Foetal Alcohol Syndrome An overview of the Literature

Foetal Alcohol Syndrome An overview of the Literature Dr Raja Mukherjee Specialist Registrar / Honorary Lecturer St Georges Hospital Medical School London April 7th 2004 Outline        History Epidemiology Characteristic features Diagnosis Aetiology Management The problem for the future Raja Mukherjee SGHMS 2004 2 Background History     Greek Middle Ages 18th Century 20th Century   Lemoine Smith + Jones  Ongoing Work to date Raja Mukherjee SGHMS 2004 4 Terminology FAS  Partial FAS  FAE  ARND  FASD  Raja Mukherjee SGHMS 2004 5 Epidemiology Prevalence P.A. May 1991 Pilot study O'Leary 2002 1979-1983 All SW Indians 2.0 / 1000 E.L Abel 1995 Review of 35 studies reporting the incidence of FAS 1973- 1992 US Incidence European Incidence 1.95 /1000 0.08 / 1000 Centres for disease control 1995 National (USA) birth defects monitoring programme 1979 –1993 Not Given 0.1 /1000 Sampson et al 1997 Critique of published incidence studies of FAS in three population based studies 1979-1981 1977 –1990 1975 –1981 Seattle Cleveland France FAS + ARND Seattle 2.8 / 1000 4.6 /1000 1.3 – 4.8 / 1000 9.1 / 1000 Raja Mukherjee SGHMS 2004 7 Prevalence 2 G.M. Egeland 1998 Multiple data source surveillance in Alaska O'Leary 2002 1977 –1992 Alaska 4.1/1000 H. Grinfeld 1999 Cross sectional survey four genetic clinics Brazil Community based study in the Western cape of South Africa Multiple source FAS data from Southern Australia 1.0/ 1000 1997 Not Given P.A. May 2000 Not stated Community wide age specific rate 6-7 year olds (48 cases) 39.2 /1000 C. O Learey 2002 1980 -1997 Birth defects register and Rural paediatric service database 0.18 per 1000 Raja Mukherjee SGHMS 2004 8 Problems with Studies      Inconsistent diagnostic methods Lack of agreement over FASD Differing methodologies applied Accepted rate 1/ 1000 FASD 3-4 times more but possibly as high as 1/100 Raja Mukherjee SGHMS 2004 9 Tip of the iceberg Slide copied from presentation by E Riley Raja Mukherjee SGHMS 2004 10 Maternal Risk Indicators Health Stratton 96, Abel 98 Older than 25 when child born, 3 or more children prior to birth of affected child, Use of other drugs, Premature morbidity from alcohol related causes Low SES, Social transience, Unemployment Socio-economic Status (SES) Drinking Pattern Psychological profile Family Social Traits Local Culture Early age of onset regular drinking, Frequent binge drinking (5+ drinks 2* per week), Frequent drinking, High Blood Alcohol Concentrations, No reduction of drinking during pregnancy Low self esteem, Depression, Sexual dysfunction Family alcohol misuse, Male partners alcohol misuse, Tenuous marital status, Previous loss of child to fostering / adoption Tolerant to drinking Raja Mukherjee SGHMS 2004 11 Who is at risk? Every woman who drinks whilst pregnant Raja Mukherjee SGHMS 2004 12 Protective factors     Living stable and nurturing home greater than 72% of life Diagnosis before aged 6 No experience of violence directed at self Staying in each living situation for more than 2.8 years     Streissguth 96,00 Experiencing good quality home from age 8 –12 Being eligible for Learning Disability services Having diagnosis of FAS rather than FASD Having basic needs met for more than 13% of life 13 Raja Mukherjee SGHMS 2004 Patterns of drinking     Chronic Drinking Binge drinking Moderate drinking Low levels Raja Mukherjee SGHMS 2004 14 Chronic drinking     Classically associated with abnormalities Upto 40% of people who drink chronically during pregnancy will have a child with FAS Unable to predict who will / will not be at risk