We already know that pregnant mothers who drink alcohol risk harming their baby's development. What we do not know is how much, if any, alcohol is acceptable during pregnancy. Nor do we know, relative to brain development, exactly how toxic alcohol may be at different stages. But now, scientists may be one step closer to understanding how alcohol hampers the brain development of exposed fetuses during the third trimester.
"Alcohol is a 'dirty drug' as it affects a variety of systems in the brain," said James R. West, Professor and Head of Anatomy and Neuroscience at the Texas A&M University Health Science Center. "Alcohol does different things at different times in different parts of the brain. During the third trimester, for example, alcohol kills some kinds of brain cells, but earlier in development, alcohol interferes with cell division." Alcohol's itinerant nature makes it a challenge to track whereas a drug like cocaine, said West, is much easier to study because it specifically affects the absorption of a neurotransmitter called dopamine.
Researchers discovered that high levels of alcohol during late fetal development kill an important group of neurons called Purkinje cells, which act to filter and synthesize information leaving the cerebellum for other brain regions. As reported in the October issue of Alcoholism: Clinical & Experimental Research, Purkinje cells need a trophic (growth-enhancing) factor called Glial Derived Neurotrophic Factor (GDNF) to survive. GDNF is one of the key growth factors necessary for Purkinje cell survival. Alcohol deprives Purkinje cells of GDNF, thereby depriving them of a means of survival.
West and his colleagues used rats to model alcohol effects on fetal brain development. Although human gestation lasts approximately nine months, compared to 22 days for a rat, West noted that all mammals pass through the same stages of brain development despite the different timing of those stages. In other words, what happens in the fetal brain during the third trimester in humans happens in a baby rat brain during the early post-natal period.
The alcohol dosages used in the study were high in order to mimic heavy alcohol use during pregnancy. "Binge drinking is extremely important in terms of producing brain damage," said West. "For example, drinking four cans of beer in an hour can cause more damage than drinking six cans of beer over 12 hours." And even though researchers disagree about the incidence of children who are born with FAS, said West, "that number, whatever it may be, is just the tip of the iceberg."
Fetal Alcohol Syndrome (FAS)
FAS is the name given to a group of physical and mental birth defects caused by a woman drinking heavily during pregnancy. It is characterized by facial abnormalities, growth retardation, and central nervous system problems. Children with FAS may have problems with learning, memory, attention span, problem solving, speech, learning and behavior. FAS is an irreversible, lifelong condition.
According to the Centers for Disease Control and Prevention, the prevalence of FAS is not known. Study results using different methods and data sources show prevalence rates for the United States that range from three to 22 cases per 10,000 births. This means that each year in the U.S., between 1,300 and 8,800 children are born with FAS. The National Organization on Fetal Alcohol Syndrome estimates that the institutional and medical costs for one child with FAS are $1.4 million during their lifetime.
"Almost everyone will agree that alcohol abuse during pregnancy is the biggest leading cause of mental retardation that we know about," said West. "But when people at cocktail parties ask me, 'How much can you drink and have it not cause damage,?' I have to answer that we don't know. The lower limit has not been determined."
"The data on lower level exposure is certainly equivocal," said Professor Edward P. Riley of the Department of Psychology, San Diego State University. "Some people believe it and some people don't." Riley observed that prenatal alcohol exposure likely interacts with a number of factors, such as genetics, nutrition, socio-economic status, prenatal care, etc. "But since we don't know how much is safe," he continued, "the most prudent course for any individual person would be to avoid alcohol while pregnant. They don't know that they may be one of those people who are susceptible -- because of other risk factors."
Another complication is the lack of clear identification 'markers' for FAS, said Claire D. Coles, Associate Professor of Psychiatry and Behavioral Science, Emory University School of Medicine. "If you suspect something like Down's Syndrome because of a child's facial features," she said, "you can draw blood and test for an associated chromosomal abnormality." But FAS shares both physical and neurological markers with other developmental and neurological disorders, she explained, which often makes FAS difficult to identify.
West said that researchers are still trying to figure out the mechanisms of how alcohol affects fetal brain development. "It's important to understand that alcohol damages the developing brain in a number of ways," said West. "We think this study provides an important piece to the puzzle, but it's just that, one piece of a very complex puzzle."
Co-authors of the Alcoholism: Clinical & Experimental Research paper included: Robert E. McAlhany Jr. of the Texas A&M University Health Science Center; Rajesh C. Miranda of the Texas A&M University Health Science Center and Texas A&M University Center for Environmental and Rural Health, College Station; and Richard H. Finnell of the Texas A&M College of Veterinary Medicine and Texas A&M University Center for Environmental and Rural Health, College Station. The study was funded in part by the National Institutes of Health.