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Folates for prevention of neural tube defects

Neural tube defects (NTDs) are one of the most important birth defects related to maternal folate deficiency. NTDs are severe congenital malformations of the brain and spinal cord caused by the incomplete closure of the neural tube between the days 21 – 28 after conception. Defects have two major forms, spina bifida and anencephaly. They are associated with life-long disabilities and require intensive health care. NTDs occur in > 300,000 cases a year where over 95% of them are first occurrence. Smithells et al. suggested in 1976 that the folate deficiency was causally related to NTDs (1). Only in the early 1990s it became evident that the periconceptional FA intake in women prevented the first occurrence of NTDs (2).

A Cochrane review including 6,425 women from four studies reported that periconceptional folate supplementation reduced the incidence of NTDs significantly (relative risk (RR) 0.28, confidence interval 0.13 to 0.58) (3). For the prevention of NTDs supplementation with FA is especially recommended for women of childbearing age prior and in the first trimester of the pregnancy. In 1992, the Centre for Disease Control and Prevention recommended a daily oral intake of 400 µg FA for all women of childbearing age who are capable of becoming pregnant to reduce the risk of having a pregnancy affected by NTDs (4). For women who already have a NTD affected child, the recommendations are 4 mg/d. 


Folic acid for the prevention of the second occurrence

According to a study from three European countries, the mean daily folate intake of pregnant European women is 311 – 327 µg/d (5). Only 5 – 7% of the women reached the recommended folate intake for pregnant women (600 µg/d) in Germany, Austria, and Switzerland and only 23 – 29% had a dietary total folate intake of 400 µg/d. It is obvious that in the most cases the higher need of folates before and during the pregnancy cannot be covered by the dietary folate intake alone. This led to a mandatory food fortification of grain products in some countries like the U.S., Canada, and meanwhile 50 other countries round the world, the last one was Australia, which resulted in a significant decline of the NTD incidence by ~ 30 – 50% (6). Other common maternal risk factors for the birth of a child with NTD are obesity, smoking, and diabetes.


1.    Smithells RW, Sheppard S, Schorah CJ. Vitamin dificiencies and neural tube defects. Arch Dis Child 1976;51:944-50.
2.     Kirke PN, Daly LE, Elwood JH. A randomised trial of low dose folic acid to prevent neural tube defects. The Irish Vitamin Study Group. Arch Dis Child 1992;67:1442-6.
3.     Lumley J, Watson L, Watson M, Bower C. Periconceptional supplementation with folate and/or multivitamins for preventing neural tube defects. Cochrane Database Syst Rev 2001;CD001056.
4.     Centers for Disease Control and Prevention. Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects. MMWR Recomm Rep 1992;41:1-7.
5.     Franke C, Verwied-Jorky S, Campoy C, Trak-Fellermeier M, Decsi T, Dolz V, Koletzko B. Dietary intake of natural sources of docosahexaenoic acid and folate in pregnant women of three European cohorts. Ann Nutr Metab 2008;53:167-74.
6.     Liu S, West R, Randell E, Longerich L, O'connor KS, Scott H et al. A comprehensive evaluation of food fortification with folic acid for the primary prevention of neural tube defects. BMC Pregnancy Childbirth 2004;4:20.