Comparison of Serum and Red Blood Cell Folate Microbiologic Assays for National Population Surveys

National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA.
Journal of Nutrition (Impact Factor: 3.88). 07/2011; 141(7):1402-9. DOI: 10.3945/jn.111.141515
Source: PubMed


Three laboratories participated with their laboratory-specific microbiologic growth assays (MA) in the NHANES 2007-2008 to assess whether the distributions of serum (n = 2645) and RBC folate (n = 2613) for the same one-third sample of participants were comparable among laboratories. Laboratory (L) 2 produced the highest and L1 the lowest serum and RBC folate geometric means (nmol/L) in the NHANES sample (serum: L1, 39.5; L2, 59.2; L3, 47.7; and RBC: L1, 1120; L2, 1380; L3, 1380). Each laboratory produced different reference intervals for the central 95% of the population. Pearson correlation coefficients were highest between L3 and L1 (serum, r = 0.95; RBC, r = 0.92) and lowest between L2 and L1 (serum, r = 0.81; RBC, r = 0.65). Notable procedural differences among the laboratories were the Lactobacillus rhamnosus microorganism (L1 and L3: chloramphenicol resistant, L2: wild type) and the calibrator [L1: [6S]5-methyltetrahydrofolate (5-methylTHF), L2: [6R,S] 5-formyltetrahydrofolate ([6R,S] 5-formylTHF), L3: folic acid (FA)]. Compared with 5-methylTHF as calibrator, the folate results were 22-32% higher with FA as calibrator and 8% higher with 5-formylTHF as calibrator, regardless of the matrix (n = 30 serum, n = 28 RBC). The use of different calibrators explained most of the differences in results between L3 and L1 but not between L2 and L1. The use of the wild-type L. rhamnosus by L2 appeared to be the main reason for the differences in results between L2 and the other 2 laboratories. These findings indicate how assay variations influence MA folate results and how those variations can affect population data. To ensure data comparability, better assay harmonization is needed.

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    • "The red blood cell folate concentrations presented by Pfeiffer et al 2012 and Branum et al 2013 were generated by a microbiological assay (calibrated with 5' methylTHF) that was normalized to the microbiological assay used in the Folic Acid Dosing Trial and the Daly study (calibrated with folic acid) using the equation: NHANES red blood cell folate (nmol/L)=(Daly and Folic Acid Dosing Trial red blood cell folate (nmol/L)×0.7876)+34.2802 (nmol/L) (personal communication from the data presented in Pfeiffer et al 2011). 33-35 We normalized the pre-fortification folate concentration data to the microbiological assay in the original manuscript 33 ; we then converted them by using the same conversion equation to approximate a match to the Daly et al data. "
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    ABSTRACT: Objective To determine an optimal population red blood cell (RBC) folate concentration for the prevention of neural tube birth defects. Design Bayesian model. 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.
    BMJ Clinical Research 07/2014; 349(jul29 3):g4554. DOI:10.1136/bmj.g4554 · 14.09 Impact Factor
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    American Journal of Clinical Nutrition 07/2011; 94(1):297S-302S. DOI:10.3945/ajcn.111.017392 · 6.77 Impact Factor
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