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Updated: May 17, 2026

The Caco-2 Cell Bioassay for Measurement of Food Iron Bioavailability
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Ferritin Reference Curves and Optimal Curves in Preadolescent Children.

Vid Bijelic1,2, Franco Momoli1, Mira Liebman3

  • 1School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.

JAMA Network Open
|May 15, 2026
PubMed
Summary

New ferritin reference curves (RCs) and optimal curves (OCs) for children show lower limits significantly below current iron deficiency thresholds. This impacts clinical interpretation and decision-making for pediatric iron status assessment.

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Last Updated: May 17, 2026

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Area of Science:

  • Pediatric Health
  • Biochemistry
  • Clinical Diagnostics

Background:

  • Ferritin levels are crucial for assessing iron status in children.
  • Traditional interpretation relies on age-partitioned reference intervals (RIs).
  • Existing RIs may not accurately reflect optimal iron levels in preadolescents.

Purpose of the Study:

  • To estimate sex-specific continuous ferritin reference curves (RCs) and optimal curves (OCs) for preadolescents.
  • To develop age- and sex-specific RIs and optimal intervals (OIs).
  • To interpret these curves alongside iron deficiency thresholds and develop a computational tool.

Main Methods:

  • Cross-sectional analysis of a longitudinal cohort study involving 4935 children aged 2 weeks to 10 years.
  • Sex-specific RCs estimated using generalized additive models.
  • OCs derived from a subsample meeting optimality criteria; interpretation against WHO and ASH thresholds.

Main Results:

  • Ferritin RCs and OCs were estimated for children aged 2 weeks to 10 years.
  • Curves showed sharp declines in early childhood and gradual increases in later preadolescence.
  • Lower limits of RCs and OCs were substantially lower than established iron deficiency thresholds.

Conclusions:

  • Ferritin RCs and OCs in a low-risk pediatric population reveal lower limits below current iron deficiency thresholds.
  • Findings challenge existing interpretation methods for ferritin measurements in children.
  • This research informs the ongoing debate on distributional vs. physiologic approaches to pediatric iron status assessment.