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Cholesterol could be key to treating fetal alcohol syndrome

March 09, 2007

DURHAM, N.C. — Small amounts of alcohol can interfere with the growth of a fetus, but added cholesterol may help prevent a wide array of neurological and physical defects from alcohol exposure, according to a new study in laboratory fish.

Cholesterol is so important to fetal development that pregnant women who do not have high enough cholesterol levels are at increased risk of having babies with developmental problems, even without consuming alcohol. Researchers at Duke University Medical Center, led by Yin-Xiong Li, MD., Ph.D., found that alcohol, even in small amounts, blocks the ability of cholesterol to orchestrate the complex series of events involved in regulating cell fates and organ development in the embryo. Encouragingly, the researchers also found that giving supplemental cholesterol to zebrafish embryos exposed to alcohol restored normal development.

Fetal alcohol syndrome is a term to describe an array of developmental defects affecting the nervous and cardiovascular systems. The syndrome also can lead to growth retardation, facial abnormalities and lowered mental functioning. It is estimated that approximately 100 babies are born in the United States each day with some degree of alcohol induced birth defects, at an annual cost of $10 billion to the health care system.

What alcohol does is interfere with a precisely orchestrated biochemical signaling pathway that guides fetal development. Cholesterol is essential for a single pathway that governs the pattern of tissue development and it is vulnerable to the effects of alcohol.

"This new insight into the molecular basis of fetal alcohol syndrome could have far-reaching implications and suggests new prenatal care that might prevent the developmental defects caused by alcohol consumed during pregnancy," Li said.

The researchers published the findings in the March 2007 issue of the journal Laboratory Investigation. The research was supported by the National Institutes of Health and the American Heart Association.

Li said that the keys to fetal alcohol syndrome's severity are the amount of alcohol consumed, the duration of the consumption and the timing of the pregnancy. For example, alcohol consumed by a mother with a one-month-old fetus could alter the development of the brain; at four to eight weeks, facial structures, heart and eyesight could be affected. Two to three months into fetal development, alcohol consumption could lead to the growth of extra digits.

"The amount of alcohol consumed is important as well," Li said. "Even the equivalent of one 12-ounce beer, consumed at the wrong time, could disrupt the signaling pathway and lead to a defect."

The team also found that increased amounts of alcohol exposure by the fetus led to increased severity of the syndrome.

Li pointed out that the findings could have other theoretical implications as well. He said giving alcoholics supplemental cholesterol could help slow down or prevent the occurrence of alcoholic liver disease, even chronic alcoholic induced cirrhosis, characterized by replacement of liver tissue by scar tissue, leading to progressive loss of liver function.

Also, he said the findings provide further credence to current practice of ensuring that pregnant women should not lower their cholesterol too low. A recent study found that women who took cholesterol-lowering drugs known as statins were at greater risk of giving birth to babies with developmental problems.

Duke University Medical Center