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

Raghu Rao, Gabriele R. Lubach, Kathleen M. Ennis-Czerniak, Eric F. Lock, Pamela J. Kling, Michael K Georgieff, Christopher L. Coe

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: 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. Objectives: 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. Methods: 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. Results: 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%). Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)148-157
Number of pages10
JournalJournal of Nutrition
Volume153
Issue number1
DOIs
StatePublished - Jan 2023

Bibliographical note

Funding Information:
This work was supported by the National Institute of Health/Eunice Kennedy Shriver National Institute of Child Health and Development (Grants HD089989 , HD080201 , HD057064 , and HD39386 ) and Sysmex America, Inc., Lincolnshire, Illinois. In addition, Sysmex America, Inc. provided the Sysmex XN-V Hematology Analyzer ( Model XN-1000N ), all reagents, and other materials. The funding agencies were not involved in study design; collection, analysis, and interpretation of data; or writing and publication of the report.

Publisher Copyright:
© 2022 American Society for Nutrition

Keywords

  • anemia
  • diagnosis
  • hemoglobin
  • infancy
  • iron deficiency
  • nonhuman primate
  • prediction
  • reticulocyte hemoglobin equivalent
  • transferrin saturation

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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