Studies of pregnancy outcomes in Israel and Ukraine find that families with a high incidence of neural tube defects also have an unexpectedly high incidence of Down syndrome, says a report in the April 19 issue of The Lancet. The research was done by a group led by Howard Cuckle, a professor of reproductive endocrinology at the University of Leeds in England.
Abnormal metabolism of folic acid appears to underlie both defects, the researchers say.
The link between folic acid and neural tube detects is well established; the U.S. Public Health Service recommends that women who are pregnant or might become pregnant take 400 micrograms of folic acid daily to prevent the defect, which affects the brain and spinal cord. But the new study is among the first to suggest a link with Down syndrome, which causes mental retardation.
The researchers are confident enough of their belief, Cuckle says, to have begun a trial in which pregnant women at high risk of having a baby with Down syndrome will be given massive doses of folic acid -- 5 milligrams a day, more than 10 times the recommended amount.
"We are enrolling about a thousand women in Israel, and within a couple of years we expect to have a handle on it," he says.
The criterion for entry in the study is simply age, since the incidence of Down syndrome is known to be higher in older women, Cuckle says, and he sees no reason why any pregnant woman should not take the supplement. "As far as we know, it does no harm," he says.
The report originated with an observation by doctors at the Interregional Medico-Genetics Center in Ukraine of a higher-than-expected incidence of neural tube defects in babies born to women referred to the center because of a history or diagnosis in the womb of Down syndrome.
Led by Cuckle, researchers then began examining the number of cases of Down syndrome in women seen at the Danek Gertner Institute of Human Genetics in Tel Aviv and other centers in the area because of a high risk of neural tube defects.
Overall, the two research centers reported 11 cases of Down syndrome in the 1,492 families at high risk of neural tube defects, about five times the expected incidence. And there were seven cases of neural tube defects in the 1,847 pregnancies at high risk of Down syndrome, compared to an expected incidence of 1.37.
Laboratory research points to a flaw in folic acid metabolism as a common, underlying mechanism for both conditions, Cuckle says.
Dr. Nancy Green, medical director of the March of Dimes Birth Defects Foundation, calls the new study "an interesting but very preliminary finding." The foundation's advice is that all women of childbearing age should take the daily 400-microgram folic acid supplements recommended by the Public Health Service.
But there are women who can benefit from much larger doses, she says. Four micrograms a day are recommended for women who have borne a child with a neural tube defect or have a neural tube defect themselves. Such large doses "may be helpful" for women who are obese or have diabetes, Green says.
And the 5-milligram dose being used in the Israeli study appears to do no harm "as far as we can tell, but it hasn't been studied," Green says. "I would add some caution to that."