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

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

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

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

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

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

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%

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

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

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

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)

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

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

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

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

MC

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 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

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

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 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

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):628-630Confirmation of exposure…

After excluding other causes…

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

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 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

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

FASD Is a Diagnosis For

Two

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.

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 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%)