Foetal Alcohol Syndrome An overview of the Literature

Document Sample
Foetal Alcohol Syndrome An overview of the Literature Powered By Docstoc
					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                             O'Leary 2002
    P.A. May      Pilot study
    1991                          1979-1983    All SW       2.0 / 1000
                                               Indians



    E.L Abel      Review of 35
    1995          studies         1973- 1992   US           1.95 /1000
                  reporting the                Incidence
                  incidence of                 European     0.08 / 1000
                  FAS                          Incidence


    Centres for   National
    disease       (USA) birth     1979 –1993   Not Given    0.1 /1000
    control       defects
    1995          monitoring
                  programme


    Sampson et    Critique of
    al 1997       published       1979-1981    Seattle      2.8 / 1000
                  incidence       1977 –1990   Cleveland    4.6 /1000
                  studies of      1975 –1981   France       1.3 – 4.8 /
                  FAS in three                              1000
                  population                   FAS + ARND   9.1 / 1000
                  based                        Seattle
                  studies
                          Raja Mukherjee SGHMS 2004                       7
Prevalence 2                                    O'Leary 2002

    G.M.          Multiple data
    Egeland       source           1977 –1992    Alaska          4.1/1000
    1998          surveillance
                  in Alaska

    H. Grinfeld   Cross                                          1.0/ 1000
    1999          sectional        1997          Not Given
                  survey four
                  genetic
                  clinics Brazil

    P.A. May      Community
    2000          based study      Not stated    Community       39.2 /1000
                  in the                         wide age
                  Western                        specific rate
                  cape of                        6-7 year olds
                  South Africa                   (48 cases)

    C. O Learey   Multiple
    2002          source FAS       1980 -1997    Birth defects   0.18 per
                  data from                      register and    1000
                  Southern                       Rural
                  Australia                      paediatric
                                                 service
                                                 database


                        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
                                       Slide copied from presentation by E Riley

Tip of the iceberg




           Raja Mukherjee SGHMS 2004                                           10
Maternal Risk Indicators                                                        Stratton 96, Abel 98



Health             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


Socio-economic     Low SES, Social transience, Unemployment

Status (SES)
Drinking Pattern   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

Psychological      Low self esteem, Depression, Sexual dysfunction

profile
Family Social      Family alcohol misuse, Male partners alcohol misuse, Tenuous marital status,
                   Previous loss of child to fostering / adoption
Traits
Local Culture      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                    Experiencing good
       nurturing home greater                quality home from age 8
       than 72% of life                      –12
      Diagnosis before aged 6              Being eligible for
      No experience of                      Learning Disability
       violence directed at self             services
      Staying in each living               Having diagnosis of FAS
       situation for more than               rather than FASD
       2.8 years                            Having basic needs met
                                             for more than 13% of life
Streissguth 96,00

                         Raja Mukherjee SGHMS 2004                       13
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


                                               DD
   Foetal Toluene Syndrome
   Cornelia Du Lange
   Noonans
   Others…                                  Morse and Weiner 95




                 Raja Mukherjee SGHMS 2004                         23
Facial features




           Raja Mukherjee SGHMS 2004   24
www.FASSTAR.COM



                  Raja Mukherjee SGHMS 2004   25
                                           Mattson + Reiley 1997

CNS Deficits                               Streisguth 1997,2000



   Small head / brain                   Hyperactivity and
   Structural abnormalities              attention
       Absent Corpus callosum           Sustained attention
       Small cerebellum                 Focused attention
   Neurological soft signs              Cognitive flexibility
   In coordination                      Planning
                                         Learning and memory
   Impaired hand eye
                                                 Problems declarative
    coordination                                  memory
                                                 Arithmetic
                                         Socioemotional

                      Raja Mukherjee SGHMS 2004                          26
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                                                       PEA
                            *                   *               *
                                                                            FAS
                                                                     *
                   85           **                   *
                   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

                                                                           4          FAS
           Starting position

                                                                                  P<0.001
               1                                                           2
                   2
                   3
                                                                           0
                                                                                            Group
          Ending position
Slide copied from presentation by E Riley                                                   Mattson, et al., 1999
                                                Raja Mukherjee SGHMS 2004                                      30
        Visio-spatial Functioning
              Rats shown spatial difficulties    (Kelly et al 88, Reyes et al 89)



              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



Matteson and Reiley 97
                                 Raja Mukherjee SGHMS 2004                           31
Physical Conditions associated
                Drooping eyelids, Strabismus, Short-sighted, Underdeveloped optic nerve,
Eyes            Blindness

                Hearing loss, Recurrent ear infections, Central auditory processing disorder
Ears            secondary to brain damage

                Improper aligned and misshapen secondary teeth, Faulty enamel
Teeth
                Minor problems with hands, Fingers, arms and toes. Foot position defects,
Musculo-        Problems with some joint movement, Cervical spine abnormalities,
                Thoracic abnormalities
skeletal
                Septal defects of heart, Underdeveloped or misplaced kidneys
Internal
Organs
                Abnormal genital development
Genitourinary
                     Raja Mukherjee SGHMS 2004                                                 32
Secondary Disabilities
   Disability               %
   Psychiatric problem      90
   Disrupted School         60
   experience
   Trouble with the law     60
   Confinement              50
   Inappropriate sexual     50
   behaviour
   Alcohol /Drug            30
                                             Streissguth et al 1996, 2000
   problems
                 Raja Mukherjee SGHMS 2004                             33
   Psychiatric presentations
                  Diagnosis             All Subjects   FAS         FAE

                                        No.     %      No.   %     No.   %

                  Total                 23      92     11    100   12    86

                  Alcohol / Drug        15      60     6     55    9     64
                  dependence
                  Major Depression      11      44     4     36    7     50
                  Psychotic             10      40     5     45    5     36
                  disorder
                  Bipolar I             5       20     1     9     4     29

                  Anxiety Disorder      5       20     2     18    3     21
                  Eating disorder       4       16     2     18    2     14
                  Personality           10      48     3     38    7     54
Famy et al 1998   Disorder
                                    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

           Threshold for damage
                                              concentrations post consumption of alcohol

           Binge drinking/ chronic
            drinking more likely to                                            Threshold
            exceed threshold
    
                                                                               level for

            Potential for damage        B                                      damage


            from both the rising        A                                       High levels intake
                                                                                Low levels intake
            phase and withdrawal        C
            phase
           Every person varies as to
            the exact level of
            consumption required to
            exceed limit
                                                      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
                                          Olney et al 2004, Thomas and Reiley 1998
   Apoptosis                             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
                                     size
                     Change in brain Mattson et al., 1994
Cerebrum
                                                                   Cerebrum     Cerebellum
                                                           100

                                                            95

                                                            90                        ***
                                                                                      **
                                                            85
                                                                    p < 0.010
                                                            80
                                                                        PEA

                                                            75          FAS        p < 0.001


Corpus Callosum                       Cerebellum
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
   Frontal Lobe features
       Cognitive flexibility
       Planning
   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
   Capacity / Diminished capacity
       Requires mental illness
       These secondary symptoms
        common in FAS
   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


                  Raja Mukherjee SGHMS 2004   55
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
   FAS Sufferer
       Ongoing support from multidisciplinary team
       Some evidence in children for use of Stimulant
        medication (Nanson et al 1997)
                    Raja Mukherjee SGHMS 2004                 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

				
DOCUMENT INFO
Shared By:
Categories:
Stats:
views:150
posted:4/14/2008
language:
pages:60