Preconceptional intake of folate and vitamin B12 in the prevention of neural tube defects and Down syndrome

Abstract

Neural tube defects, which encompass a broad spectrum of phenotypes ranging from spina bifida to anencephaly, affect approximately 1 in 1000 neonates in the United States. Folic acid supplementation has been reported to decrease both the occurrence and recurrence of neural tube defects.1Czeizel AE Dudás I Prevention of the first occurrence of neural tube defects by periconceptional vitamin supplementation.N Engl J Med. 1992; 327: 1832-1835Crossref PubMed Scopus (2680) Google Scholar In 1992 the United States Public Health Service recommended that all women of childbearing age who are capable of becoming pregnant consume 400 μg folate daily. Down syndrome occurs at an estimated frequency of 1 in 600 live births. Abnormal folate metabolism may be a maternal risk factor for this condition. Mean serum folate concentration has increased from 12.6 μg/L in 1994 to 14.9 μg/L in 1997 and ultimately to 18.7 μg/L in 19982Lawrence JM Petitti DB Watkins M Umekubo MA Trends in serum folate after food fortification [letter].Lancet. 1999; 354: 915-916Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar; however, the concomitant decrease in the incidence of Down syndrome and neural tube defects per 1000 live births could indirectly be a result of an increase in prenatal detection and termination of affected pregnancies. A second nutrient that has been implicated in the occurrence of neural tube defects is vitamin B12, with its deficiency being suggested as an independent risk factor. Both folate and vitamin B12 are essential in methionine metabolism and are required for remethylation of homocysteine to methionine. Although effective treatment of vitamin B12 deficiency with oral cyanocobalamin supplements has been reported,3Kuzminski AM Del Giacco EJ Allen RH Stabler SP Lindenbaum J Effective treatment of cobalamin deficiency with oral cobalamin.Blood. 1998; 92: 1191-1198PubMed Google Scholar supplementation of foods with cyanocobalamin has not been recommended, and there have not been any studies showing the effect of such supplementation on the trend in serum vitamin B12 levels. It would be interesting to see whether fortification of foods or oral supplementation with cyanocobalamin in addition to folic acid would further decrease the incidences of neural tube defects and Down syndrome. 6/8/110953