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Serum ferritin values in neonates <29 weeks’ gestation are highly variable and do not correlate with reticulocyte hemoglobin content

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Abstract

Objectives

To compare serum ferritin and RET-He values among extremely low gestational age neonates ELGANs with other markers of iron-deficient erythropoiesis.

Study Design

This is a secondary analysis of the NICHD Darbepoetin Trial. Study data from placebo recipients who had a serum ferritin, a RET-He, and a mean corpuscular volume (MCV) measurement within a 24-hour period were analyzed for correlation.

Results

Mixed linear regression models showed no association between ferritin and RET-He at both early (β = 0.0016, p = 0.40) and late (β = −0.0001, p = 0.96) time points. Positive associations were observed between RET-He and MCV at baseline, early, and late time points (p < 0.01, =0.01, <0.001, respectively), while ferritin was not associated with MCV at any time point.

Conclusions

Our study shows that RET-He is better correlated with MCV as a marker of iron-limited erythropoiesis than ferritin. The results suggest that ferritin is limited as a marker of iron sufficiency in premature infants.

Study Identification

FDA IND Number 100138; ClinicalTrials.gov number NCT03169881; NRN ID number NICHD-NRN-0058 (Darbe).

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Fig. 1: Scatter plots showing the relationship between simultaneous obtained RET-He and serum ferritin concentration measurements in neonates born at less than 29 weeks gestation who did not receive darbepoetin alpha.
Fig. 2: Scatter plots showing the relationship between simultaneous obtained RET-He and MCV, a red blood cell index where low values are associated with iron-limited erythropoiesis.
Fig. 3: Scatter plots showing the relationship between simultaneous obtained serum ferritin concentration and MCV, a red blood cell index where low values are associated with iron-limited erythropoiesis.
Fig. 4: Scatter plots showing the relationship between cumulative iron dose administered (mg/kg) and markers of iron sufficiency.

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Data availability

Inquiries regarding data access can be addressed to the corresponding author.

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Acknowledgements

The National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the NIH National Heart Lung and Blood Institute (NHLBI) provided grant support for the Neonatal Research Network’s Darbepoetin Trial through cooperative agreements. While NICHD staff had input into the study design, conduct, analysis, and manuscript drafting, the comments and views of the authors do not necessarily represent the views of NICHD, the National Institutes of Health, the Department of Health and Human Services, or the U.S. Government. Participating NRN sites collected data and transmitted it to RTI International, the data coordinating center (DCC) for the network, which stored, managed and analyzed the data for this study. On behalf of the NRN, RTI International had full access to all of the data in the study, and with the NRN Center Principal Investigators, takes responsibility for the integrity of the data and accuracy of the data analysis.We are indebted to our medical and nursing colleagues and the infants and their parents who agreed to take part in this study.

Funding

Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (UG1HD087226) and by a grant from the NIH National Heart Lung and Blood Institute (U01HL136318).

Author information

Authors and Affiliations

  1. Division of Neonatology, Department of Pediatrics, University of Utah Health, Salt Lake City, UT, USA

    Timothy M. Bahr, Carrie Rau, Mariana C. Baserga, Robert D. Christensen, Robin K. Ohls, Bradley A. Yoder, Stephen D. Minton, Mark J. Sheffield, Jill Burnett, Susan Christensen, Kathleen Coleman, Brandy Davis, Jennifer O. Elmont, Barbara L. Francom, Jamie Jordan, Manndi C. Loertscher, Trisha Marchant, Earl Maxson, Kandace M. McGrath, Hena G. Mickelsen, Melody Parry, Susan T. Schaefer, Katherine Tice, Kimberlee Weaver Lewis & Kathryn D. Woodbury

  2. Department of Neonatology, Intermountain Healthcare, Murray, UT, USA

    Timothy M. Bahr & Robert D. Christensen

  3. Social, Statistical and Environmental Sciences Unit, RTI International, Washington, DC, USA

    Sylvia Tan, Emily Smith, Kristin Zaterka-Baxter, Abhik Das, Marie G. Gantz, Carla M. Bann, Dennis Wallace, Dhuly Chowdhury, Jenna Gabrio, David Leblond & Jeanette O’Donnell Auman

  4. Department of Pediatrics, University of New Mexico, Albuquerque, NM, USA

    Sandra S. Beauman, Jean R. Lowe, Kristi L. Watterberg, Janell Fuller, Conra Backstrom Lacy, Mary Hanson & Elizabeth Kuan

  5. Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Kurt R. Schibler, Cathy A. Grisby, Stephanie Merhar, Brenda B. Poindexter, Kristin Kirker & Julia Thompson

  6. Department of Pediatrics, University of Iowa, Iowa City, IA, USA

    Edward F. Bell, Tarah T. Colaizy, Karen J. Johnson, Mendi L. Schmelzel, Jacky R. Walker, Claire A. Goeke & Sarah E. Faruqui

  7. Department of Pediatrics, Brown University, Providence, RI, USA

    Abbot R. Laptook, Martin Keszler, Tamara I. Arnautovic, Angelita M. Hensman, Elisa Vieira & Lucille St. Pierre