Larger percentage develop behavioural correlates Jones+Smith 75, Streissguth 96 Raja Mukherjee SGHMS 2004 15 Binge drinking   Pattern increasingly seen UK (National reduction Strategy interim report)     20% Drink more than recommended 13% Binge drink 22% all drinking episodes : Binge type Pathology of binge drinking Vulnerable periods for malformation differ (Heaton et al 2003) Raja Mukherjee SGHMS 2004 16 Moderate / Low level consumption    Differing views as to the level of harm Polygenis et al 97 and Knupfer 91 argue that insufficient evidence exists to support this assumption This is in contrast to increasing animal and prospective literature showing neuro behavioural damage Zhou et al 2003, Sulik et al 81, Hanson 78  As little as one drink per day can be seen as harmful Sood et al 2001, Rolater et al 2000 Raja Mukherjee SGHMS 2004 17 Characteristic features and Diagnosis Diagnostic Criteria     Growth retardation Facial Dysmorphology Neurodevelopmental problems Alcohol supportive not essential Raja Mukherjee SGHMS 2004 19 IOM Guidelines for diagnosis Sampson 97 Raja Mukherjee SGHMS 2004 20 4 Digit Diagnostic Code   Astley and Clarren 96,00,02 4 broad categories     Growth Facial features Brain Alcohol exposure  Based on defined criteria giving score each areas and then diagnosis Raja Mukherjee SGHMS 2004 21 Comparison of two methods    Diagnosing FAS easier than FASD If no evidence of alcohol consumption reliability significantly worse More work still needed Burd et al 2003 Raja Mukherjee SGHMS 2004 22 Main Differential Diagnosis       Foetal Hydantoin Syndrome PKU Foetal Toluene Syndrome Cornelia Du Lange Noonans Others… DD Morse and Weiner 95 Raja Mukherjee SGHMS 2004 23 Facial features Raja Mukherjee SGHMS 2004 24 www.FASSTAR.COM Raja Mukherjee SGHMS 2004 25 CNS Deficits  Mattson + Reiley 1997 Streisguth 1997,2000  Small head / brain Structural abnormalities       Absent Corpus callosum Small cerebellum    Neurological soft signs In coordination Impaired hand eye coordination   Hyperactivity and attention Sustained attention Focused attention Cognitive flexibility Planning Learning and memory   Problems declarative memory Arithmetic  Socioemotional 26 Raja Mukherjee SGHMS 2004 Effect on IQ      Majority fall within normal range Normal distribution shifted to left Roughly 20 point shift FAS average IQ 79 - 72 FAE average IQ 90 NOTE :NOT TO SCALE DIAGRAMATIC REPRESENTATION ONLY Streissguth 78,96, Matteson 96 Olegard 79 Raja Mukherjee SGHMS 2004 27 General Intellectual Performance 115 NC Standard score 100 85 * * * * PEA ** * FAS 70 55 40 FSIQ VIQ PIQ IQ scale Slide copied from presentation by E Riley Mattson, S.N., 1997. Raja Mukherjee SGHMS 2004 28 Neuropsychological Performance Slide copied from presentation by E Riley Mattson, et al., 1998 Raja Mukherjee SGHMS 2004 29 Executive functioning deficits Move only one piece at a time using one hand and never place a big piece on top of a little piece 3 1 2 6 NC Rule Violations PEA Starting position 1 4 FAS 2 P<0.001 2 3 0 Ending position Slide copied from presentation by E Riley Group Raja Mukherjee SGHMS 2004 Mattson, et al., 1999 30 Visio-spatial Functioning     Rats shown spatial difficulties Deficits on stepping stone maze: Tests short term recall complex patterns(Streissguth 94) At 7 .5 years such visuoconstructional tasks one of the most sensitive measures of alcohol teratogenesis Global Locus test used to differentiate hierarchical visual processing. Found to focus more on Global than local components (Kelly et al 88, Reyes et al 89) Matteson and Reiley 97 Raja Mukherjee SGHMS 2004 31 Physical