Abstract
Objective
To determine an optimal population red blood cell (RBC) folate concentration for the prevention of neural tube birth defects.
Setting
Data from two population based studies in China.
Participants
247 831 participants in a prospective community intervention project in
China (1993-95) to prevent neural tube defects with 400 μg/day folic
acid supplementation and 1194 participants in a population based
randomized trial (2003-05) to evaluate the effect of folic acid
supplementation on blood folate concentration among Chinese women of
reproductive age.
Intervention
Folic acid supplementation (400 μg/day).
Main outcome measures
Estimated RBC folate concentration at time of neural tube closure (day 28 of gestation) and risk of neural tube defects.
Results
Risk of neural tube defects was high at the lowest estimated RBC folate
concentrations (for example, 25.4 (95% uncertainty interval 20.8 to
31.2) neural tube defects per 10 000 births at 500 nmol/L) and decreased
as estimated RBC folate concentration increased. Risk of neural tube
defects was substantially attenuated at estimated RBC folate
concentrations above about 1000 nmol/L (for example, 6 neural tube
defects per 10 000 births at 1180 (1050 to 1340) nmol/L). The modeled
dose-response relation was consistent with the existing literature. In
addition, neural tube defect risk estimates developed using the proposed
model and population level RBC information were consistent with the
prevalence of neural tube defects in the US population before and after
food fortification with folic acid.
Conclusions
A threshold for “optimal” population RBC folate concentration for the
prevention of neural tube defects could be defined (for example,
approximately 1000 nmol/L). Population based RBC folate concentrations,
as a biomarker for risk of neural tube defects, can be used to
facilitate evaluation of prevention programs as well as to identify
subpopulations at elevated risk for a neural tube defect affected
pregnancy due to folate insufficiency.
Extracts:
How much natural food folate and/or folic acid intake is necessary to achieve red blood cell folate concentrations in the 1000-1300 nmol/L range in any given person or population is unknown. In the Folic Acid Dosing Trial in northern China, people consuming 100 μg/day in addition to usual diet (which is relatively low in other sources of folate) did not achieve a red blood cell folate concentration of 1000 nmol/L by the end of the six month supplementation trial. Those with the CC and CT genotypes who consumed 400 μg/day reached a red blood cell folate concentration of 1000 nmol/L between three and six months of supplementation, whereas those with the TT genotype
did not achieve a geometric mean red blood cell folate concentration of 1000 nmol/L by the six month sample.
did not achieve a geometric mean red blood cell folate concentration of 1000 nmol/L by the six month sample.
Source:
Krista S Crider, et al, Population red blood cell folate concentrations for prevention of neural tube defects: bayesian model, BMJ 2014;349:g4554
Free Fulltext:
http://www.bmj.com/content/349/bmj.g4554
