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Immune System Attack Tied to Birth Defects

Study bolsters case for folic acid supplements

WEDNESDAY, Jan. 7, 2004 (HealthDayNews) -- A misguided immune system attack that prevents the activity of a chemical required for normal development of a fetus could be one cause of the birth malformations called neural tube defects, researchers say.

Antibodies that prevent the chemical, folic acid, from reaching cells in the developing fetus have been found in 75 percent of women with current or past pregnancies affected by neural tube defects, a team at the State University of New York (SUNY) Downstate Medical Center in Brooklyn reports in the Jan. 8 issue of the New England Journal of Medicine.

The finding reinforces the standing advice that women who might become pregnant should take folic acid supplements, experts say.

A neural tube defect prevents the brain or spinal cord from developing normally. Defects such as spina bifida and anencephaly occur in about one of every 1,000 pregnancies in the United States.

More than a decade ago, a number of studies showed folic acid is needed for proper development of the central nervous system. Flour and other grain products have been fortified with folic acid in the United States since 1998, and women of childbearing age are advised to take folic acid supplements.

The SUNY researchers say they began looking for immune system molecules called antibodies that could block the receptors for folic acid in fetal tissue because many women with pregnancies affected by neural tube defects have normal blood levels of folic acid.

They found such antibodies in nine of 12 women with affected pregnancies, compared to only two of 20 women with current or earlier normal pregnancies, the researchers say.

"The good thing is that we have developed something that can help women avoid neural tube defects," says Dr. Sheldon P. Rothenberg, a professor of medicine and biochemistry at SUNY and leader of the research team.

The finding could lead to a test for the antibodies, to help identify women at high risk of neural tube defects. "Companies may well want to develop such a test for clinical use," he says.

But the journal paper cautiously adds that more studies are needed to be sure the activity of these antibodies does in fact cause the birth defects.

Dr. Nancy Green, medical director of the March of Dimes Birth Defects Foundation, has a less cautious interpretation.

"What this paper does is add to the list of conditions for which women need more than the standard amount of folic acid," Green says. "The list is growing."

A supplement containing at least 400 micrograms of folic acid should be taken every day by any woman who has had a pregnancy affected by a neural tube defect, Green says. Other conditions calling for supplementation include diabetes and obesity, she says.

Women of childbearing age who take medications for seizures should also be taking the supplements, Green adds.

Indeed, it does no harm if "any woman who is pregnant or trying to become pregnant takes folic acid," she says.

An accompanying editorial by Dr. Nicholas J. Wald of the University of London notes that about 250,000 pregnancies with neural tube defects occur worldwide every year.

"Half of these cases could be prevented simply and safely through adequate fortification, and 85 percent of them could be prevented if all women took a 500-microgram folic acid supplement before pregnancy and during the first trimester," Wald writes.

More information

An overview of neural tube defects and folic acid can be found at the National Library of Medicine and the March of Dimes.

SOURCES: Sheldon P. Rothenberg, M.D., professor of medicine and biochemistry, State University of New York Downstate Medical Center, Brooklyn; Nancy Green, M.D., medical director, March of Dimes Birth Defects Foundation, White Plains, N.Y.; Jan. 8, 2004, New England Journal of Medicine
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