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Using the refineR algorithm to generate indirect reference intervals for newborn infants for the parameters “Micro-R” and “HYPO-He”

Journal of Perinatology volume 45, pages 1624–1626 (2025)Cite this article

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The erythrocyte parameters “Micro-R” and “HYPO-He” are measured by certain popular hematology analyzers as biomarkers of iron-limited erythropoiesis [1,2,3]. Micro-R, a sensitive method of quantifying abnormally small RBC, is the percentage of red blood cells (RBC) with a mean corpuscular volume (MCV) < 60 fL [3]. HYPO-He, a metric of hypo-hemoglobinized RBC, is the percentage of RBC with mean corpuscular hemoglobin (MCH) < 17 pg. In healthy adults, both measurements are typically <1% [3]. Adults with early iron deficiency have elevated Micro-R and HYPO-He values before the MCV or MCH have fallen to the point where they are recognized as abnormal [1]. Our previously published data suggest that this pattern is also apparent in term and preterm infants [1, 2]. Because traditional markers of iron status, like serum iron and serum ferritin concentration, are problematic in preterm infants, elevated Micro-R and HYPO-He may prove to be early and sensitive markers of iron deficiency.

We previously sought to develop reference intervals for Micro-R and HYPO-He in neonates using our standard method, involving “curating” the Intermountain Health clinical database by removing values from neonates with diagnoses associated with microcytosis or hypochromia [1]. However, we recognize flaws in our curation method; specifically, not all pathological values can be recognized and removed, and many values from neonates with pathology are normal. Indirect approaches to determining reference intervals are those that use statistical methods to identify the non-pathologic distribution of interest from a mixed population of diseased and non-diseased individuals, instead of relying on human curation [4]. One such popular method is the “refineR” algorithm [5]. We used refineR to create reference intervals for Micro-R and HYPO-He of newborn infants.

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Fig. 1: Refine R reference intervals.

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

References

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Authors and Affiliations

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

    Timothy M. Bahr, Robin K. Ohls & Robert D. Christensen

  2. Women and Newborn’s Research, Intermountain Healthcare, Murray, UT, USA

    Timothy M. Bahr & Robert D. Christensen

  3. Department of Pathology, University of Utah Health and ARUP Laboratories, Salt Lake City, UT, USA

    Kelly Doyle

Authors
  1. Timothy M. Bahr
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  2. Kelly Doyle
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  3. Robin K. Ohls
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  4. Robert D. Christensen
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Contributions

TMB, KD, RKO, RDC: study design, collection and assembly of data, analysis and interpretation, manuscript writing, editing, and final approval of manuscript.

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Correspondence to Timothy M. Bahr.

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Bahr, T.M., Doyle, K., Ohls, R.K. et al. Using the refineR algorithm to generate indirect reference intervals for newborn infants for the parameters “Micro-R” and “HYPO-He”. J Perinatol 45, 1624–1626 (2025). https://doi.org/10.1038/s41372-025-02251-y

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