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5 Research Although the benefit of periconceptional folat supplementation on the prevention of NTDs seems well established, there are several issues that still merit further research. These include determination of the most feasible and cost-effective of supplementing large at-risk populations, determination of the most appropriate dose and other potential beneficial effects on outcome of pregnancy. The following may merit further consideration : Since a placebo-controlled trial will no longer be ethical, a trial looking at different doses of folate supplementation and its effect in decreasing the prevalence of NTD would be helpful to determine not only the minimum effective dose (which is presently regarded as 0,4 mg/day) for decreasing the incidence of occurrence of NTDs but also the minimum dose required to decrease the prevalence of recurrent nTD (which presently is 4 mg/day). A community-based effectiveness trial should be conducted to look at the most costeffective and sustaineble method of providing folate supplementation during the periconseptional period. This may involve comparisons of approaches like food fortification, dietery counseling, folate supplementation in primary health clinics or a combination of methods. A recent study (12), of the relationship between red blood cell folate and consumption of different sources of folate demonstrated that those receiving folic acid had higher mean red blood cell folate levels than those consuming cereals fortified with folic acid. Red blood cell folate levels higher than 400 mcg/ml (a level consideredto be optimal for the prevention of NTDs) were found nearly exclusively among folic acid supplement users. Several studies have also revealed highly variable rates of folate consumption by both pregnant and non-pregnant women. A study to determine the knowladge, attitudes and practices of mothers regardin folic acid intake during the periconceptional period (13), showed that only 76 % of the woman were cognizant of its importance and of these only 44 % had taken the supplements. Thus, further research is needed on strategies to improve compliance with folic acid intake. Although the evidence linking folate deficiency cannot be excluded. Further research should be conducted to determine the associations between the prevalence of deficiencies of other vitamins and micronutrients and risk of NTDs. Such studies could then be followed up with randomized controlled trials to evaluate at any beneficial effect of administering additional supplements along with folate The reportedly increased incident of multiple pregnancies among women administered folate supplements, merit further evaluation.

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