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Do Extremely Low Gestational Age Neonates Regulate Iron Absorption via Hepcidin?
Kendell R German1, Bryan A Comstock2, Pratik Parikh3
1Department of Pediatrics, University of Washington, Seattle, WA.
Insights
Extremely preterm infants appear to regulate iron status via hepcidin, as indicated by urine hepcidin levels correlating with iron markers. Treatment with erythropoietin affects these levels, suggesting active iron status regulation in neonates.
Area of Science:
- Neonatal physiology
- Iron metabolism
- Endocrinology
Background:
- Extremely preterm infants often experience iron deficiency due to various factors.
- Hepcidin is a key regulator of systemic iron homeostasis.
- Understanding iron regulation in this vulnerable population is crucial for optimal growth and development.
Purpose of the Study:
- To investigate whether extremely preterm neonates can regulate their iron status through hepcidin.
- To assess the correlation between urine hepcidin levels and established serum iron markers.
- To determine the impact of erythropoietin treatment on hepcidin regulation in preterm infants.
Main Methods:
- Retrospective analysis of urine samples from the Preterm Epo Neuroprotection (PENUT) Trial.
- Measurement of urine hepcidin normalized to creatinine (Uhep/UCr).
- Correlation analysis between Uhep/UCr and serum ferritin, zinc protoporphyrin-to-heme ratio (ZnPP/H), and iron dose.
Main Results:
- Uhep/UCr values showed significant correlations with serum ferritin and ZnPP/H levels at various time points.
- Median Uhep/UCr concentrations varied over time in placebo-treated infants.
- Erythropoietin treatment significantly affected Uhep/UCr values, particularly at 2 weeks.
Conclusions:
- Urine hepcidin levels in extremely preterm infants correlate with serum iron markers, indicating a capacity for iron status regulation.
- Hepcidin regulation is dynamic in this population and influenced by erythropoietin therapy.
- Hepcidin appears suppressed in extremely preterm neonates, especially those receiving erythropoietin.
Objectives:
To evaluate whether extremely preterm infants regulate iron status via hepcidin.
Study Design:
In this retrospective analysis of infants from the Preterm Epo Neuroprotection (PENUT) Trial, urine hepcidin (Uhep) normalized to creatinine (Uhep/UCr) was evaluated among infants randomized to erythropoietin (Epo) or placebo.
Results:
The correlation (r) between Uhep/UCr and serum markers of iron status (ferritin and zinc protoporphyrin-to-heme ratio [ZnPP/H]) and iron dose was assessed. A total of 243 urine samples from 76 infants born at 24-276/7 weeks gestation were analyzed. The median Uhep/UCr concentration was 0.3, 1.3, 0.4, and 0.1 ng/mg at baseline, 2 weeks, 4 weeks, and 12 weeks, respectively, in placebo-treated infants. The median Uhep/UCr value in Epo-treated infants were not significantly different, with the exception of the value at the 2-week time point (median Uhep/UCr, 0.1 ng/mg; P < .001). A significant association was seen between Uhep/UCr and ferritin at 2 weeks (r = 0.63; P < .001) and at 4 weeks (r = 0.41; P = .01) and between Uhep/UCr and ZnPP/H at 2 weeks (r = -0.49; P = .002).
Conclusions:
Uhep/UCr values correlate with serum iron markers. Uhep/UCr values vary over time and are affected by treatment with Epo, suggesting that extremely preterm neonates can regulate hepcidin and therefore their iron status. Uhep is suppressed in extremely preterm neonates, particularly those treated with Epo.
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