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Prognostic Performance of Hematological and Serum Iron and Metabolite Indices for Detection of Early Iron Deficiency
Brian J Sandri1, Jonathan Kim2, Gabriele R Lubach3
1Division of Neonatology, Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States; Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, United States.
Insights
Early detection of infant iron deficiency (ID) is crucial. Reticulocyte hemoglobin (RET-He) and specific metabolites like homostachydrine show promise in identifying preanemic ID and predicting brain metabolic dysfunction in infants.
Area of Science:
- Pediatrics
- Neuroscience
- Biochemistry
Background:
- Current infant iron deficiency (ID) screening at one year of age is insufficient.
- It fails to detect preanemic ID and prevent later neurocognitive deficits.
Purpose of the Study:
- Identify biomarkers for iron-related metabolic alterations in serum and brain.
- Assess the sensitivity of conventional iron and heme indices in predicting brain metabolic dysfunction in infantile ID using a nonhuman primate model.
Main Methods:
- Analyzed serum iron and RBC indices, along with serum and CSF metabolomic profiles in iron-sufficient and iron-deficient rhesus infants at 2 and 4 months.
- Compared metabolic profiles and iron indices between groups.
Main Results:
- Reticulocyte hemoglobin (RET-He) was lower in the ID group at 2 weeks.
- Serum and CSF metabolomic profiles differed significantly between iron-sufficient and iron-deficient infants by 2 months.
- Key metabolites, homostachydrine and stachydrine, were significantly lower in the ID group's serum and CSF.
- RET-He and serum iron indices at 2 months correlated with altered CSF metabolic profiles at 4 months.
Conclusions:
- Preanemic ID in infants is linked to serum and CSF metabolic alterations.
- RET-He emerged as a predictor of abnormal CSF metabolic profiles, comparable to serum iron indices.
- Homostachydrine and stachydrine in serum and CSF show potential as early biomarkers for brain metabolic dysfunction in infantile ID.
Background:
The current pediatric practice of monitoring for infantile iron deficiency (ID) via hemoglobin (Hgb) screening at one y of age does not identify preanemic ID nor protect against later neurocognitive deficits.
Objectives:
To identify biomarkers of iron-related metabolic alterations in the serum and brain and determine the sensitivity of conventional iron and heme indices for predicting risk of brain metabolic dysfunction using a nonhuman primate model of infantile ID.
Methods:
Simultaneous serum iron and RBC indices, and serum and cerebrospinal fluid (CSF) metabolomic profiles were determined in 20 rhesus infants, comparing iron sufficient (IS; N = 10) and ID (N = 10) infants at 2 and 4 mo of age.
Results:
Reticulocyte hemoglobin (RET-He) was lower at 2 wk in the ID group. Significant IS compared with ID differences in serum iron indices were present at 2 mo, but Hgb and RBC indices differed only at 4 mo (P < 0.05). Serum and CSF metabolomic profiles of the ID and IS groups differed at 2 and 4 mo (P < 0.05). Key metabolites, including homostachydrine and stachydrine (4-5-fold lower at 4 mo in ID group, P < 0.05), were altered in both serum and CSF. Iron indices and RET-He at 2 mo, but not Hgb or other RBC indices, were correlated with altered CSF metabolic profile at 4 mo and had comparable predictive accuracy (area under the receiver operating characteristic curve scores, 0.75-0.80).
Conclusions:
Preanemic ID at 2 mo was associated with metabolic alterations in serum and CSF in infant monkeys. Among the RBC indices, only RET-He predicted the future risk of abnormal CSF metabolic profile with a predictive accuracy comparable to serum iron indices. The concordance of homostachydrine and stachydrine changes in serum and CSF indicates their potential use as early biomarkers of brain metabolic dysfunction in infantile ID.
