Hearing assessment is recommended for infants exposed to
high levels of alcohol in utero and where appropriate an
intervention program commenced for the hearing-impaired
infant,*''*''
CONCLUSION
The current data do not demonstrate an association between a
low level of alcohol consumption and FAS or FAE, but clearly
identify an association between the pattern and quantity of
alcohol consumption, the timing of intake and a range of
component causes.

These findings are reflected in the recently published 2001
National Heatth and Medical Research Council Australian
Alcohol Guidelines, which for the first time have not advocated
abstinence during pregnancy,*** The new Guidelines recom-
mend that 'women who are pregnant or might soon become
pregnant:
• may consider not drinking at all
• should never become intoxicated
• if they choose to drink, should have less than seven standard
drinks per week and no more than two standard drinks on
any one day (spread over at least two hours)
• should note that the risk is highest in the early stages of
pregnancy, including the time from conception to the first
missed period'.
The lack of validated, objective diagnostic or screening tools
to identify children with FAS limits the ability of health
professionals to implement early intervention strategies to
reduce the negative long-term impact of this disorder,® The
evidence that many of the clinical sequelae of FAS, such as
intellectual handicap, cannot be improved emphasizes the
importance of implementing strategies to prevent FAS/FAE,
Screening for alcohol use/misuse does not occur routinely in
primary and community health services,^' settings that are ideal
for identifying high-risk clients. Prevention strategies address-
ing alcohol misuse by women who are of childbearing age and
during the antenatal period would ideally incorporate the evi-
dence on component factors such as nutrition, social factors,
and smoking in their message.
Following the birth of a child with FAS or FAE there is
evidence that all subsequent offspring of that mother will also
be affected unless the mother refrains from consuming alcohol.
This highlights the importance of implementing targeted pre-
vention strategies for this high-risk group of women. Interven-
tions should utilize both a woman-centred and family-centred
approach that emphasize the development of a non-judgmental
relationship between the health professional and the client.
ACKNOWLEDGEMENTS
My interest and knowledge of the issue of FAS was fostered
through my work for the National Expert Advisory Committee
on Alcohol and I would like to thank Professor C Watson and
Professor M Hamilton for their support in progressing this
issue, I also thank Professor C Bower, Dr P O'Leary, and
Ms M Cox for their comments on the drafts of this article.
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