title: Moderately high intake of folic acid has a negative impact on mouse embryonic development.
abstract: BACKGROUND
  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 had 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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Our work suggests that even moderately high levels of FA supplementation may adversely affect fetal mouse development. Additional studies are warranted to evaluate the impact of high folate intake in pregnant women. Birth Defects Research (Part A), 2013. © 2012 Wiley Periodicals, Inc.
authors.affiliation: Departments of Human Genetics and Pediatrics, McGill University, Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada.
authors.forename: Leonie G
authors.initials: LG
authors.lastname: Mikael
authors.forename: Liyuan
authors.initials: L
authors.lastname: Deng
authors.forename: Ligi
authors.initials: L
authors.lastname: Paul
authors.forename: Jacob
authors.initials: J
authors.lastname: Selhub
authors.forename: Rima
authors.initials: R
authors.lastname: Rozen
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D020964:Embryo Loss / Q000139:chemically induced; D004622:Embryo, Mammalian / Q000187:drug effects*; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D005492:Folic Acid / Q000633:toxicity*; D006321:Heart / Q000187:drug effects / Q000196:embryology; D006345:Heart Septal Defects, Ventricular / Q000139:chemically induced; D006352:Heart Ventricles / Q000187:drug effects / Q000196:embryology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000097:blood / Q000172:deficiency; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D014803:Vitamin B Complex / Q000633:toxicity*
chemical_list: D014803:Vitamin B Complex; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)