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

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 multi-

disciplinary 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 pre-

teen 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