Risk factors influencing FAS and FASD Conditions
The variation in the range of phenotypes of individuals with PAE suggests that alcohol’s teratogenic effects can be moderated or exacerbated by other variables. Not every woman who drinks heavily during pregnancy will give birth to a child with an FASD (Warren and Foudin, 2001), and not all children with an FASD have the same deficits (Bertrand et al., 2004). In fact, there have been reports of discordance among twin pairs in regards to FAS (Warren and Li, 2005 ; Streissguth and Dehaene, 1993).
Numerous biological and environmental factors have been shown to influence the effects of alcohol on the developing fetus, with the most obvious and important factors being those related to the nature of the PAE. The amount of alcohol consumed is highly correlated with the severity of outcome; typically, a higher level of alcohol consumption, along with longer duration of exposure, will generally lead to more adverse effects (Bonthius and West, 1988 ; Maier, Chen, and West, 1996). However, a linear relationship between dosage and severity may not always be expected. Studies in both animals and humans have revealed that the pattern of alcohol consumption may moderate dose effects. A binge-like exposure results in more severe neuropathology and behavioral alterations than does chronic exposure (Bonthius, Goodlett, and West, 1988), and those women who binge drink are at a higher risk of having a child with neurobehavioral deficits than those who drink chronically during pregnancy (Maier and West, 2001). In fact, Jacobson et al. (1998) have proposed that describing consumption by the average number of drinks per occasion is more useful in predicting outcome than the average number of drinks per week. A high peak blood alcohol concentration induced during binge episodes appears to be a significant risk factor for prenatal injury (Streissguth et al., 1993 ; Warren and Foudin, 2001).
Phenotype can also differ as a function of the developmental timing of alcohol exposure. For example, exposure during different critical periods of development will strongly influence not only the specific systems affected but also the severity of the deficit, as different organ systems develop at different rates and times during gestation.
The clearest example of this “critical period” relates to the facial features required for a diagnosis of FAS. Studies in mice have shown the dysmorphic facies to be a result of alcohol exposure during a limited period of gestation, the human equivalent of which would be gestation weeks 3 and 4 (Sulik, 2005). Alcohol exposure during the first trimester interferes with the proliferation, migration, and differentiation of precursor cells in the cerebral cortex (Cook, Keiner, and Yen, 1990 ; Miller, 1993 ; Miller, 1996); however, exposures at other times might have other effects, such as altered synapse formation or changes in myelinization.
Alcohol exposure during the third trimester interferes with the development of specific brain structures, including the hippocampus, cerebellum, and prefrontal cortex (Livy et al., 2003 ; Maier et al., 1999 ; Maier, Miller, and West, 1999). Thus, alcohol’s teratogenicity interferes with various ontogenetic stages of neural development. Consequently, the pattern of structural and functional abnormalities will vary depending on alcohol exposure during particular critical periods of development, as different aspects of the developing nervous system become more or less vulnerable to alcohol’s toxicity.
Fetal Alcohol Syndrome can be diagnosed without knowledge of mother’s alcohol consumption during pregnancy providing all other characteristics necessary to diagnose Fetal Alcohol Syndrome are present.
Partial Fetal Alcohol Syndrome (pFAS) is a term used to describe individuals who do not have all of the characteristics necessary to receive a diagnosis of FAS. To be described as having Partial Fetal Alcohol Syndrome, the following criteria are necessary:
-knowledge that there was alcohol consumption during pregnancy
-some of the facial anomalies which are characteristic of Fetal Alcohol Syndrome
One of the following three characteristics:
-growth retardation in at least one of the following ways:
-low birth weight,
-weight loss that is not due to poor nutrition,
-low weight to height ratio
Central nervous system abnormalities in at least one of the following areas:
-small head size at birth,
-structural abnormalities in the brain,
-poor fine motor skills,
-poor hand-eye coordination,
-hearing loss which is not related to injury or illness,
and/or poor gait when walking.
A pattern of behaviour or cognitive abnormalities that are not age-appropriate and cannot be explained by heredity or environment alone.
These abnormalities include:
-poor school performance,
-deficits in language (both expression and comprehension) and specific mathematical skills,
-poor abstract thinking ability,
-poor impulse control,
-inability to interpret and respond to social situations, problems with memory, attention, and judgment .
