Periconceptional supplementation with folate and/or multivitamins for preventing neural tube defects

Cochrane Review by Lumley J, Watson L, Watson M, Bower C

This record should be cited as: Lumley J, Watson L, Watson M, Bower C. Periconceptional supplementation with folate and/or multivitamins for preventing neural tube defects. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD001056. DOI: 10.1002/14651858.CD001056.



Periconceptional supplementation with folate and/or multivitamins for preventing neural tube defects


Neural tube defects arise during the development of the brain and spinal cord.


The objective of this review was to assess the effects of increased consumption of folate or multivitamins on the prevalence of neural tube defects periconceptionally (that is before pregnancy and in the first two months of pregnancy).

Search strategy

We searched the Cochrane Pregnancy and Childbirth Group trials register. Date of last search: April 2001.

Selection criteria

Randomised and quasi-randomised trials comparing periconceptional supplementation by multivitamins with placebo, folate with placebo, or multivitamins with folate; different dosages of multivitamins or folate; prepregnancy dietary advice and counselling in primary care settings to increase the consumption of folate-rich foods, or folate-fortified foods, with standard care; increased intensity of information provision with standard public health dissemination.

Data collection and analysis

Two reviewers assessed trial quality and extracted data.

Main results

Four trials of supplementation involving 6425 women were included. The trials all addressed the question of supplementation and they were of variable quality. Periconceptional folate supplementation reduced the incidence of neural tube defects (relative risk 0.28, 95% confidence interval 0.13 to 0.58). Folate supplementation did not significantly increase miscarriage, ectopic pregnancy or stillbirth, although there was a possible increase in multiple gestation. Multivitamins alone were not associated with prevention of neural tube defects and did not produce additional preventive effects when given with folate. One dissemination trial, a community randomised trial, was identified involving six communities, matched in pairs, and where 1206 women of child-bearing age were interviewed following the dissemination intervention. This showed that the provision of printed material increased the awareness of the folate/neural tube defects association by 4%, (odds ratio 1.37, 95% confidence interval 1.33 to 1.42).

Authors' conclusions

Periconceptional folate supplementation has a strong protective effect against neural tube defects. Information about folate should be made more widely available throughout the health and education systems. Women whose fetuses or babies have neural tube defects should be advised of the risk of recurrence in a subsequent pregnancy and offered continuing folate supplementation. The benefits and risks of fortifying basic food stuffs, such as flour, with added folate remain unresolved.