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Diagnosis of FASD in The
Presence of Co-morbidity
Dr. Irena Nulman
The Motherisk Program
Division of Clinical Pharmacology & Toxicology
Hospital for Sick Children, University of Toronto
JR
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Learning problems
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Behavioral problem
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• Poor attention
• Problems with memory, writing, planning,
concepts of time.
• Poor anger control
• Unstable mood
• Impaired attachment
Psychiatric evaluation
• Dx: ADHD, ODD, emotional instability
Physical examination
• Short palpebral fissure, flat midface, long
flattened philtrum, narrow upper lip, low set
ears
• Head circumference, height, and weight = 3
percentile
JR

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Biological mother diagnosed
with a bipolar disorder and
abused alcohol in pregnancy
Age 3, apprehended by CAS
for neglect
4 foster homes
Age 7, adopted by R’s
JR - diagnosed with FAS
MC

Learning Difficulties

Behavior Problems
• Poor reading and comprehension
• Difficulties with math
• Lying, stealing
• Does not learn from experiences
• Difficulties appreciating social context
 Psychiatric evaluation

•
•
•
•
•
•
Oppositional (ODD)
Inattentive (ADHD)
Abnormal involuntary movements
Needs constant stimulation
Frequent explosive temper tantrums
Aggressive
No physical sign of in utero alcohol toxicity
Test Results
JR
MC
Reduced intelligence
Nonverbal IQ>Verbal IQ
Strengths
• Receptive language
• Story recall
• Rote memory
• Reading
Borderline intelligence
Nonverbal IQ>Verbal IQ
Strengths
• Receptive language
• Story recall
• Verbal knowledge
• Rote memory
• Reading
• Visuospatial ability
Deficits
• Visuomotor skills
• Attention: impulsivity
• Math
• Executive: planning, flexibility,
organization
Deficits
• Visuomotor skills
• Attention: impulsivity
• Spatial memory
• Math
• Executive: planning,
organization, flexibility
ARND
The label ARND was proposed for
children who exhibit neurodevelopment
abnormalities
in isolation
FASD Is a
Diagnosis For
Two
Exposure to alcohol
???!!!
MC

Mother
•
•
•
•
•

Receptionist
Learning difficulties, “slow”
Depression
Severe NVP t/o, PROM, prolonged labor
34 weeks, jaundice
Father
•
•
•
•
•
•
Salesman
ADHD at school
Often changes jobs?
Family history of suicide in a first
degree relative
12 beers in weekends
MC
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Parents in a divorce process for
3 years
Mother - denies drugs of abuse
Father – accusing mother of
drinking in pregnancy
MC - sharing custody, unstable
home
Assessment reviled no
exposure to alcohol
Psychiatric Disorders in Children
 12% – 15% children have a mental disorder
 2.2% – 9.9%

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Attention-Deficit/Hyperactivity Disorder in nonclinical settings
1.5% – 5.5%
Conduct Disorder
<1% – 2.7%
Major Depressive Disorder in prepubescent populations
3.5% – 5.4%
Separation Anxiety
1% – 6%
Motor Skills disorders
Communication Disorders
Feeling and Elimination Disorders
<1%
Major Retardation
ADHD
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Persistent symptoms of inattention, hyperactivity, or
impulsivity that are more frequent and sever than what is
typically observed in other individuals at the same
developmental level
ADHD is the most common childhood diagnosis
Boys are 3 times more likely than girls to be diagnosed
with ADHD
50-70% of children with ADHD have other mental
disorders
• 40-50% have ODD and Conduct Disorder
• 15-20% have Mood Disorders
• 25% have Anxiety Disorders
• 25% have Learning Disorders
Symptoms tend to decrease with age
Major Depressive Disorder
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Common & recurrent
• 2% in children
• 5-8% in adolescents
Higher rates in adolescent girls than in
adolescent boys
Associated with morbidity & mortality 1.5% –
5.5%
Children with depression have persistent
functional impairment (even after recovery)
5-15% of depressed adolescents will complete
suicide within 15 years of their initial episode of
MDD
Anxiety Disorders

Social Phobia = Social Anxiety Disorder
• As children mature, rates of anxiety in social situations tend
to increase

