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

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.

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Use of the retinol-binding protein : transthyretin ratio for assessment of vitamin A status during the acute-phase response

British Journal Of Nutrition ◽

10.1017/s0007114500000659 ◽

2000 ◽

Vol 83 (5) ◽

pp. 513-520 ◽

Cited By ~ 21

Author(s):

Suzanne M. Filteau ◽

Juana F. Willumsen ◽

Keith Sullivan ◽

Karin Simmank ◽

Mary Gamble

Keyword(s):

Vitamin A ◽

Sensitivity And Specificity ◽

Assessment Tool ◽

Binding Protein ◽

Vitamin A Deficiency ◽

Retinol Binding Protein ◽

Serum Retinol ◽

Vitamin A Status ◽

Plasma Retinol

The ratio plasma retinol-binding protein (RBP) : transthyretin (TTR) has been proposed as a means to improve the assessment of vitamin A status of individuals with concurrent infection or inflammation. We have measured RBP and TTR in stored sera from South African children who had accidentally ingested kerosene. Samples were collected from these children in hospital when suffering acute inflammation and respiratory distress, and from them and neighbourhood control children 3 months later. Vitamin A status was defined by modified relative dose response (MRDR) tests of liver retinol stores at 3 months and by serum retinol concentration both when children were ill and when they were well. Illness was defined as either being in hospital or, at follow-up, as having a raised plasma α1-acid glycoprotein (AGP) level. The RBP : TTR value was significantly decreased by both illness and low liver retinol stores. When the effects on RBP : TTR of illness and vitamin A stores were considered together for the 3-month follow-up samples, only vitamin A status significantly decreased the value. We calculated sensitivity and specificity of the RBP : TTR ratio against established measures of vitamin A status using a cut-off value of 0·3 for RBP : TTR and standard cut-off values for MRDR (0·06) and plasma retinol (0·7 μmol/l). Compared with MRDR, RBP : TTR had sensitivities of 76 % and 43 % and specificities of 22 % and 81 % to detect vitamin A deficiency in hospitalized and well children respectively. Compared with plasma retinol, sensitivities were 88 % and 44 % and specificities were 55 % and 64 % in hospitalized and well children respectively. Only for the case of clinically well children with biochemical evidence of subclinical inflammation did sensitivity (62 % and 100 % against MRDR and plasma retinol respectively) and specificity (100 % and 60 % against MRDR and retinol) approach useful levels for an assessment tool. Overall, although a trend supporting the theory behind the use of the RBP : TTR for assessment of vitamin A status in infection was observed in the current study, the ratio did not provide adequate sensitivity and specificity to be a useful assessment tool.

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Vitamin A intake and infection are associated with plasma retinol among pre-school children in rural Zambia

Public Health Nutrition ◽

10.1017/s1368980012000924 ◽

2012 ◽

Vol 15 (9) ◽

pp. 1688-1696 ◽

Cited By ~ 38

Author(s):

Christine Hotz ◽

Justin Chileshe ◽

Ward Siamusantu ◽

Uma Palaniappan ◽

Emmanuel Kafwembe

Keyword(s):

Vitamin A ◽

Dose Response ◽

Acute Phase Proteins ◽

Vitamin A Deficiency ◽

Dietary Vitamin ◽

Response Test ◽

Post Harvest ◽

Vitamin A Status ◽

Plasma Retinol ◽

Modified Relative Dose Response

AbstractObjectiveTo determine the prevalence of vitamin A deficiency, infection and adequacy of vitamin A intakes among Zambian children, and the contribution of dietary vitamin A and infection to vitamin A status.DesignA cross-sectional survey of vitamin A intakes by the 24 h recall method, vitamin A status by plasma retinol and the modified relative dose-response test, and infection by acute-phase proteins.SettingRural communities in Central and Eastern Provinces of Zambia.SubjectsChildren 2–5 years of age.ResultsThe prevalence of vitamin A deficiency was 56 % by plasma retinol, 48 % with infection-adjusted plasma retinol and 22 % by the modified relative dose-response test. The majority of children (61 %) had a current infection. Vitamin A intakes were relatively high (331 to 585 μg retinol activity equivalents/d in the harvest/early post-harvest and late post-harvest seasons, respectively) and the prevalence of inadequate intakes was <1 % when compared with the Estimated Average Requirement (210 and 275 μg retinol activity equivalents/d for children aged 1–3 and 4–8 years, respectively). Elevated α-1-acid glycoprotein was negatively associated with plasma retinol (P< 0·0 0 1) and vitamin A intake was positively associated with plasma retinol (P< 0·05), but only when estimated assuming a 26:1 retinol equivalence for provitamin A from green and yellow vegetables.ConclusionsInfection and vitamin A intakes were significant determinants of plasma retinol. We cannot conclude which indicator more accurately represents the true vitamin A status of the population. Reasons for the persistent high prevalence of vitamin A deficiency in the presence of adequate vitamin A intakes are unclear, but the high rates of infection may play a role.

