Background
It has been reported that neural tube defects can be prevented with periconceptional folic acid supplementation. The effects of different doses, forms and schemes of folate supplementation for the prevention of other birth defects and maternal and infant outcomes are unclear.
Objectives
This review updates and expands a previous Cochrane Review assessing the effects of periconceptional supplementation with folic acid to reduce neural tube defects (NTDs). We examined whether folate supplementation before and during early pregnancy can reduce neural tube and other birth defects (including cleft palate) without causing adverse outcomes for mothers or babies.
Search methods
We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (July 2010). Additionally, we searched the international clinical trials registry platform and contacted relevant organisations to identify ongoing and unpublished studies.
Selection criteria
We included all randomised or quasi-randomised trials evaluating the effect of periconceptional folate supplementation alone, or in combination with other vitamins and minerals, in women independent of age and parity.
Data collection and analysis
We assessed trials for methodological quality using the standard Cochrane criteria. Two authors independently assessed the trials for inclusion, one author extracted data and a second checked for accuracy.
Main results
Five trials involving 6105 women (1949 with a history of a pregnancy affected by a NTD and 4156 with no history of NTDs) were included. Overall, the results are consistent in showing a protective effect of daily folic acid supplementation (alone or in combination with other vitamins and minerals) in preventing NTDs compared with no interventions/placebo or vitamins and minerals without folic acid (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.15 to 0.52). Only one study assessed the incidence of NTDs and the effect was not statistically significant (RR 0.08, 95% CI 0.00 to 1.33) although no events were found in the group that received folic acid. Folic acid had a significant protective effect for reoccurrence (RR 0.32, 95% CI 0.17 to 0.60). There is no statistically significant evidence of any effects on prevention of cleft palate, cleft lip, congenital cardiovascular defects, miscarriages or any other birth defects. There were no included trials assessing the effects of this intervention on maternal blood folate or anaemia at term.
We found no evidence of short-term side effects.
Authors’ conclusions
Folic acid, alone or in combination with vitamins and minerals, prevents NTDs but does not have a clear effect on other birth defects.
Intermittent iron supplementation in menstruating women is a feasible intervention in settings where daily supplementation is likely to be unsuccessful or not possible. In comparison with daily supplementation, the provision of iron supplements intermittently is less effective in preventing or controlling anaemia. More information is needed on morbidity (including malaria outcomes), side effects, work performance, economic productivity, depression and adherence to the intervention.
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