A chronic in vivo supplementation protocol with deuterium-labeled folic acid under controlled metabolic conditions will be used to estimate folate requirements of pregnant women. The primary research goal is to provide folate requirement estimates for pregnant women to be used for dietary intake recommendations and prenatal folic acid supplementation polices to ensure normal fetal development and maternal health. The specific objectives are to estimate folate requirements by (1) the application of kinetic methodology; and (2) quantitation of urinary folate excretory products. Deuterium labeled and unlabeled folic acid (D5, or D0) will be given throughout gestation beginning at 14 wks to 2 groups of pregnant women consuming controlled intakes of folate (400 or 800 micrograms/d). Requirement estimates will be compared to estimates determined in 2 nonpregnant control groups. The appearance and disappearance of the labeled folates and catabolites as determined by isotope enrichment of urine and blood will be the basis of the kinetic requirement- determination. The data will be fit to specific models and the requirement based on the estimation of total body pool and fractional catabolic rate. A second approach will be the quantitation of the sum of (1) urinary folate catabolites [D5, or D0 p-aminobenzyolglutamate (pABG) and derivatives (apABG, pABA); and (2) metabolized intact folate (CH3THFA). The contribution of catabolites present in the diet to urinary excretory products will be based on the recovery of D4 pABG added to the diet. Changes in kinetic parameters and quantitation of metabolized folate excretory products in response to the two levels of intake will serve as the basis for prenatal folate requirement estimates. These data will provide a justification for dietary folate and supplemental folic acid recommendation polices for pregnant women. Application of these new requirement data will ensure adequate intake of folate for prevention of health related consequences (i.e. neural tube defects, impaired fetal growth, megaloblastic anemia) of folate inadequacy in women of reproductive age.
