Primary prevention

The US Centers for Disease Control and Prevention (CDC) recommends a 5-a-day consumption of fruits and vegetables with high levels of natural folates and that all women of childbearing age consume 0.4 mg/day of supplemental folic acid.[52] The US Preventive Services Task Force specifies 0.4 to 0.8 mg/day of supplemental folic acid to prevent neural tube defects.[50] The American College of Obstetricians and Gynecologists recommends that women planning a pregnancy, or capable of becoming pregnant, take supplemental folic acid. Supplementation should begin at least 1 month before pregnancy and continue through the first 12 weeks of pregnancy. Initiating supplemental folic acid at the time of missed menses is insufficient, because neural tube formation has already begun.[60]

Canadian guidelines recommend that the level of oral folic acid supplementation for women planning pregnancy reflects the risk status of the woman and her male partner (e.g., low, moderate, or high): between 0.4 and 5 mg/day of folic acid from at least 3 months before conception until 12 weeks gestation, followed by between 0.4 mg and 1 mg/day until 4 to 6 weeks postpartum, or for as long as breastfeeding continues.[61]

Daily supplemental folic acid can reduce spina bifida and other neural tube defects by more than 70%; however, only 40% of women report daily consumption of a supplement containing folic acid.[13][62]

Fortification of staple foods

Mandatory food fortification with folate to prevent spina bifida has been shown to be safe, cost-effective, and sustainable. Fortification of staple food such as wheat and corn products is a population-wide approach to primary prevention that has been implemented in over 80 nations worldwide, including the US, Canada, Chile, and South Africa.[63] In 1998, the US Food and Drug Administration (FDA) required the fortification of enriched cereal grain products with folic acid at the level of 140 micrograms/100 grams of grain, thereby increasing folic acid consumption by US women to an average of 0.1 mg/day. This was associated with a 26% reduction of neural tube defects between 1999 and 2000.[42][64] The overall birth prevalence of spina bifida declined an additional 6.9% by 2003 to 2005, despite the obesity epidemic.[5]

One systematic review found evidence that folic acid supplementation of wheat or maize flour increased erythrocyte and serum folate concentrations and decreased the risk of neural tube defects, but the evidence was of low certainty due to limitations in the included studies.[63]

The World Health Organization recommends fortification of wheat flour with folic acid to reduce the risk of occurrence of pregnancies affected by neural tube defects among women of reproductive age and to improve folate status in populations. In one non-randomised controlled trial of women of reproductive age and pregnant women, wheat flour fortified with folic acid and other micronutrients was associated with significantly lower occurrence of total neural tube defects, spina bifida, and encephalocele compared with unfortified flour (total neural tube defects: risk ratio 0.32, 95% confidence interval 0.21 to 0.48; 8037 births).[65]

It is estimated that current fortification programmes are preventing just 25% of the estimated folate-preventable spina bifida and anencephaly cases worldwide. The World Health Assembly has issued a resolution to accelerate food fortification programmes worldwide.[66][67]

Although the benefits of fortification are well documented, there is controversy regarding the potential risk of masking vitamin B12 deficiency, and the possible increased risk of colorectal cancer with high folate intake.[20][21][22][23][24] [ Cochrane Clinical Answers logo ]

Previous pregnancy affected by neural tube defect

Women who have had a previous pregnancy affected by a neural tube defect, or who have spina bifida themselves, have a significant excess risk of having a baby with a neural tube defect compared with the general population. Risk is also higher if a male partner has had a neural tube defect affecting himself or his children.[61]

Risk of recurrence can be reduced substantially by high-dose folic acid supplementation.[51][60][61][68] The CDC recommends 4 mg/day of folic acid for 1 month prior to pregnancy and during the first trimester.[52] Higher doses may be recommended in some countries (e.g., 4-5 mg/day is recommended in the UK and Canada).[61][69][70] See local guidance for more information on suitable doses.

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