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Updated: May 4, 2026

Real-time Analyses of Retinol Transport by the Membrane Receptor of Plasma Retinol Binding Protein
Published on: January 28, 2013
The relative dose response test based on retinol-binding protein 4 is not suitable to assess vitamin A status in very
Bettina Schmiedchen1, Ann Carolin Longardt, Christoph Bührer
1Department of Physiology and Pathophysiology, University of Potsdam, Nuthetal, Germany.
Insights
The relative dose response (RDR) test using retinol-binding protein 4 (RBP4) is not a reliable substitute for the retinol-based RDR test in preterm infants. This study found poor agreement between the two methods for assessing vitamin A status.
Area of Science:
- Neonatal Nutrition
- Biochemistry
- Clinical Chemistry
Background:
- The relative dose response (RDR) test assesses liver vitamin A stores by measuring serum retinol increase post-administration.
- Feasibility of the RDR test in preterm infants is limited by small blood sample volumes.
Purpose of the Study:
- To evaluate if retinol-binding protein 4 (RBP4) RDR can substitute the retinol-based RDR test.
- To assess vitamin A status in very preterm infants.
Main Methods:
- Included 63 preterm infants (<1500g birth weight).
- Administered 5,000 IU retinyl palmitate intramuscularly 3x/week for 4 weeks.
- Calculated RDR using serum retinol and RBP4 on day 3 and day 28.
Main Results:
- Both retinol and RBP4 concentrations increased significantly from day 3 to day 28.
- Retinol-RDR and RBP4-RDR showed no significant correlation.
- Agreement between retinol-RDR and RBP4-RDR was poor (Cohen's κ = 0.12 on day 3, κ = 0.18 on day 28).
Conclusions:
- RDR test using RBP4 is unlikely to reflect hepatic vitamin A status in preterm infants.
- Retinol-based RDR remains the standard for assessing vitamin A status in this population.
Background:
The relative dose response (RDR) test, which quantifies the increase in serum retinol after vitamin A administration, is a qualitative measure of liver vitamin A stores. Particularly in preterm infants, the feasibility of the RDR test involving blood is critically dependent on small sample volumes.
Objectives:
This study aimed to assess whether the RDR calculated with retinol-binding protein 4 (RBP4) might be a substitute for the classical retinol-based RDR test for assessing vitamin A status in very preterm infants.
Methods:
This study included preterm infants with a birth weight below 1,500 g (n = 63, median birth weight 985 g, median gestational age 27.4 weeks) who were treated with 5,000 IU retinyl palmitate intramuscularly 3 times a week for 4 weeks. On day 3 (first vitamin A injection) and day 28 of life (last vitamin A injection), the RDR was calculated and compared using serum retinol and RBP4 concentrations.
Results:
The concentrations of retinol (p < 0.001) and RBP4 (p < 0.01) increased significantly from day 3 to day 28. On day 3, the median (IQR) retinol-RDR was 27% (8.4-42.5) and the median RBP4-RDR was 8.4% (-3.4 to 27.9), compared to 7.5% (-10.6 to 20.8) and -0.61% (-19.7 to 15.3) on day 28. The results for retinol-RDR and RBP4-RDR revealed no significant correlation. The agreement between retinol-RDR and RBP4-RDR was poor (day 3: Cohen's κ = 0.12; day 28: Cohen's κ = 0.18).
Conclusion:
The RDR test based on circulating RBP4 is unlikely to reflect the hepatic vitamin A status in preterm infants.
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