Complex biological patterns of hematology parameters in childhood necessitating age‐ and sex‐specific reference intervals for evidence‐based clinical interpretation

Bohn, Mary Kathryn; Higgins, Victoria; Tahmasebi, Houman; Hall, Alexandra; En, Liu; Adeli, Khosrow; Abdelhaleem, Mohammed

doi:10.1111/ijlh.13306

Cited by 19 publications

(38 citation statements)

References 35 publications

(134 reference statements)

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“…Second, the geographic and ethnic composition of the analyzed cohorts varies. For example, we compare reference intervals obtained for children in Canada (CALIPER studies 31 – 35 ), the US 40 , Austria 36 , and Germany 37 . Third, the time range of measurement and measurement sites differ leading to potential time- and site-specific effects although we compared only studies using Roche cobas or Sysmex instruments.…”

Section: Discussionmentioning

confidence: 99%

“…For these biomarkers, we estimated reference intervals using refineR and kosmic with N = 200 bootstrap iterations and compared the results to reference intervals obtained from different direct method studies from literature 31 – 40 . The comparison studies include reference intervals obtained as part of the CALIPER project ( CA nadian L aboratory I nitiative in PE diatric R eference Intervals) 31 – 35 , package inserts accompanying the analytical devices 38 – 40 , a study obtained on a German pediatric cohort 37 and one carried out in an Austrian adolescent cohort 36 . Sample sizes in comparison studies were between 26 and 1872 (median: 200).…”

Section: Methodsmentioning

confidence: 99%

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refineR: A Novel Algorithm for Reference Interval Estimation from Real-World Data

Ammer

Schützenmeister

Prokosch

et al. 2021

Sci Rep

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Reference intervals are essential for the interpretation of laboratory test results in medicine. We propose a novel indirect approach to estimate reference intervals from real-world data as an alternative to direct methods, which require samples from healthy individuals. The presented refineR algorithm separates the non-pathological distribution from the pathological distribution of observed test results using an inverse approach and identifies the model that best explains the non-pathological distribution. To evaluate its performance, we simulated test results from six common laboratory analytes with a varying location and fraction of pathological test results. Estimated reference intervals were compared to the ground truth, an alternative indirect method (kosmic), and the direct method (N = 120 and N = 400 samples). Overall, refineR achieved the lowest mean percentage error of all methods (2.77%). Analyzing the amount of reference intervals within ± 1 total error deviation from the ground truth, refineR (82.5%) was inferior to the direct method with N = 400 samples (90.1%), but outperformed kosmic (70.8%) and the direct method with N = 120 (67.4%). Additionally, reference intervals estimated from pediatric data were comparable to published direct method studies. In conclusion, the refineR algorithm enables precise estimation of reference intervals from real-world data and represents a viable complement to the direct method.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

refineR: A Novel Algorithm for Reference Interval Estimation from Real-World Data

Ammer

Schützenmeister

Prokosch

et al. 2021

Sci Rep

View full text Add to dashboard Cite

show abstract

“…20 Study participation from community clinics has been described in detail by previous CALIPER studies. 20 Briefly, community participation involved completion of a health questionnaire and a blood donation following informed consent. Inclusion criteria included nonpregnant children and adolescents from birth to 18 years of age.…”

Section: Participant Recruitment and Sample Acquisition And Analysismentioning

confidence: 99%

“…20 Instrument performance was monitored through routine quality control practices and was concurrently used for clinical care, passing all manufacturer and hospital specifications. Quality control data for each parameter throughout study duration can be found in the Supplemental Material of Bohn et al 20…”

Section: Participant Recruitment and Sample Acquisition And Analysismentioning

confidence: 99%

Continuous reference curves for common hematology markers in the CALIPER cohort of healthy children and adolescents on the Sysmex XN‐3000 system

