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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 JR Learning problems Behavioral problem • Poor attention • Problems with memory, writing, planning, concepts of time. • 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 - diagnosed with FAS MC Learning Difficulties Behavior Problems • Poor reading and comprehension • Difficulties with math • 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 Results JR MC Reduced intelligence Nonverbal IQ>Verbal IQ Strengths • Receptive language • Story recall • Rote memory • Reading 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 Deficits • Visuomotor skills • Attention: impulsivity • Spatial memory • Math • Executive: planning, organization, flexibility 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 disorders Communication Disorders Feeling 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 Separation Anxiety Disorder Panic Disorders Specific Phobia Posttraumatic Stress Disorder (PTSD) • Exhibits high rates of comorbidity with other anxiety disorders • Usually develops during middle childhood • Age-related decline is present • Very rare before adolescence • Onset typically occurs during childhood 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 Disorders Mathematics 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 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% Ethanol is a treatment 2 Increased risk of substance use 1 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):628-630 Confirmation of exposure… After excluding other causes… Canadian FASD Diagnostic Guidelines FAS P-FAS ARND 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 Growth impairment Differential diagnosis After excluding After excluding After excluding other causes other causes other causes Multidisciplinary team 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 MCV (Mean red blood cell volume): >98 fL WBAA (Whole blood-associated acetaldehyde): >9.0 mmol/L Hair GGT (g-Glutamyl transpeptidase): > 0.50 mkat/L (reflects liver damage) CDT (Carbohydrate-deficient transferrin): positive result is above 99th percentile 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 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%)