Choline during pregnancy may avoid, reverse Fetal Alcohol Syndrome symptoms

Fetal Alcohol Syndrome (FAS) occurs far more frequently than generally believed. Although estimates vary widely, when combined with the milder afflictions of Alcohol Related Birth Defects (ARBD) and several others, the Centers for Disease Control puts the frequency of FAS/ARBD as high as one in 100.

Researchers at Tripler Army Medical Center, Honolulu, showed that by including choline, a U.S.-required ingredient in baby formula, in the pre-natal diet of a rat, that symptoms of prenatal alcohol weren’t evident in the young adult animal. At the same time, “we believe we have identified several physiological approaches that could serve as post-natal screening methods to identify babies with possible FAS or related diseases,” John Claybaugh, head of the Tripler team said.

In addition, Claybaugh said there is some indication, or at least a possible correlation, that vasopressin could serve some function in cognitive development.

Claybaugh points out that vasopressin, along with the other neurohypophyseal hormone, oxytocin, was discovered over 100 years ago, before it was even known what a hormone was. “When most mammal fetuses are developing, the nerves in the brain that make vasopressin become almost fully developed,” Claybaugh noted. “We recently published a paper showing that if alcohol is consumed during pregnancy, a rat’s developing vasopressin nerves are damaged, and this damage lasts through adulthood because they synthesize less vasopressin in the brain and store less in the pituitary.”

Could diabetes insipidus-like symptoms lead to FAS test?

With insufficient vasopressin, the rats drank more water and produced more dilute urine (diuresis) than normal. These are some of the classic symptoms of diabetes insipidus, a disease that also affects humans. Claybaugh’s team found that stimuli which normally prompt vasopressin release – such as low fluid volume or high osmotic concentration – were much less effective in animals that had been exposed to pre-natal alcohol feed. With proper guidelines, he believes monitoring infants’ urine flow and vasopressin content could serve as future tests for Fetal Alcohol Syndrome.

Claybaugh is presenting his research at the American Physiological Society’s 2005 Conference, “Neurohypophyseal Hormones: From Genomics and Physiology to Disease,” plus the latest developments toward clinical applications, July 16-20 in Steamboat Springs.

Claybaugh also is participating in the symposium, “Renal actions of NH hormones: pathophysiology,” chaired by Jeff Sands, Emory University School Medicine, and Peter Gross, University of Gallen, Switzerland.

“Amelioration of fetal alcohol-induced diabetes insipidus by dietary choline during pregnancy in the rat.” John Claybaugh, Ginger Pole, Aileen Sato, Danielle Bird, Catherine Uyehara, Tripler Army Medical Center, Honolulu. Funded in part by Hawaii Community Foundation and Clinical Research Center.

Choline completely reverses diuresis, osmolality, while increasing water drinking

The Tripler team compared four litters whose dams were on differing diets through the normal 22-day gestation period:

1. control liquid diet days 7-21

2. control liquid diet with ethanol (35% of caloric intake) days 7-21

3. same as #1 but with choline chloride added to diet days 10-21

4. same as #2 but with choline chloride added to diet days 10-21

They tested the 8-week-old young adult rats and found that the addition of choline to the diet of the alcohol-fed dam completely reversed the diuresis and increased water drinking , and restored urine osmolality to normal. These results, Claybaugh said, “are consistent with the hypothesis that supplemental dietary choline fed to the pregnant dam can prevent the alcohol-induced partial diabetes insipidus seen in the young adult offspring.”

Next steps toward FAS-related progress

The rats’ alcohol-induced symptoms are somewhat similar to the human babies’ FAS symptoms, which include learning disabilities, mental retardation and sleep and suckling disturbances in infancy. Claybaugh believes there is reason to continue research on several levels:

# Study whether prenatal ethanol-induced vasopressin and oxytocin system damage can be overridden by post-natal administration of choline in pups. (Post-natal choline experiments in rats done by others have demonstrated a reversal of the learning disability, but the underlying hormone levels weren’t tested.)

# Test known FAS infants to see if there are symptoms of diabetes insipidus, such as excess urine or decreased excretion of vasopressin. Tripler is currently measuring rats’ urinary vasopressin from these experiments to see if it is decreased . If so, testing for such DI symptoms could become FAS screens in humans.

From American Physiological Society

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