Novel Erythroid Indices Have Better Prognostic Accuracy than Conventional Erythroid Indices for Early Diagnosis of Iron Deficiency and Associated Brain Metabolomic Changes in Nonhuman Primate Infants.

BACKGROUND

Hemoglobin (Hgb) lacks sensitivity for early detection of iron deficiency (ID) and associated brain metabolic dysregulation in infancy. The utility of newer erythroid indices for early diagnosis of ID and altered brain metabolome is unknown.

OBJECTIVES

This study aimed to compare conventional and newer erythroid indices for predicting ID, anemia, and altered brain metabolome using a nonhuman primate model of infantile ID.

METHODS

Serum iron panel and erythroid indices were determined at 2 wk and 2, 4, and 6 months in male and female infant rhesus monkeys born to mothers consuming a 180 mg Fe/kg diet (n = 51). Cerebrospinal fluid (CSF) metabolomic profiles were obtained at 2 and 4 months in a subset of ID and iron-sufficient infants (n = 10). Accuracy for prediction of ID [transferrin saturation (TSAT) <20%], anemia (Hgb <10 g/dL), and CSF metabolomic changes was evaluated using t tests, regression models, and canonical correlation analysis (CCA).

RESULTS

Twenty infants (39.2%) developed ID and 13 (25.5%) progressed to anemia. At 2 wk, newer erythroid indices-immature reticulocyte fraction, reticulocyte hemoglobin equivalent (RET-He), and difference between hemoglobin in reticulocytes and that in mature red blood cells (Delta-He)-were altered in infants who subsequently developed ID, and, along with percentage hypohemoglobinized and hyperhemoglobinized erythrocytes, predicted the future likelihood of ID and anemia (false discovery rate <0.05). Hgb was not predictive of ID or anemia until 2 mo. Among erythroid indices, Delta-He was the best predictor, with an accuracy of 84% for both, and was comparable with TSAT. CCA demonstrated correlations between 4-mo CSF metabolomic profile and 2-wk (r = 0.71), 2-mo (r = 0.82), and 4-mo (r = 0.79) erythroid profiles. Mean corpuscular hemoglobin and RET-He were the largest contributors to the correlations between the 2-wk and 2-mo erythroid profiles and the 4-mo CSF metabolomic profile.

CONCLUSIONS

Newer erythroid indices detect ID, anemia, and brain metabolomic alterations earlier than conventional indices in infant monkeys.