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Not all cases of neural-tube defect can be prevented by increasing the intake of folic acid

  • Helmut B. Heseker (a1), Joel B. Mason (a2), Jacob Selhub (a3), Irwin H. Rosenberg (a4) and Paul F. Jacques (a5)...

Abstract

Some countries have introduced mandatory folic acid fortification, whereas others support periconceptional supplementation of women in childbearing age. Several European countries are considering whether to adopt a fortification policy. Projections of the possible beneficial effects of increased folic acid intake assume that the measure will result in a considerable reduction in neural-tube defects (NTD) in the target population. Therefore, the objective of the present study is to evaluate the beneficial effects of different levels of folic acid administration on the prevalence of NTD. Countries with mandatory fortification achieved a significant increase in folate intake and a significant decline in the prevalence of NTD. This was also true for supplementation trials. However, the prevalence of NTD at birth declined to approximately five cases at birth per 10 000 births and seven to eight cases at birth or abortion per 10 000 births. This decline was independent of the amount of folic acid administered and apparently reveals a ‘floor effect’ for folic acid-preventable NTD. This clearly shows that not all cases of NTD are preventable by increasing the folate intake. The relative decline depends on the initial NTD rate. Countries with NTD prevalence close to the observed floor may have much smaller reductions in NTD rates with folic acid fortification. Additionally, potential adverse effects of fortification on other vulnerable population groups have to be seriously considered. Policy decisions concerning national mandatory fortification programmes must take into account realistically projected benefits as well as the evidence of risks to all vulnerable groups.

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Corresponding author

*Corresponding author: Helmut B. Heseker, fax +49 5251 603425, email helmut.heseker@uni-paderborn.de

