| Excerpt from The WHO Reproductive Health Library | Published by Update Software Ltd. |
The primary objective of this review was to determine the beneficial effect, if any, of the administration of folate and/or multivitamins (FMV) during the periconceptional period primarily on the incidence of neural tube defects (NTDs) but also on other congenital abnormalities and fetal survival.
Four trials were included in the meta-analysis. The analysis demonstrated a beneficial effect of folate supplementation on the incidence of NTDs. The odds ratio (OR) of delivering a neonate with NTD in the group that received supplementation was 0.28 (95% CI 0.15-0.53). This beneficial effect was equally beneficial in reducing recurrence (OR: 0.13; 95% CI: 0.03-0.65) and first-time occurrence of the defect (OR: 0.32; 95% CI: 0.16-0.64). The analysis also showed a statistically significant association between folate supplementation specifically and reduction in the prevalence of NTDs, whereas the administration of multivitamins without folate was of little benefit in this regard. A direct comparison of folate versus multivitamin groups indicated a statistically significant reduction in the incidence of NTDs in the folate group (OR 0.28; 95% CI: 0.09 to 0.92).
There was no statistically significant increase in adverse effects of folate supplementation such as incidence rates of spontaneous abortion or ectopic pregnancy. However, the primary reviewer highlighted one potential area of concern. Three of the four trials included in the meta-analysis demonstrated an increase in multiple pregnancies, although the results did not reach statistical significance (OR: 1.4; 95% CI: 0.93-2.11). The reviewers concede that even a small increase in multiple pregnancies at a population level could alter markedly the risk-benefit ratio of folate supplementation.
The quality of the four trials included varied. All evaluated trials had relatively low power to identify any impact of FMV supplementation on the prevalence of major congenital defects other than NTDs. Overall, however, all trials were consistent in showing a strong beneficial effect of folate supplementation on the incidence of NTDs.
A new large-scale trial conducted in China (1), corroborated the above findings. In this quasi-experimental trial conducted in areas with both low and high prevalence of NTDs, women who were planning to marry and thus underwent a premarital examination, were asked to take 400 mcg of folic acid daily until the end of the first trimester of pregnancy. Women who took folate in the periconceptional period and who had a high compliance rate (defined as at least 80% use rate of the supplement) showed an 85% reduction in risk in the area with high rates of NTDs and a 40% decrease in risk in the area with lower NTD rates.
Overall, the review strongly supports the use of periconceptional folate supplementation for the prevention of NTDs.
Overall, the search strategy was adequate, although the trial from China (1), and India (2), were not included. The review does not adequately address the need to evaluate the most effective means of delivering folate supplementation.
Although the principle outcomes measured were NTDs and other congenital malformations, the effect of folate supplementation on other adverse pregnancy outcomes should have been mentioned. The reviewer does not refer to the related Cochrane Review by Mahomed (3), which evaluated the effect of folate supplementation during pregnancy on various pregnancy outcomes.
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