Call to strengthen UK folic acid policy to prevent birth defects

The UK’s new legal requirement for folic acid to be added to non-wholemeal wheat flour does not go far enough and a bolder policy would prevent hundreds more birth defects each year, say researchers including UCL’s Professor Sir Nicholas Wald.

In a new study, published in the Archives of Disease in Childhood, the research team argues that the evidence has been consistent that higher levels of folic acid fortification would prevent about 80% of neural tube defects—defects that result in life-threatening and disabling spinal conditions such as spina bifida and anencephaly.

In the U.K., this would translate to about 800 cases a year that would be prevented—whereas the Government expects its new requirement, which will come into force in 2026, to prevent 200 cases a year, or 20%.

Folic acid is vitamin B9, which is important in early pregnancy, aiding proper development of the baby’s brain, skull and spinal cord.

Women who may become pregnant are advised to take folic acid in supplement form. The addition of folic acid to flour under the new legal requirements in the U.K. will not change this. Supplement use and fortification will both be needed.

Lead author Professor Sir Nicholas Wald (UCL Institute of Health Informatics) said, “The U.K.’s new legal requirement for folic acid to be added to non-wholemeal wheat flour is welcome. However, fortifying all flour and rice to a higher level of fortification would prevent many more serious cases of disability. Our new findings show the evidence is consistent on this, despite past disagreement among researchers.”

Professor Wald added, “Preventing about four out of five neural tube defects instead of one out of five would be a major public health benefit.

“Limiting fortification to non-wholemeal wheat flour, as is planned in the U.K., would exclude women who eat wholemeal bread and communities that eat rice as their carbohydrate staple.

“This new research resolves uncertainty over how much folic acid is enough for fully effective fortification.”

In the new study, the research team looked at past papers that reached different conclusions about the optimal level of folate in the blood to prevent neural tube defects.

They compared analyses of two large-scale studies carried out in Ireland and China involving 56,000 and 230,000 women respectively. The studies looked at blood folate levels or estimates of blood folate levels based on folic acid supplementation in these women as well as the incidence of neural tube defects to work out how blood folate levels affect risk.

They argued that the authors of these studies misinterpreted the evidence to conclude a lower folate level was optimal. The researchers said this was because the authors used a graph creating a false perception that the benefits of higher levels of folate on the risk of neural tube defects leveled off.

The researchers re-plotted the relationship between folate levels and neural tube defects on a logarithmic scale, where the numbers on both axes double (1, 2, 4, 8, 16), rather than on the arithmetic scale (1, 2, 3, 4) as had been previously reported.

They found the relationship was continuous, with each doubling of serum folate amounting to an approximate halving of the risk of a neural tube defect.

Both analyses, interpreted correctly, show the same preventive benefit of higher levels of serum folate. The researchers show that a target serum folate concentration of 44 ng/mL would prevent about 80% of neural tube defects.

This is in line with the results of a U.K. randomized trial, the MRC Vitamin Study, that more than 30 years ago definitively established folate deficiency as a cause of neural tube defects.

The UK’s new legal requirement for folic acid to be added to non-wholemeal wheat flour does not go far enough and a bolder policy would prevent hundreds more birth defects each year, say researchers including UCL’s Professor Sir Nicholas Wald.

In a new study, published in the Archives of Disease in Childhood, the research team argues that the evidence has been consistent that higher levels of folic acid fortification would prevent about 80% of neural tube defects—defects that result in life-threatening and disabling spinal conditions such as spina bifida and anencephaly.

In the U.K., this would translate to about 800 cases a year that would be prevented—whereas the Government expects its new requirement, which will come into force in 2026, to prevent 200 cases a year, or 20%.

Folic acid is vitamin B9, which is important in early pregnancy, aiding proper development of the baby’s brain, skull and spinal cord.

Women who may become pregnant are advised to take folic acid in supplement form. The addition of folic acid to flour under the new legal requirements in the U.K. will not change this. Supplement use and fortification will both be needed.

Lead author Professor Sir Nicholas Wald (UCL Institute of Health Informatics) said, “The U.K.’s new legal requirement for folic acid to be added to non-wholemeal wheat flour is welcome. However, fortifying all flour and rice to a higher level of fortification would prevent many more serious cases of disability. Our new findings show the evidence is consistent on this, despite past disagreement among researchers.”

Professor Wald added, “Preventing about four out of five neural tube defects instead of one out of five would be a major public health benefit.

“Limiting fortification to non-wholemeal wheat flour, as is planned in the U.K., would exclude women who eat wholemeal bread and communities that eat rice as their carbohydrate staple.

“This new research resolves uncertainty over how much folic acid is enough for fully effective fortification.”

In the new study, the research team looked at past papers that reached different conclusions about the optimal level of folate in the blood to prevent neural tube defects.

They compared analyses of two large-scale studies carried out in Ireland and China involving 56,000 and 230,000 women respectively. The studies looked at blood folate levels or estimates of blood folate levels based on folic acid supplementation in these women as well as the incidence of neural tube defects to work out how blood folate levels affect risk.

They argued that the authors of these studies misinterpreted the evidence to conclude a lower folate level was optimal. The researchers said this was because the authors used a graph creating a false perception that the benefits of higher levels of folate on the risk of neural tube defects leveled off.

The researchers re-plotted the relationship between folate levels and neural tube defects on a logarithmic scale, where the numbers on both axes double (1, 2, 4, 8, 16), rather than on the arithmetic scale (1, 2, 3, 4) as had been previously reported.

They found the relationship was continuous, with each doubling of serum folate amounting to an approximate halving of the risk of a neural tube defect.

Both analyses, interpreted correctly, show the same preventive benefit of higher levels of serum folate. The researchers show that a target serum folate concentration of 44 ng/mL would prevent about 80% of neural tube defects.

This is in line with the results of a U.K. randomized trial, the MRC Vitamin Study, that more than 30 years ago definitively established folate deficiency as a cause of neural tube defects.