ALCOHOL AS A TERATOGEN- FETAL ALCOHOL SYNDROME Fetal Alcohol Syndrome

In 1973, K.L. Jones, D.W. Smith and their colleagues realized that a substantial number of children affected by prenatal exposure to alcohol exhibited a characteristic set of facial abnormalities, growth deficiencies, and psychomotor disorders. They named this characteristic covariance Fetal Alcohol Syndrome (FAS) (Jones et al. 1973). There were so many different definitions for FAS. The Fetal Alcohol Study Group of the Research Society on Alcoholism (Rosett 1980) requires presence of signs in each of three following categories:

prenatal and/or postnatal growth retardation (weight, length, and/or head circumference below the tenth percentile corrected for gestational age) central nervous system involvement (indications of neurological abnormality, developmental delay, or intellectual impairment) facial abnormalities (with at least two of the following signs: head circumference below the third percentile; narrow eye slits; flat and long upper lip; underdeveloped midface; and flattened nose bridge)

Etiology: There is no safe dose of alcohol in pregnancy and there does not appear to be a safe period during
pregnancy for drinking. It has been shown that mothers who drink earlier in pregnancy and drink more alcohol (four to ten drinks) have more children with fully expressed FAS. Mothers who drink less (one to two drinks) and in late gestation have an increased frequency of premature deliveries and deliveries of babies small for gestational age. Risk factors important when assessing the effects of alcohol exposure on fetal brain development include maternal drinking patterns, differences in maternal metabolism, differences in genetic susceptibility, timing of the alcohol consumption during pregnancy, and variation in the vulnerability of different brain regions. Ethanol is the causative agent of Fetal Alcohol Syndrome (FAS). FAS is seen in approximately 2 in 1000 live births depending upon culture and socioeconomic status. FAS does seem to be dose dependant in that greater amounts of alcohol consumed increases the chances of having an FAS child. The following are the areas of brain that are affected by alcohol consumption. Fig 1: Areas of brain that can be damaged in utero by maternal alcohol consumption

Source: From Vol. 18, No. 1, 1994 of the journal Alcohol Health & Research World.

Symptoms & Signs:

The most serious characteristics of FASD are the invisible symptoms of neurological damage that results from prenatal exposure to alcohol, These symptoms include: Attention deficits Memory deficits Hyperactivity Difficulty with abstract concepts Inability to manage money Poor problem solving skills Difficulty learning from consequences Immature social behavior Inappropriately friendly to strangers Lack of control over emotions Poor impulse control Poor judgment

Fig 2 : FAS Facial Characteristics. Babies diagnosed with Fetal Alcohol Syndrome may have some but not all of the following physiological characteristics: Small birth weight Small head circumference Small, widely spaced eyes Flat midface Short, upturned nose Smooth, wide philtrum Thin upper lip
Note: Facial characteristics may not be as apparent immediately after birth or during adolescence or adulthood as they are between the ages of two and ten. Facial characteristics may not be present at all if the mother did not drink during the brief period that the midface was forming - around the 20th day of pregnancy.

Source: http:www.come-over.to/FAS/faschar.htm 12/7/2003.

Mechanism of Action: Alcohol is able to permeate the placenta and enter fetal circulatory system, thereby
causing developmental abnormalities. Ethanol impairs placental blood flow to the fetus by constricting blood vessels: inducing hypoxia and fetal malnutrition. Alcohol rapidly crosses the placenta and blood-brain barrier of the fetus. The damage produced depends on gestational period, dosage, and chronicity of abuse. There are many proposed mechanisms of action for ethanol such as altered neural crest cell migration/increased neural crest cell death or general cell death by superoxide radial lysis of cells, mitochondrial cell dysfunction, may inhibit growth factors regulating cell proliferation and survival, effects on Glial cells, effects on development of neurotransmitter systems, effects on cell adhesion and altered developmental regulation of gene expression. Most of these proposed mechanisms need to be proved. Recent studies by scientists of Harvard university in October 2002 proved that alcohol interferes with L1 adhesion molecules which are useful in cell adhesion process of development, and hinders the cell to cell attachments. They also found that the active peptides from NAP and SAL (Brain proteins) protect nerve cells against a variety of toxins and alcohol. There's still a lot of research need to be done to finalize the mechanisms of action of alcohol in the FAS causation.

