Folate is a naturally occurring form of vitamin B found in food, while folic acid is synthetically produced and used in fortified foods and supplements. Taking folic acid before and during early pregnancy is linked to a reduction in the risk of neural tube defects like spina bifida. The current recommended dose is 400 ìg (micrograms) a day though it is unclear how much daily folic acid is needed to prevent neural tube defects.

A previous study carried out in Ireland showed the risk of a having a child with a neural tube defect increased as red blood cell folate concentrations decreased, suggesting that this could be used as a 'biomarker' to predict neural tube defect risk in a population – and help inform prevention programs. So an international team of researchers set out to determine an optimal red blood cell folate concentration for the prevention of neural tube defects.

They used data from two population based studies in China involving over 220,000 births and 250 babies with neural tube defects. Mathematical models were used to estimate the association between red blood cell folate concentration at the time of completion of neural tube closure (day 28 of pregnancy) and neural tube defect risk.

The estimated risk of a neural tube defect was highest at lower red blood cell folate concentrations (neural tube defect risk of 25.4 per 10,000 births at a red blood cell folate concentration of 500 nmol/L).

But the estimated risk was substantially attenuated at red blood cell folate concentrations above 1,000 nmol/L. For example, estimated neural tube defect risk was 6 per 10,000 births at a red blood cell folate concentration of 1,180 nmol/L.

"Our results indicate that a red blood cell folate concentration of roughly 1,000 to 1,300 nmol/L might achieve optimal prevention of folate sensitive neural tube defects, with a resulting overall risk of neural tube defect of about 6 per 10,000," say the authors.

This range seems to be applicable to women in different countries and could be useful in the development and monitoring of folic acid fortification programs, they add.

They point out that it is not known how much natural food folate and/or folic acid intake is necessary to achieve red blood cell folate concentrations in the 1,000 to 1,300 nmol/L range in any given person or population and say this should be the focus of future research.

Setting "optimal" or target population red blood cell folate concentration cutoffs "will be useful in assessing the need for and monitoring the success of programs for the prevention of folate sensitive neural tube defects," they conclude.

In an accompanying editorial, researchers from the Nuffield Department of Population Health at the University of Oxford say tracking red cell concentrations will help to guide important policy decisions worldwide "and allow public health leaders to monitor a population's response with the ultimate goal of reducing the incidence of largely preventable neural tube defects."