Retinol-binding protein, retinol, and modified-relative-dose response in Ugandan children aged 12–23 months and their non-pregnant caregivers

Abstract

Retinol-binding protein (RBP), retinol, and modified-relative-dose response (MRDR) are used to assess vitamin A status. We describe vitamin A status in Ugandan children and women using dried blood spot (DBS) RBP, serum RBP, plasma retinol, and MRDR and compare DBS-RBP, serum RBP, and plasma retinol. Blood was collected from 39 children aged 12–23 months and 28 non-pregnant mothers aged 15–49 years as a subsample from a survey in Amuria district, Uganda, in 2016. DBS RBP was assessed using a commercial enzyme immunoassay kit, serum RBP using an in-house sandwich enzyme-linked immunosorbent assay, and plasma retinol/MRDR test using high-performance liquid chromatography. We examined (a) median concentration or value (Q1, Q3); (b) R2 between DBS-RBP, serum RBP, and plasma retinol; and (c) Bland-Altman plots. Median (Q1, Q3) for children and mothers, respectively, were as follows: DBS-RBP 1.15 µmol/L (0.97, 1.42) and 1.73 (1.52, 1.96), serum RBP 0.95 µmol/L (0.78, 1.18) and 1.47 µmol/L (1.30, 1.79), plasma retinol 0.82 µmol/L (0.67, 0.99) and 1.33 µmol/L (1.22, 1.58), and MRDR 0.025 (0.014, 0.042) and 0.014 (0.009, 0.019). DBS RBP-serum RBP R2 was 0.09 for both children and mothers. The mean biases were −0.19 µmol/L (95% limits of agreement [LOA] 0.62, −0.99) for children and −0.01 µmol/L (95% LOA −1.11, −1.31) for mothers. DBS RBP-plasma retinol R2 was 0.11 for children and 0.13 for mothers. Mean biases were 0.33 µmol/L (95% LOA −0.37, 1.03) for children, and 0.29 µmol/L (95% LOA −0.69, 1.27) for mothers. Serum RBP-plasma retinol R2 was 0.75 for children and 0.55 for mothers, with mean biases of 0.13 µmol/L (95% LOA −0.23, 0.49) for children and 0.18 µmol/L (95% LOA −0.61, 0.96) for mothers. Results varied by indicator and matrix. The serum RBP-retinol R2 for children was moderate (0.75), but poor for other comparisons. Understanding the relationships among vitamin A indicators across contexts and population groups is needed.

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

“…Comparing the prevalence of VAD among children with other studies, one in Ghana found baseline MRDR values for infants in intervention and control groups at 0.032 ± 0.018 (6.9% VAD) and 0.031 ± 0.018 (11.8% VAD), respectively ( 34 ), which is quite similar to our mean values, and which are also consistent with values found among well-nourished American children residing in the United States ( 10 ) and in Ugandan children ( 35 ). Previous work in Indonesian children has shown generally higher MRDR values (indicating lower TLR and higher prevalence of VAD).…”

“…A study of nonpregnant Indonesian women found a mean MRDR value of 0.034 ± 0.015 (7% VAD), just slightly higher than the women in our study ( 37 ). Nonpregnant Ugandan women had a lower adequate median MRDR value of 0.014 (95% CI: 0.009, 0.019) ( 35 ).…”

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

“…There are no WHO recommendations for the use of RBP to define VAD, although a 1:1 molar ratio of retinol to RBP has been expected (5) , and the cutoff for serum retinol (<0•7 μmol/l) is often substituted for serum RBP (<0•7 μmol/l) to signify deficiency (4,6) . However, research shows the molar ratio between retinol and RBP is inconsistent and can have a substantial (range 0•91-1•52) (5,(7)(8)(9)(10)(11) . A recommended approach for using RBP in population-based studies is to measure serum retinol concentrations from a subset of the population of interest and use these data to predict serum retinol from RBP (2) .…”