Folate status of reproductive age women and neural tube defect risk in New Zealand: the effect of long term folic acid supplementation at 140 and 400 μg per day.
Hursthouse, Nicola Ann
Background: Neural tube defects (NTDs) are severe birth defects affecting the brain and spinal cord resulting in the death of a foetus, or disabilities in those babies that survive. The risk of a pregnancy being affected by a NTD has been shown to decrease when maternal red blood cell (RBC) folate concentrations are >906 nmol/L. The Ministry of Health currently recommends that all women planning a pregnancy consume 400 μg folic acid/day to reduce the risk of NTDs. Food Standards Australia New Zealand (FSANZ) has issued notice for the mandatory folic acid fortification of bread to increase the daily folic acid intake of reproductive aged women. However, there is no national data on the folate status of New Zealand women and questions remain about the relative effectiveness of folic acid at both the recommended supplemental dose and food fortification levels. Objective: The overall aim of the study was to evaluate the long-term effect of folic acid supplementation at the level proposed for mandatory folic acid fortification in New Zealand, on the folate status of reproductive women and respective estimated reduction in NTD risk. Specifically, we aimed to identify the predictors of folate status, and evaluate the long-term effect of 140 μg/d (a dose designed to mimic the average folic acid intake provided by the proposed mandatory bread fortification programme) and 400 μg/d (the dose recommended for primary neural tube defect prevention) on plasma and RBC folate levels and estimated NTD risk in reproductive aged women over a 40 week intervention period. Design: One hundred and forty four women aged 18 – 40 years were randomly assigned a daily folic acid supplement of 140 μg (n = 49), 400 μg (n = 48) or a placebo (n = 47) for 40 weeks. Plasma and RBC folate concentrations were measured at baseline, week 6, 12, 29 and 40. Sociodemographic characteristics, anthropometric measurements and dietary folate intake were assessed at baseline. Results: Of the 144 women enrolled in the study, 119 completed the intervention. The average age of participants was 25 years and the majority identified as New Zealand European (76%; 109 of 144). While only 3% of participants had RBC folate < 317 nmol/L at baseline, two-thirds (66%) had RBC folate concentrations < 906 nmol/L. After the 40 week intervention, mean blood folate concentrations were significantly greater relative to the placebo group (P < 0.001). Specifically, plasma folate concentrations increased by 50% (95% CI: 18, 90) in the 140 μg group which was significantly lower than the 107% (95% CI: 63, 164) increase observed in the 400 μg group. In contrast, the increase in RBC folate concentrations over 40 weeks, ranging from 51 – 63%, did not differ between the folic acid treatment groups (P = 0.340). At week 40, the overall prevalence of a RBC folate < 906 nmol/L decreased to 35% and 18% in the 140 μg and 400 μg groups, respectively, while remaining relatively unchanged at 58% in the placebo group. After 40 weeks there was no evidence of a difference in RBC folate concentrations between the two treatment groups (P = 0.340), nor was there evidence of a difference in the odds of a RBC folate < 906 nmol/L (P = 0.078). Conclusion: A significant portion of the population sampled had a RBC folate below the protective level of 906 nmol/L. Given a sufficient duration of time, our results suggest that the average daily intake of folic acid provided from the proposed mandatory fortification programme would increase RBC folate concentrations in reproductive age women to levels associated with a low risk of NTDs.
Advisor: Houghton, Lisa
Degree Name: Master of Science
Degree Discipline: Department of Human Nutrition
Publisher: University of Otago
Keywords: Folate; Neural Tube Defect; Supplementation; Reproduction
Research Type: Thesis