Diagnosis of Fetal Alcohol Spectrum Disorder Gideon Koren MD, FRCPC Director, Motherisk Program, U of Toronto Ivey Chair in Mol. Toxicology, U of Western Ontario

Epidemilogy(1) Half to 60% of women in North America drink. CDC(anonymous phone interviews):0.14% of pregnant women drink above 12drinks/wk Abel(1998): based on 29 prospective studies: FAS incidence of 0.97 per 1000 births Rate of 190 per 1000 in some First Nations studies. B.c and Northern Manitoba: per 1000 Sampson et al: Incidence of the whole FASD: 9.1 per 1000

Epidemiology (2) Out of heavy drinkers: 40% have at least some fetal effects Only around 4% have the full blown syndrome A mother giving birth to FAS child-much higher risk than population risk Risk increases with maternal age.

History of FAS Biblic time: Infertile mom of prophet Samuel warned not to drink after conceiving UK late 19 th century: inmates”drunken”- poor pregnancy outcome Lemoine (France):1967;127 cases Jones&Smith(1973): coined the term FAS

Diagnostic Criteria for FAS Evidence of maternal drinking. Intrauterine/postnatal growth retardation Characteristic facial changes Complex/pervasive pattern of neurobehavioral deficits Other-less common, associated birth defects.

Diagnostic Criteria –Institute of Medicine FAS with confirmed maternal drinking FAS without confirmed maternal drinking Partial FAS with confirmed maternal drinking Alcohol related birth defects (without confirmed maternal drinking) Alcohol related neurodevelopmental disorder (ARND)

Confirming Maternal Drinking (1) History: self report;by others close to mom. 1 beer = 1 glass wine = 1oz liquor Screening questionnaires: TWEAK: 1)Tolerance;how many drinks to get high? 2)Worry: close friends worry about you? 3)Eye Opener: drinking when first get up? 4)Amnesia: people telling you things you did not remember? 5)Cut Down? Feel a need to decrease alcohol?

Confirming Maternal Drinking (2) Maternal biomarkers: Alcohol in blood/breath test Liver enzymes Hair measures of FAEEs (Fatty Acid Ethyl Esters) Neonatal Biomarkers: Measuring FAEEs in baby’s meconium

Confirming Maternal Drinking (3) Meconium FAEE: First fecal excretion of the child(days 1-3) Meconium forming at 14wk pregnancy Some baseline level even w/o drinking FAEEs above 2nM/mg in babies exposed to problem maternal drinking Rare-social drinking-not higher than baseline FAEEs

Maternal Alcohol History in Pregnancy Which of the following is documented as part of the diagnostic workup? Please tick all relevant: 1. Prenatal alcohol exposure confirmed by the mother or other reliable source such as medical records for index pregnancy _______________ 2. Number and types of alcoholic beverages consumed, pattern of drinking and frequency of drinking during index pregnancy ________________ 3. Co-occurring disorders, significant psychosocial stressors and pre-natal exposure to other substances in index and previous pregnancies ________________ 4. Comments: ____________________________________________________________ 5. ______________________________________________________________________ 6. ______________________________________________________________________ 7. ______________________________________________________________________ 8. ______________________________________________________________________

Intrauterine-Postnatal Growth Use standard growth curves:Height, Weight, Head Circumference. Decelerating weight over time not due to nutrition or other known pathology Disproportional low weight to height Always consider parental weight, height, head circumference

Facial Measures Qualitative changes: Midface hypoplasia Short palpebral fissures (less than 2 SD for age) Long flattened filtrum Narrow upper lip

PHYSICAL EXAMINATION AND DIFFERENTIAL DIAGNOSIS Which of the following domains are assessed ? Please tick all relevant: 1. Growth: Assess for pre or post-natal growth deficiency, below 10 th percentile ___ 2. Facial Features: Facial Features Measured ___ Software used ___ 3. Short palpebral fissures, at or below the 3 rd -percentile (2 standard deviations below the norm) ___ 4. Smooth or flattened philtrum, 4-5 on the 5-point Likert scale of lip-philtrum guide ____ 5. Thin vermilion border of the upper lip, 4-5 on 5-point Likert scale/lip –philtrum guide __ 6. Assess and record associated physical features and abnormalities ___ 7. Other genetic screening ____ 8. Comments if necessary ____________________________________________________ 9. ________________________________________________________________________

Evidence of Central Nervous System impairment(1) Decreased head circumference at birth Hard/soft age-appropriate neurological signs(e.g fine motor skills) Learning difficulties(e.g math) Language deficits Poor impulse control Hyperactivity, poor attention(ADHD)

Evidence of CNS impairment (2) Problem in social perception No friends ( Stade, 2003 ) Poor capacity for abstract thinking Rule breaking-problems with the law Presently-no pathognomonic behavioral Phenotype of FASD

Evidence of CNS Impairment (3) Canadian Pediatric Society(2002): Lack of organization: sequencing, inability to make choices Inability to foresee consequences;inability to learn from experience Impulsivity Inappropriate behavior: Excessive friendliness, lack of inhibition;unresponsive to social cues;inability to make/keep friends Difficulty with adaptive living skills

Evidence of CNS Impairment (4) Motherisk 2004: Comparison of FASD to ADHD ( Connors and Achenbach questionnaires) Externalizing behavior Rule braking Cruelty Steals No guilt

