122 Water Soluble Vitamins

Requirements for most water-soluble vitamins increase during pregnancy. Folate and vitamin B6 will be emphasized in the following discussion because increases in demand associated with pregnancy are relatively high (50% for folate, 46% for vitamin B6), and average intakes of these water-soluble vitamins relative to requirements are generally lower than for other water-soluble vitamins.

i.2.2.1 Folate

Folate is involved in single-carbon transfer reactions, notably important for the synthesis of nucleic acids and certain amino acids for new cell and tissue production. Erythrocyte folate is considered the best marker of long-term folate status in pregnancy; serum folate can also be used but reflects more recent changes in dietary intake. With inadequate folate intake, serum and erythrocyte folate concentrations decline, and megaloblastic anemia can develop. Impaired folate status during pregnancy may be involved with adverse outcomes such as pregnancy complications, spontaneous abortion, preterm delivery, and low birth weight [14]. Results from supplementation trials suggest that an additional 200 mcg of dietary folate equivalent* is required to maintain optimal folate status during pregnancy [15].

Neural tube defects (NTDs), a group of heterogeneous malformations involving neural tissue in the brain and/or spinal cord, occur in less than 1 per 1,000 births in the United States [16]. The etiology of NTDs is an ongoing area of research; however, inadequate maternal folate status prior to and in the first few weeks after conception appears to play a role in at least some cases of neural tube defects. According to 1999-2000 National Health and Nutrition Examination Survey (NHANES) data, the average folate intake of 20- to 39-year-old women in the United States is 327 mcg/day [17]. Results from supplementation studies suggest that women capable of becoming pregnant should consume an additional 400 mcg/day of folic acid from supplements and/or fortified foods in addition to consuming food folate from a varied diet.**

It is recommended that women consume 400 mcg/day of synthetic folate at least 1 month prior to conception to optimize folate status at the time of neural tube closure [5]. Based on evidence from randomized controlled trials, it has been estimated that this level of folate supplementation could prevent up to half of NTD cases [18]. A 19%

*Dietary folate equivalents are used to account for the differences in bioavailability between food folate (ยป50% bioavailable) and folic acid used in supplements and food fortification (~85% available)[15].

**Available evidence suggests that synthetic folic acid (found in supplements and fortified foods) is more effective at preventing neural tube defects than is food folate [15].

reduction in NTD prevalence occurred after the mandatory fortification with folate of enriched breads, cereals, flours, and other grain products in 1998 [16]. It should be noted that the additional 400 mcg/day folic acid supplementation is not included in the recommendations for pregnant women because by the time a woman is normally aware that she is pregnant, the window of opportunity for the effective prevention by folate of NTD (due to the embryological timing of the initial development and closure of the neural tube) has passed.

Vitamin B6, in the form of pyridoxal phosphate, is a coenzyme involved in over 100 metabolic reactions, most of which involve amino acid and protein metabolism. During pregnancy, vitamin B6 plays important roles in the synthesis of nonessential amino acids, heme, erythrocytes, immune proteins, and hormones. In observational studies, vitamin B6 has been positively associated with improved pregnancy outcomes such as reduced incidence of preeclampsia and higher Apgar scores and neonatal behavior [3]. Results from randomized, controlled supplementation trials suggest limited clinical benefit of vitamin B6 supplementation [19]. However, few such trials have been done and few pregnancy outcomes have been investigated.

Maternal and fetal accumulation during pregnancy totals approximately 25 mg, which translates into an increase in the daily requirement of about 0.25 mg after accounting for an average 75% bioavailability of food B6 and allowing for increased weight of the mother [15]. Because the needs for vitamin B6 predominate in the last half of pregnancy and because vitamin B6 is not stored in the body to any appreciable extent, increased intake in early pregnancy is not likely to be adequate to meet needs later in pregnancy. Therefore, the DRI was set at an additional 0.6 mg/day [15].

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