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Paediatric reference intervals and curves for haemoglobin and ferritin: protocol for a systematic review and
Vid Bijelić1, Beth Potter2, Patricia C Parkin3
1School of Epidemiology and Public Health, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada vbije016@uottawa.ca.
Insights
This review synthesizes evidence on reference intervals for pediatric ferritin and hemoglobin. It aims to quantify heterogeneity and identify sources of variation in their estimation methods.
Area of Science:
- Pediatric Laboratory Medicine
- Clinical Biochemistry
- Evidence Synthesis
Background:
- Reference intervals are crucial for interpreting pediatric laboratory test results.
- Established guidelines exist for creating reference intervals, with global initiatives for children.
- Synthesized evidence on pediatric reference intervals for iron biomarkers, specifically ferritin and hemoglobin, is lacking.
Purpose of the Study:
- To identify studies providing reference intervals and curves for pediatric ferritin and hemoglobin.
- To synthesize available evidence on these pediatric reference intervals.
- To quantify heterogeneity and identify sources of variation in their estimation.
Main Methods:
- Comprehensive literature search across EMBASE, MEDLINE, SCOPUS, and The Cochrane Library.
- Inclusion of grey literature for unpublished reference intervals from healthy cohorts.
- Independent screening of studies by two researchers, followed by data extraction and both narrative and quantitative synthesis.
Main Results:
- Eligible studies will provide reference intervals and curves for serum/plasma ferritin and hemoglobin in pediatric populations.
- Extracted data will encompass study characteristics, reference population details, and methodological considerations.
- Heterogeneity across estimated reference intervals and curves will be quantified and analyzed.
Conclusions:
- This systematic review will provide a comprehensive synthesis of pediatric reference intervals for ferritin and hemoglobin.
- Understanding heterogeneity will aid in standardizing the estimation of these vital biomarkers.
- Findings will inform clinical practice and future research in pediatric iron status assessment.
Introduction:
Reference intervals and reference curves provide clinicians with a point of reference when evaluating patients' laboratory test results. In practical applications, the 2.5th and 97.5th percentiles of healthy reference population are typically used as lower and upper reference limits. Guidelines outlining analytical and methodological steps involved in reference intervals and curves estimation are available and there have been large-scale world-wide initiatives to provide reference intervals and curves for children. However, there is a lack of synthesised evidence regarding the results of such initiatives in general, but specifically in iron-related biomarkers, ferritin (in serum and plasma) and haemoglobin. Objectives of this review are to identify studies that have produced reference intervals and curves for ferritin and haemoglobin in paediatric populations and to synthesise all available evidence. We also aim to quantify heterogeneity across reference intervals and curves and identify and elucidate sources of heterogeneity, including heterogeneity in the methods employed in their development.
Methods And Analysis:
Using a comprehensive search strategy, we will identify eligible studies. Following electronic databases will be searched from inception: EMBASE, MEDLINE, SCOPUS and The Cochrane Library. We will also perform grey literature search to capture unpublished reference intervals and curves from healthy cohorts. Two researchers will independently screen retrieved citations against eligibility criteria in two stages, focusing first on titles and abstracts and then on full-text articles. Studies that provide reference intervals and curves for ferritin and haemoglobin for paediatric population will be eligible. Data extraction will include study characteristics, characteristics of reference population, methodological and analytical considerations and estimated reference intervals and curves. We will consider narrative synthesis and quantitative synthesis when appropriate.
Ethics And Dissemination:
Ethical approval is not required as data from already published studies will be used. Results will be disseminated through peer-reviewed publications and conference presentations.
Prospero Registration Number:
CRD42023399802.
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