OUTLINE
Fetal Alcohol Syndrome (FAS)
An Overview
Lauren D. Williams, M.D.
University of Miami School of Medicine
The
purpose of this lecture is to give an overview of Fetal Alcohol Syndrome, one
of the leading causes of mental retardation in the USA, and one which is highly
preventable.
S2. A. Definition (1)
1. FAS is a
serious developmental disorder caused by prenatal alcohol exposure of the fetus
and characterized by:
a) prenatal and/or postnatal growth retardation
b) central nervous system dysfunction
c) characteristic craniofacial abnormalities
S3. 2. FAS
a) first described by Lemoine in 1968
b) term coined by Jones and Smith in 1973
In 1968 Lemoine and his colleagues in Western France
first described children born to mothers who drank heavily in pregnancy. They
exhibited physical abnormalities particularly in the face, reduced size and
problems of behavior and cognition. Little interest was placed on these
observations. Then in 1973, Jones and Smith described similar pattern of
abnormalities in children of alcoholic mothers and coined the term- Fetal
Alcohol Syndrome. It was then the scientific community recognized the potential
harm to the fetus that was exposed to alcohol. (1,2)
S4. 3. Facies in FAS (3)
The
discriminating features:
a) short palpebral fissures
b) flat midface
c) short nose
d) indistinct philtrum
e) thin upper lip
considered
definitive signs of FAS
The
associated signs:
a) epicanthal folds
b) low nasal bridge
c) minor ear anomalies
d) microagnathia
not
sufficient to determine the presence of FAS.
Microcephaly
is not a facial feature but a central nervous system characteristic. It is
important to note that it is not any one characteristic that makes the FAS face
distinctive, but rather the “gestalt” or the overall presentation of the
facies.(3,4)
S5. 3. Facies in FAS (cont.)
Eyes
and midface of a child with FAS, showing short eye openings and drooping
eyelids. Slow nasal growth in the
outward direction from the face results in a crescent shaped fold of skin
covering the inner corner of the eye. (5)
S6. 3. Facies in FAS (cont.)
FAS
face showing a long smooth philtrum without ridges. Slightly short nose and narrow red margin of the upper lip. (5)
S7. 4. Spectrum of Effects
FAS
does not represent all individuals exposed to alcohol in utero but indicates
those on the severe end of the spectrum of effects. Some individuals are
unaffected while others may have partial expression of FAS referred to as Fetal
Alcohol Effects (FAE). FAE is further subdivided into Alcohol Related Birth Defects
(ARBD) which primarily presents with physical anomalies and Alcohol Related
Neurodevelopmental Disorder (ARND) which has more central nervous system
damage. (5)
S8. B. Diagnostic Criteria (1)
1.
In 1980 the criteria
for diagnosis of FAS were developed by the Fetal Alcohol Study Group of the
Research Society on Alcoholism. These criteria were based on the original
description of FAS by Jones and Smith in 1973. The three major characteristics
in this paradigm are:
a) prenatal and /or postnatal growth retardation, i.e.,
weight, length, or head circumference below the 10th percentile when
corrected for gestational age
b) central nervous system dysfunction-signs of
neurological abnormalities, developmental delays or cognitive impairment
c) distinctive facial features with at least two of the
following signs
i) short
palpebral fissure
ii) poorly developed philtrum
iii) thin upper lip
iv) flat midface
v) microphthalmia
vi) head circumference below the 3rd
percentile
A diagnosis of FAS is based on the presence of one characteristic from
(a) and (b) and at least two from (c).
S9. C. Pathogenesis
How
does alcohol produce its teratogenic effects? The mechanism(s) for alcohol
teratogenicity remains unknown. Several mechanisms have been proposed and
include:
1. Direct toxic effects of alcohol (7,8)
a) alcohol’s toxic effects on the fetus is related to
exposure at critical periods of fetal development
b) first trimester exposure(embryonic development)
generally results in skeletal and visceral anomalies
c) exposure at later stages of brain development results
in behavioral defects
2. Toxic effects of acetaldehyde (7,8)
a) first metabolite of alcohol metabolism, rapidly
crosses the placenta
b) more embryotoxic than alcohol
3. Placental dysmorphology/function (9,10)
a) placental
weight and pathologic changes (e.g. Intervillous thrombi, villitis) have been
observed in alcoholic women
b) above
changes believe to alter placental function, particularly transport functions
c) alcohol
causes umbilical vessels to collapse. This results in decreased placental/fetal
blood flow. This leads to hypoxia which has been implicated in alcohol induced
growth retardation
d) variable
induction of human placental CYP2E1 may play a role in fetal susceptibility to
intrauterine alcohol exposure-increases acetaldehyde
4. Prostaglandin synthesis (7,8)
alcohol can increase prostaglandins which in turn inhibits
placental/fetal blood flow
5. Early cell death (apoptosis) (11)
a) alcohol causes blockade of N-methyl-D-aspartate
(NMDA) glutamate receptors and excessive activation of GABA-A receptors which
results in stimulation of apoptosis or early deliberate cell death
b) vulnerability occurs during synaptogenisis (6 months
gestation to several years after birth) and this leads to death of neuronal
cells in the developing brain.
