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Folic Acid and the Prevention of Neural Tube Defects (NTDs) Challenges and Recommendations for Public Health Heidi S. Reisch, RD1 Mary A.T. Flynn, PhD, RD, RPH Nutr2 ABSTRACT Objective: To outline specific challenges facing public health in Canada that need to be addressed to ensure that all women of childbearing years can attain optimal folate status for prevention of NTDs. Methods: The new Dietary Reference Intake (DRI) for folate was examined in terms of the literature on the effective form of the vitamin, the level of folic acid provided by the Canadian food supply and the folic acid content of available supplements. Findings: There are six major challenges facing public health in Canada on this issue. These include confusion among health professionals and the general public on the effective form of the vitamin, requirements, and the necessity of taking supplements. Further obstacles to ensuring optimal folate status in all women of childbearing age in Canada include the limited amounts of folic acid that are currently permitted in foods and the difficulties involved in identifying the amount of folic acid provided in these foods in relation to needs. Interpretation: These challenges must be addressed to enable women in Canada to make an informed choice about folic acid. This has the potential to prevent up to 70% of the 300 births affected by NTDs each year. La traduction du résumé se trouve à la fin de l’article. Health Promotion & Disease Prevention, Healthy Communities, Calgary Health Region 1. Nutrition Specialist 2. Coordinator, Nutrition & Active Living Correspondence and reprint requests: Mary A.T. Flynn, P.O. Box 4016, Station “C”, Calgary, AB T2T 5T1, Tel: 403-943-8123, Fax: 403-943-8132, E-mail: [email protected] 254 REVUE CANADIENNE DE SANTÉ PUBLIQUE I n Canada, approximately 300 (or 1 of every 1000) births are affected by Neural Tube Defects (NTDs) each year, with spina bifida being the most common NTD.1 Direct health care costs for children with spina bifida could be up to $1.7 million per year. These costs do not account for the physical and emotional tolls upon the families affected nor do they reflect the lost economic potential associated with NTDs. While prenatal screening for NTDs can be performed with reasonable accuracy and reliability, no treatment is available in utero for the correction of NTDs. One of the most important medical breakthroughs in recent times was the discovery that taking a simple B vitamin, folic acid, in the peri-conceptual period could protect as many as 70% of babies affected by neural tube defects.2-4 Given the limitations of prenatal screening, primary prevention of NTDs is an issue of tremendous importance. However, by the time most women realize that they are pregnant, the period where folic acid is protective will have passed because the neural tube closes within 3 to 4 weeks after conception. Therefore, one of the greatest challenges for public health is to ensure that all women of childbearing years have optimal folate status for prevention of NTDs. This paper outlines the specific challenges facing Public Health in Canada. Challenge 1: Health professionals and the public do not fully understand that it is folic acid, the synthetic form of the B vitamin, rather than the folate found naturally in foods that plays a role in the prevention of NTDs. Scientific evidence has demonstrated that a maternal red blood cell folate level of >400 ng/mL, at the time of conception, is optimal in reducing risk of NTDs developing in the fetus. 5 This optimal level is much greater than the cut-off level used to determine folate deficiency leading to megaloblastic anemia (red cell folate ≤ 140 ng/mL.)6 It has been demonstrated that the optimal level of folate status can only be achieved through the consumption of 0.4 mg of the synthetic form of the vitamin (folic acid) and not through the consumption of foods naturally rich in folate.6-9 This is because folic acid is much more stable and bioavailable than its natural form, folate. VOLUME 93, NO. 4 CHALLENGES FOR PREVENTION OF NTDs USING FOLIC ACID In 1998, Canada and the United States harmonized nutrition recommendations, and introduced a special recommendation that all women of childbearing age consume 0.4 mg/day of synthetic folic acid from fortified foods or vitamin supplements (see Table I) in addition to natural food folate to help prevent NTDs.6 Challenge 2: All women need to be aware of their specific folic acid requirements for occurrence and recurrence of NTDs. Factors that put women at much higher risk of having a pregnancy affected by NTDs include having had a previously affected pregnancy (i.e., a high risk of recurrence), having a family history of NTDs, poor maternal health, diabetes, treatment with anticonvulsant