Inflammation Adjustments to Serum Retinol and Retinol-Binding Protein Improve Specificity but Reduce Sensitivity when Estimating Vitamin A Deficiency Compared with the Modified Relative Dose-Response Test in Ghanaian Children

Abstract

Background Serum retinol and retinol-binding protein (RBP) concentrations are commonly used biomarkers of vitamin A deficiency (VAD); however, evidence indicates that they are not always accurate, especially in populations with high exposure to inflammation. Objective Assess sensitivity and specificity of serum retinol and RBP concentrations to predict VAD, with and without adjustment for inflammation (using categorical and regression-adjusted approaches) using the modified-relative-dose response (MRDR) as the reference standard for liver reserves. Design This secondary analysis of diagnostic accuracy used inflammation and RBP data, and analyzed serum retinol and MRDR from a sub-sample of women of reproductive age (n = 178) and preschool children (n = 166) in the cross-sectional 2017 Ghana Micronutrient Survey. Results Inflammation (elevated C-reactive protein and/or α1-acid-glycoprotein) was present in 41% of children and 16% of women. Among children, estimates of VAD prevalence were: 7% (MRDR), 40% (serum retinol), 29% (categorical-adjusted serum retinol), 24% (RBP), 13% (categorical-adjusted RBP), and 7% (regression-adjusted RBP). Sensitivity (95% CI) ranged from 22.2% (2.81, 60.0; both adjusted RBPs) to 80.0% (44.4, 97.5; serum retinol), while specificity ranged from 63.3% (54.7, 71.3; serum retinol) to 93.5% (88.0, 97.0; regression-adjusted RBP). Among women, VAD prevalence ranged 1% (RBP) to 4% (all others); sensitivity was 0% and specificity was > 96% for all indicators. Conclusions Serum retinol and RBP had varying accuracy in estimating VAD, especially in children; adjustment for inflammation increased accuracy by increasing specificity at the expense of sensitivity. Effects of inflammation adjustment in the context of high inflammation and VAD prevalence need to be further explored. Especially in populations with high inflammation, the MRDR test should accompany serum retinol or RBP measurements in a subsample of subjects in population-based surveys. Registered with Open Science Framework registry (DOI: 10.17605/OSF.IO/J7BP9).

Vitamin A biomarkers were associated with α(1)-acid glycoprotein and C-reactive protein over the course of a human norovirus challenge infection

“…This means that the using the cut-off for serum RBP (<0·7 μmol/l), in lieu of serum retinol (<0·7 μmol/l), to signify deficiency (4,6) is also likely inappropriate. Researchers have proposed methods to adjust serum retinol and RBP concentrations for inflammation, but the utility of these adjustments need further exploration (28) . These results highlight the need for extra consideration of appropriate cut-offs in studies and surveys that use RBP to estimate VAD prevalence.…”