S10. II. Epidemiology
A. Incidence
1. 0.26-4.6 per 1000 live births
a) the incidence of FAS is difficult to estimate as the
rates are generally influenced by the population studied (6,12)
b) the rate is ten times higher in African Americans and
Native Americans than that of middle and upper socioeconomic status Americans
(13)
2. In the Seventh Special Report to the U.S. Congress on
Alcohol and Health, the incidence of FAS is estimated at 1 to 3 per 1000 live
births. The incidence is nearly double that of Down’s syndrome and almost five
times that of Spina bifida (14)
S11. B. Risk factors
FAS
occur in the context of alcohol use during pregnancy. But as noted previously
in the spectrum of effects, prenatal alcohol exposure alone is not sufficient
to cause FAS in some cases.
1. Alcohol intake pattern/quantity
a) bingeing (at least 5 drinks per occasion) is more
teratogenic than consumption of the same amount of alcohol over an extended
period of time. The more chronic the bingeing, the greater the damage, as
exposure is more likely to occur in critical periods of development (1)
b) the
shorter the time period in which alcohol is consumed, the higher the blood
alcohol concentration (BAC), which results in greater brain damage (1)
c) how much alcohol is too
much?
There is no safe dose of alcohol in pregnancy. However, all cases of FAS
have been diagnosed in alcoholic women (1)
2. Maternal age/parity
a) FAS
increases as maternal age and parity increase. This may be due to progressively
greater blood alcohol blood level associated with increasing age. Increase parity is associated with increased
uterine collagen and elastin content.
This can lead to decreasing blood flow to the fetus, contributing to
fetal hypoxia and exacerbation of alcohol effects (1)
b) older
age leads to increased ratio of body fat to water resulting in higher peak
blood levels of alcohol (1)
c) age
related differences in absorption may also contribute to different blood
alcohol levels and toxicities (1)
3. Race/Socioeconomic status (SES)
a) FAS
occur in all races but seems to be identified more often among lower SES
population (1,4)
b) lower
SES maybe correlated with inadequate diet , higher parity, smoking and abuse of
other drugs (15)
4. Genetic susceptibility
a) genetic
factors influence alcohol metabolism (1)
b) genotype
affects alcohol toxicity with varying sensitivities to in utero exposure (1)
c) monozygotic
twins- concordance rate 100% (15)
d) dizygotic
twins- concordance rate 63% (15)
S12. III. Clinical Course
A. Morphological Abnormalities
1. newborn/infant-characteristic
facies subtle and difficult to assess (3,4)
S13. A. Morphological
Abnormalities (cont)
2. Preschool/school
age (3,4)
a) facies
more distinguishable
b) short
stature and microcephaly more prominent
c) thin
torso is characteristic
3. Adolescent
(3,4)
a) increase length of chin and nose may make
identification more difficult in adolescence. Facial anomalies are more subtle
in adolescence and adults.
b) thin torso gives way to normal weight-height
proportion
c) prepubertal females may even exhibit plumpness. This
modifies the physical phenotype after puberty
d) puberty may be delayed in males
S14. Slide
showing patient with FAS at age 8 and 18. (3)
S15. A. Morphological Abnormalities (cont)
1. Adult
(3,4)
a) in some
adults the face becomes normalized, others retain some of the characteristic
facial anomalies e.g. The short palprebral fissure, thin upper lip, smooth
philtrum
S16. B. Neurobehavioral Effects
1. Newborn/Infant
(4)
a) disturbed
sleep patterns
b) excessive
arousal
c) feeding
difficulties and failure to thrive
2. Preschool/School
Age (3,1)
a) hyperactivity
may be found in up to 80% of children
b) attentional
problems
c) impaired
cognitive function- mental retardation occur in about half of FAS patients (IQ
less than 60)
S17. 3. Adolescence (3,16)
a) continue
to have significant impairment in academic functioning, particularly math
skills
b) severe
impairment of their math skills leads to difficulty with independent living,
poor judgment and dysfunctional lives
c) difficulty
with abstractions like time and space, cause and effect, and generalizing from
one situation to the next
d) conduct
problems such as lying and defiance occur in a number of these individuals
S18. 4. Adulthood (3)
a) mental
problems constitute the most severe manifestation, also have intellectual
retardation
b) persistent
behavior problems that interfere with their intellectual function and even
their manual skills, unable to focus on activities.
