Blood folate level needed for fully effective neural tube defect prevention

IntroductionNeural tube defects (NTDs) are a folate deficiency disorder. NTDs are preventable; increasing folic acid intake through food fortification or use of supplements increases serum and red blood cell folate and reduces the risk of a woman having an NTD pregnancy. There is controversy over whether there is a blood folate level needed to achieve the full preventive effect because of discrepant conclusions from studies investigating the relationship between folate levels and NTD risk. Resolving the controversy is important in determining public health policy. MethodsData from two studies conducted in Ireland and China were used to determine the relationship between serum folate and NTD risk. The relationship from each study was compared with the observed result in a randomised trial of folic acid that increased serum folate from 5 ng/ml to 44 ng/ml among the women who took the daily folic acid supplement before and during early pregnancy. ResultsData from both studies showed a proportional (logarithmic) relationship between serum folate and NTD risk with no evidence of a folate threshold above which there is no further NTD risk reduction. Both studies accurately predicted the observed result from the randomised trial that achieved serum folate levels beyond the average levels found in the general population with an 83% preventive effect. This is higher than can be achieved with current levels of folic acid food fortification or with the recommended peri-conceptional use of 0.4mg supplements. The suggestion of a threshold is not due to discrepant data but the incorrect interpretation of the folate-NTD risk association when plotted on arithmetic scales which conceals the proportional relationship between the two. ConclusionTo achieve fully effective fortification serum folate levels need to be about 44ng/ml. Key MessagesO_ST_ABSWhat is already known on this topicC_ST_ABSNeural tube defects (NTDs), among the most common serious birth defects worldwide, are a folate deficiency disorder. Increasing folic acid (vitamin B9) intake increases serum folate and reduces the risk of an NTD pregnancy. There is a difference of opinion on the serum folate level needed for fully effective NTD prevention. What this study addsThere is no threshold above which NTD risk does not decrease and population folate levels need to be substantially increased to have the expected potential achieve effect on the prevention of NTDs. How this study might affect research, practice or policyA serum folate level of about 44ng/ml is a reasonable target to achieve an approximate 83% reduction in the prevalence of NTD pregnancies. This result can be used to help influence folic acid fortification policy.