mercredi 13 août 2014

Population red blood cell folate concentrations for prevention of neural tube defects: bayesian model

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.

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