Better Safe Than Better Safe Than Sorry:Sorry:

The Biological The Biological Basis of Basis of

Fetal Alcohol Fetal Alcohol Syndrome Syndrome and otherand other

Alcohol-Related Alcohol-Related Birth DefectsBirth Defects

When a mother When a mother drinks, her unborn drinks, her unborn child is exposed to child is exposed to

alcohol.alcohol.

Alcohol-Related Birth Defects Alcohol-Related Birth Defects Include:Include:

• Fetal Alcohol SyndromeFetal Alcohol Syndrome (FAS)(FAS)

which is characterized bywhich is characterized by1. central nervous system problems 1. central nervous system problems

2. low birth weight and 2. low birth weight and heightheight

3. typical facial features3. typical facial features

• Fetal Alcohol EffectsFetal Alcohol Effects (FAE)(FAE)which result from maternal alcohol abuse but are which result from maternal alcohol abuse but are found in the absence of the full-blown syndromefound in the absence of the full-blown syndrome

The facial features ofThe facial features ofFetal Alcohol Syndrome are:Fetal Alcohol Syndrome are:

• Small eyelid openings (palpebral Small eyelid openings (palpebral fissures)fissures)

• Short, upturned noseShort, upturned nose

• Long upper lip (from nose to mouth) Long upper lip (from nose to mouth) with a thin red border and a deficient with a thin red border and a deficient central groove (philtrum) central groove (philtrum)

• Reduced size of the head Reduced size of the head (microcephaly)(microcephaly)

FASFASNORMALNORMAL

Full-blown fetal Full-blown fetal alcohol syndrome (FAS) alcohol syndrome (FAS) represents only the represents only the “tip of the iceberg” “tip of the iceberg”

relative to all relative to allalcohol-related birthalcohol-related birth defects (ARBDs). defects (ARBDs).

FASFAS

ARBDsARBDs

MATERNAL ALCOHOL MATERNAL ALCOHOL ABUSE IS THE LEADING ABUSE IS THE LEADING

KNOWN CAUSE OF KNOWN CAUSE OF MENTAL RETARDATION IN MENTAL RETARDATION IN

THE WESTERN WORLDTHE WESTERN WORLD

Children with alcohol-related Children with alcohol-related birth defects typically have:birth defects typically have:

• attention deficitsattention deficits

• language difficultieslanguage difficulties

• learning disabilitieslearning disabilities

• impulsive behaviorimpulsive behavior

• poor judgmentpoor judgment

Cross-sectionCross-sectionWhole brainWhole braincerebral hemispherescerebral hemispheres

cerebellumcerebellum

corpuscorpuscallosumcallosum

PRENATAL ALCOHOL EXPOSURE CAN PERMANENTLY PRENATAL ALCOHOL EXPOSURE CAN PERMANENTLY DAMAGE THE BRAIN, AFFECTING IMPORTANT STRUCTURES DAMAGE THE BRAIN, AFFECTING IMPORTANT STRUCTURES

SUCH AS THE CEREBELLUM AND CORPUS CALLOSUM,SUCH AS THE CEREBELLUM AND CORPUS CALLOSUM,AS WELL AS SPECIFIC CELL POPULATIONS IN MANY OTHER AS WELL AS SPECIFIC CELL POPULATIONS IN MANY OTHER

REGIONS OF THE BRAINREGIONS OF THE BRAIN

Visualization of the brain of a normal individual (A) and Visualization of the brain of a normal individual (A) and two with FAS (B,C) shows permanent loss of the tissue two with FAS (B,C) shows permanent loss of the tissue

indicated by the arrows (portions of the corpus callosum).indicated by the arrows (portions of the corpus callosum).

Images courtesy of Dr. S. MattsonImages courtesy of Dr. S. Mattson

NormalNormal FASFAS FASFAS

Similarities in mouse and human embryogenesis Similarities in mouse and human embryogenesis provide opportunities to study the effects provide opportunities to study the effects

of alcohol on development.of alcohol on development.

5 mm.

Mouse (10 days old)

Human (approx. 28 days old)

EYE

HEART

UPPER LIMB (ARM)3 mm.3 mm.

