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Paediatric Reference Intervals and Curves for Haemoglobin Estimated Using Direct Methods: A Systematic Review and
Vid Bijelić1,2, Marijana Bijelić1, Josh Larock3
1School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
International Journal of Laboratory Hematology
|May 3, 2025
Summary
This study synthesized evidence on pediatric hemoglobin reference intervals (RIs) and reference curves (RCs), finding significant heterogeneity. More rigorous global estimates are needed to accurately define anemia in children, especially the youngest.
Area of Science:
- Clinical Chemistry
- Pediatric Hematology
- Public Health
Background:
- Hemoglobin testing is crucial for assessing child health.
- Laboratories use reference intervals (RIs) and reference curves (RCs) to interpret pediatric hemoglobin results.
- Existing RIs/RCs show considerable variation, impacting anemia diagnosis.
Purpose of the Study:
- To systematically review and synthesize evidence on pediatric hemoglobin RIs/RCs.
- To investigate sources of heterogeneity in existing pediatric hemoglobin RIs/RCs.
- To compare findings with World Health Organization (WHO) anemia thresholds.
Main Methods:
- Systematic review of studies on pediatric hemoglobin RIs/RCs (PROSPERO: CRD42023399802).
- Searched EMBASE, MEDLINE, SCOPUS, and Cochrane libraries up to July 31, 2023.
- Included studies adhering to CLSI guidelines and reporting confidence intervals; excluded unhealthy children and cord-blood RIs.
Main Results:
- Analyzed 48 studies (123,498 participants) from 25 countries.
- Pooled estimates for 0-3 months not possible; for older children, RIs generally increased with age.
- Significant heterogeneity found, with sources including age, sex, analyzer type, and country; many RIs differed from WHO thresholds.
Conclusions:
- Substantial heterogeneity in pediatric hemoglobin RIs/RCs necessitates more robust global estimates.
- Improved RIs/RCs are needed to align with WHO anemia thresholds for consistent diagnosis.
- Further research on RIs for infants and the use of percentile curves is recommended.
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