High Prevalence of Iron Deficiency Despite Standardized High-Dose Iron Supplementation During Recombinant Erythropoietin Therapy in Extremely Low Gestational Age Newborns

J Pediatr. 2020 Jul:222:98-105.e3. doi: 10.1016/j.jpeds.2020.03.055. Epub 2020 May 14.

Abstract

Objective: To assess the effects of protocolized recombinant human erythropoietin (r-HuEPO) therapy and standardized high dose iron supplementation on hematologic and iron status measures in a cohort of extremely low gestational age newborns (ELGANs).

Study design: Charts of extremely low gestational age newborns admitted from 2006 to 2016 and who had received r-HuEPO per neonatal intensive care unit protocol were reviewed. The r-HuEPO was started at a dose of 900 IU/kg per week after 7 days of age and continued until 35 weeks postmenstrual age. Oral iron supplementation at 6-12 mg/kg per day was used to maintain a transferrin saturation of >20% during r-HuEPO treatment. Data on demographic features, hematologic and iron panel indices, red blood cell transfusions, and clinical outcomes were collected. Quartile groups were created based on serum ferritin levels at the conclusion of the r-HuEPO treatment and the quartiles were compared.

Results: The cohort included 116 infants with mean gestational age 25.8 ± 1.5 weeks and birth weight 793 ± 174.1 g. The r-HuEPO promoted erythropoiesis as indicated by increasing hemoglobin, hematocrit, and reticulocyte count. Serum ferritin decreased over time and was ≤75 ng/mL in 60.2% of infants at the conclusion of r-HuEPO therapy; 87% received packed red blood cell transfusions. Transfusion volume, total iron intake, total iron binding capacity, and transferrin concentration differed among infants in the different serum ferritin quartiles (P < .05).

Conclusions: In extremely low gestational age newborns, r-HuEPO therapy promoted erythropoiesis. Despite a biomarker-based standardized high-dose iron supplementation, the majority of infants had evidence of iron deficiency to a degree that is associated with reduced brain function.

Keywords: erythropoietin; extremely low gestational age neonates; iron; iron deficiency; serum ferritin; transferrin saturation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Iron-Deficiency / blood
  • Anemia, Iron-Deficiency / drug therapy*
  • Anemia, Iron-Deficiency / epidemiology*
  • Drug Therapy, Combination
  • Erythropoietin / therapeutic use*
  • Female
  • Ferrous Compounds / therapeutic use*
  • Hematinics / administration & dosage*
  • Humans
  • Infant, Extremely Premature
  • Infant, Newborn
  • Iron-Dextran Complex / administration & dosage*
  • Male
  • Prevalence
  • Recombinant Proteins / therapeutic use
  • Retrospective Studies

Substances

  • EPO protein, human
  • Ferrous Compounds
  • Hematinics
  • Recombinant Proteins
  • Erythropoietin
  • ferrous sulfate
  • Iron-Dextran Complex