References

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1van der Linden, IJ, Afman, LA, Heil, SG, et al. (2006) Genetic variation in genes of folate metabolism and neural-tube defect risk. Proc Nutr Soc 65, 204215.
2MRC Vitamin Study Research Group (1991) Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 338, 131137.
3Berry, RJ, Li, Z, Erickson, JD, et al. (1999) Prevention of neural-tube defects with folic acid in China. N Engl J Med 341, 14851490.
4Buttriss, J (2005) Strategies designed to increase awareness about folates and health and to increase folate intake: a review. Trends Food Sci Technol 16, 246252.
5Czeisel, AE & Kökény, M (2002) Bread is fortified with folic acid in Hungary. Br Med J 325, 391.
6Bower, C, Miller, M, Payne, J, et al. (2005) Promotion of folate for the prevention of neural tube defects: who benefits? Paediatr Perinat Epidemiol 19, 435444.
7Finglas, PM, de Meer, K, Molloy, A, et al. (2006) Research goals for folate and related B vitamin in Europe. Eur J Clin Nutr 60, 287294.
8Food Safety Authority of Ireland (2006) Report of the National Committee on Folic Acid Food Fortification. Dublin: FSAI.
9Krawinkel, M, Brönstrup, A, Bechthold, A, et al. (2006) Strategien zur Verbesserung der Folatver-sorgung in Deutschland – Nutzen und Risiken. Ernaehrungs-Umschau 53, 468479.
10SACN (2006) Folate and Disease Prevention. London: The Stationery Office.
11Food Standards Agency (2008) Folic Acid Fortification. http://www.food.gov.uk/healthiereating/folicfortification.
12White Junod, S (2001) Folic Acid Fortification: Fact and Folly. Food and Law Institute: update issues 4, 5, 6. http://www.fda.gov/oc/history/makinghistory/folicacid.html.
13Botto, LD, Lisi, A, Bower, C, et al. (2006) Trends of selected malformations in relation to folic acid recommendations and fortification: an international assessment. Birth Defects Res A Clin Mol Teratol 76, 693705.
14Cornel, MC, de Smit, DJ & de Jong-van den Berg, LTW (2005) Folic acid – the scientific base for a public health policy. Reprod Toxicol 20, 411415.
15Chen, CP (2008) Syndromes, disorders and maternal risk factors associated with neural tube defects (IV). Taiwan J Obstet Gynecol 47, 141150.
16Mitchell, LE (2005) Epidemiology of neural tube defects. Am J Med Genet C Semin Med Genet 135C, 8894.
17Mills, JL & Signore, C (2004) Neural tube defect rates before and after food fortification with folic acid. Birth Defects Res 70, 844845.
18Joò, JG, Beke, A, Papp, Z, et al. (2007) Risk of recurrence in major central nervous system malformations between 1976 and 2005. Prenat Diag 27, 10281032.
19Grosse, SD & Collins, JS (2007) Folic acid supplementation and neural tube defect recurrence prevention. Birth Defects Res A Clin Mol Teratol 79, 737742.
20Queisser-Luft, A, Stolz, G, Wiesel, A, et al. (2002) Malformations in newborn: results based on 30 940 infants and fetuses from Mainz congenital birth defect monitoring system (1990–1998). Arch Gynecol Obstet 266, 163167.
21ICMR, Central Technical Co-ordinating Unit (2000) Multicentric study of efficacy of periconceptional folic acid containing vitamin supplementation in prevention of open neural tube defects from India. Indian J Med Res 112, 206211.
22Rothenberg, SP, da Costa, MP, Sequeira, JM, et al. (2004) Autoantibodies against folate receptors in women with a pregnancy complicated by a neural-tube defect. N Engl J Med 350, 134142.
23López-Camelo, JS, Orioli, IM, da Graça Dutra, M, et al. (2005) Reduction of birth prevalence rates of neural tube defects after folic acid fortification in Chile. Am J Med Genet 135A, 120125.
24CDC (2004) Spina bifida and anencephaly before and after folic acid mandate – United States, 1995–1996 and 1999–2000. MMWR Morb Mortal Wkly Rep 53, 362365.
25Williams, LJ, Rasmussen, SA, Flores, A, et al. (2005) Decline in the prevalence of spina bifida and anencephaly by race/ethnicity: 1995–2002. Pediatrics 116, 580586.
26De Wals, P, Tairou, F, Van Allen, MI, et al. (2007) Reduction in neural-tube defects after folic acid fortification in Canada. N Engl J Med 357, 135142.
27Gucciardi, E, Pietrusiak, MA, Reynolds, DL, et al. (2002) Incidence of neural tube defects in Ontario, 1986–1999. CMAJ 167, 237240.
28Moore, LL, Bradlee, ML, Singer, MR, et al. (2003) Folate intake and the risk of neural tube defects: an estimation of dose-response. Epidemiology 14, 200205.
29Czeizel, AE, Dobó, M & Vargha, P (2004) Hungarian cohort-controlled trial of periconceptional multivitamin supplementation shows a reduction in certain congenital abnormalities. Birth Defects Res A Clin Mol Teratol 70, 853861.
30Klusmann, A, Heinrich, B, Stoepler, H, et al. (2005) A decreasing rate of neural tube defects following the recommendations for periconceptional folic acid supplementation. Acta Paeditrica 94, 15381542.
