Reticulocyte Hemoglobin Equivalent has Comparable Predictive Accuracy as Conventional Serum Iron Indices for Predicting Iron Deficiency and Anemia in a Nonhuman Primate model of Infantile Iron Deficiency

• Published in: The Journal of nutrition 2023-01, Vol.153 (1), p.148-157
• Main Authors: Rao, Raghavendra B., Lubach, Gabriele R., Ennis-Czerniak, Kathleen M., Lock, Eric F., Kling, Pamela J., Georgieff, Michael K., Coe, Christopher L.
• Format: Article
• Language: English
• Subjects: Accuracy; Anemia; Anemia - metabolism; Anemia, Iron-Deficiency; Animals; Binding; Biomarkers; diagnosis; Diagnostic systems; Equivalence; Erythrocytes; Female; Hemoglobin; Hemoglobins - metabolism; infancy; Infants; Iron; Iron - metabolism; Iron Deficiencies; Iron deficiency; Male; Multiple regression models; nonhuman primate; Nutrient deficiency; Nutrition and Disease; prediction; Primates - metabolism; Regression analysis; reticulocyte hemoglobin equivalent; Reticulocytes; Reticulocytes - chemistry; Reticulocytes - metabolism; Risk factors; Sensitivity; Transferrin; transferrin saturation; Vitamin deficiency
• ISSN: 0022-3166; 1541-6100; 1541-6100
• DOI: 10.1016/j.tjnut.2022.11.002

Infantile iron deficiency (ID) causes anemia and compromises neurodevelopment. Current screening relies on hemoglobin (Hgb) determination at 1 year of age, which lacks sensitivity and specificity for timely detection of infantile ID. Low reticulocyte Hgb equivalent (RET-He) indicates ID, but its predictive accuracy relative to conventional serum iron indices is unknown. The objective was to compare diagnostic accuracies of iron indices, red blood cell (RBC) indices, and RET-He for predicting the risk of ID and IDA in a nonhuman primate model of infantile ID. Serum iron, total iron binding capacity, unsaturated iron binding capacity, transferrin saturation (TSAT), Hgb, RET-He, and other RBC indices were determined at 2 wk and 2, 4, and 6 mo in breastfed male and female rhesus infants (N = 54). The diagnostic accuracies of RET-He, iron, and RBC indices for predicting the development of ID (TSAT < 20%) and IDA (Hgb < 10 g/dL + TSAT < 20%) were determined using t tests, area under the receiver operating characteristic curve (AUC) analysis, and multiple regression models. Twenty-three (42.6%) infants developed ID and 16 (29.6%) progressed to IDA. All 4 iron indices and RET-He, but not Hgb or RBC indices, predicted future risk of ID and IDA (P < 0.001). The predictive accuracy of RET-He (AUC = 0.78, SE = 0.07; P = 0.003) for IDA was comparable to that of the iron indices (AUC = 0.77–0.83, SE = 0.07; P ≤ 0.002). A RET-He threshold of 25.5 pg strongly correlated with TSAT < 20% and correctly predicted IDA in 10 of 16 infants (sensitivity: 62.5%) and falsely predicted possibility of IDA in only 4 of 38 unaffected infants (specificity: 89.5%). RET-He is a biomarker of impending ID/IDA in rhesus infants and can be used as a hematological parameter to screen for infantile ID.