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 riskO’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

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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