Fetal Alcohol Syndrome – Pathophysiology
The effects of alcohol consumption have been shown to cause malformations of cardiac, skeletal, ocular, auditory systems and cognitive function. Even a small amount of alcohol during pregnancy can have an effect on the fetus health since the underdeveloped organs are unable to cope with the toxins produced.
How quickly alcohol is metabolized depends on size and gender, food intake, and overall health status. Women are at higher risk for alcoholic diseases than men, because women’s bodies tend to absorb more alcohol and take longer to process it. Among pregnant women, 1 in 10 reported alcohol use and 1 in 33 reported binge drinking in the past 30 days. This is a significant factor in the development of Fetal alcohol Syndrome (FAS).
Alcohol is absorbed into the bloodstream through the intestinal lining and readily distributed throughout the body. It is one of the most dangerous tetragons to fetal health. When alcohol is consumed, the body produces the enzyme alcohol dehydrogenase (ADH) in the liver. ADH interacts with the alcohol in the stomach and liver in an attempt to detoxify the substance. Some of these intermediate metabolites can have very harmful effects on the growth and health of the fetus. ADH then transforms ethanol into a toxic compound called acetaldehyde (CH3CHO), a known carcinogen. The toxic and other adverse effects of alcohol on organs and tissues in humans are largely a consequence of this conversion to acetaldehyde, with the formation of reactive oxygen and nitrogen compounds. Acetaldehyde has been shown to damage DNA and some research implies that a single binge-drinking dose of alcohol during pregnancy may be sufficient to cause permanent damage to a baby’s genome.
The maternal ingestion of alcohol passes easily through the placenta, with alcohol levels in the fetus equal to or greater than the mother and are eliminated at a slower rate. This in turn, prolongs the effects on the fetus. Moreover, amniotic fluid may store alcohol and its byproducts, prolonging fetal exposure. Exposure to alcohol, and therefore ADH and acetaldehyde is thought to cause cell death by disrupting the development of nerve cells in the brain. These toxins are also believed to become concentrated in neurological tissue. A study in mice showed there was a reduction in brain size and decreased in neuronal cell numbers in the cortex and impaired cognitive function in mice exposed to alcohol during the time of synaptogenesis. Other animal studies show that fetuses of pregnant animals showed delayed ossification and skeletal malformations of the face and limbs. This interaction with acetaldehyde may be the cause of cranial and facial abnormalities seen in children with FAS.
Another effect of alcohol consumption is vasoconstriction. This in turn leads to decreased placental blood flow with subsequent decrease in the delivery of amino acids, glucose, zinc, folate and oxygen across the placental barrier. Levels of erythropoietin in newborns have shown a state of chronic hypoxia thought to be caused by poor placental oxygenation. The decreased levels of zinc and folate may also be caused by poor nutritional intake by the mother in conjunction with alcohol consumption. Low levels of maternal folate are known to increase the risk of neuronal deficits in fetuses. Decreased placental blood flow may also explain the intrauterine growth retardation and low birth weights of children with FAS.
References:
Lee, D.H. et al. (2016). Effects of postnatal alcohol exposure on hippocampal gene expression and learning in adult mice. Genes and Genetic Systems, 90 (6), 335-342. Retrieved from https://www.jstage.jst.go.jp/article/ggs/90/6/90_15-00026/_html.
Addressing Fetal Alcohol Spectrum Disorders (FASD). SAMHSA. Retrieved from https://store.samhsa.gov/shin/content/SMA13-4803/TIP58_LiteratureReview….
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