Optimizing Iron Supplementation by Monitoring Ferritin Concentration

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Iron (Fe) is essential for growth and neurodevelopment, but the optimal intake remains controversial.  Many preterm infants develop Fe deficiency due to low stores and phlebotomy losses, but they are also susceptible to oxidant injury from excess circulating Fe from diet or transfusions. The AAP recommends supplementing Fe for preterm infants feeding human milk (but not formula because of its higher Fe content) starting by 4 weeks but acknowledges that supplementation based on physiologic measures could be more effective.  A recent expert panel recommendation suggested that Fe be initiated and adjusted based on serum levels of ferritin, a protein that binds circulating Fe.  Our current NICU practice was to supplement Fe (2 mg/kg/d) for all preterm infants receiving full-volume human milk feeds.    


Our objectives in this quality improvement project were to:  1) implement a protocol for initiating and titrating Fe dosages based on therapeutic monitoring of ferritin levels, and 2) assess the impact of this protocol on the timing and dosing of Fe supplementation for preterm infants.  


Preterm infants (< 32 wks GA or < 1500 g, n=43) who reached full feeding volume of 160 ml/kg/day by day 30 were included.  Ferritin levels were measured every other week after full feeding volume was achieved.  For ferritin 40-300 µg/L, Fe was started at 2 mg/kg/d or continued at current dose; for ferritin < 40 µg/L, Fe was increased by 1-2 mg/kg/d; for ferritin > 300 µg/L, Fe was held until ferritin decreased.  


The protocol was rapidly adopted by clinicians.  Serum ferritin levels were not directly correlated with dietary Fe intake.  Overall, Fe was initiated later using the ferritin protocol, but peak doses were higher.  Fe supplementation was deferred in 29% of infants because of initial ferritin > 300 µg/L, and only 42% of those were predictable based on diet or transfusions.  One infant required Fe despite transfusion.  34% of infants required escalating Fe doses (> 2 mg/kg/d).  Surprisingly, all formula-fed infants needed additional Fe despite intake of approximately 2 mg/kg/day from feeds.    


An evidence-based protocol for Fe supplementation based on ferritin levels is easily adopted in NICU.  Fe requirements are not predictable based on dietary or transfusion history, and standard protocols appear to over- and undertreat infants.  We speculate that physiologic supplementation with Fe based on ferritin levels will decrease the incidence of both deficiency and overload, improving outcomes for preterm infants.   


Cohen Children's Medical Center, Northwell Health
Cohen Children's Medical Center of New York
Cohen Children's Medical Center

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