FDA study finds possible link between Down syndrome
and lower maternal folic acid levels

A study funded by the Food and Drug Administration’s (FDA) Office of Women’s Health and conducted by FDA’s National Center for Toxicological Research (NCTR) has identified possible maternal risk factors for having a child with Down syndrome, a leading genetic cause of mental retardation that occurs in one out of every 700 live births. The preliminary study, published in the American Journal of Clinical Nutrition, found that mothers of children with Down syndrome show biochemical and genetic evidence of impaired folate metabolism.

"This study reflects the agency’s emphasis on state-of-the-art science as the basis for regulatory decisions," said Jane E. Henney, M.D., the Commissioner of Food and Drugs, "and lends additional support for the FDA’s March 1996 decision to require the fortification of certain grain products with folic acid."

Beginning in January 1998, FDA mandated the addition of 140 micrograms of folic acid, a B vitamin, to every 100 grams of certain grain products, such as flour, breakfast cereals, and pasta. This decision based on evidence that inadequate folate status in early pregnancy increases the risk of neural tube defects, was intended to reduce the incidence of birth defects in the brain and spinal cord in this country.

Down syndrome, or trisomy 21, is a complex genetic disease that is caused by an extra copy of chromosome 21. The origin of the extra chromosome is maternal in most cases and is due to an error in chromosome separation before conception. The results of the new study, led by S. Jill James, Ph.D., a biochemist at NCTR, indicated that mothers of children with Down syndrome have an imbalance in folate metabolism that may be explained, in part, by a common genetic variation in an enzyme involved in the folic acid pathway.

It is important to note that while this study may provide some new insights into possible causes of this disease, larger clinical studies will be necessary to confirm the NCTR findings and to definitively determine whether folic acid supplementation, at least 2 months before pregnancy, will reduce the incidence of Down Syndrome.

Source: U.S. Food and Drug Administration, September 28, 1999

http://www.fda.gov/bbs/topics/NEWS/NEW00690.html
http://medicalreporter.health.org/tm...nsyndrome.html



Folic acid may have no immediate impact on Down Syndrome

by Janet Wong

July 31, 2003 -- U of T researchers have found that fortifying foods with folic acid may not reduce the incidence of Down Syndrome. But they suggest we may to need to wait another 20 years or so for the next generation of women to give birth before the real answer is known.

Folic acid has been shown previously to dramatically decrease the incidence of neural tube defects (e.g. spina bifida) in newborns. Dr. Joel Ray, of the Departments of Medicine at U of T and St. Michael's Hospital, and co-researchers decided to examine the prevalence of Trisomy 21 (commonly known as Down Syndrome) following the introduction of folic acid fortification into most Canadian cereal grains by 1998. They examined prenatal and postnatal incidence rates of Trisomy 21 in Ontario, screening nearly 219,000 women prior to fortification and 118,000 women afterward. They found virtually no decline in the incidence of Trisomy 21 in relation to fortification.

However, Ray explains that folic acid and vitamin B12 are essential for the proper development of genes, which lie in chromosomes and are copied as cells divide. He says it's possible that part of the reason they saw no impact of folic acid fortification on Trisomy 21 rates is that the amount of folic acid intake was not high enough. But, he adds, another possibility may be that Trisomy 21 originates even before a woman is born.

"A woman's eggs are formed when she herself is a fetus in her mother's womb," says Ray. "So while taking folic acid may have no impact on the eggs of a woman now to prevent Trisomy 21, it may modify the eggs of her daughter to reduce the risk when she has her own child."

This research, published in the July 30 issue of the American Journal of Medical Genetics Part A, was supported by the Ontario Ministry of Health and Long-Term Care.

http://www.news.utoronto.ca/bin5/030731b.asp