Red Blood Cell Folate Likely Overestimated in Australian National Survey: Implications for Neural Tube Defect Risk

Shannon E Hunt,Maria Makrides,Tim J Green,Lisa A Houghton,Merryn J Netting,Karen P Best,Thomas R Sullivan,Beverly S Muhlhausler

doi:10.3390/nu12051283

Abstract

In 2009, the Australian government mandated the addition of folic acid to bread flour to reduce the incidence of neural tube defects (NTD)-affected pregnancies. In 2011–2012, the Australian Health Measures Survey (AHMS) reported a mean red blood cell (RBC) folate in women of reproductive age (16–44 y) of 1647 nmol/L. Over 99% of women had an RBC folate ≥ 906 nmol/L, a concentration consistent with a very low risk of NTDs if a woman became pregnant. However, RBC folate was measured using an immunoassay, which is not a recommended method due to questionable accuracy. The microbiological assay is the preferred method for RBC folate measurement. To determine whether the immunoassay method may have led to spurious conclusions about the folate status of Australian women, we collected fasting blood samples from 74 healthy non-pregnant, non-lactating women (18–44 y) and measured RBC folate using both the immunoassay and microbiological methods. Mean RBC folate (95% confidence interval) concentration measured with the immunoassay method was 1735 (1666, 1804) nmol/L compared with 942 (887, 1012) nmol/L using the microbiological method. No woman had an RBC folate < 906 nmol/L using the immunoassay method, whereas 46% of women had an RBC folate < 906 nmol/L using the microbiological method. The NTD risk was estimated to be 0.06% using the immunoassay method and 0.14% using the microbiological method. RBC folate using AHMS survey may have underestimated NTD risk in Australian women.

Highlights

Neural tube defects (NTD), such as spina bifida and anencephaly, are caused by the failure of the neural tube to close normally, at around 28 days post-conception
To achieve a maximal reduction in NTDs with folic acid fortification, it is generally accepted that achieving a red blood cell (RBC) folate ≥ 906 nmol/L among women of reproductive age is desirable [6,7]
Mean RBC folate (95% confidence interval) concentration measured with immunoassay method was almost twice that of the microbiological method; 1735 (1666, 1804) compared with 942 (887, 1012)

Summary

Introduction

Neural tube defects (NTD), such as spina bifida and anencephaly, are caused by the failure of the neural tube to close normally, at around 28 days post-conception. It has been shown that folic acid taken prior to conception and early pregnancy reduces the incidence of NTDs by up to. In 2005 the Australian National Health and Medical Research Council recommended that all Nutrients 2020, 12, 1283; doi:10.3390/nu12051283 www.mdpi.com/journal/nutrients. NTDs occur before many women know they are pregnant, more than 80 countries have mandated the addition of folic acid to food staples, typically wheat flour. Ministerial Council mandated the fortification of bread flour with folic acid [4]. This increased folic acid intakes of the population and reduced the incidence of NTDs, especially among teenagers and Indigenous women [5]. In the nationally representative 2011-2012 Australian Health Measures Survey (AHMS)

Results

Discussion

Conclusion