Fetal Alcohol Syndrome (FAS)

An Overview


Lauren D. Williams, M.D.

University of Miami School of Medicine




S1.      I.      Introduction


The purpose of this lecture is to give an overview of Fetal Alcohol Syndrome, one of the leading causes of mental retardation in the USA, and one which is highly preventable.


S2.      A. Definition (1)

1.      FAS is a serious developmental disorder caused by prenatal alcohol exposure of the fetus and characterized by:

a)     prenatal and/or postnatal growth retardation

b)     central nervous system dysfunction

c)     characteristic craniofacial abnormalities


S3.     2.     FAS

a)     first described by Lemoine in 1968

b)     term coined by Jones and Smith in 1973


In 1968 Lemoine and his colleagues in Western France first described children born to mothers who drank heavily in pregnancy. They exhibited physical abnormalities particularly in the face, reduced size and problems of behavior and cognition. Little interest was placed on these observations. Then in 1973, Jones and Smith described similar pattern of abnormalities in children of alcoholic mothers and coined the term- Fetal Alcohol Syndrome. It was then the scientific community recognized the potential harm to the fetus that was exposed to alcohol. (1,2)


S4.      3.      Facies in FAS (3)

The discriminating features:

a)      short palpebral fissures

b)      flat midface

c)      short nose

d)      indistinct philtrum

e)      thin upper lip

considered definitive signs of FAS


The associated signs:

a)     epicanthal folds

b)     low nasal bridge

c)     minor ear anomalies

d)     microagnathia

not sufficient to determine the presence of FAS.


Microcephaly is not a facial feature but a central nervous system characteristic. It is important to note that it is not any one characteristic that makes the FAS face distinctive, but rather the “gestalt” or the overall presentation of the facies.(3,4)


S5.      3.      Facies in FAS (cont.)

Eyes and midface of a child with FAS, showing short eye openings and drooping eyelids.  Slow nasal growth in the outward direction from the face results in a crescent shaped fold of skin covering the inner corner of the eye. (5)


S6.      3.      Facies in FAS (cont.)

FAS face showing a long smooth philtrum without ridges.  Slightly short nose and narrow red margin of the upper lip. (5)


S7.      4.      Spectrum of Effects


FAS does not represent all individuals exposed to alcohol in utero but indicates those on the severe end of the spectrum of effects. Some individuals are unaffected while others may have partial expression of FAS referred to as Fetal Alcohol Effects (FAE). FAE is further subdivided into Alcohol Related Birth Defects (ARBD) which primarily presents with physical anomalies and Alcohol Related Neurodevelopmental Disorder (ARND) which has more central nervous system damage. (5)


S8.      B.      Diagnostic Criteria (1)


1.      In 1980 the criteria for diagnosis of FAS were developed by the Fetal Alcohol Study Group of the Research Society on Alcoholism. These criteria were based on the original description of FAS by Jones and Smith in 1973. The three major characteristics in this paradigm are:


a)     prenatal and /or postnatal growth retardation, i.e., weight, length, or head circumference below the 10th percentile when corrected for gestational age

b)     central nervous system dysfunction-signs of neurological abnormalities, developmental delays or cognitive impairment

c)     distinctive facial features with at least two of the following signs

i)      short  palpebral fissure

ii)      poorly developed philtrum

iii)      thin upper lip

iv)      flat midface

v)      microphthalmia

vi)      head circumference below the 3rd percentile


A diagnosis of FAS is based on the presence of one characteristic from (a) and (b) and at least  two from (c).