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Assessment of Vitamin A Status of Preschool Children in Indonesia Using Plasma Retinol-binding Protein

Journal of Tropical Pediatrics ◽

10.1093/tropej/48.2.84 ◽

2002 ◽

Vol 48 (2) ◽

pp. 84-87 ◽

Cited By ~ 16

Author(s):

R. D. Semba

Keyword(s):

Preschool Children ◽

Vitamin A ◽

Binding Protein ◽

Retinol Binding Protein ◽

Vitamin A Status ◽

Plasma Retinol

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Comparison of Serum Retinol and Retinol-Binding Protein with the Modified Relative Dose-Response Test in Estimating Vitamin A Deficiency Among Ghanaian Women and Children

Current Developments in Nutrition ◽

10.1093/cdn/nzaa053_118 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 913-913

Author(s):

Devika Suri ◽

James Wirth ◽

Nicolai Petry ◽

Fabian Rohner ◽

Seth Adu-Afarwuah ◽

...

Keyword(s):

Vitamin A ◽

Sensitivity And Specificity ◽

Dose Response ◽

Roc Curve ◽

Binding Protein ◽

Vitamin A Deficiency ◽

Retinol Binding Protein ◽

Serum Retinol ◽

Women And Children ◽

Modified Relative Dose Response

Abstract Objectives To evaluate the sensitivity and specificity of serum retinol (SR) and retinol-binding protein (RBP) in determining vitamin A deficiency (VAD) using the modified relative dose-response (MRDR) test as the reference. Methods Subjects included a subset of women and children participating in the Ghana Micronutrient Survey 2017. VAD was determined by the following cut-offs: SR or RBP < 0.7 mmol/L; MRDR ratio of 3,4-didehydroretinol to SR ³0.060. Sensitivity, specificity and the area-under-the-receiver operating characteristic (ROC) curve were calculated for unadjusted and inflammation-adjusted VAD cut-offs (based on C-reactive protein (CRP) and a1-acid-glycoprotein (AGP) for SR and RBP using the MRDR test as the reference. Results In 167 children and 178 women, inflammation (elevated CRP and/or elevated AGP) was present in 41% and 16%, respectively. Prevalence of VAD ranged, depending on the indicator used, from 7% (MRDR) to 40% (unadjusted SR) in children and 1% (RBP) to 4% (SR and MRDR) in women. Among children, sensitivity and specificity of unadjusted and adjusted SR and RBP were highly variable among the children. Highest sensitivity was achieved by unadjusted SR (80% of children with VAD correctly identified), while highest specificity was achieved by adjusted RBP (86% of children without VAD correctly identified). The best predictor of VAD in children compared with MRDR was adjusted SR, with a sensitivity of 78%, specificity of 73%, and an area under the ROC curve of 0.76. Among women, specificity was 97% for unadjusted and adjusted SR with an area under the ROC curve of 0.48; additional values could not be calculated due to lack of VAD cases. Conclusions SR and RBP were only moderately sensitive and specific for identifying VAD in children in Ghana. Low specificity—falsely identifying VAD—is especially problematic when populations are covered by one or more vitamin A interventions. Overlapping sources of preformed vitamin A can lead to hypervitaminosis, which may affect bone metabolism and growth. More accurate measures should be used in conjunction with SR and RBP for evaluating VAD especially in vulnerable populations. Funding Sources UNICEF, Canada's Ministry of Foreign Affairs, Trade and Development.

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Saliva for Assessing Vitamin A Status in Extremely Preterm Infants: A Diagnostic Study

Neonatology ◽

10.1159/000506132 ◽

2020 ◽

Vol 117 (3) ◽

pp. 365-368

Author(s):

Abhijeet A. Rakshasbhuvankar ◽

Michael W. Clarke ◽

Karen Simmer ◽

Sanjay K. Patole ◽

J. Jane Pillow

Keyword(s):

Vitamin A ◽

Preterm Infants ◽

High Performance ◽

Invasive Procedure ◽

Enzyme Linked Immunosorbent Assay ◽

Diagnostic Study ◽

Vitamin A Status ◽

Extremely Preterm ◽

Extremely Preterm Infants ◽

Plasma Retinol

Background: Salivary measurement of hormones and vitamins is gaining prominence as a minimally invasive procedure with the negligible potential for harm. We aimed to assess the utility of saliva for assessing vitamin A status in extremely preterm infants. Methods: Paired saliva and blood samples were collected at 4 weeks of age from infants born <28 weeks of gestation using a proprietary polymer swab. Plasma retinol was measured using high-performance liquid chromatography, and salivary retinol was measured using enzyme-linked immunosorbent assay. Results: Thirty infants were recruited with a median (IQR) gestation and birth weight of 26.2 weeks (24.8–27.2) and 865 g (718–1,002), respectively. An adequate volume of saliva (>50 µL) was obtained in 68%. There was no significant correlation (Spearman’s correlation coefficient = 0.16, p = 0.3) between individual plasma and salivary retinol levels. Bland-Altman analysis showed wide limits of agreement (–113 to +119%) between individual plasma and salivary retinol levels. Conclusion: Individual vitamin A status cannot be determined reliably from saliva in extremely preterm infants using current collection materials and analysis techniques.

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