Folate is a water-soluble vitamin occurring either naturally in food or as folic acid, which is the synthetic form in supplements or fortified foods [1]. Folate must be consumed in adequate amounts prior to and during pregnancy to ensure an optimal pregnancy outcome as recently reviewed [2]. DNA synthesis is dependent on folate and when intake is limited, cell division slows down at a time when the developing embryo has the greatest need. One of the most significant public health discoveries of this century was the finding that periconceptional folic acid significantly reduces the risk of neural tube defects (NTDs). This scientific fact has been translated into public health policy throughout the world, including widespread recommendations from professional

From: Nutrition and Health: Handbook of Nutrition and Pregnancy Edited by: C.J. Lammi-Keefe, S.C. Couch, E.H. Philipson © Humana Press, Totowa, NJ

organizations for periconceptional folic acid supplementation in addition to mandated and voluntary folic acid fortification policies.

In addition to the role of folic acid in the development of the neural tube, which takes place during the first 28 days of gestation, folate is of vital importance throughout gestation for a positive pregnancy outcome. Folate coenzymes are also involved in one-carbon transfer reactions required for amino acid metabolism including the remethylation of homocysteine to form the essential amino acid methionine and the body's primary methylating agent, S- adenosylmethionine (SAM), which is utilized in over 100 different methylation reactions including DNA methylation. Folate requirements are increased in pregnancy to meet the demands for increased DNA synthesis and thus cell division [3]. The increase in cell division is associated with the rapidly growing fetus and placenta coupled with the increasing size of the maternal reproductive organs. Folate is required for the formation of red blood cells, and the expansion in the number of red blood cells for maternal and fetal circulation further increases the requirement for folate during pregnancy [4].

Restricted folate intake during pregnancy has been associated with poor pregnancy outcomes including preterm delivery, low infant birth weight, and fetal growth retardation [3]. Biochemical indicators of depleted maternal folate status have been linked to increased spontaneous abortion and pregnancy complications (e.g., abruptio placenta or placental infarction with fetal growth retardation and preeclampsia), which increase the risk of low birth weight and preterm delivery [5, 6]. The requirement for folate to support the rapid cell division and growth of pregnancy is clear, and evidence for an increased folate requirement during pregnancy is well documented. This chapter will address specific recommendations for periconceptional folic acid use to reduce NTD risk in addition to recommendations for folate intake throughout pregnancy to optimize pregnancy outcome.

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