S9.      C.      Pathogenesis

How does alcohol produce its teratogenic effects? The mechanism(s) for alcohol teratogenicity remains unknown. Several mechanisms have been proposed and include:


1.      Direct toxic effects of alcohol (7,8)

a)     alcohol’s toxic effects on the fetus is related to exposure at critical periods of fetal development

b)     first trimester exposure(embryonic development) generally results in skeletal and visceral anomalies

c)     exposure at later stages of brain development results in behavioral defects


2.      Toxic effects of acetaldehyde (7,8)

a)     first metabolite of alcohol metabolism, rapidly crosses the placenta

b)     more embryotoxic than alcohol


3.      Placental dysmorphology/function (9,10)

a)   placental weight and pathologic changes (e.g. Intervillous thrombi, villitis) have been observed in alcoholic women

b)   above changes believe to alter placental function, particularly transport functions

c)   alcohol causes umbilical vessels to collapse. This results in decreased placental/fetal blood flow. This leads to hypoxia which has been implicated in alcohol induced growth retardation

d)   variable induction of human placental CYP2E1 may play a role in fetal susceptibility to intrauterine alcohol exposure-increases acetaldehyde


4.      Prostaglandin synthesis (7,8)

alcohol can increase prostaglandins which in turn inhibits placental/fetal blood flow


5.      Early cell death (apoptosis) (11)

a)     alcohol causes blockade of N-methyl-D-aspartate (NMDA) glutamate receptors and excessive activation of GABA-A receptors which results in stimulation of apoptosis or early deliberate cell death

b)     vulnerability occurs during synaptogenisis (6 months gestation to several years after birth) and this leads to death of neuronal cells in the developing brain.


S10.    II.      Epidemiology


A.     Incidence

1.     0.26-4.6 per 1000 live births

a)     the incidence of FAS is difficult to estimate as the rates are generally influenced by the population studied (6,12)

b)     the rate is ten times higher in African Americans and Native Americans than that of middle and upper socioeconomic status Americans (13)

2.     In the Seventh Special Report to the U.S. Congress on Alcohol and Health, the incidence of FAS is estimated at 1 to 3 per 1000 live births. The incidence is nearly double that of Down’s syndrome and almost five times that of Spina bifida (14)


S11.    B.      Risk factors

FAS occur in the context of alcohol use during pregnancy. But as noted previously in the spectrum of effects, prenatal alcohol exposure alone is not sufficient to cause FAS in some cases.


1.     Alcohol intake pattern/quantity

a)     bingeing (at least 5 drinks per occasion) is more teratogenic than consumption of the same amount of alcohol over an extended period of time. The more chronic the bingeing, the greater the damage, as exposure is more likely to occur in critical periods of development (1)

b)      the shorter the time period in which alcohol is consumed, the higher the blood alcohol concentration (BAC), which results in greater brain damage (1)

c)      how much alcohol is too much?

There is no safe dose of alcohol in pregnancy. However, all cases of FAS have been diagnosed in alcoholic women (1)


2.   Maternal age/parity

a)      FAS increases as maternal age and parity increase. This may be due to progressively greater blood alcohol blood level associated with increasing age.  Increase parity is associated with increased uterine collagen and elastin content.  This can lead to decreasing blood flow to the fetus, contributing to fetal hypoxia and exacerbation of alcohol effects (1)

b)      older age leads to increased ratio of body fat to water resulting in higher peak blood levels of alcohol (1)

c)      age related differences in absorption may also contribute to different blood alcohol levels and toxicities (1)


3.   Race/Socioeconomic status (SES)

a)      FAS occur in all races but seems to be identified more often among lower SES population (1,4)

b)      lower SES maybe correlated with inadequate diet , higher parity, smoking and abuse of other drugs (15)


4.   Genetic susceptibility

a)      genetic factors influence alcohol metabolism (1)

b)      genotype affects alcohol toxicity with varying sensitivities to in utero exposure (1)

c)      monozygotic twins- concordance rate 100% (15)

d)      dizygotic twins- concordance rate 63% (15)


S12.    III.      Clinical Course


A.      Morphological Abnormalities

1.   newborn/infant-characteristic facies subtle and difficult to assess (3,4)


S13.    A.      Morphological Abnormalities (cont)

