Iron is prioritized to red blood cells over the brain in phlebotomized anemic newborn lambs

Abstract

Background: Critically ill preterm and term neonates are at high risk for negative iron balance due to phlebotomy that occurs with frequent laboratory monitoring, and the high iron demand of rapid growth. Understanding the prioritization of iron between red blood cells (RBCs) and brain is important given iron's role in neurodevelopment.

Methods: Ten neonatal twin lamb pairs (n = 20) underwent regular phlebotomy for 11 d. Lambs were randomized to receive no iron or i.v. daily iron supplementation from 1 to 5 mg/kg. Serum hemoglobin concentration and reticulocyte count were assayed, iron balance calculated, and iron content of RBCs, liver, brain, muscle, and heart measured at autopsy.

Results: Among phlebotomized lambs: (i) liver iron concentration was directly related to net iron balance (r = 0.87; P < 0.001) and (ii) brain iron concentration was reduced as a function of net iron balance (r = 0.63) only after liver iron was depleted. In animals with negative iron balance, total RBC iron was maintained while brain iron concentration decreased as a percentage of the iron present in RBCs (r = -0.70; P < 0.01) and as a function of reticulocyte count (r = -0.63; P < 0.05).

Conclusion: Phlebotomy-induced negative iron balance limits iron availability to the developing brain.

Figure 1

Net iron balance in phlebotomized, non- supplemented lambs, phlebotomized lambs receiving varying amounts of IV iron supplementation, and the control group consisting of non-phlebotomized lambs receiving an average daily dose of 3 mg/kg-day of IV iron supplementation is shown (a>b>c>d>e>f, p<0.01). Values are mean ± SEM.

Figure 2

Mean hemoglobin concentration values of phlebotomized lambs by IV iron supplementation group over the phlebotomy period are shown. Initial drop in hemoglobin represents the early exchange transfusion, with ongoing phlebotomy until sacrifice by day 12. Solid circle = 0 mg/kg, solid triangle = 1 mg/kg, open circle = 2mg/kg, open square = 5 mg/kg, X = control

Figure 3

The distribution of total body iron in all phlebotomized as well as non- phlebotomized control lambs are shown. Percents of total body iron located within the liver ((panel a) R=0.82, p<0.01), RBC ((panel b) R=0.76, p<0.01), and brain ((panel c) R=0.64, p<0.01) are shown as a function of the net iron balance. Solid circle = 0 mg/kg, solid triangle = 1 mg/kg, open circle = 2mg/kg, open square = 5 mg/kg, X = control

Figure 4

Brain iron concentration as a function of liver iron concentration in phlebotomized lambs and in non-phlebotomized iron supplemented control lambs is shown. Solid circle = 0 mg/kg, solid triangle = 1 mg/kg, open circle = 2mg/kg, open square = 5 mg/kg, X = control

Figure 5

Brain iron concentration as a function of the percent of total measured iron found in RBCs in the two groups with net negative total body iron balance (n=13; R=0.70, p<0.01). This relationship was not present in animals in net positive iron balance (n=12, R=0.37, p> 0.15 (not shown)). Solid circle = 0 mg/kg, solid triangle = 1 mg/kg

Figure 6

Brain iron concentration as a function of mean reticulocytes (%) in the peripheral blood of animals in negative iron balance with no iron supplementation (R=0.55, p<0.05). Solid circle = 0 mg/kg 28