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Paediatric reference intervals are heterogeneous and differ considerably in the classification of healthy paediatric blood samples

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Abstract

The aim was to elude differences in published paediatric reference intervals (RIs) and the implementations hereof in terms of classification of samples. Predicaments associated with transferring RIs published elsewhere are addressed. A local paediatric (aged 0 days to < 18 years) population of platelet count, haemoglobin level and white blood cell count, based on first draw samples from general practitioners was established. PubMed was used to identify studies with transferable RIs. The classification of local samples by the individual RIs was evaluated. Transference was done in accordance with the Clinical and Laboratory Standards Institute EP28-A3C guideline. Validation of transference was done using a quality demand based on biological variance. Twelve studies with a combined 28 RIs were transferred onto the local population, which was derived from 20,597 children. Studies varied considerably in methodology and results. In terms of classification, up to 63% of the samples would change classification from normal to diseased, depending on which RI was applied. When validating the transferred RIs, one RI was implementable in the local population. Conclusion: Published paediatric RIs are heterogeneous, making assessment of transferability problematic and resulting in marked differences in classification of paediatric samples, thereby potentially affecting diagnosis and treatment of children.

What is Known:

• Reference intervals (RIs) are fundamental for the interpretation of paediatric samples and thus correct diagnosis and treatment of the individual child.

• Guidelines for the establishment of adult RIs exist, but there are no specific recommendations for establishing paediatric RIs, which is problematic, and laboratories often implement RIs published elsewhere as a consequence.

What is New:

• Paediatric RIs published in peer-reviewed scientific journals differ considerably in methodology applied for the establishment of the RI.

• The RIs show marked divergence in the classification of local samples from healthy children.

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Abbreviations

RI:

Reference interval

plt:

Platelet count

hgb:

Haemoglobin level

WBC:

White blood cell

GP:

General practitioner

CLSI:

Clinical and Laboratory Standards Institute

QD:

Quality demand

IFCC:

Federation of Clinical Chemistry and Laboratory Medicine

CBC:

Complete blood count

LH:

Lillebaelt Hospital

OUH:

Odense University Hospital

SD:

Standard deviation

IQR:

Interquartile range

ER:

Emergency room

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Authors and Affiliations

  1. Department of Clinical Biochemistry and Immunology, Lillebaelt Hospital, Sygehusvej 24, 6000, Kolding, Denmark

    Anne Bryde Alnor

  2. Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, 5000, Odense, Denmark

    Pernille Just Vinholt

Authors
  1. Anne Bryde Alnor
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  2. Pernille Just Vinholt
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Both authors contributed equally to the present study.

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Correspondence to Anne Bryde Alnor.

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Communicated by Peter de Winter

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Alnor, A.B., Vinholt, P.J. Paediatric reference intervals are heterogeneous and differ considerably in the classification of healthy paediatric blood samples. Eur J Pediatr 178, 963–971 (2019). https://doi.org/10.1007/s00431-019-03377-w

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  • DOI: https://doi.org/10.1007/s00431-019-03377-w

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