drugs, medically diagnosed obesity and overconsumption of alcohol. Women affected by these factors require larger doses of folic acid than the recommended daily 0.4 mg.6,11 The daily requirement for these women is commonly estimated as 1.0 - 4.0 mg of folic acid but the exact dose needs to be medically recommended. Due to the uncertainty of the effects of these higher doses (see Table IV, Challenge 6 below) it is recommended that vitamin B12 status be monitored and that the higher dose be discontinued at 8 weeks gestation, after the neural tube has closed.6 Challenge 3: The complex differences between folic acid, folate and DFEs need to be simplified with folic acid being clearly identified as the effective form of the vitamin for the prevention of NTDs. The special recommendation of a folic acid intake of 0.4 mg/day, to prevent NTDs, is targeted specifically for women in the childbearing age range. However, for all individuals over the age of 14 years, the Recommended Daily Allowance (RDA) for folate is estimated to be 0.4 mg of Dietary Folate Equivalents (DFEs) with pregnant and lactating women having slightly higher RDAs (see Table I). DFEs represent a measure of estimated bioavailability considering the profound differences that exist between folic acid and folate.7,12,13 DFEs are a very useful tool for assessing overall dietary intakes of folates and folic acid in the ongoing quest for assessing the effective dose JULY – AUGUST 2002 TABLE I Dietary Reference Intakes (Recommended Dietary Allowances (RDAs)*, Special Recommendations, Upper Limits (UL)†, and Estimated Dietary Intakes of Folate and Folic Acid for Women6,10 Recommended Dietary Intakes Age (years) Special RDA Recommendation‡ (DFE mg/ Folic Acid day)§ (mg/day) 14-18 0.4 0.4 Pre-menopausal 19-50+ 0.4 0.4 Postmenopausal – 0.4 Pregnancy 14-18 0.4 0.6 Pregnancy 19+ 0.4 0.6 Lactation 14-18 0.4 0.5 Lactation 19+ 0.4 0.5 Estimated Dietary Intakes UL Folic Acid (mg/day) 0.8 1.0 1.0 0.8 1.0 0.8 1.0 Estimated Estimated Folate from Folic Acid Diet (mg/day)|| from Diet¶ (mg/day) 0.274 0.08 – 0.1 0.257 0.08 – 0.1 0.241 0.08 – 0.1 – 0.08 – 0.1 – 0.08 – 0.1 – 0.08 – 0.1 – 0.08 – 0.1 * RDA (Recommended Dietary Allowance) – the average daily dietary intake level that meets the nutrient requirement of nearly all (97 to 98 percent) healthy individuals in particular life stages and gender group † UL (The tolerable upper intake level) = upper safe level of intake of folic acid from fortified foods and/or supplements ‡ Special Recommendation – that all women of childbearing age consume 0.4 mg per day of synthetic folic acid from fortified foods or vitamin supplements in addition to natural food folate to help prevent NTDs. § DFE (Dietary Folate Equivalents) = naturally occurring food folate (µg) + [1.7 X of synthetic folic acid (µg)]8 || Weighted mean nutrient intake, Food Habits of Canadians, data provided between August 1997April 19989 ¶ From fortified flour-based products TABLE II Level of Folic Acid Fortification of Permitted Foods in Canada and the US, and the Amount of Folic Acid Delivered in Serving Sizes14,15 US Folic Acid Content per Serving Food Product Serving Size White* flour White* bread Enriched pasta (i.e., macaroni, spaghetti), noodles, rice (white) Ready-to-eat cold cereal 100 g 25-30 g (1 slice) 0.14 0.02 (35-40 g dry pasta) equivalent to 140 g (1 cup cooked) 0.06 – 0.09 30 g (1 cup to ½ cup puffed to dense cereal) 0.1 – 0.4 Canada Folic Acid Content per Serving (mg) 0.15 0.02 – 0.03 0.095 – 0.11 0.018 – 0.025 *Note: Whole-grain products do not have to be enriched. for prevention of occurrence and recurrence of NTDs. However, the validity of the DFE measure is an ongoing research issue. Therefore there are very complex differences between folic acid, folates and the DFE measure, with folic acid being the only effective form of the vitamin in relation to prevention of NTDs.7,9 The problem is that health professionals use these terms interchangeably, and are not clear on the ultimate importance of ensuring 0.4 mg of folic acid (or more for women at greater risk) for the prevention of NTDs. As an example, even the authors, who are registered dietitians working in public health, did not fully understand that naturally occurring folates in foods, measured as mg of folate or DFEs, do not provide optimal protection against NTDs. Challenge 4: Currently women can meet only 25% of their folic acid requirements through the Canadian food supply. As of November 1998, fortification of flour and selected grains with folic acid became mandatory in both Canada and the US.14,15 This is estimated to increase the daily intake of folic acid among women 18-34 years of age by 0.08 - 0.1 mg, representing 25% of women’s special folic acid needs (see Table II). The benefits from fortification are expected to reduce the number of NTD-affected