Population RBC folate concentrations can be accurately estimated from measured whole blood folate, measured hemoglobin, and predicted serum folate—cross-sectional data from the NHANES 1988–2010

Abstract

ABSTRACT Background RBC folate (RBF) is an indicator of folate status and risk of neural-tube defects. It is calculated from whole blood folate (WBF), serum folate (SFOL), and hematocrit (Hct). SFOL and/or Hct are sometimes unavailable; hemoglobin (Hb) is generally available in surveys. Objectives We assessed the ability of different RBF approximations to generate population data in women aged 12–49 y. Methods Using SFOL, RBF, Hct, Hb, and mean corpuscular Hb content (MCHC) from prefortification (1988–1994) and postfortification (1999–2006, 2007–2010) NHANES we applied 6 approaches: #1) assume SFOL = 0; #2) impute SFOL (population median); #3) impute Hct (population median); #4) estimate Hct (Hb/MCHC); #5) assume SFOL = 0 and estimate Hct; and #6) predict SFOL (from WBF) and estimate Hct. For each approach, we calculated the paired percentage difference to the “true” RBF and estimated various statistics. Results For 2007–2010 (unweighted data), the median relative difference from “true” RBF was lowest for approaches #2 (−0.74%), #4 (−0.96%), and #6 (−1.15%), intermediate for #3 (−3.36%), and highest for #5 (4.96%) and #1 (5.78%). The 95% agreement limits were smallest for approach #1 (2.33%, 13.0%) and largest for #3 (−20.8%, 11.3%). Approach #2 showed concentration-dependence (negative compared with positive differences at low compared with high RBF). Using weighted data, we found similar patterns across approaches for mean relative differences by demographic subgroup for all 3 time periods. Conclusions We obtained the best agreement between estimated and “true” RBF when we predicted SFOL using a regression equation obtained from a subset of samples (approach #6). Alternatively, the consistent overestimation of RBF when assuming SFOL = 0 (∼6%) could be addressed by adjusting the data (approach #5). Similar observations for pre- and postfortification periods suggest applicability to low and high folate status situations, but should be confirmed elsewhere. To estimate RBF, at least WBF and Hb are needed.