Folic acid supplementation during pregnancy may reduce risk of Down's syndrome
Dynamic Chiropractic, Jul 14, 2003 by Meschino, James
It is well-established that folic acid supplementation during pregnancy is associated with a significantly lower risk of having a child with a neural-tube defect (NTD; e.g., spina bifida, anencephaly). However, a recent study in The Lancet (2003; 361 [9366]:1331-5) provides evidence that folic acid supplementation also is associated with reduced risk of Down's syndrome. Researchers compared medical data from approximately 490 families at high risk for NTD with data from 516 families at high risk for Down's syndrome, and discovered that Down's syndrome was much more prevalent in pregnancies involving families at high risk for NTD. The evidence suggests that mothers of children with Down's syndrome experience an abnormal metabolism of folate and methyl, as well as mutations in their folate gene. These traits are also seen in infants affected by NTD.
Folate (folic acid, a B vitamin) is unique in that it contains a methyl group (CH^sub 3^), which it donates to homocysteine to permit its enzymatic conversion to methionine. Once formed within the cells of the body, methionine (a methyl-containing amino acid) extracts the adenosine ring from adenosine triphosphate (ATP) and becomes S-adenosyl methionine (SAMe). SAMe is then able to donate its methyl group (originally derived from folate) to many biochemical reactions, ineluding the synthesis of DNA bases. Consequently, DNA synthesis requires a constant, adequate supply of folate on a daily basis.
During pregnancy, the rapid rate of fetal cell division demands an even greater supply of folic acid; if the demand is not met, DNA defects occur, which most often manifest as neural-tube defects. Evidence from the Lancet study suggests the same may be true for Down's syndrome. To complicate matters, some individuals have an inborn error of folate or methyl metabolism, in that they show a defect in the enzyme that converts homocysteine to methionine, and thus produce insufficient amounts of SAMe. However, studies show that these individuals can improve the conversion of homocysteine to methionine significantly if they are provided with higher supplementation levels of folic acid (which is the coenzyme for this reaction) in many cases. Therefore, mothers identified as high-risk for NTD usually express this type of folate or methyl defect and are prescribed higher supplemental levels of folic acid. The Lancet study provides evidence that these women are also at higher risk for delivering a child with Down's syndrome, indicating that higher folic-acid supplementation may be of great importance in reducing the risk of NTD and Down's syndrome.
The researchers conclude that because of the links in the development of the two complications, folate supplementation before conception has the potential to reduce NTD and Down's syndrome during pregnancy. Most women would benefit from 400 meg of folic acid prior to conception (most multiple vitamins contain this amount) and 800 meg during pregnancy (the amount contained in prenatal vitamins). Women with folate or methyl metabolism problems require additional amounts of supplemental folic acid, which should be prescribed by their attending physicians or specialists, who can best monitor the appropriate biomarkers.
Reference
NNFA Supplement (April 28, 2003).
James Meschino, DC, MS. Dr. Meschino's articles, a "Talk Back" forum and a brief biography of the author are available online at www.chiroweb.com/columnist/meschino.
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