Folic Acid-Containing Multivitamins and Primary Prevention of Birth Defects

  • Andrew E. Czeizel
Part of the Nutrition ◊ and ◊ Health book series (NH)


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. Some of the pigs also had other defects, such as oral clefts, accessory ears, malposition of 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” (1). Further development of experimental teratology became possible when small rodents were introduced for this purpose. Joseph Warkany (1902–1992) (2), one of the founders of teratology, recognized the importance of purified diets and used these to test various vitamin deficiencies for their teratogenic effects. He found that maternal dietary deficiency can induce structural birth defects, i.e., congenital abnormalities (CAs) (3). Marjorie M. Nelson (4) introduced the use of antimetabolites, which made possible conversion of longterm nutritional experiments into short-term chemical testing. First, antimetabolites of folic acid were used and folic acid defiency was proved highly teratogenic in pregnant rats (5–7). Later it was confirmed in humans (8–10) as well. This research approach also had strong support from the French investigator, Giroud (11,12). These findings highlighted the developmental importance of folic acid (13,14). However, this first phase of history of malnutritional teratology, including folic acid deficiency, was followed by a longer silent period. The second, recent phase is related to the primary prevention of neural-tube defects in the 1980s.


Folic Acid Neural Tube Defect Renal Agenesis Multivitamin Supplementation Limb Deficiency 
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  • Andrew E. Czeizel

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