Diagnosis of FASD in The Presence of Co-morbidity

2. 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

3. JR • 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

4. 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 - diagnosed with FAS

5. 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

6. JR Reduced intelligence Nonverbal IQ>Verbal IQ Strengths Receptive language Story recall Rote memory Reading Deficits Visuomotor skills Attention: impulsivity Spatial memory Math Executive: planning, organization, flexibility MC 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 Test Results

7. ARND The label ARND was proposed for children who exhibit neurodevelopment abnormalities in isolation

8. FASD Is a Diagnosis For Two

9. Exposure to alcohol ???!!!

10. 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

11. 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

12. 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 disorders Communication Disorders Feeling and Elimination Disorders • <1% Major Retardation

13. 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

14. 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

15. 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)

16. 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

17. 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

18. 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

19. 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

20. MC • Assessment reviled no exposure to alcohol • Diagnosed with • Specific learning disabilities, ADHD, ODD, Conduct disorder?

22. 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

23. Mentalhealthis a family affair 1 Ethanol is a treatment 2 Increased risk of substance use

24. 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

25. 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

26. 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

27. 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

28. 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

29. 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

30. 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

31. 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

32. 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…

33. Canadian FASD Diagnostic Guidelines

34. 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??!!

35. 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

36. FASD • Ethanol is only oneof the factors in this multifactorialgene-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

38. 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

39. 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

40. 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

41. FASD Is a Diagnosis For Two

42. 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.

43. 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?

44. 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

45. 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%)