Diagnosis: Diagnosis is based on maternal history of alcohol consumption during pregnancy, abnormalities involving
facial features, growth deficiency, and central nervous system dysfunction. Institute of Medicine developed criteria to diagnose fetal alcohol related problems. 1.FAS with confirmed maternal alcohol exposure: Patients in this category have the classic triad of growth retardation, characteristic facial dysmorphology and neurodevelopmental abnormalities. This is often defined as full-blown FAS 2.FAS without confirmed maternal alcohol exposure: If the triad described in category 1 is present, a diagnosis of FAS is possible even without confirmed maternal drinking

3.Partial FAS with confirmed maternal alcohol exposure: Such patients may have only some of the characteristic facial anomalies plus growth retardation or central nervous system neurodevelopmental abnormalities or behavioral/cognitive abnormalities 4.FAS with confirmed maternal alcohol exposure and alcohol related birth defects: Patients in this category will have some congenital anomalies as a result of alcohol toxicity 5.FAS with confirmed maternal alcohol exposure and alcohol related neurodevelopmental disorder: Patients in this category will have evidence of central nervous system neurodevelopmental abnormalities or a complex pattern of behavioral/cognitive abnormalities, or both, but not necessarily any obvious physical changes

Fig 3: Neonatal Meconium assay for fatty acid ethyl esters (FAEEs). Source: JAMC, 25 NOV 2003, 169 (11), 1184.

Treatment & Prevention:

Treatment: Very little research done on these topics. Birth defects related to alcohol use are permanent. Surgery can repair some of the physical problems, and schools and day care centers offer programs to improve mental and physical development. However, children born with FAS remain below average in physical and mental development throughout their lives. Many children with FAS treated for their individual symptoms (e.g. stimulants for ADHD) and animal data indicates that early intervention with environmental variables might have a beneficial effect.

Prevention: Primary Prevention: In the case of FAS, this would include informing the public, particularly young people, about the dangers of drinking during pregnancy and on a broader level, addressing determinants of health. Secondary Prevention: Strategies should include screening and early intervention programs and services for pregnant women and women of childbearing potential who may be at risk for having a child with FAS Tertiary Prevention: Strategies should include diagnosis and programs designed specifically for children with FAS and their caregivers, as well as treatment for women and their partners who already have one FAS child and plan to have more children. Early recognition of women who drink alcohol during pregnancy and appropriate counseling are the corner stones of prevention. health professional play a key role in reducing the risks associated with alcohol use during pregnancy

Surveillance Programs:
CDC is conducting monitoring of FAS in 5 US states and in South Africa. CDC's FAS Surveillance Network (FASSNet) is currently conducting monitoring in Alaska, Arizona, Colorado, New York and Wisconsin. These state programs combine several data sources within each state to improve likelihood of finding all children with FAS in different populations and across various geographical areas. the state projects also educate healthcare professionals about FAS in order to increase early identification of children with FAS; increase referrals to necessary social, educational and medical services; and improve documentation of health and cognitive problems in the children's records. Wisconsin Fetal Alcohol Syndrome Screening Project: The Wisconsin Fetal Alcohol Syndrome (FAS) Screening Project (WFASSP) is a population-based triage ascertainment system with four screen levels. It is one of five projects funded by CDC to help determine the prevalence of FAS in the United States. The specific aim of this project is to try out the screening test so that there is a good way to identify children with FAS early. The study team also wants to find out how common FAS is and to find ways of helping these children to develop as normally as possible. Besides finding out about the screening test, and how common FAS is, this study aims to identify children who may have FAS so that they can be referred to services and family support. Children with this condition benefit from early intervention.

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