Serum retinol concentrations demonstrate high specificity after correcting for inflammation but questionable sensitivity compared with liver stores calculated from isotope dilution in determining vitamin A deficiency in Thai and Zambian children

Abstract

Background: The WHO estimates that 190 million preschool children have vitamin A deficiency (VAD). Serum retinol (SR) concentration is a common indicator of vitamin A (VA) status, but SR is homeostatically controlled and suppressed during inflammation, which may lead to misdiagnosis.

Objective: The sensitivity and specificity of SR compared with VA total liver reserves (TLRs) were evaluated for VAD in children from Thailand (n = 37) and Zambia (n = 128). SR was adjusted for inflammation in the Zambian children.

Design: Each child was classified as VA-deficient or not based on cutoffs of <0.1 μmol VA/g liver with the use of retinol isotope dilution and <0.7 μmol/L for SR concentrations. Four categories of infection status in the Zambian children were based on elevated C-reactive protein (CRP) and α1-acid glycoprotein (AGP). Sensitivity and specificity were calculated with the use of unadjusted and inflammation marker-adjusted SR cutoffs.

Results: VAD was 65% and 0% according to TLRs and SR, respectively, in Thai children and 0% and 17%, respectively, in Zambian children. No true positive VAD cases occurred; thus, sensitivity was 0% and indeterminable, respectively; specificity was 100% and 82.8%, respectively. CRP was elevated in 26.6% of Zambian children, whereas 97.7% had elevated AGP, categorizing them as having no infection (2.3%) or in early (26.6%) or late (58.6%) convalescence. With the use of marker-adjusted SR cutoffs of 0.6 μmol/L for late convalescence and 0.5 μmol/L for early convalescence, the adjusted prevalence of SR deficiency was 2.3%, increasing specificity to 97.3%.

Conclusions: No cases of VAD were identified by both TLRs and SR (true positives) in Thai or Zambian children. Specificity of SR to evaluate VAD was high, but additional research is needed to investigate sensitivity. Adjusting SR cutoffs for inflammation improved specificity by reducing false positives. SR as a VAD indicator may depend on infection rates, which should be taken into consideration. These studies were registered at clinicaltrials.gov as NCT01061307 (for Thailand) and NCT01814891 (for Zambia).

Keywords: Thailand; Zambia; school-age children; stable isotope dilution; vitamin A deficiency.

© 2015 American Society for Nutrition.

Figures

FIGURE 1

Comparison of total liver vitamin A reserves and serum retinol concentration between the Thai (n = 37) and Zambian (n = 128) study populations. Lines within boxes represent medians, boxes represent IQRs, and lines outside boxes represent upper and lower adjacent values with circles indicating outside values.

FIGURE 2

Association between serum retinol concentration and TLRs in children from Thai (n = 37, r = 0.15, P = 0.63 with Pearson’s correlation) and Zambian (n = 128, r = 0.08,P = 0.09) studies. The horizontal dashed black line represents the cutoff for VAD defined by serum retinol concentration at 0.7 μmol/L; the vertical dashed black line represents the cutoff for VAD defined by TLRs at 0.1 μmol/g. TLR, total liver reserve; VAD, vitamin A deficiency.

FIGURE 3

Kernel density estimation visually depicts the trend in serum retinol concentration shifts (μmol/L) in Zambian children in early or late convalescence stage of infection (n = 34, early convalescence; n = 75, late convalescence; 16 excluded because of missing CRP data). There were not enough children in the incubation stage (n = 3) or with no inflammation (n = 0) to produce a kernel density estimation, which produces a smoothed distribution curve of the data. CRP, C-reactive protein.

FIGURE 4

Comparison of the association between liver VA and serum retinol concentration by infection status in Zambian children. The standard cutoff for VAD defined by serum retinol concentration is 0.7 μmol/L. Gray shaded markers below that line indicate false positives; black shaded markers are the false positives identified after adjustment of the SR cutoffs to 0.6 μmol/L for children in the late convalescent infection stage (square markers) and 0.5 μmol/L for children in the early convalescent stage (triangle markers). n = 3 (no infection), n = 0 (incubation),n = 34 (early convalescence), n = 75 (late convalescence), and n = 16 (infection status unknown because of missing CRP data). CRP, C-reactive protein; SR, serum retinol; VA, vitamin A; VAD, vitamin A deficiency.