If a mother consumes alcohol during her pregnancy, she puts her unborn child at risk of facial anomalies, neurodevelopmental delay and even spontaneous abortion. Although the prevalence of FAS in the US is approximately 0.2-2.0 cases per 1,000 live births, FAS actually occurs in less than 10% of pregnancies, even if the woman drinks heavily throughout. If FAS does not impact all pregnant woman equally or to the same degree, then understanding why some women have increased risk factors for FAS is crucial. There are many cellular events during development that can be impacted by the presence of alcohol, which includes cell death, decrease in cell binding and impacts to molecules that induce growth in the embryo. It seems that the malformations that impact the fetus shows organ selectivity.
The damage induced by prenatal alcohol (PAE) is not hereditary. That means it can not be passed down from the mother to her child, the damage arises from direct contact with toxic substances during development. However, there does seem to be a genetic component to the severity of the damage that occurs. This may be why two mothers can drink the same amount at the same time during pregnancy, and one child will have severe effects and one child will have little to no impact. In a study done on mice, the severity of the effects was correlated with the alcohol concentration in the dam’s blood. The alcohol concentration would depend on the levels of alcohol dehydrogenase[ADH (an enzyme that assists in the breakdown of alcohol)], which would be controlled at the genomic level (by the genes). This suggests that mother’s who metabolize (break down) alcohol at different rates may lead to differences in fetal alcohol exposure, and differences in the level of resulting FAS symptoms.
After a mother drinks alcohol, it is quickly absorbed by the intestines. The rate of absorption depends on the amount, the concentration and the timing of the drink. Over 90% of the ingested alcohol is metabolized by the liver. The genes that code for the enzymes that remove the alcohol in the liver vary in their catalytic activity. This means the rate at which the enzyme works to remove the alcohol can vary depending on the genes that control it. These features and their different frequency in various ethnic populations may act as a protective/enhancing factor towards alcohol abuse and alcohol-related pathologies, such as FAS.
A study done on a mixed race population in South Africa found a prevalence of 39-46 FAS cases out of 1,000 births. They found a variation on the allele that codes for ALDH (ALDH2*2). It seemed that either a mother or a fetus with the ALDH2*2 variation had a protective quality against FAS, and those with the other variations on the gene did not have the same protective factors. It is important to note that the ALDH2*2 is more catalytically active than the other variants. This means the enzyme coded for by the ALDH2*2 works to break down alcohol faster than the other variations of the gene. Breaking down the alcohol consumed by the mother faster, would decrease the concentration of alcohol the fetus is exposed to, and possible provide protective factors against the effects of FAS. When the mothers took a breathalyzer test, it was found the FAS mothers had a higher breath alcohol concentration compared to the non-FAS mothers.
When
a pregnant woman ingests alcohol, it is delivered directly to her fetus through the placental barrier. The placental barrier is not a natural barrier to alcohol, and has the ability to let alcohol pass into the fetal circulation. Although the placenta does have enzymatic activity, the levels are much lower in comparison to the levels present in the mother’s blood. The fetus can remove some toxins (like alcohol) from the blood on their own, but not on the same scale or at the same rate as the mother could. By having a decrease in the enzymatic activity, the fetus would take longer to remove the alcohol from their blood, and the longer the alcohol in present in their blood stream, the greater the possibility of ending up with alcohol-related birth defects.
There are many potential factors that go into a child developing FAS. However, by examining the genetic basis behind it, more education and awareness can be generated about potential causes of the disease. More research would be needed to determine if the genes impacted are controlled by multiple factors, or just one.
Article Reference
Gemma, S., S. Vichi & E. Testai (2007). Metabolic and Genetic Factors Contributing to Alcohol Induced Effects and Fetal Alcohol Syndrome. Neuroscience and Behavioural Reviews. 31(2): 221-229.
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