Am J Perinatol
DOI: 10.1055/a-2806-3017
Original Article

Iron Deficiency Screening with Reticulocyte–Hemoglobin Content and 2-Year Neurodevelopmental Outcomes in Extremely Low Birth Weight Infants

Authors

  • Whitley N. Hulse

    1   Division of Neonatology and Newborn Nursery, Department of Pediatrics, University of Wisconsin, Madison, Wisconsin, United States
    2   Division of Neonatology, Department of Pediatrics, University of Utah Health, Salt Lake City, Utah, United States
  • Timothy M. Bahr

    2   Division of Neonatology, Department of Pediatrics, University of Utah Health, Salt Lake City, Utah, United States
    3   Department of Neonatology, Intermountain Healthcare, Salt Lake City, Utah, United States
  • Betsy Ostrander

    4   Division of Pediatric Neurology, Department of Pediatrics, University of Utah Health, Salt Lake City, Utah, United States
  • Sarah Winter

    5   Department of Pediatrics, University of Utah Health, Salt Lake City, Utah, United States
  • Robin K. Ohls

    2   Division of Neonatology, Department of Pediatrics, University of Utah Health, Salt Lake City, Utah, United States
  • Tara L. DuPont

    2   Division of Neonatology, Department of Pediatrics, University of Utah Health, Salt Lake City, Utah, United States

Abstract

Objective

The objective of this study is to assess reticulocyte–hemoglobin (RET–He) and daily iron dosing with 2-year cognitive outcomes.

Study Design

A multicenter retrospective cohort study of 78 infants born between 2014 and 2018 at less than 28 weeks' gestation or less than 1,250 g birth weight throughout level III or IV neonatal intensive care units (NICUs). RET–He measurement, iron supplementation, and the Bayley Scales of Infant and Toddler Development-III (Bayley-III) test were analyzed using multiple linear regression models.

Results

For every 1 mg/kg increase in mean total daily iron supplementation, the Bayley-III cognitive score increased by 2.9 points (95% confidence interval [CI]: 0.4–5.4, p = 0.023). No associations were identified between minimum or maximum RET–He and Bayley-III cognitive outcomes. Infants with a RET–He value < 29 pg tended to be 2.53 times more likely to have a Bayley-III language score below 70 (odds ratio: 2.53, 95% CI: 0.92–6.95, p = 0.071). Thirty-eight out of 78 (38.4%) infants were iron-deficient during their NICU hospitalization, with at least one RET–He < 29 pg.

Conclusion

An association was identified between a higher mean daily iron dose and improved cognitive outcomes for infants, but not between the iron index RET–He and neurodevelopmental outcomes. Iron deficiency remains common among NICU patients undergoing follow-up, suggesting that standard iron dosing may be inadequate for high-risk neonates.

Key Points

  • Higher daily iron dose improves cognitive outcomes.

  • Reticulocyte–hemoglobin level is not associated with neurodevelopmental outcomes.

  • Iron deficiency is common in very low birth weight infants, affecting 38.4%.

Data Availability Statement

These data are original and have not been previously published. Data are not available for sharing outside of the institution.


Contributors' Statement

W.N.H.: Conceptualization, data curation, formal analysis, investigation, methodology, project administration, writing—original draft, writing—review and editing. T.M.B.: Formal analysis, writing—original draft, writing—review and editing. B.O.: Conceptualization, methodology, writing—original draft, writing—review and editing. S.W.: Conceptualization, methodology, writing—original draft, writing—review and editing. R.K.O.: Conceptualization, methodology, writing—original draft, writing—review and editing. T.L.D.: Conceptualization, formal analysis, methodology, project administration, supervision, writing—original draft, writing—review and editing.




Publication History

Received: 12 June 2025

Accepted: 04 February 2026

Article published online:
20 February 2026

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