Ebook The Relationship Between Dietary Folate Intake Of Women Of Child-Bearing Age And Risk Of Neural Tube Defects In The Foetus
Folate is a water-soluble B vitamin that occurs naturally in food. Folic acid is a synthetic form of folate. Because of its high stability and bioavailability, folic acid is the form of folate that is used in supplements and added to fortified foods. Folate helps produce and maintain new cells and is, therefore, important during periods of rapid growth such as pregnancy. Neural tube defects (NTD), serious birth defects that occur around 28 days post conception, result in malformations of the brain (anencephaly) and spine (spina bifida). Infants with anencephaly die at birth or soon after and those with spina bifida are often afflicted with varying degrees of paralysis and disability. Over 30 years ago it was first suggested that folic acid taken periconceptionally could reduce a woman’s chance of having an NTD-affected pregnancy.
There is now convincing evidence that folic acid taken prior to and during the first month of pregnancy can reduce a woman’s risk of having an NTD affected pregnancy. No fewer than 15 cross sectional and case-control studies have examined this relationship and nearly all have been supportive. The most convincing evidence comes from three randomized controlled trials and a public health campaign conducted in China. In one study, periconceptional folic acid taken alone (4 mg) or as part of a multi vitamin reduced the risk of NTD by 72% in women with a prior NTD affected pregnancy. In another study of primary NTD prevention there were no cases of NTD in women receiving folic acid (800 µg) as part of a multivitamin supplement and six cases in women receiving a placebo, representing a complete protective effect (Czeizel & Dudas, 1992). In a population based prevention campaign in China, risk of an affected pregnancy was reduced by 80% in women taking 400 µg folic acid in a northern province of China. Although there is now convincing evidence that folate lowers NTD risk we are no closer at saying how folate prevents NTDs. Most women who have an NTD affected pregnancy are not folate deficient. It has been suggested that additional folic acid during the periconceptional period helps overcome some metabolic block in genetically sensitive women.
Improved folate status during the peri-conceptional period will not prevent all NTDs. Nevertheless, folic acid taken during the periconceptional period has been shown to be effective against NTD in a wide range of populations and study designs. There is no reason to expect that increasing folic acid intake periconceptionally would not be effective against NTD in Australia and New Zealand. NTD rates are low in Australia and New Zealand. Accordingly, the magnitude of reduction in NTD with folic acid may be diminished.
Public health advice is that women who are planning a pregnancy should take a folic acid supplement providing 400 µg/d folic acid at least one month before conception through the third month of pregnancy. Women planning a pregnancy should not rely on natural sources of folate or fortified foods for NTD prevention. Up to 50% of pregnancies are unplanned and as a result strategies are needed to provide additional folate to women who could become pregnant.
The strength of evidence indicating that natural folate is protective against NTDs is possible at best. Further, issues of bioavailability, stability, and measurement of natural folate make it is impossible to indicate the dose, if any, of natural folate required to prevent NTD. Consideration should be given to amount of folic acid a food should contain to be allowed to carry the claim. The minimum amount of folate required to prevent NTD is not known with any certainty. The lowest dose of folic acid demonstrated to be effective in an intervention trial is 400 µg/d. However, based on changes in red cell folate, doses of folic acid as low as 100-200 µg folic acid per day consumed chronically may confer some protection. A woman would have to eat approximately six and eleven servings of a fortified food containing, for example, 35 µg folic acid to achieve folic acid intakes of 200 and 400 µg, respectively.
CONTENTS
BACKGROUND INFORMATION
- Folate Terminology
Areas Not Covered in this Review
PART 1. CRITICAL APPRAISAL OF PREVIOUS REVIEW OF THIS DIET-HEALTH RELATIONSHIP
- (Presently Unavailable)
PART 2. REVIEW OF EVIDENCE RELEASED SINCE THE TIME OF THE CANADIAN REVIEW
PART 3. RELEVANCE OF THE RELATIONSHIP TO AUSTRALIA AND NEW ZEALAND
PART 4. RELATIONSHIP OF FOLATE INTAKE WITH RELEVANT BIOMARKERS OF DISEASE OUTCOME
PART 5. OVERALL CONCLUSIONS
- Summary
REFERENCES
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