2.      Preschool/school age (3,4)

a)      facies more distinguishable

b)     short stature and microcephaly more prominent

c)     thin torso is characteristic


3.      Adolescent (3,4)

a)     increase length of chin and nose may make identification more difficult in adolescence. Facial anomalies are more subtle in adolescence and adults.

b)     thin torso gives way to normal weight-height proportion

c)      prepubertal females may even exhibit plumpness. This modifies the physical phenotype after puberty

d)     puberty may be delayed in males


S14.    Slide showing patient with FAS at age 8 and 18. (3)


S15.    A.      Morphological Abnormalities (cont)

1.      Adult (3,4)

a)      in some adults the face becomes normalized, others retain some of the characteristic facial anomalies e.g. The short palprebral fissure, thin upper lip, smooth philtrum


S16.    B.      Neurobehavioral Effects


1.   Newborn/Infant (4)

a)      disturbed sleep patterns

b)      excessive arousal

c)      feeding difficulties and failure to thrive

2.   Preschool/School Age (3,1)

a)      hyperactivity may be found in up to 80% of children

b)      attentional problems

c)      impaired cognitive function- mental retardation occur in about half of FAS patients (IQ less than 60)


S17.          3.      Adolescence (3,16)

a)      continue to have significant impairment in academic functioning, particularly math skills

b)      severe impairment of their math skills leads to difficulty with independent living, poor judgment and dysfunctional lives

c)      difficulty with abstractions like time and space, cause and effect, and generalizing from one situation to the next

d)      conduct problems such as lying and defiance occur in a number of these individuals


S18.          4.      Adulthood (3)

a)      mental problems constitute the most severe manifestation, also have intellectual retardation

b)      persistent behavior problems that interfere with their intellectual function and even their manual skills, unable to focus on activities.

c)      IQ remains stable over time

d)      spatial memory problems are particularly notable, this results in failure to perceive social cues


S19.    C.      Secondary Disabilities (3,16)

1.      school failure

2.      delinquency

3.      difficulty with employment

4.      difficulty with independent living


The more severe the presentation of the individuals with prenatal alcohol exposure, the more often they required special education, were temporarily, or permanently taken into care.  In adulthood, maladaptive behaviors present the greatest challenge. These individuals are at risk for victimization, joblessness, and homelessness


S20.    IV.      Treatment Interventions


A.      Medical Care

1.   depends on presenting symptomatology rather than diagnosis of FAS itself

2.     generally, routine medical care is all that is needed (4)

3.     specific problems addressed individually e.g. Cardiac defects, skeletal abnormalities (1)

4.     growth deficiency- although a part of FAS, other medical causes of failure to thrive should be excluded . Catch up growth is generally not observed (1, 4)


B.      Cognitive rehabilitation and special education

Use of compensation strategies for areas of deficit (e.g. problem solving) and attempts to ameliorate these directly (16,17)


C.      Structured environment/supervision

Behavioral strategies used in a highly structured environment, concrete rules and regulations and close caretaker supervision may help (16,17)


S21.    V.      Prevention


A.      Identification

1.      history

2.      screening instruments – AUDIT, TWEAK (4,18,19)

T = tolerance

W = worried

E = eye-openers

A = amnesia (blackouts)

K (c) = cut-down


S22.          3.            biological markers(20,21,22)

     -gamma-glutamyl transpeptidase(GGT)

     -carbohydrate-deficient transferring(CDT)

     -mean corpuscular volume(MCV)


FAS is a preventable consequence of alcohol consumption during pregnancy. Drinking history should be routine during a woman’s prenatal visit to her health care provider. Because of the stigma regarding drinking in women, they are known to under report alcohol use.  As a result screening instruments  (AUDIT and TWEAK ) and biological markers (GGT, CDT MCV) may be helpful in identifying high risk women (4,19,20,21,22). The TWEAK test is easy to administer and requires no training.


