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.