aThe difference between folate-supplemented and unsupplemented groups was statistically significant in all studies except Mills etal. (1989).

effect of dietary folate and folic acid supplementation in virtually all these different types of studies is very striking. Further evidence implicating folate comes from studies linking maternal folate status to pregnancies affected by NTDs. The main studies that have been published on serum/plasma folate and red cell folate (RCF) are summarized in Tables 3 and 4. The differences between affected and unaffected pregnancies are more pronounced in the first trimester of pregnancy. Maternal use of folic acid antagonists during early pregnancy increases the risk not only of NTDs but also of other congenital defects.

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