T-tolerance: “How many drinks can you hold?”


W-worried: “Have close friends or relatives worried or complained about your drinking in the past year?”


E-eye-openers: “Do you sometimes take a drink in the morning when you first get up?”


A-amnesia(blackouts): “ Has a friend or family member ever told you about things you said or did while you were drinking that you could not remember?”


K(C)-cut down:” Do you sometimes feel the need to cut down on your drinking?”


A 7-point scale is used to score the test. If a woman can hold five or more drinks without passing out she is positive for tolerance and scores 2 points. A positive response to the worry question also scores 2 points. Each of the last three questions scores one point for positive responses. A total of three or more points indicates the woman is likely to be a heavy or problem drinker.


GGT- detect ~ 40-60% of alcohol abusing and dependent individuals. About 80% level of specificity. Consumption of greater than 40 grams of alcohol per day elevates GGT levels and after cessation of alcohol use, values return to normal in ~ 4-5 weeks.


CDT- is a deglycosylated form of the liver synthesized protein, transferring. It is produced during heavy alcohol use(50-80 g/day) for seven days and remains elevated for about two weeks after alcohol consumption stops. CDT test is said to be highly specific and sensitive.


MCV- is increased, generally higher than 90 cubic microns.


The biological markers may not identify pregnant females who consume potentially harmful but lesser quantities of alcohol.


S23.    B.      Intervention (23)

1.   universal approaches – aimed at all females of childbearing age regardless of risk of FAS.  Universal prevention strategies are used to increase public awareness of the risk of drinking during pregnancy.  Media campaigns, messages in reading material, radio and television advertisements and labeling of alcoholic beverages are examples of universal prevention strategies.  Labeling of alcoholic beverage is reported to have a greater effect on lighter than heavier drinkers who are at the greatest risk of having a child with FAS.  Awareness of risks of alcohol use in pregnancy does not necessarily translate into changes in drinking behaviors.

2.   selective strategies – targets women who are at increased increase of FAS.  These women should be identified earlier, as discussed previously, through screening.  Counseling should occur ideally prior to conception and continue throughout the pregnancy with total abstinence being the goal.  Women who receive therapy and case management services were more likely to remain abstinent than those who did not receive these services.

3.   indicated approaches – targeted to women at the highest risk, especial those who have had one child with FAS.  Brief interventions therapy, referral to special programs, and changes in environment (halfway houses, shelter living) are examples of indicated approaches interventions.


S24.    VI.      Summary



1.      severe developmental disability resulting from prenatal alcohol exposure

2.      one of the leading causes of mental retardation

3.   not just a childhood problem

4.      early diagnosis and intervention important

5.      preventable


FAS is a severe developmental disability resulting from drinking during pregnancy. It is one of the leading causes of mental retardation. It is not just a childhood problem as the cognitive/emotional deficits persist through to adulthood resulting in difficulties in many aspects of the affected individual’s life. Early diagnosis and intervention are important so that appropriate levels of care can be given to decrease handicaps and improve life adaptation.


FAS is not a natural phenomenon and is highly preventable.




1.   Abel E: Fetal Alcohol Abuse Syndrome. Plenum Press, New York 1998


2.   Roebuck TM, Mattson SN, Riley EP: A Review of the Nueroanatomical Findings in Children with Fetal Alcohol Syndrome or Prenatal Exposure to Alcohol. Alcohol Clin Exp Res 1998; 22: 339-344


3.      Streissguth AP: A Long Term Perspective of FAS. Alcohol Health & Research World 1994; 18: 74-81


4.   Stratton K, Howe C, Battaglia F: Fetal Alcohol Syndrome. Diagnosis, Epidemiology,Prevention and Treatment. National Academy Press 1996


5.      Aase John M.: Clinical Recognition of FAS. Difficulties of Detection and Diagnosis. Alcohol Health & Research World 1994; 18: 5-9