The genetic background of both the mother and fetus is another important factor that influences the effect of alcohol on the developing fetus. Genes affect the metabolism of alcohol and an organism’s functional sensitivity to alcohol. For example, particular alleles for alcohol dehydrogenase (ADH1B*2 and ADH1B *3) allow for a faster alcohol metabolism, thereby reducing the risk of exposure to the fetus (McCarver et al., 1997).
Environmental factors related to prenatal care and nutrition are also important risk modifiers in FASD. Many mothers who drink during pregnancy do not receive proper prenatal care and nutrition. A complex interaction exists between nutrition and alcohol: food affects the rate of alcohol absorption and metabolism (Sedman et al., 1976), but alcohol often alters the requirement for and absorption of nutrients (Morgan and Levine, 1988). Alcohol exposure in combination with low nutrient levels increases the risk for FASD. Other risk factors for FASD include polysubstance abuse, maternal age, ethnicity, and socioeconomic status (Warren and Foudin, 2001).
Five factors affect how severe the damage will be to the unborn baby:
1. The time in the pregnancy at which alcohol is consumed:
Damage to the fetus can occur anytime during the pregnancy. Alcohol
may affect whatever growth or development is taking place at the time
of the mother’s consumption. The unborn baby’s brain develops
throughout the pregnancy and is always vulnerable to alcohol.
2. The amount of alcohol consumed during the pregnancy:
There is a significant risk to damage the fetus as well as stillbirth and
spontaneous abortion with “heavy” drinking. However, no one knows
how much alcohol a pregnant woman can drink without hurting the baby.
“Binge” drinking (five or more drinks in a drinking episode) sharply
raises the amount of alcohol in the blood and greatly increases the risk
to the baby.
3. Individual susceptibility to alcohol:
Genetic factors determine the baby’s ability to deal with the alcohol in
its system and how quickly the alcohol in the baby’s system can be
broken down.
4. Nutrition:
Alcohol affects how the placenta transfers important nutrients necessary
for fetal growth. Good nutrition for the fetus is important throughout the
entire pregnancy. It is important for women to eat a nutritious diet
including a daily multivitamin with folic acid.
5. Additional Risks:
The damage to the baby because of prenatal alcohol exposure may be
compounded if the mother has poor nutritional status, smokes, is in
poor health, is under increased stress, and/or uses other drugs.
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Tanya T. Nguyen, Jennifer Coppens, and Edward P. Riley
Edited by Edward P. Riley, Sterling Clarren, Joanne Weinberg, and Egon Jonsson
Tanya T Nguyen practices as a Pediatrician in Alhambra, CA.
Jennifer Coppens, Medical Student, University of Alberta
Prof. Dr. Edward P. Riley San Diego State University Center for Behavioral Teratology
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REFERENCES
- Abel, E.L. (1999) Was the fetal alcohol syndrome recognized by the Greeks and Romans? Alcohol Alcohol., 34 (6), 868 – 872.
- Adnams, C.M., Sorour, P., Kalberg, W.O., Kodituwakku, P., Perold, M.D., Kotze, A., September, S., Castle, B., Gossage, J., and May, P.A. (2007) Language and literacy outcomes from a pilot intervention study for children with fetal alcohol spectrum disorders in South Africa. Alcohol, 41 (6), 403 – 414.
- Barry, K.L., Caetano, R., Chang, G., DeJoseph, M.C., Miller, L.A., O’ Connor, M.J., Olson, H.C., Floyd, R.L., Weber, M.K., DeStefano, F., Dolina, S., Leeks, K., and National Task Force on Fetal Alcohol Syndrome and Fetal Alcohol Effect (March 2009) Reducing Alcohol - Exposed Pregnancies: A Report of the National Task Force on Fetal Alcohol Syndrome and Fetal Alcohol Effect, Centers for Disease Control and Prevention, Atlanta, GA.
- Bertrand, J. (2009) Interventions for children with fetal alcohol spectrum disorders (FASDs): overview of findings for five innovative research projects. Res. Dev. Disabil., 30 (5), 986 – 1006.