FAS The Silent Epidemic

1
FASThe Silent Epidemic

• Dr. Irena Nulman
• The Motherisk Program
• Division of Clinical Pharmacology Toxicology
• Hospital for Sick Children, University of Toronto
  

2
JR

• Learning problems
• Poor attention
• Problems with memory, writing, planning, concepts
  of time.
• Behavioral problem
• Poor anger control, unhappy
• Impaired attachment
• Physical examination
• Short palpebral fissure, flat midface, long
  flattened philtrum, narrow upper lip, low set
  ears
• Head circumference, height, and weight 3
  percentile
• Psychiatric evaluation
• Dx ADHD, ODD

3
JR

• Biological mother had mental illness and abused
  alcohol in pregnancy
• Age 3, apprehended by CAS for neglect
• 4 foster homes
• Age 7, adopted by Rs

JR - diagnosed with FAS
4
MC

• Behavior Problems
• Oppositional
• Inattentive
• Needs constant stimulation
• Frequent explosive temper tantrums
• Social
• Lying, stealing
• Difficulties appreciating social context
• Learning Difficulties
• No physical sign of alcohol toxicity
• Abnormal involuntary movements

5
MC

• Mother
• Receptionist
• Learning difficulties, slow
• Depression
• Severe NVP, 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

6
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

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Test Results

• JR
• Reduced intelligence
• Nonverbal IQgtVerbal IQ
• Strengths
• Receptive language
• Story recall
• Rote memory
• Reading
• Deficits
• Visuomotor skills
• Attention impulsivity
• Spatial memory
• Math
• Executive planning, organization, flexibility

• MC
• Normal intelligence
• Nonverbal IQgtVerbal IQ
• Strengths
• 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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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 gt 94 FASD is associated with later mental
  health disorders

10

• Are MCs problems due to assumed fetal alcohol
  exposure?
• Do we need to diagnose the ARND?
• Do we need a differential diagnosis?
• Should ARND be a diagnosis of exclusion?
• When ethanol is the cause and when it is a
  confounder?
• Do we need a comprehensive diagnostic approach to
  put the puzzle together?

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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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• Why a DD 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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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)

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Child Presentation

• Dont behave as expected
• ADHD
• Conduct and oppositional
• OCD
• Can not regulate emotions
• Worry
• Anxious-avoidant
• Sad
• Dont learn properly as expected for age
• Head trauma
• Inhibition
• Depression
• Do weird things
• Psychosis
• Tourette

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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
• Caregiver
• Teacher/School
• Child

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Caregivers

• Confirmation of any exposure
• Screening tests
• Family history
• mental health
• genetic and developmental disorders
• learning disabilities
• Head trauma
• Stability of caregivers environment
• History of head trauma
• Developmental history
• Description of behavior at home /social
  situations
• Consider childs 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 childs age

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The Mother

• Pregnancy
• Exposure during 1st, 2nd, 3d trimesters
• Maternal infections, medical care, NVP
• Unwonted, unplanned pregnancies
• Perinatal complications, labor duration, mode of
  delivery forceps, vacuum
• Fetal distress (O2 deprivation, cord around the
  neck)
• The Child
• Neonatal infections (meningitis)
• Neonatal jaundice - kernicterus
• Neonatal respiratory distress, meconium
  aspiration, seizures
• How many days in the hospital???
• Developmental milestones
• Stages of Psychological Development( adjusted for
  age and gender)

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• FASD Is a Diagnosis For Two

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ARND

• Alcohol is a CNS drug
• Parental psychopathology and psychosocial
  adversity act as strong determinants of alcohol
  abuse
• Associated with polydrug use
• High risk of fetal exposure

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Mental health is a family affair
1 Ethanol is a treatment 2 Increased risk of
substance use
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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
• lt1 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
• lt1
• 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 Oppositional Defiant Disorder and
  Conduct Disorder
• 15-20 have Mood Disorders
• 25 have Anxiety Disorders
• 20 have Learning Disorders
• Symptoms tend to decrease with age

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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
  criteria
• 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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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)
• 5-10 of depressed adolescents will complete
  suicide within 15yrs of their initial episode of
  MDD

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Mental Retardation

• Characteristics
• IQ 70 or below
• onset before 18 years of age
• deficits or impairments in adaptive functioning
• Predisposing factors
• Heredity (e.g., Tay-Sachs disease)
• Early alterations of embryonic development (e.g.,
  prenatal damage due to toxins)
• Pregnancy perinatal problems
• General medical conditions
• Environmental influences
• Individuals with Mental Retardation have 3 to 4
  times greater prevalence of comorbid mental
  disorders, than the general population
• Mental Retardation is more commonly associated
  with the following disorders (compared to the
  general population)
• ADHD
• Mood Disorders
• Pervasive Developmental Disorders
• Stereotypic Movement Disorder

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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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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 Disorder
• Disorder of Written Expression

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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
• Aspergers 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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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
• Adolescents with alcohol /or substance
  dependence disorders are 6 to 21 times more
  likely to have a physical /or sexual abuse
  history
• Depression is prior to substance abuse in women
• Depressed ? substance ? inherit FAS depression

31
Fetal alcohol spectrum disorder Canadian
guidelines for diagnosis. CMAJ 2005172 (suppl)
S1-S21Identifying fetal alcohol spectrum
disorder in primary care. CMAJ 2005172
(5)628-630

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How Much is Too Much ?

• No one knows how much is safe
• Where FAS is concerned, we can be reasonably
  confident alcohol abuse is involved, and
  even more confident moderate drinking is
  not
• E. Abel, 1998.
• Threshold or linear response?

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Canadian FASD Diagnostic Guidelines
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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 gt 90 FASD is associated with later mental
  health disorders

35
Developing 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 offsprings
  neurodevelopmental trajectories

36
Developing DD for ARND

• 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 are considered

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No specific treatment available

• 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?

38
Why a DD 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

39
FASD, What is new ?

• 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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Confounding Variables

• Mothers age
• Psychiatric disorders
• Polydrug use
• Drinking patterns during pregnancy
• Time of exposure
• STD

• Poor medical care
• Poor nutrition
• Mode of delivery, labor
• Home environment
• SES
• Infant health

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Methodological Differences

• Methods of recruitment, time of exposure
• Sample size
• Diagnostic criteria of FAS/ARND
• Childs age at testing
• Controls
• Polydrug use
• Pattern of drinking
• Reporting bias
• Measurement bias
• Maternal health
• Specific sensitivity to alcohol
• Additional exposure, breastfeeding

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• FASD Is a Diagnosis For Two

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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

44
Maternal Biological Markers

• FAS
• GGT (g-Glutamyl transpeptidase) gt 0.50 mkat/L
  (reflects liver damage)
• MCV (Mean red blood cell volume) gt98 fL
• CDT (Carbohydrate-deficient transferrin)
  positive result is above 99th percentile
• WBAA (Whole blood-associated acetaldehyde) gt9.0
  mmol/L
• Hair

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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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Developing Differential Diagnosis for Alcohol
Related 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.