Reference intervals for hemoglobin and mean corpuscular volume in an ethnically diverse community sample of Canadian children 2 to 36 months

Jemila S Hamid, Eshetu G Atenafu, Cornelia M Borkhoff, Catherine S Birken, Jonathon L Maguire, Mary Kathryn Bohn, Khosrow Adeli, Mohamed Abdelhaleem, Patricia C Parkin, Jemila S Hamid, Eshetu G Atenafu, Cornelia M Borkhoff, Catherine S Birken, Jonathon L Maguire, Mary Kathryn Bohn, Khosrow Adeli, Mohamed Abdelhaleem, Patricia C Parkin

Abstract

Objective: To establish reference intervals for hemoglobin and mean corpuscular volume (MCV) in an ethnically diverse community sample of Canadian children 36 months and younger.

Methods: We collected blood samples from young children at scheduled primary care health supervision visits at 2 weeks, 2, 4, 6, 9, 12, 15, 18, 24, and 36 months of age. Samples were analyzed on the Sysmex XN-9000 Hematology Analyzer. We followed the Clinical and Laboratory Standards Institute guidelines in our analysis. Data were partitioned by sex and also combined. We considered large age partitions (3 and 6 months) as well as monthly partitions. Reference intervals (lower and upper limits) and 90% confidence intervals were calculated.

Results: Data from 2106 children were included. The age range was 2 weeks to 36 months, 46% were female, 48% were European and 23% were of mixed ethnicity. For hemoglobin, from 2 to 36 months of age, we found a wide reference interval and the 90% confidence intervals indicated little difference across age groups or according to sex. For MCV, from 2 to 7 months of age there was considerable decrease in the reference interval, which was lowest during the second year of life, followed by a slight increase in the last months of the third year of life.

Conclusion: These findings suggest adoption of a single hemoglobin reference interval for children 2-36 months of age. Further studies in children under 4 months of age are needed.

Trial registration: TARGet Kids! cohort is registered at ClinicalTrials.gov. www.clinicaltrials.gov . Identifier: NCT01869530 .

Keywords: Hemoglobin; Mean corpuscular volume; Reference intervals.

Conflict of interest statement

CMB received the following unrelated to this study: an unrestricted research grant for a completed investigator-initiated study from the Sickkids Center for Healthy Active Kids (2015–2016).

CSB received the following unrelated to this study: a research grant from the Center for Addiction and Mental Health Foundation (2017–2020).

JLM received the following unrelated to this study: an unrestricted research grant for a completed investigator-initiated study from the Dairy Farmers of Canada (2011–2012), and Ddrops provided nonfinancial support (vitamin D supplements) for an investigator-initiated study on vitamin D and respiratory tract infections (2011–2015).

KA received the following unrelated to this study: a foundation grant from the Canadian Institutes of Health Research (Funding Reference Number: 353989).

PCP received the following related to this study: a grant from the Hospital for Sick Children Foundation, a grant from Canadian Institutes of Health Research (Funding Reference Number 115059); and the following unrelated to this study: nonfinancial support from Mead Johnson Nutrition (Fer-In-Sol liquid iron supplement; 2011–2017) for a completed investigator-initiated trial of iron deficiency in young children; unrestricted research grants for completed investigator-initiated studies from Danone Institute of Canada (2002–2004 and 2006–2009) and Dairy Farmers of Ontario (2008–2010).

These agencies had no role in the design, collection, analyses, or interpretation of the results of this work or in the preparation, review, or approval of this article; the other authors have indicated they have no financial relationships relevant to this article to disclose.

Figures

Fig. 1
Fig. 1
a and b Age-specific scatter plots by sex for hemoglobin (a) and MCV (b) for children from 2 weeks to 36 months of age

