Half of population at risk of birth defects, folic acid important

It underscores the importance of folic acid supplementation for all women of childbearing age to prevent neural tube defects and could also add fuel to the debate for folate fortification of foods.

During periods of rapid growth, such as pregnancy and foetal development, the body's requirement for folic acid increases and insufficient levels of the vitamin in mothers have been linked to higher risk of neural tube defects, causing the permanently disabling disease spina bifida, in offspring.

Nutritionists and public health campaigns have long recommended folic acid supplements for women who are trying to conceive but recent research​ suggests that only about 25 per cent of women in many countries voluntarily take folic acid tablets before conception.

Yet in the new study, researchers in Ireland and the United States have identified that more people than previously thought, about half of the population, could be at high risk of birth defects.

The researchers identified the genetic make-up (genotype) of 395 individuals born with neural tube defects (spina bifida or encephalocele) and 848 controls.

The TT (homozygous variant) form of the gene responsible for processing folate is associated with an increased risk of neural tube defects, but the team set out to investigate the possibility that the CT (heterozygous variant) form would also increase the risk of these malformations.

Both genotypes are linked to lower tissue concentrations of folate, higher levels of homocysteine (an amino acid), and lower enzyme activity than the wild CC genotype.

The CT genotype was responsible for at least as many neural tube defects in the population as the TT genotype. This is because a much greater proportion of the general population (38 per cent) are CT compared with 10 per cent who are TT.

The combined CT and TT genotypes account for about 26 per cent of neural tube defects in Ireland, say the authors. And folate or folic acid is estimated to be involved in about 50-70 per cent of these defects. Thus, up to half of the folate related neural tube defects may be explained by this single genetic variant, they argue.

Both the lower folate and higher homocysteine levels associated with CT and TT genotypes can be corrected by folic acid, add the authors, therefore underscoring the importance of public health intervention programmes of folic acid supplementation and food fortification targeted at all women of childbearing age.

In Canada, which introduced folic acid fortification of grain-based foods in 1998, the prevalence of neural-tube defects among both unborn and newborn children has been halved and it has also had a similar benefit on incidence of the deadly childhood cancer neuroblastoma.

Europe remains fearful of possible side-effects of a wide-ranging fortified food initiative. A two-year investigation into flour fortification by the UK's Food Standards Agency concluded in 2002 that this could mask a deficiency of vitamin B12 in elderly people.

However a report in this month's British Journal of Obstetrics and Gynaecology​ (vol 111, issue 5, p399) underlines the problems for individuals relying on self-supplementation. The neural tube is fully developed 22 to 28 days after conception but many women are not aware they are pregnant until after this time and starting folic acid supplements after this period is too late to realize benefits, the researchers write.

In addition, a fortification programme could also turn out to have other public health benefits, such as the prevention of heart disease, conclude the authors of the BMJ article.

Folic acid has also recently been linked to bone health​.