Transcript NAPAS Annual Meeting and Conference

Foetal Alcohol Spectrum Disorders.
Primary and Secondary Prevention.
September 9th 2009,
Euro Care Conference,
Brussels.
Dr. Kieran D. O’Malley,
Child & Adolescent Psychiatrist ,
Belfast Trust.
ANIMAL STUDIES IN FASD
• 35 years of animal research has created an animal
model of this developmental neuropsychiatric disorder
• there is no safe amount of alcohol in pregnancy
• alcohol is teratogenic throughout the whole of pregnancy
• the classic facial dysmorphology does not correlate with
the level of brain neurotoxic injury
• animals exposed to low doses of alcohol may still show
significant impairment in cognitive functioning
• prenatal alcohol causes a chronic cognitive, behavioral
and neurological impairment and does not increase
mortality
• Animals exposed prenatally to alcohol crave alcohol in
later life
O’Malley 2009
Dose related effects
• Binge drinking is the most destructive
exposure i.e. high levels of prenatal
alcohol exposure in a short time period
• Low dose prenatal alcohol exposure still
can have an effect on the developing brain
• There is no truly safe amount of prenatal
alcohol exposure in the pregnancy period
O’Malley 2009
Face not related to behaviour
• Characteristic physical hyperactive
behaviours are not anticipated by FAS
facial features
• Affective/ Mood instability features are not
anticipated by FAS facial features
• Autistic type behaviours are not
anticipated by FAS facial features
Riley 1990,Driscoll et al 1990,O’Malley 2009
Face not related to brain
dysfunction
• Brain imaging studies have shown that
the dysmorphic FAS facial features are not
the markers for brain dysfunction
i.e. Abnormalities in the corpus callosum,
cerebellum or hippocampus
Sulik et al 1981, Abel 1984,O’Malley 2009
General Principles
Foetal Alcohol Spectrum Disorders, FASDs
Two Disorders:
• Foetal Alcohol Syndrome, FAS,
dysmorphic (10-15%)
• Alcohol Related Neurodevelopmental
Disorder , ARND, non dysmorphic (85-90%)
• Foetal Alcohol Spectrum Disorder (singular)
is the same as ARND (Canada & UK)
Streissguth & O’Malley 2000, O’Malley 2009
Primary Prevention
1. Warning Labels on bottles of alcohol
saying that alcohol causes defects if
taken during pregnancy
Initially achieved in USA IN 1981
O’Malley 2009
Primary Prevention
2. Assistance programmes for alcohol or
substance –abusing women
-community based
-hospital based
O’Malley 2009
Primary Prevention
3. Alcohol counselling programmes for
teenage girls
-community based
-school based
O’Malley 2009
Primary Prevention
4.Incorporation of FASD in basic medical ,
nursing and social work training in
Universities
O’Malley 2009
Secondary Prevention
1.
-
Identification of high risk pregnancies
Age
Social class
Ethnic group
Alcohol or drug use
Exposure to domestic violence
Exposure to abuse
Transgenerational risk
O’Malley 2009
Secondary Prevention
2. Identification of at risk or alcohol-affected
infants
-alcohol exposure in pregnancy
-transgenerational risk
-biomarkers in pregnancy,
blood( mother), meconium,( foetus, infant)
cranial ultrasound( ?foetus,infant)
foetal breathing (foetus)
Waas et al 2001,Little et al 2002,O’Malley /Streissguth 2006
Secondary Prevention
3.Use of neuro-protective agents in
pregnancy
-vitamin B12, folate, thiamine, ASA, choline,
zinc, magnesium, vitamin D, long chain fatty
acids, indomethicin
Dreosti 1993, Riley et al 2005, O’Malley 2009
Secondary Prevention
4.Specialized early intervention multidisciplinary clinics
-community based
-hospital based
-university based
O’Malley 2009
Secondary Prevention
5.Educated use of psychotropic medication
- Safety a major factor because of ARBD
i.e. effects of prenatal alcohol on
developing heart, kidney and liver
-atypical medication response as patient
has organic brain dysfunction
Byrne 2008, Dubovsky 2008,0’Malley 2008, 2009
Secondary Prevention
6. Identification of at risk school children
-identification of children expelled or
suspended from school because of
aggressive or’ hyperactive’ behaviour
Streissguth et al 1996, 0’Malley 2009
Parenting effect not related to
dose
• Characteristic disorganized, hyperactive or
emotionally reactive/volatile parenting is
not related to the dosage of prenatal
alcohol exposure.
Future studies may highlight the effect of
high dose alcohol in a short time period ,or
binge drinking exposure, and unravel its
relationship to trans generational parenting
problems in FASD.
O’Malley 2009
Alcohol craving related to
prenatal alcohol exposure
• Animal studies have shown this
phenomenon for over 30 years
• Does sugar craving pre-date alcohol
craving?
• Relationship to high prevalence of preteen alcoholic problems
Bond & Di Gusto 1976, Reyes et al 1985, Dominguez et al
1993
?Epigenetic effect of prenatal alcohol exposure
-
-Recent research evidence of prenatal alcohol effect
on DNA methylation via effect on methione, choline,
vitamin B12, folate, zinc.
This turns some genes on and others off
-Effect of chronic alcoholism on male spermatogenesis.
This can effect protein synthesis and mRNA
Waterland 2003,Song et al 2003,Anway et al 2005,O’Malley 2009
Epigenetic Research Proposals
1. Identification of imprinted genes where
expression is altered by alcohol exposure.
2. Determining if methyl supplementation or other dietary
supplementation during pregnancy and lactation prevent
alcohol-induced epigenetic changes.
3. Determining epigenetic trans-generational actions on
alcohol-exposed individuals.
O’Malley 2009
Future Directions (O’Malley 2009)
--
a transcription protein in neuron nucleus of the Nucleus
Accumbens increases sensitivity to alcohol, cocaine and
morphine( linked to CdK5 gene)
• genetic variants such as ADH2 locus decrease alcohol
dehydrogenase and cytochrome P4502E1 metabolism of
ethanol to acetaldehyde ( protective factor)
• mRNA & Protein expression of selective alpha subunits
of G proteins are abnormal in prefrontal cortex of suicide
victims
• reduced prefrontal gray matter volume & reduced
autonomic activity in antisocial personality disorder
• role of mesolimbic dopamine pathway in alcohol craving