Submitted to: Birth Defects Research Part A: Clinical and Molecular Teratology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/25/2012
Publication Date: 9/25/2012
Citation: Mikael, L.G., Deng, L., Paul, L., Selhub, J., Rozen, R. 2012. Moderately high intake of folic acid has a negative impact on mouse embryonic development. Birth Defects Research Part A: Clinical and Molecular Teratology. 97(1):47-52. Interpretive Summary: In a previous study done in collaboration with investigators from McGill University in Canada we found that feeding a pregnant mouse with folic acid doses that were 20-fold higher than the Recommended Daily Allowance (RDA) resulted in abnormal development of the embryo. In this study the pregnant mice were fed with half (10-fold higher than the RDA) the amount of folic acid than previously done. The results were the same as before. Embryo development was abnormal which includes embryonic loss, embryonic delays, and a higher incidence of heart defects, compared to mothers fed the control diet. For humans 10-fold the RDA is equal to 4 milligrams per day and many pregnant women are prescribed 5 milligrams per day.
Technical Abstract: The incidence of neural tube defects has diminished considerably since the implementation of food fortification with folic acid (FA). However, the impact of excess FA intake, particularly during pregnancy, requires investigation. In a recent study, we reported that a diet supplemented with 20-fold higher FA than the recommended intake for rodents adverse effects on embryonic mouse development at embryonic days (E)10.5 and 14.5. In this report, we examined developmental outcomes in E14.5 embryos after administering a diet supplemented with 10-fold higher FA than recommended to pregnant mice with and without a mild deficiency of methylenetetrahydrofolate reductase (MTHFR). Pregnant mice with or without a deficiency in MTHFR were fed a control diet (recommended FA intake of 2 mg/kg diet for rodents) or an FA-supplemented diet (FASD; 10-fold higher than the recommended intake [20 mg/kg diet]). At E14.5, mice were examined for embryonic loss and growth retardation, and hearts were assessed for defects and for ventricular wall thickness. Maternal FA supplementation was associated with embryonic loss, embryonic delays, a higher incidence of ventricular septal defects, and thinner left and right ventricular walls, compared to mothers fed control diet.