Folic acid and neural tube defects: what the evidence shows

Few findings in nutrition are as well established as the link between folic acid and the prevention of neural tube defects (NTDs) — serious birth defects of the brain and spine, such as spina bifida and anencephaly, that form in the first weeks of pregnancy, often before a woman knows she is pregnant.

The landmark evidence

A pivotal 1999 study led by Berry and colleagues, published in the New England Journal of Medicine, followed hundreds of thousands of women in China. It found that periconceptional intake of 400 micrograms of folic acid a day substantially reduced the risk of neural tube defects — with the largest reductions in regions where baseline rates were highest.^[1] Because the neural tube closes so early, the protective intake must occur before and around conception, which is precisely why a continuous dietary source matters.

What happens when whole countries fortify

The clearest demonstration comes from national fortification programmes. A systematic review of folic-acid flour fortification found significant reductions in NTDs in every country that reported results.^[2] Among the documented outcomes: Chile saw roughly a 43% reduction after fortifying wheat flour in 2000; Canada around 40% and the United States about 28% within a decade of mandatory fortification in 1998; Costa Rica close to 60%; and Brazil about 30%.^[2]

Adequate folic acid intake before conception and during early pregnancy can prevent a substantial share of neural tube defects — making it one of the great success stories of preventative nutrition.

Why fortification reaches further than supplements alone

Folic-acid supplements work — but only for women who know to take them, before they conceive. Many pregnancies are unplanned, and supplement programmes depend on consistent access and awareness. Fortifying a staple food closes that gap: it delivers a steady, low dose to the whole population, including women who are not yet planning a pregnancy. This is why the WHO recommends fortifying maize flour and corn meal with folic acid to reduce the risk of NTD-affected births.^[3]

The takeaway

For a micronutrient that must be present at a specific, early, and easily-missed window, building it into everyday food is one of the most reliable ways to protect future pregnancies — quietly, continuously, and at population scale.