c) IQ
remains stable over time
d) spatial
memory problems are particularly notable, this results in failure to perceive
social cues
S19. C. Secondary Disabilities (3,16)
1. school
failure
2. delinquency
3. difficulty
with employment
4. difficulty
with independent living
The
more severe the presentation of the individuals with prenatal alcohol exposure,
the more often they required special education, were temporarily, or
permanently taken into care. In
adulthood, maladaptive behaviors present the greatest challenge. These
individuals are at risk for victimization, joblessness, and homelessness
S20. IV. Treatment Interventions
A. Medical Care
1. depends on
presenting symptomatology rather than diagnosis of FAS itself
2. generally, routine medical care is all that is needed
(4)
3. specific problems addressed individually e.g. Cardiac
defects, skeletal abnormalities (1)
4. growth deficiency- although a part of FAS, other
medical causes of failure to thrive should be excluded . Catch up growth is
generally not observed (1, 4)
B. Cognitive rehabilitation and special
education
Use of compensation strategies for areas of deficit (e.g. problem
solving) and attempts to ameliorate these directly (16,17)
C. Structured environment/supervision
Behavioral
strategies used in a highly structured environment, concrete rules and
regulations and close caretaker supervision may help (16,17)
S21. V. Prevention
A. Identification
1. history
2. screening instruments – AUDIT, TWEAK (4,18,19)
T
= tolerance
W
= worried
E
= eye-openers
A
= amnesia (blackouts)
K
(c) = cut-down
S22. 3. biological
markers(20,21,22)
-gamma-glutamyl
transpeptidase(GGT)
-carbohydrate-deficient
transferring(CDT)
-mean
corpuscular volume(MCV)
FAS is a preventable
consequence of alcohol consumption during pregnancy. Drinking history should be
routine during a woman’s prenatal visit to her health care provider. Because of
the stigma regarding drinking in women, they are known to under report alcohol
use. As a result screening
instruments (AUDIT and TWEAK ) and
biological markers (GGT, CDT MCV) may be helpful in identifying high risk women
(4,19,20,21,22). The TWEAK test is easy to administer and requires no training.
T-tolerance:
“How many drinks can you hold?”
W-worried:
“Have close friends or relatives worried or complained about your drinking in
the past year?”
E-eye-openers:
“Do you sometimes take a drink in the morning when you first get up?”
A-amnesia(blackouts):
“ Has a friend or family member ever told you about things you said or did
while you were drinking that you could not remember?”
K(C)-cut
down:” Do you sometimes feel the need to cut down on your drinking?”
A 7-point scale is used to
score the test. If a woman can hold five or more drinks without passing out she
is positive for tolerance and scores 2 points. A positive response to the worry
question also scores 2 points. Each of the last three questions scores one
point for positive responses. A total of three or more points indicates the
woman is likely to be a heavy or problem drinker.
GGT- detect ~ 40-60% of
alcohol abusing and dependent individuals. About 80% level of specificity.
Consumption of greater than 40 grams of alcohol per day elevates GGT levels and
after cessation of alcohol use, values return to normal in ~ 4-5 weeks.
CDT- is a deglycosylated
form of the liver synthesized protein, transferring. It is produced during
heavy alcohol use(50-80 g/day) for seven days and remains elevated for about
two weeks after alcohol consumption stops. CDT test is said to be highly
specific and sensitive.
MCV- is increased, generally
higher than 90 cubic microns.
The biological markers may
not identify pregnant females who consume potentially harmful but lesser
quantities of alcohol.
S23. B. Intervention (23)
1. universal approaches – aimed at all females of
childbearing age regardless of risk of FAS.
Universal prevention strategies are used to increase public awareness of
the risk of drinking during pregnancy.
Media campaigns, messages in reading material, radio and television
advertisements and labeling of alcoholic beverages are examples of universal
prevention strategies. Labeling of
alcoholic beverage is reported to have a greater effect on lighter than heavier
drinkers who are at the greatest risk of having a child with FAS. Awareness of risks of alcohol use in
pregnancy does not necessarily translate into changes in drinking behaviors.
2. selective strategies – targets women who are at
increased increase of FAS. These women
should be identified earlier, as discussed previously, through screening. Counseling should occur ideally prior to
conception and continue throughout the pregnancy with total abstinence being
the goal. Women who receive therapy and
case management services were more likely to remain abstinent than those who
did not receive these services.
3. indicated approaches – targeted to women at the
highest risk, especial those who have had one child with FAS. Brief interventions therapy, referral to
special programs, and changes in environment (halfway houses, shelter living)
are examples of indicated approaches interventions.
S24. VI. Summary
FAS:
1. severe
developmental disability resulting from prenatal alcohol exposure
2. one of
the leading causes of mental retardation
3. not just a
childhood problem
4. early
diagnosis and intervention important
5. preventable
FAS
is a severe developmental disability resulting from drinking during pregnancy.
It is one of the leading causes of mental retardation. It is not just a
childhood problem as the cognitive/emotional deficits persist through to
adulthood resulting in difficulties in many aspects of the affected individual’s
life. Early diagnosis and intervention are important so that appropriate levels
of care can be given to decrease handicaps and improve life adaptation.
FAS is not a natural phenomenon and is highly
preventable.
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