The relationship between increased folate catabolism and the increased requirement for folate in pregnancy

Objectives: To estimate the rate of folate catabolism in pregnant and nonpregnant women and to derive the recommended dietary allowance for folate. Design: Prospective, observational study. Setting: Rotunda Hospital, Dublin. Women: Twenty-four healthy gravid women were studied once during each trimester and postpartum. Twenty-five nonpregnant controls were assessed before and after folic acid supplementation. Interventions: Women provided 24-hour urine collections while adhering to a strict dietary regimen containing no exogenous folate catabolites. Main outcome measures: Urinary levels of p-acetamidobenzoylglutamate and p-aminobenzoylglutamate were measured by high pressure liquid chromatography. Results: The 24-hour excretion of folate catabolites, expressed as mean [95% CI] folate equivalents in μg) progressively increased during pregnancy. A peak was reached in the third trimester (349.1 μg [308.1 to 390.1]) where the rate was more than twice the rate in the nonpregnant control group (136.4 μg [112.4 to 160.4]) (P < 0.001). Based on our results the recommended dietary allowance for folate in nonpregnant women should be 250 μg and this should rise during pregnancy to 430 μg in the second trimester and 540 μg in the third trimester. Conclusions: The rate of folate catabolism progressively increases during pregnancy reaching a peak in the third trimester at the time of maximal fetal growth. The increased demand for folate during pregnancy appears to be due to the accelerated breakdown of the vitamin because of its participation in cellular biosynthesis. These results provide a quantitative basis for the current debate on the appropriate recommended dietary allowance for folate in both pregnant and nonpregnant women.