Folic Acid/Folic Acid-Containing Multivitamins and Primary Prevention of Birth Defects and Preterm Birth

Abstract

The deficiency or overdosage of certain nutrients may have a role in the origin of birth defects. First, in 1932, Hale (1) demonstrated that a vitamin A-free diet during early pregnancy of sows resulted in offspring without eyeballs, oral clefts, accessory ears, malposition of the kidney and defects of hind legs. Hale’s conclusion was the condition is illustrative of the marked effect that a deficiency may have in the disturbance of the internal factors that control the mechanism of development . Further development of experimental teratology became possible when small rodents were introduced for this purpose. Joseph Warkany (1902–1992), one of the founders of teratology, recognized the importance of purified diets and used these to test various vitamin deficiencies for their teratogenic effects. Warkany (2,3) found that maternal dietary deficiency can induce structural birth defects, i.e. congenital abnormalities (CAs). Marjorie M. Nelson (4) introduced the use of antimetabolites which made possible conversion of long-term nutritional experiments into short-term chemical testing. First, antimetabolites of folic acid were used and folate deficiency was proven to be highly teratogenic in pregnant rats (5–7), producing multiple CAs, neural-tube defects, orofacial clefts, and other CAs. Later the teratogenic effect of 4-aminopteroylglutamic acid (aminopterin), a folic acid antagonist, was confirmed in man (8–10) as well. Recently the human teratogenic effect of some other folic acid antagonist drugs, e.g. trimethoprim has been shown (11,12).