pregnancies by 6 to 31%. Optimal fortification providing 0.4 mg of folic acid per day could reduce the number of NTD-affected pregnancies by up to 70% without causing any associated adverse effects. CANADIAN JOURNAL OF PUBLIC HEALTH 255 CHALLENGES FOR PREVENTION OF NTDs USING FOLIC ACID TABLE III Vitamin and Mineral Supplements: Random Survey of 5 Leading Pharmacies from Outlets in Calgary: Folic Acid Content, Vitamins and Minerals Above RDA and UL for Women of Childbearing Age and Cost for 30 Days Including all Women of Childbearing Age Folic Acid Vitamin and/or Vitamin and/or Content Range Mineral Above RDA Mineral Above (mg/daily dose) and Below UL UL (% above UL) Multivitamins and Minerals Regular Strength 0.1 – 0.4 Vitamin B1, B2, B6, B12, Niacin* and D-pantothenic acid, (13-25%) Biotin, Vitamin A, C, D Women Specific 0.4 Vitamin B1, B2, B6, B12, niacin and D-pantothenic acid, Zinc, Vitamin A, D High Potency 0.4 – 1.0 Vitamin B1, B2, B6, B12, Niacin* and/or Stress Tabs and D-pantothenic acid, (13-40%) Zinc, Vitamin D B-complex 1.0 Vitamin B1, B2, B6, B12, niacin and D-pantothenic acid Prenatal vitamin 0.8 – 1.0 Vitamin B1, B2, B6, B12, supplements niacin and D-pantothenic acid,Vitamin C, D, Zinc, Copper, Manganese Folic Acid 0.4 – 1.0 Cost per 30 Days ($) ~ 3.00 ~ 2.50 ~ 5.00 – 8.00 ~2.80 ~ 4.20 ~ 0.95 * Case reports and clinical trials have reported flushing effects of oral doses of 30 to 1000 mg niacin/day within 30 minutes to 6 weeks of the initial dose (40 - 100 mg of niacin were found in the multivitamin and mineral supplements). Individuals with hepatic dysfunction or a history of liver disease, diabetes mellitus, active peptic ulcer disease, gout, cardiac arrhythmia, inflammatory bowel disease, migraine headaches, and alcoholism are distinctly susceptible to the adverse effects of excess niacin intake. Therefore, people with these conditions may not be protected by the UL for niacin for the general population.6 In Canada, folic acid may be added to ready-to-eat breakfast cereals up to a maximum of 0.06 mg/100g, which provides 0.02 - 0.03 mg of folic acid per 30 g serving size (~5% of women’s special needs). The United States permit fortification of breakfast cereals in amounts that provide from 0.1 mg of folic acid up to 0.4 mg per 30 g serving size (25 to 100% of women’s special needs – see Table II). In Europe, voluntary fortification permits the addition of folic acid to foods other than grains, such as dairy products. In the United Kingdom, in addition to the wider range of foods that may have folic acid added, mandatory fortification of flour, at double the level currently added to Canadian flour, has been proposed. This fortification is estimated to increase folic acid intake by 0.2 mg per day, reducing NTD risk by approximately 42%,9 which represents an 11 to 36% greater decrease in risk than can be achieved through Canada’s current fortification program. Due to the limited range of foods that may be fortified and the restrictions on the amounts of folic acid that may be added to these foods, Canadian women cannot meet the special recommendation (0.4 mg folic acid/day) through diet. 256 REVUE CANADIENNE DE SANTÉ PUBLIQUE Challenge 5: Currently it is difficult for women to identify foods fortified with folic acid and to determine the amount provided in relation to their needs. The new mandatory nutrition labelling gives Canadians the control to make judicious food choices to optimize their health. However, in relation to folic acid, the initial period of labelling in Canada will not allow easy identification of foods fortified with folic acid or make it simple for women to determine the amount provided in relation to their special needs. This is because the reference amount of folic acid indicated on the label will initially be based on the 1983 nutrient recommendations, which represent slightly over half the special recommendation of 0.4 mg and do not distinguish between folate and folic acid. The new labelling makes it mandatory to report the content of 13 nutrients considered to be important for public health on labelled foods. Despite its public health significance, folic acid is not included as one of these crucial nutrients. In addition, the units (milligrams, mg) that will be used on labels to express the folic acid content in foods will compel women to calculate intake using decimal points rather than whole numbers (i.e., amounts that add up to 0.4 mg). Challenge 6: The only effective way that Canadian women can use folic acid to protect their babies from NTDs necessitates taking a daily vitamin supplement that is not readily available (in optimal nutrient doses) and represents an ongoing cost ($11 $35 per year) to them throughout their childbearing years. In Canada, health professionals have no option but to promote the use of a daily supplement