diagnosis of fasd in the presence of co-morbidity dr. irena nulman the motherisk program division of...
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Diagnosis of FASD in The Presence of Co-morbidity
Dr. Irena NulmanThe Motherisk Program
Division of Clinical Pharmacology & Toxicology
Hospital for Sick Children, University of Toronto
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Learning problems• Poor attention • Problems with memory, writing, planning,
concepts of time.
Behavioral problem• 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
JR - diagnosed with FAS
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MC Learning Difficulties
• Poor reading and comprehension• Difficulties with math
Behavior Problems• 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
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Test ResultsJRReduced intelligenceNonverbal IQ>Verbal IQStrengths• Receptive language• Story recall • Rote memory• Reading
Deficits• Visuomotor skills• Attention: impulsivity• Spatial memory• Math• Executive: planning,
organization, flexibility
MCBorderline intelligenceNonverbal IQ>Verbal IQStrengths• Receptive language• Story recall • Verbal knowledge• Rote memory• Reading• Visuospatial ability
Deficits• Visuomotor skills• Attention: impulsivity• Math• Executive: planning, flexibility,
organization
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ARND
The label ARND was proposed for children who exhibit neurodevelopment abnormalities
in isolation
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FASD Is a Diagnosis For
Two
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Exposure to alcohol ???!!!
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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
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MC
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
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Psychiatric Disorders in Children 12% – 15% children have a mental disorder 2.2% – 9.9%
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 disordersCommunication DisordersFeeling and Elimination Disorders
<1% Major Retardation
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ADHD 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
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Major Depressive Disorder 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
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Anxiety Disorders Social Phobia = Social Anxiety Disorder
• As children mature, rates of anxiety in social situations tend to increase
Generalized Anxiety Disorder• Exhibits high rates of comorbidity with other anxiety disorders
Separation Anxiety Disorder• Usually develops during middle childhood• Age-related decline is present
Panic Disorders• Very rare before adolescence
Specific Phobia• Onset typically occurs during childhood
Posttraumatic Stress Disorder (PTSD)
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Conduct Disorder 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
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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 DisordersMathematics Problems Disorder of Written Expression
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Mental Retardation 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
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Other Disorders in Childhood 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
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MC
Assessment reviled no exposure to alcohol
Diagnosed with • Specific learning disabilities, ADHD,
ODD, Conduct disorder?
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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
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Mental health is a family affairGeneral 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%
1 Ethanol is a treatment
2 Increased risk of substance use
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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
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Pregnancy Course and Outcome
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
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Caregivers 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
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Teacher Academic achievement Behavior in structured and non- structured
learning contexts
Child Physical examination Genetic evaluation Laboratory Psychiatric examination Psychological assessment
Consider child’s age
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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
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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
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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
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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
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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):628-630Confirmation of exposure…
After excluding other causes…
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Canadian FASD Diagnostic Guidelines
FAS P-FAS ARND
Growth impairment 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
Differential diagnosis
Multidisciplinary team
After excluding other causes
After excluding other causes
After excluding other causes
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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??!!
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Why a Diagnosis is Needed Lack of access to resources Lack of proper interventions Increased risk for secondary disabilities Specific learning disorders Mood and anxiety disorders Mislead research
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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
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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
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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
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Maternal Biological Markers
FAS
GGT (g-Glutamyl transpeptidase): > 0.50 mkat/L (reflects liver damage)
MCV (Mean red blood cell volume): >98 fL
CDT (Carbohydrate-deficient transferrin): positive result is above 99th percentile
WBAA (Whole blood-associated acetaldehyde): >9.0 mmol/L
Hair
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FASD Is a Diagnosis For
Two
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Differential Diagnosis for Child Neurodevelopmental Disorder
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.
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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?
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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
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Secondary disabilitiesAppear 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%)