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.