Study Offers More Evidence of Role Folic Acid Plays Against Down Syndrome

Women who have trouble metabolizing the vitamin folic acid are at a higher risk of having children with Down syndrome, a discovery by government researchers that raises the question of whether folic acid supplements might fight the syndrome.

Expectant mothers with a genetic abnormality that hinders how the body processes folic acid were 2.6 times more likely to have a child with Down syndrome than women without that genetic defect, concludes the study published Tuesday in the American Journal of Clinical Nutrition.

But the discovery by Food and Drug Administration researchers is only one piece in the complicated puzzle of Down syndrome, cautioned FDA Commissioner Jane Henney. That’s because millions of women appear to have this genetic abnormality, yet the risk of having a child with Down syndrome actually is small--one in 600 births.

So something else has to help trigger the devastating condition.

Still, “this opens the door to look at other genes,” explained S. Jill James, an FDA biochemist who led the study.

And birth defect experts were excited because the study points to a possible, albeit still unproven, way to reduce the risk: Eating more folic acid.

“If you have this mutation and you happen to have a very poor diet, it magnified the problem,” James said. “We call it a gene-nutrient interaction.”

Folic acid is a B vitamin found naturally in leafy green vegetables, beans, tuna, eggs and other foods. Also, in 1998 the government ordered some grain products such as flour, breakfast cereal and pasta to be fortified with folic acid.

Women who eat 400 micrograms of folic acid a day cut in half their chances of having babies with birth defects of the brain and spinal cord, such as spina bifida.

Down syndrome is a genetic disorder that combines mental retardation with such physical abnormalities as a broad, flat face and slanting eyes. Affected children are at high risk of heart defects, visual or hearing impairment and other health problems. The March of Dimes estimates there are 250,000 Americans with Down syndrome.

The gene MTHFR plays a role in how chromosomes separate during ovulation, and in how much folic acid people need for various bodily reactions.

So James studied whether an MTHFR abnormality also could affect Down syndrome. She compared 57 mothers of Down syndrome children with 50 mothers of healthy children, and concluded the gene abnormality did indeed increase the risk of Down syndrome.

The FDA researchers did not give women folic acid supplements to see if they would prove enough--and at what dose--to counter the genetic defect. Experts said a treatment study is the next step.

Also, the study was in younger mothers, and women over 40 have the highest risk of a Down syndrome baby. So how age complicates the genetics is a big question.

However, 28% of the Down syndrome mothers claimed they had taken folic acid supplements at the time of conception.

If eating extra folic acid does prove protective, getting women to take it for several months before they conceive--in time to protect eggs produced during ovulation--would be vital, said Dr. Donald Mattison, medical director of the March of Dimes.