Narrow foreheadNarrow forehead

Short palpebral fissuresShort palpebral fissures

Small noseSmall nose

Small midfaceSmall midface

Long upper lip withLong upper lip withdeficient philtrumdeficient philtrum

child with FASchild with FAS

normalnormalalcohol-exposedalcohol-exposed

mouse fetusesmouse fetuses

The facial features of Fetal Alcohol Syndrome The facial features of Fetal Alcohol Syndrome can be seen in both a child and a mouse fetus can be seen in both a child and a mouse fetus that were exposed to alcohol during development.that were exposed to alcohol during development.

The amount and timingThe amount and timingof maternal alcohol use of maternal alcohol use determine the type and determine the type and extent of resulting birth extent of resulting birth

defects.defects.

Alcohol can cause malformations and brain abnormalities in embryos that are only three to four weeks old.

22 day old human embryo ( about 2 mm. long, the length of the ear on the US dime)

Developing brain

ALCOHOL KILLS SPECIFIC CELLS IN THE DEVELOPING BRAIN

Arrows surround a portion of the brain of a mouse Arrows surround a portion of the brain of a mouse embryo (viewed from the back) that is at a develop-embryo (viewed from the back) that is at a develop-

mental stage corresponding to a 22-23 day human.mental stage corresponding to a 22-23 day human.

Cells killed by alcohol in the brain of a mouse Cells killed by alcohol in the brain of a mouse embryo (at a comparable stage of development embryo (at a comparable stage of development to that on the left) have taken up a dark blue stain.to that on the left) have taken up a dark blue stain.

CELLS THAT SHOULD FORM MIDLINE STRUCTURES CELLS THAT SHOULD FORM MIDLINE STRUCTURES OF THE BRAIN AND FACE ARE OF THE BRAIN AND FACE ARE

KILLED BY ALCOHOLKILLED BY ALCOHOL

DevelopingDevelopingbrain andbrain and

face face

HeartHeart

Mouse embryo (viewed fromMouse embryo (viewed from the front) at a stage corresponding the front) at a stage corresponding

to a 22-23 day old human.to a 22-23 day old human.

A close-up view of an alcohol-exposed A close-up view of an alcohol-exposed mouse embryo shows cells killed by alcoholmouse embryo shows cells killed by alcohol

that have taken up a dark blue stain.that have taken up a dark blue stain.

EYEEYE EYEEYE

A C

B D

MOUTHMOUTHMOUTHMOUTH

NOSTRILSNOSTRILS

NOSTRILSNOSTRILS

MIDLINE STRUCTURES OF THE FACE AND BRAIN ARE DEFICIENT INMIDLINE STRUCTURES OF THE FACE AND BRAIN ARE DEFICIENT INALCOHOL-EXPOSED MOUSE EMBRYOS AND IN INDIVIDUALS WITH FASALCOHOL-EXPOSED MOUSE EMBRYOS AND IN INDIVIDUALS WITH FAS

THE FACE OF A CHILDTHE FACE OF A CHILDWITH FULL-BLOWN FASWITH FULL-BLOWN FAS

HAS FEATURES THATHAS FEATURES THATCAN BE CAUSED BY CAN BE CAUSED BY

DAMAGE TO MIDLINEDAMAGE TO MIDLINESTUCTURES.STUCTURES.

COMPARISON OF THE FACE (A) AND INTERIOR OF THE BRAIN (B) OF A NORMAL COMPARISON OF THE FACE (A) AND INTERIOR OF THE BRAIN (B) OF A NORMAL

MOUSE EMBRYO AND ONE DAMAGED BY ALCOHOL (C&D) SHOWS THAT THE NOSTRILS MOUSE EMBRYO AND ONE DAMAGED BY ALCOHOL (C&D) SHOWS THAT THE NOSTRILS

ARE ABNORMALY POSITIONED (C) AND THE BRAIN IS MISSING MIDLINE STRUCTURES (D).ARE ABNORMALY POSITIONED (C) AND THE BRAIN IS MISSING MIDLINE STRUCTURES (D).