Alcohol Related Birth Defects Other birth defects associated with FASD: Cardiac:ASD, VSD, TOF Skeletal: Pectus excavatum, scoliosis, Renal: Aplastic/dysplastic/horseshoe kidneys Ocular: strabismus, refractive problems Hearing: conductive/neurosensory H.loss

NEUROBEHAVIORAL ASSESSMENT Which of the following domains are assessed? If assessed routinely mark R, if assessed based on known or suspected problem mark P. If test is never performed mark ND: a. Hard and soft neurological signs (including sensory- motor signs) ______ b. Brain structure (occipitofrontal circumference, MRI etc) ______ c. Cognition (IQ) _____ d. Communication: receptive and expressive ______ e. Academic achievement ______ f. Memory _____ g. Executive functioning and abstract reasoning _____ h. Attention deficit/hyperactivity _______ i. Adaptive behaviour, social skills, social communication _____ Please note that an in-depth review of the role of the psychologist is an additional part of this project.

Neurobehavioural assessment cont’d Please specify professional who assesses each domain. Mark TM after their prof. designation if they are a member of the clinic team (i.e. funded though clinic). DOMAINProfessionalTestClinical Observation Only Hard and soft neurological signs Brain Structure Cognition (IQ) Communication Academic Achievement Memory Executive Functioning Attention Deficit Hyperactivity Adaptive Behaviour

Diagnostic Criteria for FAS The following are the Canadian criteria for diagnosis of FAS after excluding other diagnoses. Please tick all criteria that you routinely assess as part of your current diagnostic protocol. GROWTH : Evidence of prenatal or postnatal growth impairment, in at least 1 of the following > Birth weight or birth length at or below the 10 th percentile for gestational age ________ Height and weight at or below the 10 th percentile for age. _______ Disproportionately low weight-to-height ratio (= 10 th percentile) _______ FACIAL FEATURES : Simultaneous presentation of all 3 of the following > Short palpebral fissure length, 2 or more standard deviations below the mean ____ Smooth or flattened philtrum, rank 4 or 5 on the lip-philtrum guide ____ Thin upper lip,rank 4 or 5 on the lip-philtrum guide ____ CNS : Evidence of impairment in 3 or more of the following central nervous system domains > Hard and soft neurological signs ___ Brain structure ___ Cognition ____ Social communication __ Communication ___ Academic achievement _ Memory ___ Social skills ___ Executive functioning __ Abstract reasoning ___ AD/HA ___ Adaptive behaviour __ ALCOHOL EXPOSURE: Confirmed (or unconfirmed) maternal alcohol exposure _____________

Diagnostic Criteria for Partial- FAS The following are the Canadian criteria for diagnosis of P-FAS after excluding other diagnoses. Please tick all criteria that you routinely assess as part of your current diagnostic protocol. FACIAL FEATURES: Simultaneous presentation of 2 of the following facial anomalies at any age > Short palepebral fissure length (2 or more standard deviations below the mean). _____ Smooth or flattened philtrum (rank 4 or 5 on the lip- philtrum guide). _______ Thin upper lip (rank 4 or 5 on the lip-philtrum guide). _______ CNS: Evidence of impairment in 3 or more of the following neurological signs > Hard and soft neurological signs ___ Brain structure ___ Cognition ____ Social communication __ Communication ___ Academic achievement _ Memory ___ Social skills ___ Executive functioning __ Abstract reasoning ___ AD/HA ___ Adaptive behaviour __ ALCOHOL EXPOSURE: Confirmed maternal alcohol exposure > ______

Diagnostic Criteria for ARND The following are the Canadian criteria for diagnosis of Alcohol- Related Neurodevelopmental Disorder (ARND) after excluding other diagnoses. Please tick all criteria that you routinely assess as part of your current diagnostic protocol. CNS: Evidence of impairment in 3 or more of the following neurological signs > Hard and soft neurological signs ___ Brain structure ___ Cognition ____ Social communication __ Communication ___ Academic achievement _ Memory ___ Social skills ___ Executive functioning __ Abstract reasoning ___ AD/HA ___ Adaptive behaviour __ ALCOHOL EXPOSURE: Confirmed maternal alcohol exposure > ______ Note: The term alcohol-related birth defects (ARBD) should not be used as an umbrella or diagnostic term, for the spectrum of alcohol effects (as per Canadian Guidelines).

Secondary Disabilities Sreissguth: Appear later in life Believed to be the result of complications of undiagnosed or untreated primary disabilities: Mental health problems(90%) Dependent living(80%) Employment problems(80%) Disruptive school experience(60%) Trouble with law(60%) Confinement(50%) Inappropriate sexual behavior(50%) Alcohol/drug problems(30%)

The cost of FASD in Canada Motherisk Study (Stade 2003): 140 Canadian families coast to coast Rural, urban, suburban, all races, adopted, fostered and natural mothers Interviewed on all aspect of health and other costs Estimated cost:$840,000(Cdn) per case to age 65yr

FASD-Major Challenges No treatment/insufficient programs for problem drinking women Lack of diagnostic facilities Physicians do not know how to diagnose No school programs/solutions for diagnosed children No preparation/program in the correction systems No facilities/plans for adults with FASD No investment for FASD by Canadian governments