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.  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

4.  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

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. Test Results 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

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. 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% 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):628-630 Confirmation of exposure… After excluding other causes…

33. Canadian FASD Diagnostic Guidelines FASP-FASARND Growth impairmentYesYes/NoNo Facial anomalies SPFL, SP, TUL All 3 presentLes then 3 present None are present CNS involvementMinimum of 3 domains Confirmation of prenatal exposure Confirmed or unconfirmed Confirmed Differential diagnosis Multidisciplinary team After excluding other causes

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 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

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%)