Folate status of reproductive age women and neural tube defect risk: the effect of long-term folic acid supplementation at doses of 140 µg and 400 µg per day.

Nicola A Hursthouse,Jody C Miller,Andrew R Gray,Meredith C Rose,Lisa A Houghton

doi:10.3390/nu3010049

Abstract

Primary prevention of most folate-responsive neural tube defects (NTDs) may not require 400 μg folic acid/day but may be achieved by attaining a high maternal folate status. Using RBC folate ≥906 nmol/L as a marker for NTD risk reduction, the study aimed to determine the change in blood folate concentrations in reproductive age women in response to long-term folic acid supplementation at 400 µg/day and 140 µg/day (dose designed to mimic the average daily folic acid intake received from New Zealand’s proposed mandatory bread fortification program). Participants were randomly assigned to a daily folic acid supplement of 140 µg (n = 49), 400 µg (n = 48) or placebo (n = 47) for 40 weeks. RBC folate concentrations were measured at baseline, and after 6, 12, 29 and 40 weeks. At 40 weeks, the overall prevalence of having a RBC folate <906 nmol/L decreased to 18% and 35% in the 400 µg and 140 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 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). In conclusion, the average daily intake of folic acid received from the proposed fortification program would increase RBC folate concentrations in reproductive age women to levels associated with a low risk of NTDs.

Highlights

It is widely accepted that adequate maternal consumption of folic acid before pregnancy and during the early weeks of gestation can reduce the risk of having a child with a neural tube defect (NTD)
No statistically significant evidence of differences were observed in treatment group, participant age, BMI category, ethnicity, education or baseline plasma and red blood cell (RBC) folate concentrations between those participants who remained in the study and those who withdrew before the end of the study
The present study demonstrates that the prevalence of folate deficiency is low, nearly two-thirds of our study population had baseline RBC folate concentrations below the level thought to be protective against NTDs (i.e., ≥906 nmol/L)

Summary

Introduction

It is widely accepted that adequate maternal consumption of folic acid before pregnancy and during the early weeks of gestation can reduce the risk of having a child with a neural tube defect (NTD). Public health authorities worldwide have recommended consuming 400 μg folic acid per day during the periconceptional period to reduce the risk of first occurrence NTDs [1,2,3,4]. This recommended dose is based mainly on the amount of folic acid observed to be associated with a reduction in NTDs in the majority of epidemiological studies [5,6,7,8,9]. The relation of NTD risk to maternal red blood cell (RBC)

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