6.      Sampson PD, Streissguth AP, Bookstein FL, Little RE, Sterling CK, Dehaene P, Hanson JN: Incidence of Fetal Alcohol Syndrome and Prevalence of Alcohol Related Neurodevelopmental Disorder.Teratology 1997; 56: 317-326


7.      Phillips DK, Henderson GI, Schenker S: Pathogenesis of Fetal Alcohol Syndrome. Alcohol Health & Research World 1989; 13: 219-237


8.      Schenker S, Becker HC, Randall CL, Phillips DK, Baskin GS, Henderson GI: Fetal Alcohol Syndrome: Current Status of Pathogenesis. Alcohol Clin Exp Res 1990; 14: 635-647


9.      Randall CL, Ekbald V, Anton RF: Perspective on the Pathophysiology of Fetal Alcohol Syndrome. Alcohol Clin Exp Res 1990; 14: 807-812


10. Rasheed A, Hines RN, McCarver-May GD: Variation in Induction of Human Placental CYP2E1: Possible Role in Susceptibility to Fetal Alcohol Syndrome? Toxicology and Applied Pharmacology 1997; 144: 396-400


11. Ikonomidou C, Bittigau P, Ishimaru MJ, Woziniak DF, Koch C, Genz K, Price MT, Stefovska V, Horster F, Tenkova T, Dikraniank K, Olney JN: Ethanol-Induced Apoptic Nuerodegeneration and Fetal Alcohol Syndrome. Science February 2000; 287: 1056-1060


12. Abel EL: An Update on Incidence of FAS: FAS is not An Equal Opportunity Birth Defect. Neurotoxicology and Teratology 1995; 17: 437-443


13. Budd K, Ross-Alaolmolki K, Zella RA: Two Prenatal Alcohol use Screening Instruments compared with a Physiologic Measure. JOGNN March/April 2000; 29: 129-136


14. National Institute on Alcohol Abuse and Alcoholism: Seventh Special Report to the US Congress on Alcohol and Health. Rockville, MD, US Department of Health and Human Services,1990


15. Bagheri M, Burd L, Mantsolf JT, Klug MG: Fetal Alcohol Syndrome: Maternal and Neonatal Characteristics. J. Perinatal Med 1998; 26: 263-269


16. Streissugth AP, Aase JM, Clarren CK, Randels SP, LaDue RA, Smith DF: Fetal Alcohol Syndrome in Adolescents and Adults. JAMA 1991; 265: 1961-1967


17. Connor Paul D, Streissguth  Ann P: Effects of Prenatal Exposure to Alcohol    Across the Life Span.  Alcohol Health & Research World 1996; 20:170-174


18. Tavenner Mitchell K, Donaldson T: Preventing Fetal Alcohol Syndrome. Journal of Pediatric Health Care March/April 1999;13: 87-89


19. Russel Marcia: New Assessment Tools for Risk Drinking During Pregnancy. T-ACE, TWEAK, and Others. Alcohol Health & Research World 1994; 18: 55-61


20. Stoler JM, Huntington KS, Peterson CM, Peterson KP, Daniel P, Aboagye KK, Lierberman E, Ryan L, Holmes LB: The Prenatal Detection of Significant Alcohol Exposure with Maternal Blood Markers. J. Pediatr  September 1998;133: 346-352


21. Anton Raymond F, Moak Darlene H : Carbohydrate-Deficient Transferrin and Gamma-Glutamyltranferase as Markers of Heavy Alcohol Consumption: Gender Differences. Alcohol Clin Exp Res 1994; 18: 747-754


22. Schuckit Marc A. Drug and Alcohol Abuse. A Clinical Guide to Diagnosis and Treatment. Plenum Publishers, New York.2000


23. National Institute on Alcohol Abuse and Alcoholism: Tenth Special Report to the US Congress on Alcohol and Health. Rockville, MD, US Department of Health and Human Services,2000