  8. Department of Pediatrics, Wayne State University, Detroit, MI, USA

    Seetha Shankaran

  9. Department of Pediatrics, Emory University, Atlanta, GA, USA

    David P. Carlton, Ravi M. Patel, Yvonne Loggins, Colleen Mackie & Diane I. Bottcher

  10. Department of Pediatrics, University of Pennsylvania, Philadelphia, PA, USA

    John Flibotte, Sara B. DeMauro, Eric C. Eichenwald, Barbara Schmidt, Haresh Kirpalani, Aasma S. Chaudhary, Soraya Abbasi, Toni Mancini, Sarvin Ghavam, Jonathan Snyder, Christine Catts & Megan A. Dhawan

  11. Division of Extramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA

    Michele C. Walsh, Andrew A. Bremer & Rosemary D. Higgins

  12. Division of Neonatology, College of Physicians and Surgeons, Columbia University, New York City, NY, USA

    Richard A. Polin

  13. Sanford Research, Sioux Falls, SD, USA

    Michelle L. Baack, Chelsey Elenkiwich, Megan M. Henning, Megan Broadbent & Sarah Van Muyden

Authors
  1. Timothy M. Bahr
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  2. Sylvia Tan
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  3. Emily Smith
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  4. Sandra S. Beauman
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  5. Kurt R. Schibler
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  6. Cathy A. Grisby
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  7. Jean R. Lowe
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  8. Edward F. Bell
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  9. Abbot R. Laptook
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  11. David P. Carlton
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  12. Carrie Rau
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  14. John Flibotte
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  15. Kristin Zaterka-Baxter
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  18. Robert D. Christensen
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  19. Robin K. Ohls
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Consortia

the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network

  • Richard A. Polin
  • , Martin Keszler
  • , Tamara I. Arnautovic
  • , Angelita M. Hensman
  • , Elisa Vieira
  • , Lucille St. Pierre
  • , Stephanie Merhar
  • , Brenda B. Poindexter
  • , Kristin Kirker
  • , Julia Thompson
  • , Ravi M. Patel
  • , Yvonne Loggins
  • , Colleen Mackie
  • , Diane I. Bottcher
  • , Andrew A. Bremer
  • , Rosemary D. Higgins
  • , Marie G. Gantz
  • , Carla M. Bann
  • , Dennis Wallace
  • , Dhuly Chowdhury
  • , Jenna Gabrio
  • , David Leblond
  • , Jeanette O’Donnell Auman
  • , Tarah T. Colaizy
  • , Karen J. Johnson
  • , Mendi L. Schmelzel
  • , Jacky R. Walker
  • , Claire A. Goeke
  • , Sarah E. Faruqui
  • , Michelle L. Baack
  • , Chelsey Elenkiwich
  • , Megan M. Henning
  • , Megan Broadbent
  • , Sarah Van Muyden
  • , Kristi L. Watterberg
  • , Janell Fuller
  • , Conra Backstrom Lacy
  • , Mary Hanson
  • , Elizabeth Kuan
  • , Sara B. DeMauro
  • , Eric C. Eichenwald
  • , Barbara Schmidt
  • , Haresh Kirpalani
  • , Aasma S. Chaudhary
  • , Soraya Abbasi
  • , Toni Mancini
  • , Sarvin Ghavam
  • , Jonathan Snyder
  • , Christine Catts
  • , Megan A. Dhawan
  • , Bradley A. Yoder
  • , Stephen D. Minton
  • , Mark J. Sheffield
  • , Jill Burnett
  • , Susan Christensen
  • , Kathleen Coleman
  • , Brandy Davis
  • , Jennifer O. Elmont
  • , Barbara L. Francom
  • , Jamie Jordan
  • , Manndi C. Loertscher
  • , Trisha Marchant
  • , Earl Maxson
  • , Kandace M. McGrath
  • , Hena G. Mickelsen
  • , Melody Parry
  • , Susan T. Schaefer
  • , Katherine Tice
  • , Kimberlee Weaver Lewis
  •  & Kathryn D. Woodbury

Contributions

TMB: collection and assembly of data, data analysis and interpretation, manuscript writing, editing and final approval of manuscript. ST, ES, AD: collection and assembly of data, editing and final approval of manuscript. data analysis and interpretation, editing and final approval of manuscript. SSB, KRS, CAG, JRL, EFB, ARL, SS, DPC, CR, JF, KZ, MCW: conception and design, data interpretation, manuscript writing, editing and final approval of manuscript. RDC, MCB, RKO: conception and design, collection and assembly of data, manuscript writing, data analysis and interpretation, editing and final approval of manuscript.

Corresponding author

Correspondence to Timothy M. Bahr.

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Bahr, T.M., Tan, S., Smith, E. et al. Serum ferritin values in neonates <29 weeks’ gestation are highly variable and do not correlate with reticulocyte hemoglobin content. J Perinatol 43, 1368–1373 (2023). https://doi.org/10.1038/s41372-023-01751-z

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