containing folic acid for prevention of NTDs (see above). A random survey of five leading Calgary pharmacy outlets found that the supplements available provide folic acid (expressed in mg) in varying amounts. These supplements include multivitamin/mineral, and prenatal specific supplement formulations, and single folic acid vitamin supplements (see Table III). Regular strength multivitamin/mineral formulations provide between 0.1 - 0.4 mg of folic acid per tablet (i.e., between 25 - 100% of women’s special needs). With the exception of regular multivitamin/mineral supplements, the majority of the supplements available were found to provide more than double the daily amount of folic acid recommended (see Table III). In addition, some of these supplements were found to provide more than the daily tolerable upper level intake (UL) for another vitamin, niacin. The long-term safety of this is unknown (see Table III). There are limited data on the safety of consuming folic acid doses over the UL (1.0 mg) and it is recommended that women consume no more than this.6 Large amounts of folic acid (between 1 and 5 mg/day) have been found to mask vitamin B12 deficiency by correcting the early symptom of megaloblastic anemia. Untreated vitamin B12 deficiency results in irreversible neurological damage. 6 Therefore long-term excessive supplemental folic acid intake has the potential to increase the prevalence of compromised neurological function in groups at risk of Vitamin B12 deficiency (e.g., vegans). Resulting neurological damage may be serious, irreversible and crippling. It is a matter of concern that with the fortification of Canadian flour (providing ~ 0.1 mg/day) and the majority of available folic acid supplements containing a 1 mg daily dose, many Canadian women will exceed the UL for folic acid, risking potential long-term VOLUME 93, NO. 4 CHALLENGES FOR PREVENTION OF NTDs USING FOLIC ACID TABLE IV Folic Acid and the Prevention of Neural Tube Defects (NTDs): Challenges and Possible Solutions for Public Health Challenges The effective agent that prevents NTDs is the synthetic form of the B vitamin folate (folic acid) because of its superior bioavailability. Challenge 1: Health professionals and the public do not fully understand that it is folic acid, the synthetic form of the B vitamin, rather than the folate found naturally in foods that plays a role in prevention of NTDs. Possible Solutions A national Public Health campaign should be considered. This should focus on educating health professionals and the public on the specific importance of folic acid in the prevention of NTDs. To help prevent the occurrence of NTDs, there is a special recommendation that all women capable of becoming pregnant consume 0.4 mg of folic acid daily in the form of supplements and/or fortified foods, in addition to consuming food folate from a varied diet. Women who have had a baby affected by an NTD or who are at increased risk (see text) need to seek medical advice because their folic acid requirements are much higher (ranging from 1.0 – 4.0 mg/day). Optimal maternal folate levels throughout a women’s childbearing years are critical as the neural tube closes before most women even know they are pregnant. Challenge 2: All women need to be aware of their specific folic acid requirements for occurrence and recurrence of NTDs. All Canadian women capable of becoming pregnant need to know the importance of taking folic acid daily; - Women who have had a baby affected by an NTD or who are otherwise at increased risk (see text) need to be aware that they have special requirements for folic acid and need to seek medical advice. - Women taking higher than recommended doses of folic acid need to be regularly monitored by their physicians. Currently, folates, folic acid and DFEs are used interchangeably, by health professionals and the public, with little understanding of the profound differences in their effectiveness and relation to NTD prevention. Challenge 3: The complex differences between folic acid, folate and DFEs need to be simplified, with folic acid being clearly identified as the effective form of the vitamin for the prevention of NTDs. For successful prevention of NTDs, the differences between folic acid, folate, and DFEs need to be clearly understood: - Folic acid available in supplements and fortified foods protects against the development of NTDs. - Folate found naturally in foods protects against deficiency but does not provide women with optimal folate status for NTD prevention. - DFEs are a very useful tool for assessing overall dietary intakes of folates and folic acid in the ongoing quest for assessing the effective dose for prevention of occurrence and recurrence of NTDs. However, until nutrition research fully evaluates the effectiveness of the DFE measure, its use should be