Conditions associated Eyes Drooping eyelids, Strabismus, Short-sighted, Underdeveloped optic nerve, Blindness Hearing loss, Recurrent ear infections, Central auditory processing disorder secondary to brain damage Improper aligned and misshapen secondary teeth, Faulty enamel Ears Teeth Musculoskeletal Internal Organs Genitourinary Minor problems with hands, Fingers, arms and toes. Foot position defects, Problems with some joint movement, Cervical spine abnormalities, Thoracic abnormalities Septal defects of heart, Underdeveloped or misplaced kidneys Abnormal genital development Raja Mukherjee SGHMS 2004 32 Secondary Disabilities Disability Psychiatric problem Disrupted School experience % 90 60 Trouble with the law Confinement Inappropriate sexual behaviour Alcohol /Drug problems 60 50 50 30 Streissguth et al 1996, 2000 Raja Mukherjee SGHMS 2004 33 Psychiatric presentations Diagnosis All Subjects FAS FAE No. Total Alcohol / Drug dependence Major Depression Psychotic disorder Bipolar I Anxiety Disorder Eating disorder Personality Disorder % 92 60 44 40 20 No. 11 6 4 5 1 % 100 55 36 45 9 No. 12 9 7 5 4 % 86 64 50 36 29 23 15 11 10 5 5 4 10 20 16 48 2 2 3 18 18 38 3 2 7 21 14 54 Famy et al 1998 Raja Mukherjee SGHMS 2004 34 Criticisms of study   Small numbers Possible selection bias   Despite this consistent with that already seen First reports onwards report high levels of psychiatric illness Raja Mukherjee SGHMS 2004 35 FAS / ADHD    Aetiology or separate condition? Shen et al 1999 Links suggested but differences in the quality of presentation noted O’Malley + Nanson 2002 Argued however more research needed to confirm link Linnet et al 2003 Raja Mukherjee SGHMS 2004 36 Aetiology Pathology of Alcohol on the Foetus      Several Stages where alcohol can have an effect Blood alcohol concentration Binge drinking Areas of brain damage Other factors Raja Mukherjee SGHMS 2004 38 Timing of consumption causes differing patterns to be seen Not always the case full facial features will be seen Raja Mukherjee SGHMS 2004 39 Blood alcohol concentration     Diagrammatic representation of blood alcohol concentrations post consumption of alcohol Threshold for damage Binge drinking/ chronic drinking more likely to exceed threshold Potential for damage from both the rising phase and withdrawal phase Every person varies as to the exact level of consumption required to exceed limit B A C Threshold level for damage High levels intake Low levels intake Time Thomas and Riley 98 Point of consumption Raja Mukherjee SGHMS 2004 40 GABA, Glutamate and Apoptosis     Agents that mimic the effects of GABA at the GABAa trigger Effects of Glutamate on NMDA receptor and rebound excitation Acetaldehyde induced damage Apoptosis Olney et al 2004, Thomas and Reiley 1998 Menegola et al 2000 Raja Mukherjee SGHMS 2004 41 Areas of Brain damage    Corpus Callosum: Smaller / Agenesis  Similar pattern to that seen in ADHD Cerebellar Vermis : Anterior vermis smaller than controls Basal ganglia: Reduced in volume Matteson and Riley 95,97 Raja Mukherjee SGHMS 2004 42 Change in brain Mattson et al., 1994 size Cerebrum 100 95 90 85 Cerebrum Cerebellum *** ** p < 0.010 PEA FAS 80 75 Cerebellum p < 0.001 Corpus Callosum Slide copied from presentation by E Riley Mattson et al., 1994 Raja Mukherjee SGHMS 2004 43 Brain damage resulting from prenatal alcohol Slide copied from presentation by E Riley photo: Clarren, 1986 Raja Mukherjee SGHMS 2004 44 Other factors   Placental function and hormone regulation Neuronal migration Raja Mukherjee SGHMS 2004 45 Management Management  Assessment      Psychiatric Psychological Social Educational Forensic   Treatment Location of treatment Raja Mukherjee SGHMS 2004 47 Overview         Not easy to make diagnosis in Adults Features are less definitive than childhood Same areas need to be looked at Try to find developmental records Pictures from childhood Psychometric tests help Hx of Alcohol use or likely use during pregnancy Combination of all features Raja Mukherjee SGHMS 2004 48 Important!     