ALCOHOL KILLS SPECIFIC CELLS ALCOHOL KILLS SPECIFIC CELLS IN THE DEVELOPING BRAIN IN THE DEVELOPING BRAIN

A cut made through theA cut made through the area outlined by arrowsarea outlined by arrowsprovides a view of the inside of the brain of a provides a view of the inside of the brain of a 10 day mouse embryo 10 day mouse embryo (corresponding to a 28 day human)(corresponding to a 28 day human)

Cells killed by Cells killed by alcoholalcohol have taken up have taken up dark blue staindark blue stain

The pattern of cell death varies The pattern of cell death varies with the stage of development.with the stage of development.

This child with FAS has This child with FAS has a scar from a repaireda scar from a repaired cleft lip.cleft lip. Cleft lip can also be causedCleft lip can also be causedby genetic or environmentalby genetic or environmental agents other than alcohol.agents other than alcohol.

EXPOSURE TO ALCOHOL EXPOSURE TO ALCOHOL DURING DEVELOPMENTDURING DEVELOPMENTCAN CAUSE DAMAGE CAN CAUSE DAMAGE TO ORGANS AND REGIONS TO ORGANS AND REGIONS OTHER THAN THE BRAINOTHER THAN THE BRAIN

Alcohol also caused cleft lip Alcohol also caused cleft lip in this mouse.in this mouse.

By the ninth week By the ninth week of development the of development the

human fetus is human fetus is about 24mm. long. about 24mm. long. Damage caused by Damage caused by alcohol to the brain alcohol to the brain

at this time and at this time and until birth can until birth can

result in abnormal result in abnormal brain function. brain function.

Excessive alcohol exposure can causeExcessive alcohol exposure can causedamage during all stages ofdamage during all stages of

prenatal development.prenatal development.

• Pre-implantation:Pre-implantation: first 2 weeksfirst 2 weeks

• EmbryonicEmbryonic:: 3-8 weeks after conception3-8 weeks after conception

• FetalFetal: from week 9 until birth: from week 9 until birth

Alcohol can Alcohol can cause permanent cause permanent damage to a baby damage to a baby

before most before most women realize women realize

they are they are pregnant. pregnant.

Alcohol-relatedbirth defects

last a lifetime.

Alcohol-related birth defects are Alcohol-related birth defects are expensive:expensive:

• Monetarily — for treatment, Monetarily — for treatment, carecare, and lost productivity. Costs , and lost productivity. Costs are between $800,000 - $2 are between $800,000 - $2 million over a lifetime for each million over a lifetime for each individual with FAS.individual with FAS.

• Socially — relative to Socially — relative to delinquency and to emotional delinquency and to emotional drains on involved families.drains on involved families.

??????How much is too muchHow much is too much

??????

How much alcohol is in a drink?How much alcohol is in a drink?

12 oz beer = 5 oz wine = shot of liquor12 oz beer = 5 oz wine = shot of liquor

Each contains the same amount of alcoholEach contains the same amount of alcohol in a mixed drinkin a mixed drink

Some drinks contain more Some drinks contain more than a “serving” of alcoholthan a “serving” of alcohol

WARNINGWARNING

NO ONE KNOWS WHAT A NO ONE KNOWS WHAT A ““SAFE” AMOUNT OFSAFE” AMOUNT OF

ALCOHOL CONSUMPTION ALCOHOL CONSUMPTION DURING PREGNANCYDURING PREGNANCY

MAY BE.MAY BE.

Health advisories Health advisories urge women who urge women who are planning are planning pregnancy pregnancy or are pregnant or are pregnant not to drink alcohol.not to drink alcohol.

Despite warnings, frequent Despite warnings, frequent drinking among pregnant women drinking among pregnant women appears to be increasing. appears to be increasing.

Frequent drinking is defined as 7 Frequent drinking is defined as 7 or more drinks per week or 5 or more or more drinks per week or 5 or more drinks on at least one occasion.drinks on at least one occasion.

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ALCOHOL-RELATED ALCOHOL-RELATED BIRTH DEFECTS BIRTH DEFECTS ARE PREVENTABLEARE PREVENTABLE