Wilson

Bohn

Hall

et al. 2021

Int J Lab Hematology

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Introduction: Clinicians and healthcare professionals rely heavily on health-associated standards, such as reference intervals (RIs), for appropriate laboratory test result interpretation. RIs are commonly partitioned into discrete age/sex bins based on statistical and/or clinical significance. In pediatric hematology, such partitioning does not adequately represent complex variation in analyte concentrations throughout maturation. The objective of this study was to establish continuous RIs for common hematological parameters in the healthy pediatric Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort.Methods: Data from healthy CALIPER children and adolescents (6 months-<19 years) were used to generate continuous RIs (ie, 2.5th and 97.5th quantiles) for 19 hematological parameters. Continuous curves were statistically established with nonparametric quantile regressions. Flagging rate analysis was completed for the established continuous upper and lower reference limits and subsequently compared to previously published discrete CALIPER reference intervals for all parameters.Results: Continuous RIs were established for 19 hematology parameters, where seven required sex-specific reference curves. Based on flagging rate assessment, continuous RIs appear to more accurately estimate hematological reference limits over the pediatric age range, especially for analytes with complex age-and sexspecific reference value patterns.Conclusions: This is the first study to generate continuous RIs for a breadth of hematological markers in a healthy pediatric Canadian population. The increased power of continuous reference intervals to accurately estimate the complex relationship between hematological analyte concentration and age during a time of extensive growth and development is expected to improve laboratory test result interpretation and, subsequently, pediatric clinical decision-making.

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“…Diffusion capacity of the lung for carbon monoxide (DLCO) was assessed by single-breathtechnique (MasterScope Spirometer and Master Screen Body, Jaeger/CareFusion, Höchberg); in all leukemia participants, DLCO was corrected for hemoglobin. Participants in the control group were derived from former studies: as we did not draw blood in those studies, hemoglobin was calculated according to existing normal values [20,21] and DLCO corrected for this hemoglobin value. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and effective resistance (Reff ) were reported as %predicted [22].…”

Section: Pulmonary Function Testingmentioning

confidence: 99%

Does allogeneic stem cell transplantation in survivors of pediatric leukemia impact regular physical activity, pulmonary function, and exercise capacity?

et al. 2021

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Background Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has improved survival in high-risk childhood leukemia but is associated with long-term sequelae such as impaired pulmonary function and reduced exercise capacity impacting quality of life. Methods A convenience sample of 17 patients after allo-HSCT (HSCT—12 male, age 15.7±6.7 years, time after HSCT 5.3±2.8 years) underwent pulmonary function testing, echocardiography, and an incremental exercise test on a bike. Physical activity and health-related quality of life were assessed by questionnaires (7-day physical activity recall, PEDS-QL). Seventeen healthy age- and gender-matched controls served as control group (CG) for results of pulmonary function and exercise testing. Results HSCT showed reduced pulmonary function (HSCT vs. CG: FEV1 90.5±14.0 vs. 108.0±8.7%pred; FVC 88.4±19.3 vs. 107.6±6.9%pred, DLCO 75.3±23.6 vs. 104.9±12.8%pred) and exercise capacity (VO2peak 89±30.8%pred, CG 98±17.5%pred; Wmax 84±21.7%pred, CG 115±22.8%pred), but no relevant cardiac dysfunction and a good quality of life (PEDS-QL mean overall score 83.3±10.7). Differences in peak oxygen uptake between groups were mostly explained by 5 adolescent patients who underwent total body irradiation for conditioning. They showed significantly reduced diffusion capacity and reduced peak oxygen uptake. Patients reported a mean time of inactivity of 777±159min/day, moderate activity of 110±107 min/day, hard activity of 35±36 min/day, and very hard activity of 23±22 min/day. A higher amount of inactivity was associated with a lower peak oxygen uptake (correlation coefficient tau −0.48, p=0.023). Conclusions This pilot study shows that although patients after allo-HSCT reported a good quality of life, regular physical activity and exercise capacity are reduced in survivors of stem cell transplantation, especially in adolescents who are treated with total body irradiation for conditioning. Factors hindering regular physical activity need to be identified and exercise counseling should be part of follow-up visits in these patients.

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Complex biological patterns of hematology parameters in childhood necessitating age‐ and sex‐specific reference intervals for evidence‐based clinical interpretation

Cited by 19 publications

References 35 publications

refineR: A Novel Algorithm for Reference Interval Estimation from Real-World Data

refineR: A Novel Algorithm for Reference Interval Estimation from Real-World Data

Continuous reference curves for common hematology markers in the CALIPER cohort of healthy children and adolescents on the Sysmex XN‐3000 system

Does allogeneic stem cell transplantation in survivors of pediatric leukemia impact regular physical activity, pulmonary function, and exercise capacity?

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