References

    1. Baker RD, Greer FR, The Committee on Nutrition Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0-3 years of age) Pediatrics. 2010;126(5):1040–1050. doi: 10.1542/peds.2010-2576.
    1. Adeli K, Raizman JE, Chen Y, Higgins V, Nieuwesteeg M, Abdelhaleem M, Wong SL, Blais D. Complex biological profile of hematologic markers across pediatric, adult, and geriatric ages: establishment of robust pediatric and adult reference intervals on the basis of the Canadian health measures survey. Clin Chem. 2015;61(8):1075–1086. doi: 10.1373/clinchem.2015.240531.
    1. Lönnerdal B, Georgieff MK, Hernell O. Developmental physiology of iron absorption, homeostasis, and metabolism in the healthy term infant. J Pediatr. 2015;167(4 Suppl):S8–14. doi: 10.1016/j.jpeds.2015.07.014.
    1. Lönnerdal B. Development of iron homeostasis in infants and young children. Am J Clin Nutr. 2017;106(suppl):1575S–1580S. doi: 10.3945/ajcn.117.155820.
    1. Hoq M, Matthews S, Donath S, Carlin J, Ignjatovic V, Monagle P. Paediatric reference intervals: current status, gaps, challenges and future considerations. Clin Biochem Rev. 2020;41(2):43–52.
    1. Soldin S, Wong E, Brugnara C, Soldin O. Pediatric Reference Intervals. American Association for Clinical Chemistry, Washington, DC: AACC Press, Seventh edition; 2011.
    1. Zierk J, Arzideh F, Rechenauer T, Haeckel R, Rascher W, Metzler M, Rauh M. Age- and sex-specific dynamics in 22 hematologic and biochemical analytes from birth to adolescence. Clin Chem. 2015;61(7):964–973. doi: 10.1373/clinchem.2015.239731.
    1. Clinical and Laboratory Standards Institute (CLSI) Defining, establishing, and verifying reference intervals in the clinical laboratory; approved guideline—third edition CLSI document C28-A.3. 2008.
    1. Daly CH, Liu X, Grey VL, Hamid JS. A systematic review of statistical methods used in constructing pediatric reference intervals. Clin Biochem. 2013;46(13-14):1220–1227. doi: 10.1016/j.clinbiochem.2013.05.058.
    1. Daly CH, Higgins V, Adeli K, Grey VL, Hamid JS. Reference interval estimation: methodological comparison using extensive simulations and empirical data. Clin Biochem. 2017;50(18):1145–1158. doi: 10.1016/j.clinbiochem.2017.07.005.
    1. Tahmasebi H, Higgins V, Fung AWS, Truong D, White-Al Habeeb NMA, Adeli K. Pediatric reference intervals for biochemical markers: gaps and challenges, recent national initiatives and future perspectives. EJIFCC. 2017;28(1):43–63.
    1. Parkin PC, Hamid J, Borkhoff CM, Abdullah K, Atenafu EG, Birken CS, Maguire JL, Azad A, Higgins V, Adeli K. Laboratory reference intervals in the assessment of iron status in young children. BMJ Paediatri Open. 2017;1(1):e000074. doi: 10.1136/bmjpo-2017-000074.
    1. Wang GC, Li N, Niu C, Ma WB, Wang ZL, Guo H, Han LH. Establishment of complete blood count reference intervals for Chinese preschoolers. J Clin Lab Anal. 2017;31(5):e22095. doi: 10.1002/jcla.22095.
    1. Lee HR, Shin S, Yoon JH, Roh EY, Chang JY. Reference intervals of hematology and clinical chemistry analytes for 1-year-old Korean children. Ann Lab Med. 2016;36(5):481–488. doi: 10.3343/alm.2016.36.5.481.
    1. Carsley S, Borkhoff CM, Maguire JL, Birken CS, Khovratovich M, McCrindle B, Macarthur C, Parkin PC, TARGet Kids! Collaboration Cohort profile: the applied research group for kids (TARGet Kids!) Int J Epidemiol. 2015;44(3):776–788. doi: 10.1093/ije/dyu123.
    1. Horn PS, Feng L, Li Y, Pesce AJ. Effect of outliers and nonhealthy individuals on reference interval estimation. Clin Chem. 2001;47(12):2137–2145. doi: 10.1093/clinchem/47.12.2137.
    1. Shapiro SS, Wilks MB. An analysis of variance test for normality (complete samples) Biometrika. 1965;52(3–4):591–611. doi: 10.1093/biomet/52.3-4.591.
    1. R Core Team . R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2020.
    1. Guest CM, Brown EW. Erythrocytes and hemoglobin of the blood in infancy and childhood: III. Factors in variability, statistical studies. AMA Am J Dis Child. 1957;93(5):486–509. doi: 10.1001/archpedi.1957.02060040488002.
    1. Mathoth Y, Zaizov R, Varsano I. Postnatal changes in some red cell parameters. Acta Paediatr. 1971;60(3):317–323. doi: 10.1111/j.1651-2227.1971.tb06663.x.
    1. O'Brien RT, Pearson HA. Physiologic anemia of the newborn infant. J Pediatr. 1971;79(1):132–138. doi: 10.1016/S0022-3476(71)80076-8.
    1. Staffa SJ, Joerger JD, Henry E, Christensen RD, Brugnara C, Zurakowski D. Pediatric hematology normal ranges derived from pediatric primary care patients. Am J Hematol. 2020;95(10). 10.1002/ajh.25904. Online ahead of print.
    1. Aldrimer M, Ridefelt P, Rödöö P, Niklasson F, Gustafsson J, Hellberg D. Population-based pediatric reference intervals for hematology, iron and transferrin. Scand J Clin Lab Invest. 2013;73(3):253–261. doi: 10.3109/00365513.2013.769625.
    1. Ceriotti F, Hinzmann R, Panteghini M. Reference intervals: the way forward. Ann Clin Biochem. 2009;46(Pt 1):8–17. doi: 10.1258/acb.2008.008170.
    1. Sikaris K. Application of the Stockholm hierarchy to defining the quality of reference intervals and clinical decision limits. Clin Biochem Rev. 2012;33:141–148.
    1. WHO . Vitamin and mineral nutrition information system. Geneva: World Health Organization; 2011. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity.
    1. Abdullah K, Birken CS, Maguire JL, Fehlings D, Hanley AJ, Thorpe KE, Parkin PC. Re-evaluation of serum ferritin cut-off values for the diagnosis of Iron deficiency in children aged 12-36 months. J Pediatr. 2017;188:287–290. doi: 10.1016/j.jpeds.2017.03.028.

Source: PubMed

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