Generalized Anxiety Disorder

Separation Anxiety Disorder

Panic Disorders

Specific Phobia

Posttraumatic Stress Disorder (PTSD)
• Exhibits high rates of comorbidity with other anxiety disorders
• Usually develops during middle childhood
• Age-related decline is present
• Very rare before adolescence
• Onset typically occurs during childhood
Conduct Disorder
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A repetitive and persistent pattern of behavior in which the
basic rights of others or major age-appropriate norms or rules
are violated
Individuals with Conduct Disorder have little empathy & little
concern for the feelings, values, & well-being of others
Onset of conduct Disorder
• May occur as early as 5-6 years of age
• Occurs more often in later childhood or early adolescence
• Rare after 16 years of age
In adulthood - Antisocial Personality Disorder
Often associated with early onset of sexual behavior, drinking,
smoking, use of illegal substances, & reckless & risk-taking
acts
May lead to school suspension or expulsion, problems in work
adjustment, legal difficulties, sexual transmitted diseases,
unplanned pregnancy
Disorders Associated with
Academic Skills
 Learning Disorders
• 10-25% of individuals with ADHD, Conduct
Disorder, Oppositional Defiant Disorder, &
Depressive Disorders also have Learning
Disorders
 Reading Disorders
 Mathematics Problems
 Disorder of Written Expression
Mental Retardation

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IQ ~70 or below
• Onset before 18 years of age
• Deficits or impairments in adaptive functioning
Predisposing factors;
• Heredity
• Early alterations of embryonic development (e.g. toxins)
• Pregnancy & perinatal problems
• General medical conditions (chromosomal, storage)
• Environmental influences (postnatal exposure to toxins –
lead)
Individuals with Mental Retardation have 3 to 4 times greater
prevalence of comorbid mental disorders, than the general
population
• ADHD
• Mood Disorders
• Pervasive Developmental Disorders
• Stereotypic Movement Disorder
Other Disorders in Childhood
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Autistic Disorder
• Infants exhibit failure to cuddle; indifference or aversion
to affection of physical contact; lack of eye contact;
lack of facial responsiveness; lack of socially directed
smiles; fail to respond to parental voices
Asperger’s Disorder
• Qualitative impairment in social interaction,
accompanied by repetitive and stereotyped behaviors,
interests and activities that cause clinically significant
impairment in social or occupational functioning
Reactive Attachment Disorder of Infancy or Early
Childhood
• Markedly disturbed social relatedness, manifest by
either persistent failure to respond appropriately to
most social interactions or diffuse attachments
MC
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
Assessment reviled no
exposure to alcohol
Diagnosed with
• Specific learning disabilities, ADHD,
ODD, Conduct disorder?
Child Presentation
 Don’t behave as expected
• ADHD
• Conduct and oppositional
• OCD
 Can not regulate emotions
• Worry
• Anxious-avoidant
• Sad
 Don’t learn properly as expected for age
 Head trauma
• Inhibition
• Depression
 Do weird things
• Psychosis
• Tourette
Mental health is a family affair
General
populatio
n
Monozygotic
twins
Dizygotic
twins
Schizophrenia 1,2
0.5-1%
50%
15-30%
Depression 1,2
4-17%
40-80%
20-40%
ADHD 1,2
3-6%
79%
32%
Conduct Disorder 2
2-4%
70-80%
60-70%
Reading Disorder 2
4-8%
~100%
35%
Ethanol is a treatment
2 Increased risk of substance use
1
Comprehensive Diagnostic
Approach
 The diagnosis should depend on a
combination of physiological, behavioral,
and interactional measures concordant
with the clinical presentation and child’s
age
 Caregiver
 Teacher/School
 Child
 Parents
Pregnancy Course and Outcome
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The Mother
Exposure during 1st, 2nd, 3d trimesters
Maternal infections, medical care, NVP
Perinatal complications, labor duration, mode of
delivery – forceps, vacuum
Fetal distress severity and duration (O2
deprivation, cord around the neck)
The Child
Neonatal infections (meningitis)
Neonatal jaundice - kernicterus
Neonatal respiratory distress, meconium aspiration,
seizures
Developmental milestones
Caregivers
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Confirmation of any exposure
Screening tests
Family history
• mental health
• genetic and developmental disorders
• learning disabilities
 Stability of caregivers environment
 History of head trauma
 Developmental history
 Description of behavior at home /social situations
Consider child’s age
Teacher
 Academic achievement
 Behavior in structured and non- structured
learning contexts
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Child
Physical examination
Genetic evaluation
Laboratory
Psychiatric examination
Psychological assessment
Consider child’s age
Parental Morbidity
 Individuals with stress-related anxiety
disorders, BD, depression may use drugs
to control their symptoms (self medication)
&/or experience greater reward associated
with drug use
 Depression is prior to substance abuse in
women
• Depressed  substance  FAS
Alcohol Comorbidity
 Alcohol is a CNS drug
 Parental psychopathology act as strong
determinants of alcohol abuse
Associated with polydrug use
High risk of fetal exposure
FASD - ARND
 Phenotypic, morphologic, cognitive and/or
behavioral markers of ARND have not
been established yet
 The fetal/child dose effects of lesser
quantities of alcohol consumption have not
been elucidated
 In > 90% FASD is associated with later
mental health disorders
DD for ARND
 Diverse forms of brain insult (e.g., trauma,
toxic, genetic, metabolic, etc) may result in
clinical presentations where differentiation
from ARND is unattainable
 In addition to alcohol use genetic
(psychiatric disorders), environmental, and
interpersonal factors influence the
offspring’s neurodevelopmental trajectories
Fetal alcohol spectrum disorder:
Canadian guidelines for diagnosis.
CMAJ 2005;172 (suppl): S1-S21
#######
Identifying fetal alcohol spectrum
disorder in primary care. CMAJ
2005;172 (5):628-630
Confirmation of exposure…
After excluding other causes…
Canadian FASD Diagnostic
Guidelines
FAS
P-FAS
ARND
Yes
Yes/No
No
Facial anomalies
SPFL, SP, TUL
All 3 present
Les then 3
present
None are
present
CNS involvement
Minimum of 3
domains
Minimum of 3
domains
Minimum of 3
domains
Confirmation of
prenatal exposure
Confirmed or
unconfirmed
Confirmed
Confirmed
Growth impairment
Differential diagnosis After excluding After excluding After excluding
other causes
other causes
other causes
Multidisciplinary
team
No specific treatment available
Do we need to diagnose FASD?
 Do we need a differential diagnosis?
 When ethanol is the cause and when it is a
confounder?
 Do we need a comprehensive diagnostic
approach to put the puzzle together?
Should FASD be a diagnosis of exclusion?
Or a diagnosis of inclusion along with
other co-morbidity??!!
Why a Diagnosis is Needed
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Lack of access to resources
Lack of proper interventions
Increased risk for secondary disabilities
Specific learning disorders
Mood and anxiety disorders
Mislead research
FASD
 Ethanol is only one of the factors in this



