Neural tube defects (NTD) are common congenital malformations leading to severe disability or even death. The causes of NTD are multifactorial, including genetic predisposition, nutritional and environmental risk factors, and other maternal conditions. Some countries have introduced mandatory or at least voluntary folic acid fortification as an effective measure to reduce NTD, whereas others support periconceptional supplementation of women of childbearing age. 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 magnitude of the decline depends on the initial NTD rate. This review clearly shows that not all cases of NTD can be prevented by increasing the folate intake. Other relevant causes of NTD, which are largely disregarded, have also to be taken into account in research and consultation to reduce the risk and economic burden of NTD.

Keywords:
Folic acid, Neural tube defects, Prevention, Fortification, Supplementation, Obesity, Heat
1.
Yi Y, Lindemann M, Colligs A, Snowball C: Economic burden of neural-tube defects and impact of prevention with folic acid: a literature review. Eur J Pediatr 2011, E-pub ahead of print.
2.
Heseker HB, Mason JB, Selhub J, Rosenberg ICH, Jaques PF: Not all cases of neural-tube defect can be prevented by increasing the intake of folic acid. Br J Nutr 2009;102:173–180.
3.
Berry RJ, Bailey L, Mulinare J, Bower C: Fortification of flour with folic acid. Food Nutr Bull 2010;31(suppl):S22–S35.
4.
Wolff T, Witkop CT, Miller T, Syed SB: Folic acid supplementation for the prevention of neural-tube defects: an update of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2009;150:632–639.
5.
De-Regil LM, Fernández-Gaxiola AC, Dowswell T: Effects and safety of periconceptional folate supplementation for preventing birth defects. Cochrane Database Syst Rev 2010;10:CD007950.
6.
Prevention of neural-tube defects: results of the Medical Research Council Vitamin Study – MRC Vitamin Study Research Group. Lancet 1991;338:131–137.
7.
Grosse SD, Collins JS: Folic acid supplementation and neural-tube defect recurrence prevention. Birth Defects Res A Clin Mol Teratol 2007;79:737–742.
8.
Berry RJ, Li Z, Erickson JD, et al: Prevention of neural tube defects with folic acid in China. N Engl J Med 1999;341:1485–1490.
9.
De Wals P, Tairou F, Van Allen MI, et al: Reduction in neural-tube defects after folic acid fortification in Canada. N Engl J Med 2007;357:135–142.
10.
Gucciardi E, Pietrusiak MA, Reynolds DL, et al: Incidence of neural-tube defects in Ontario, 1986–1999. CMAJ 2002;167:237–240.
11.
Moore LL, Bradlee ML, Singer MR, et al: Folate intake and the risk of neural-tube defects: an estimation of dose-response. Epidemiology 2003;14:200–205.
12.
Czeizel AE, Dobó M, Vargha P: Hungarian cohort-controlled trial of periconceptional multivitamin supplementation shows a reduction in certain congenital abnormalities. Birth Defects Res A Clin Mol Teratol 2004;70:853–861.
13.
Klusmann A, Heinrich B, Stoepler H, et al: A decreasing rate of neural-tube defects following the recommendations for periconceptional folic acid supplementation. Acta Paediatr 2005;94:1538–1542.
14.
CDC: Prevalence of neural-tube defects and folic acid knowledge and consumption – Puerto Rico, 1996–2006. MMWR Morb Mortal Wkly Rep 2008;57:10–13.
15.
CDC: Spina bifida and anencephaly before and after folic acid mandate – United States, 1995–1996 and 1999–2000. MMWR Morb Mortal Wkly Rep 2004;53:362–365.
16.
Williams LJ, Rasmussen SA, Flores A, et al: Decline in the prevalence of spina bifida and anencephaly by race/ethnicity: 1995–2002. Pediatrics 2005;116:580–586.
17.
Rasmussen SA, Chu SY, Kim SY, Schmid CH, Lau J: Maternal obesity and risk of neural-tube defects: a metaanalysis. Am J Obstet Gynecol 2008;198:611–619.
18.
Stothard KJ, Tennant PW, Bell R, Rankin J: Maternal overweight and obesity and the risk of congenital anomalies: a systematic review and meta-analysis. JAMA 2009;301:636–650.
19.
Ye R, Ren A, Zhang L, Li Z, Liu J, Pei L, Zheng X: Tea drinking as a risk factor for neural-tube defects in Northern China. Epidemiology 2011;22:491–496.
20.
Milunsky A, Ulcickas M, Rothman KJ, Willett W, Jick SS, Jick H: Maternal heat exposure and neural-tube defects. JAMA 1992;268:882–885.
21.
Moretti ME, Bar-Oz B, Fried S, Koren G: Maternal hyperthermia and the risk for neural-tube defects in offspring: systematic review and meta-analysis. Epidemiology 2005;16:216–219.
22.
Li Z, Liu J, Pei L, Zhang L, Guo Z, Li Z: Maternal flu or fever, medication use, and neural-tube defects: a population-based case-control study in Northern China. Birth Defects Res A Clin Mol Teratol 2007;79:295–300.
23.
Wang ZP, Shang XX, Zhao ZT: Low maternal vitamin B(12) is a risk factor for neural-tube defects: a meta-analysis. J Matern Fetal Neonatal Med 2011, E-pub ahead of print.
© 2011 S. Karger AG, Basel
2011
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