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Quantitating Iron Transport Across the Mouse Placenta In Vivo Using Nonradioactive Iron Isotopes
Published on: May 10, 2022
Iron is prioritized to red blood cells over the brain in phlebotomized anemic newborn lambs
Tara G Zamora1,2, Sixto F Guiang2, John A Widness3
1Children's Hospitals and Clinics of Minnesota, St Paul, Minnesota, USA.
Insights
Frequent blood draws in critically ill newborns can lead to iron deficiency. This study shows that negative iron balance prioritizes red blood cells over the developing brain, impacting neurodevelopment.
Area of Science:
- Neonatal physiology
- Iron metabolism
- Neurodevelopment
Background:
- Critically ill neonates face high risk of negative iron balance.
- Phlebotomy for lab tests and rapid growth increase iron demand.
- Iron's role in neurodevelopment necessitates understanding its prioritization.
Purpose of the Study:
- To investigate iron distribution between red blood cells and the brain in neonates experiencing negative iron balance.
- To determine the impact of iron supplementation on iron prioritization.
Main Methods:
- Neonatal twin lamb pairs underwent phlebotomy for 11 days.
- Lambs were randomized to receive no iron or daily intravenous iron supplementation.
- Iron content in red blood cells, liver, brain, muscle, and heart were measured.
Main Results:
- Liver iron concentration correlated with net iron balance.
- Brain iron concentration decreased with negative iron balance only after liver iron depletion.
- Red blood cell iron was maintained, while brain iron decreased relative to red blood cell iron in negative balance.
Conclusions:
- Phlebotomy-induced negative iron balance limits iron availability to the developing brain.
- Maintaining red blood cell iron may occur at the expense of brain iron during critical illness.
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.
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History
The history of blood transfusion dates back to the 17th century, when early attempts were made in animals. In 1818 James Blundell, a British doctor, performed the first successful human blood transfusion. Later in 1900, Karl...