limited to research. It is mandatory in Canada to fortify white flour with folic acid so that 100 g of flour provides 0.15 mg of folic acid. However, this fortification is estimated to meet only 25% of the special recommendation of folic acid (0.4 mg/day). In addition to flour, only a few selected grains are permitted to be fortified with only very limited amounts of folic acid. Challenge 4: Currently, women can only meet 25% of their folic acid requirements through the Canadian food supply. Food legislation could be modified to increase: - the range of foods that can be fortified with folic acid, and - the amount of folic acid added to fortified foods. New labelling in Canada proposes: - to use half the recommended daily intake for folate as a reference in the initial introduction phase, - to exclude folic acid from the 13 nutrients mandated to be included in the nutrition label box, and - to express the amount of folic acid present in milligrams, which compels women to calculate intakes using decimal points. A time lag of 2 - 6 years for implementation of new labelling delays NTD prevention strategies using folic acid in foods. Challenge 5: Currently, it is difficult for women to identify foods fortified with folic acid and to determine the amount provided in relation to their needs. The identification of foods fortified with folic acid should be effortless and the amount of folic acid they provide should be easily understood by everyone. - The most current recommendations (DRIs) should be used as reference intakes against which women can estimate their folic acid intake. - Foods fortified with folic acid should be clearly identified – attaching a separate sticker in addition to the food label could be considered. - Consideration should be given to making nutrition labelling on folic acid mandatory – perhaps by including folic acid as the 14th nutrient to be included in the proposed nutrition labelling box. - The amount of folic acid could be expressed in micrograms instead of milligrams to make it easier for women to calculate their overall intake. - Consideration should be given to initiating interim labelling for folic acid-fortified foods immediately. Supplements represent the only effective way for Canadian women to meet their folic acid requirements for the prevention of NTDs. However, readily available supplements containing folic acid: - often provide above-optimal levels of folic acid or other nutrients, - express the amount of folic acid present in milligrams (mg), which compels women to calculate intakes using decimal points, and - represent an ongoing cost to women of childbearing age. Health professionals are often unaware of risks associated with taking above-optimal dosages of folic acid in the long term. Challenge 6: The only effective way that Canadian women can use folic acid to protect their babies from NTDs necessitates taking a daily vitamin supplement that is not readily available (in optimal nutrient doses) and represents an ongoing cost ($11 - $35 per year) to them throughout their childbearing years. Control access to supplements: - supplements that provide folic acid and other nutrients at optimal, rather than above-optimal levels, should be readily available. - those containing more than RDA for folic acid or other nutrients should be available by prescription only. Educate health professionals (especially pharmacists and physicians) on the risks associated with taking folic acid and other nutrients above their tolerable upper intake level. health effects. None of the pharmacists approached in the random survey of Calgary outlets expressed any concerns in JULY – AUGUST 2002 Promote clear and simple messages - the amount of folic acid should be expressed in micrograms instead of mg to make it easier for women to calculate their overall intake. Address the cost issue: - consideration could be given to making folic acid supplements available free of charge for all women of childbearing age. recommending 1.0 mg folic acid/day and were unaware that single folic acid supplements came in the form of a 0.4 mg dose. Encouraging folic acid supplementation throughout a woman’s entire childbearing years (n = 25 years) represents a cost to CANADIAN JOURNAL OF PUBLIC HEALTH 257 CHALLENGES FOR PREVENTION OF NTDs USING FOLIC ACID women of $285 - $865 (at today’s prices). This cost is insignificant in comparison to the costs of raising a child with a neural tube defect. Women from socio-economically disadvantaged backgrounds are at higher risk of having a pregnancy affected by NTDs.1,16,17 It is unlikely that these women would able to afford the extra long-term cost of daily folic acid supplements, even if they were aware of their particular importance. Finally, studies have shown that it is difficult to persuade women at any income level to comply with taking a daily supplement for years on end. Those who are motivated to take a folic acid supplement often take it too late, and this partly due to the fact that 50% of pregnancies are unplanned. 