Abstract
Background
Fetal and neonatal brain iron content is compromised at the time of anemia, suggesting that screening for iron deficiency by measuring hemoglobin is inadequate to protect the brain. Reticulocyte hemoglobin (Ret-He) reflects iron-deficient (ID) erythropoiesis prior to anemia.
Methods
At postnatal day (P), 10 and 20 iron-sufficient rat pups were fostered to ID dams to produce a postnatal ID (PNID) group, which was compared to 20 iron-sufficient (IS) pups fostered by IS dams. Pups were assessed from P13 to P15 for hemoglobin, hematocrit, reticulocyte count, and Ret-He. Hippocampal iron status was assessed by transferrin receptor-1 (Tfrc-1) and divalent metal transporter-1 (Slc11a2) mRNA expression.
Results
At P13, brain iron status was similar between groups; only Ret-He was lower in the PNID group. At P14, the PNID group had lower Ret-He, hematocrit, mean corpuscular volume (MCV), and reticulocyte percentage (RET%). Tfrc-1 expression was increased, consistent with brain iron deficiency. Both Ret-He and MCV correlated with brain iron status at P14 and P15.
Conclusions
Ret-He was the only red cell marker affected prior to the onset of brain ID. The clinical practice of using anemia as the preferred biomarker for diagnosis of iron deficiency may need reconsidering.
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Acknowledgements
This work was supported by grants from the National Institutes of Health (P01 HL046925; R01 HL1385430), the Sysmex Corporation, which generously donated the Sysmex XT-2000i hematology analyzer, and Mead-Johnson Nutritionals.
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Ennis, K.M., Dahl, L.V., Rao, R.B. et al. Reticulocyte hemoglobin content as an early predictive biomarker of brain iron deficiency. Pediatr Res 84, 765–769 (2018). https://doi.org/10.1038/s41390-018-0178-6
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DOI: https://doi.org/10.1038/s41390-018-0178-6
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