31CDC (2008) Prevalence of neural tube defects and folic acid knowledge and consumption – Puerto Rico, 1996–2006. MMWR Morb Mortal Wkly Rep 57, 1013.
32Busby, A, Armstrong, B, Dolk, H, et al. (2005) Preventing neural tube defects in Europe: a missed opportunity. Reprod Toxicol 20, 393402.
33Queisser-Luft, A & Spranger, J (2006) Congenital malformations. Dtsch Aertzebl 103, 24622471.
34FDA (1993) Food labeling: health claims and labeling statements: folate and neural tube defects. Fed Regist 58, 5325453295.
35Yang, QH, Carter, HK, Mulinare, J, et al. (2007) Race–ethnicity differences in folic acid intake in women of childbearing age in the United States after folic acid fortification: findings from the National Health and Nutrition Examination Survey, 2001–2002. Am J Clin Nutr 85, 14091416.
36Choumenkovitch, SF, Selhub, J, Wilson, PW, et al. (2002) Folic acid intake from fortification in United States exceeds predictions. J Nutr 132, 27922798.
37Pfeiffer, CM, Caudill, SP, Gunter, EW, et al. (2005) Biochemical indicators of B vitamin status in the US population after folic acid fortification: results from the National Health and Nutrition Examination Survey 1999–2000. Am J Clin Nutr 82, 442450.
38Dietrich, M, Brown, CJP & Block, G (2005) The effect of folate fortification of cereal-grain products on blood folate status, dietary folate intake, and dietary folate sources among adult non-supplement users in the United States. J Am Coll Nutr 24, 266274.
39CDC (2007) Folate status in women of childbearing age, by race/ethnicity – United States, 1999–2000, 2001–2002, and 2003–2004. MMWR Morb Mortal Wkly Rep 55, 13771380.
40Pfeiffer, CM, Johnson, CL, Jain, RB, et al. (2007) Trends in blood folate and vitamin B12 concentrations in the United States, 1988–2004. Am J Clin Nutr 86, 718727.
41Esfahani, ST, Cogger, EA & Caudill, MA (2003) Heterogeneity in the prevalence of methylenetetrahydrofolate reductase gene polymorphisms in women of different ethnic groups. J Am Diet Assoc 103, 200207.
42Oakley, GP (2007) When will we eliminate folic acid-preventable spina bifida? Epidemiology 18, 367368.
43Johnston, RB (2008) Will increasing folic acid in fortified grain products further reduce neural tube defects without causing harm? Consideration of the evidence. Pediatr Res 63, 13.
44Quinlivan, EP & Gregory, JF (2007) Reassessing folic acid consumption patterns in the United States (1999–2004): potential effect on neural tube defects and overexposure to folate. Am J Clin Nutr 86, 17731779.
45Botto, LD, Lisi, A, Robert-Gnansia, E, et al. (2005) International retrospective cohort study of neural tube defects in relation to folic acid recommendations: are the recommendations working? BMJ 330, 571.
46Charles, DH, Ness, AR, Campbell, D, et al. (2005) Folic acid supplements in pregnancy and birth outcome: re-analysis of a large randomised controlled trial and update of Cochrane review. Paediatr Perinat Epidemiol 19, 112124.
47Canfield, MA, Collins, JS, Botto, LD, et al. (2005) Changes in the birth prevalence of selected birth defects after grain fortification with folic acid in the United States: findings from a multi-state population-based study. Birth Defects Res A Clin Mol Teratol 73, 679689.
48Johnson, CY & Little, J (2008) Folate intake, markers of folate status and oral clefts: is the evidence converging? Int J Epidemiol 26, 118.
49Lawrence, M & Riddell, L (2007) Mandatory fortification with folic acid – what would Hippocrates say? Aust Fam Physician 36, 6973.
50Smith, AD (2007) Folic acid fortification: the good, the bad, and the puzzle of vitamin B12. Am J Clin Nutr 85, 35.
51Smith, AD, Young-In, K & Refsum, H (2008) Is folic acid good for everyone? Am J Clin Nutr 87, 517533.
52Ulrich, CM & Potter, JD (2007) Folate and cancer – timing is everything. JAMA 297, 24082409.
53Mason, JB, Dickstein, A, Jacques, PF, et al. (2007) A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis. Cancer Epidemiol Biomarkers Prev 16, 13251329.
54Morris, MS, Jacques, PF, Rosenberg, IH, et al. (2007) Folate and vitamin B12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. Am J Clin Nutr 87, 193200.
55Selhub, J, Morris, MS & Jacques, PF (2007) In vitamin B12 deficiency, higher serum folate is associated with increased total homocysteine and methylmalonic acid concenrations. PNAS 104, 1999520000.
56Bazzano, LA, Reynolds, K, Holder, KN, et al. (2006) Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. JAMA 296, 27202726.
57Winkels, RM, Brouwer, IA, Clarke, R, et al. (2008) Bread cofortified with folic acid and vitamin B-12 improves the folate and vitamin B-12 status of healthy older people: a randomized controlled trial. Am J Clin Nutr 88, 348355.

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