multifactorial gene-environment-pharmacologic
disorder
We may question the validity of this clinical
picture as an exclusive end result of
gestational exposure to ethanol
A multifactorial model where, in addition to
alcohol, other genetic, toxic and environmental
influences should be considered
More research is needed in separating the
effect of alcohol from other confounders
FASD
 Ethanol is a drug (maternal co morbidity)
 CNS- the specific pattern of effects
 ARND – (sensitive, not specific)
 FAS is a marker for maternal alcohol
abuse
 Maternal and neonatal markers available
Neonatal Biological Markers
 Hair
 Meconium
• FAEEs such as ethyl linoleate, laurate,
stearate in the meconium of newborns
• Testing is available through the Motherisk
Program at The Hospital for Sick Children
Maternal Biological Markers
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FAS
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MCV (Mean red blood cell volume): >98 fL
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WBAA (Whole blood-associated
acetaldehyde): >9.0 mmol/L
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Hair
GGT (g-Glutamyl transpeptidase): > 0.50
mkat/L (reflects liver damage)
CDT (Carbohydrate-deficient transferrin):
positive result is above 99th percentile
FASD Is a
Diagnosis For
Two
Differential Diagnosis for Child
Neurodevelopmental Disorder
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Ethanol is only one of the factors in this
multifactorial gene-environment-pharmacologic
disorder.
We question the validity of a clinical picture as an
exclusive end result of gestational exposure to
ethanol;
We propose an expanded multifactorial model where,
in addition to alcohol, other genetic, toxic and
environmental influences are considered.
Informed by this multifactorial context, a suggest a
comprehensive model of assessment and treatment,
that recognizes the contribution of different diverse
pathophysiological dimensions.
Do we need to diagnose ARND?
 Do we need a differential diagnosis?
 When ethanol is the cause and when
it is a confounder?
 Do we need a comprehensive diagnostic
approach to put the puzzle together?
Should ARND be a diagnosis of
exclusion?
More Research Needed…
 To determine dose effects
• Threshold?
• Continuum effect?
 To separate alcohol effects from other
etiological factors
 To determine alcohol-related mental health
problem?
 To develop optimal interventions
Secondary disabilities
Appear later in life as a result of complications
from primary disabilities.
 Mental health problems (94%)
 Disruptive school experience (60%)
 Trouble with law (60%)
 Confinement (50%)
 Inappropriate sexual behaviour (50%)
 Alcohol/drug problems (30%)
 Dependent living (80%)
 Employment problems (80%)