Following suggestions are just that a Suggestion Many models All overlap depending on resources The greater the evidence the greater the ability to make a diagnosis Raja Mukherjee SGHMS 2004 49 Psychiatric  Hx  Developmental   Short stature Neurobehavioral deficits  Maternal alcohol consumption during pregnancy    Secondary disabilities (as above) Mental State: Secondary disabilities Physical     Facial features Secondary physical features Cerebellar signs Neuroimaging Raja Mukherjee SGHMS 2004 50 Psychological tests  WAIS   Arithmetic FSIQ Cognitive flexibility Planning  Frontal Lobe features      Visio-spatial assessment Empathy / assessment Ability to learn consequences  Gambling test Raja Mukherjee SGHMS 2004 51 Social  Child Protection   Mother of FAS child Child of FAS parent     Needs assessment Accommodation and community support Financial Advocacy Raja Mukherjee SGHMS 2004 52 Educational    To Mother  Harm of consumption (prevent repeat) To Child/ Adult FAS  Concentrate of areas difficulty suitable to their level e.g. social functioning and arithmetic ability (difficulties will be found)  Special needs education / Statementing Community, Professional and Support groups  Non critical communication  Management strategies for behaviour  Diagnosis /advocacy issues Raja Mukherjee SGHMS 2004 53 Forensic issues  Competency  Fitness to plead Requires mental illness These secondary symptoms common in FAS  Capacity / Diminished capacity    Diposal LaDeu et al 97 Raja Mukherjee SGHMS 2004 54 Economic cost    Amounts entirely preventable but lifelong Abel 87 suggest $35.2 Million per annum Burd et al 2003 suggest a potential cost of $491,820 per person with FAS over 20 years 55 Raja Mukherjee SGHMS 2004 Treatments / support  Mother    Alcohol services to prevent further subsequent risk Long Chain Alcohol (Chen et al 2001) : Blocks mechanism of alcohol damage in rat models Increasing evidence in non human models to suggest effects of alcohol can be blocked :too early to evaluate full usefulness Ongoing support from multidisciplinary team Some evidence in children for use of Stimulant medication (Nanson et al 1997) Raja Mukherjee SGHMS 2004  FAS Sufferer   56 Type and location of service  Requirement    Psychiatrist Psychologist Social Worker    Learning Disability Team General Adult CMHT Children   Paediatricians / Dysmorphologist (Clinical Genetics) Child and Adolescent Services  Support and advice from Tertiary diagnostic service with service delivery at a local level Raja Mukherjee SGHMS 2004 57 Areas for the future  5 areas highlighted as areas to concentrate (Hankin et al 2000)      Development of valid and reliable measures to identify alcohol use in pregnant women Create training programmes for providers Generating programmes to reduce barriers to care Determining which programmes are most successful Estimating cost of different treatment approaches Raja Mukherjee SGHMS 2004 58 Questions Raja Mukherjee SGHMS 2004 59 Contact Details Dr Raja Mukherjee SpR / Honorary Lecturer Department of Mental Health Learning Disability St Georges Hospital Medical School Cranmer Terrace Tooting London SW17 0RE rmukherj@sghms.ac.uk Raja Mukherjee SGHMS 2004 60