Title: Folate-related Neural Tube Defects

Key words: Folate status, periconceptional supplementation, prevalence, neural tube closure, fortification

Date: June 1999

Category: 10. Reproduction

Type: Article

Author: Dr van Rhijn



Folate-related Neural Tube Defects

The Possible Approaches To Reducing Prevalence


It is clearly established that folate status is crucial in reducing the risk of a neural tube defect (NTD)1, 2. Studies have substantiated the fact that periconceptional supplementation with folic acid is an effective method of primary prevention of first occurrence3 and recurrence4, 5, 6 of NTDs. There is no consensus regarding the implementation of a practical and cost effective supplementation strategy. Three strategies have been proposed7, 8.

Current Situation

The prevalence of NTD is currently 0.3 per 1000 births, of which 95 % are first occurrences9. The mechanism of the protective effect of folate is not completely understood10. The Department of Health (UK) and the Public Health Service (USA) recommend that all women of childbearing age increase their consumption of folic acid through diet or supplementation to 400 m g folic acid per day, beginning 1 month before pregnancy and ending at the start of the second trimester11, 12 .

The Food Option

The recommendation to increase intake of natural, dietary, folate-rich food alone is ineffective in increasing folate status adequately13, 14. This may be due to poor chemical stability, reduced bioavailability of conjugated forms of folate in food, ignorance regarding folate food sources and/or reluctant to change dietary habits.

The Supplement Option

Targeting and supplementing the diet of women planning a pregnancy and other high-risk individuals as a practical preventative15, has a small effect on the population prevalence but can substantially change the individual's risk16. Synthetic folic acid is stable, bioavailable and the amount supplied is known and fixed. It is possible to estimate benefits plus risks and there is implied individual consent.

The majority of pregnancies are unplanned and, even if planned, occur in women who have not taken folic acid supplements preconceptionally (young, smoking and low educational attainments) at the time of neural tube closure17. Many women are unaware of the benefits of folic acid18, despite health education strategies19 and intensive publicity20.

Fortification Option

The Food and Drug Administration (FDA) has approved mandatory fortification of cereal-grain products that will increase the average intake by only 100 m g, thus reducing the risk for NTD substantially, without the risk of exposing the elderly to unacceptably high levels21, 22. There is a risk of masking Vit B12 deficiency in pernicious anaemia among the elderly23 and vegetarians, resulting in irreversible neuropathy, but a potential benefit of lowering homocysteinemia and risk of vascular disease24.

The problems of unplanned pregnancies, poor knowledge25 and compliance still remain, which strengthens the case for fortification. But individual exposure will differ, may not reach the target group and it is difficult to withhold consent. Better advice and labelling of foods may raise awareness, but a promotional health claim for ‘NTD prevention’ is prohibited in the UK.


Synthetic folic acid, taken as a supplement (starting before pregnancy)26 or preferably, in fortified foods may be the best way to increase folate levels in women of childbearing age27. A general public health strategy is needed, based on dietary advice28 and food fortification designed to achieve the benefit with adequate safety and monitored for efficacy29 and possible harm30.


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