3. 4. 5. 6. 7. 8. 9. CONCLUSION The tremendous discovery of the protective effects of folic acid supplementation raises many challenges for public health in Canada. These must be overcome before Canada can fully benefit by preventing up to 70% of the 300 births affected by NTDs each year. The point of this paper is to highlight the issues that need to be clarified so that women can make an informed choice about folic acid. Possible solutions to overcome these challenges are outlined in Table IV. REFERENCES 1. International Centre of Birth Defects. International clearinghouse for birth defects monitoring systems: Annual report, 1998. Rome, Italy. 2. Werler MM, Shapiro S, Mitchell AA. Periconceptional folic acid exposure and risk of 258 REVUE CANADIENNE DE SANTÉ PUBLIQUE 10. occurent neural tube defects. JAMA 1993;269:1257-61. Czeizel AE, Duda I. Prevention of the first occurrence of neural tube defects by periconceptional vitamin supplementation. N Engl J Med 1992;327:1832-35. Wald NJ, Law M, Jordan R. Folic acid food fortification to prevent NTDs. Lancet 1998;351:834-35. Daly LE, Kirke PN, Molloy A, Weir DG, Scott JM. Folate levels and NTDs - Implications for prevention. JAMA 1995;274:1698-702. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes: Folate, Other B Vitamins, and Choline. Washington, DC: National Academy Press, April 7, 1998. Cuskelly GJ, McNulty H, Scott JM. Effect of increasing dietary folate on red-cell folate: Implications for prevention of neural tube defects. Lancet 1996;347:657-59. Cuskelly GJ, McNulty H, Scott JM. Fortification with low amounts of folic acid makes a significant difference in folate status in young women: Implications for the prevention of neural tube defects. Am J Clin Nutr 1999;70:234-39. McNulty H, Cuskelly GJ, Ward M. Responses of red blood cell folate to intervention: Implications for folate recommendations for the prevention of neural tube defects. Am J Clin Nutr 2000;71(suppl):1308S-11S. Gray-Donald K, Jacobs-Starkey L, JohnsonDown L. Food habits of Canadians: Reduction in 11. 12. 13. 14. 15. 16. 17. fat intake over a generation. Can J Public Health 2000;91(5):381-85. MRC Vitamin Study Research Group. Prevention of NTDs: Results of the Medical Research Council vitamin study. Lancet 1991;338:131-37. Gregory JF. Bioavailability of Nutrients and Other Bioactive Components from Dietary Supplements: Case Study: Folate Bioavailability. J Nutr 2001;131:1376S-82S. Sauberlich HE, Ketsch MJ, Skala JH, Johnson HL, Taylor PC. Folate requirement and metabolism in nonpregnant women. Am J Clin Nutr 1987;46:1016-28. Canadian Food and Drug Administration (FDA) Regulations, Health Canada, 1998. DHHS (U.S. Department of Health and Human Services). Food and Drug Administration. Food Standards: Amendment of the standards of identity for enriched grain products to require addition of folic acid. Fed Regist 61:8781-807. Laurence KM, James N, Miller M, Campbell H. Increased risk of recurrence of pregnancies complicated by fetal neural tube defects in mothers receiving poor diets, and possible benefit of dietary counselling. Br Med J 1980;281:1592-94. Wasserman CR, Shaw GM, Selvin S, Gould JB, Syme SL. Socioeconomic status, neighborhood social conditions and neural tube defects. Am J Public Health 1998;88:1674-80. Received: July 30, 2001 Accepted: March 7, 2002 RÉSUMÉ Objectif : Décrire les défis particuliers que doit relever la santé publique au Canada pour que toutes les femmes en âge de procréer aient un niveau de folate optimal pour la prévention des anomalies du tube neural (ATN). Méthode : Nous avons examiné le nouvel Apport nutritionnel de référence (ANREF) pour le folate à la lumière de la documentation sur les formes efficaces de la vitamine, du niveau d’acide folique dans l’alimentation canadienne et du contenu en acide folique des suppléments nutritifs disponibles. Constatations : Les responsables de la santé publique au Canada ont six grands défis à relever dans ce dossier, notamment la confusion, parmi les professionnels de la santé et dans le grand public, sur la forme la plus efficace de cette vitamine, sur les besoins en folate et sur la nécessité ou non de prendre des suppléments. Les autres obstacles à surmonter sont les faibles quantités d’acide folique actuellement autorisées dans les aliments et la difficulté de déterminer la quantité d’acide folique dans l’alimentation par rapport aux besoins. Interprétation : Il faut se pencher sur ces questions pour permettre aux Canadiennes de faire un choix éclairé au sujet de l’acide folique. On pourrait éventuellement prévenir jusqu’à 70 % des ATN, qui touchent 300 naissances chaque année. VOLUME 93, NO. 4