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IFCC-standardized pediatric reference intervals for 10 serum proteins using the Beckman Array 360 system©
Clinical Biochemistry,Vol. 29, No. 5, pp. 489-492, 1996 Copyright © 1996The Canadian Societyof ClinicalChemists Printed in the USA.All rights reserved 0009-9120/96 $15.00 + .00 ELSEVIER
SOOO9-9120(96)OOO46-X
IFCC-Standardized Pediatric Reference Intervals for 10 Serum Proteins Using the Beckman Array 360 System © MICHAEL L. DAVIS, CATHY AUSTIN, BETTE L. MESSMER, WENDI K. NICHOLS, ANDRI~ P. BONIN, and MICHAEL J. BENNETT Department of Clinical Chemistry, Children's Medical Center of Dallas, Dallas, TX, U.S.A., Department of Clinical Chemistry, Hopital Ste. Justine Montreal, Quebec, Canada, and Departments of Pathology and Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, U.S.A. Introduction
Samples and methods
Reference ranges in clinical chemistry are frequently established by analyzing samples remaining in excess of that required for normal clinical management, following the rejection of samples from clinically inappropriate patients. This process is difficult to replicate in pediatric practice because of the small sample volumes that are normally collected, and consequent: lack of excess material. Frequently, consensus ranges derived from previously published work are utilized in pediatrics (1,2). This practice is probably satisfactory when the analytical methods conform to iinternationally standardized procedures (3,4). Standardization is particularly important when different analytical systems and reagents are used to measure the analytes in question. This is particularly true for the assay of serum proteins by nephelometry, when the properties of the various proprietary an.tibodies used by the different manufacturers may vary considerably. To date, there have been very :Fewreports of pediatric reference ranges for serum proteins using nephelometry, and no reports using reagent systems that conform to international standards (5-7). We present here the results of age- and sexrelated reference values for 10 serum proteins that are standardized to IFCC recommendations, using the Beckman Array 360 Nephelometer, and compare this data to previously published nonstandardized data.
The specimens used in this study were comprised of serum in excess of that required for normal clinical management, collected prospectively in a series of patients admitted to, or attending, outpatient clinics at The Children's Medical Center of Dallas (CMC). Samples from patients with conditions likely to result in abnormal plasma protein levels (i.e., those with impaired hematologic, hepatic, renal, or immune functions) were rejected from the study. Samples accepted for the study were coded for patient age and sex only, to maintain anonymity. This study was approved by the Institutional Review Board of The University of Texas Southwestern Medical Center at Dallas. The demographics of the patient population at CMC are as follows: 57% Caucasian, 20% Hispanic, 18% African American, 1% Asian, 4% other. The goal was to identify a minimum of 40 samples in each of the age ranges: 0-1 month, 1-2 months, 2-3 months, 3-4 months, 4-5 months, 5-6 months, 6-7 months, 7-8 months, 8-9 months, 9-10 months, 10-11 months, 11-12 months, 1-2 years, 2-3 years, 4-5 years, 5-6 years, and 6-18 years. Upon acceptance into the study, the samples were immediately stored frozen at -20 °C prior to batch analysis. Samples were typically stored for 1-2 weeks. Upon thawing for analysis, all tests were performed and no samples were refrozen. Samples were analyzed for immunoglobulins G, A, and M, prealbumin (transthyretin), ceruloplasmin, alpha-l-antitrypsin, haptoglobin, transferrin, and complements C3 (total C3) and C4 using the standard protocols developed by Beckman for use with the Array System, with no modifications. Betweenbatch performance data is presented in Table 1. These analytes have been standardized to the International Federation of Clinical Chemistry (IFCC) reference preparation for proteins in human serum
Correspondence: Dr. Michael J. Bennett, D e p a r t m e n t of Pathology, Children's Medical C e n t e r of Dallas, 1935 Motor Street, Dallas TX 75235, U.S.A. M a n u s c r i p t received F e b r u a r y 7, 1996; revised M ar ch 18, 1996; accepted Marc:h 21, 1996. CLINICAL BIOCHEMISTRY, VOLUME 29, OCTOBER 1996
489
DAVIS ET AL. TABLE 1 Between Batch Precision of IFCC Standardized Protein Assays on Beckman Array Analyte IgA (g/L) IgG (g/L) IgM (g/L) Complement C3 (g/L) Complement C4 (g/L) Ceruloplasmin (g/L) Prealbumin (g/L) Alpha-l-antitrypsin (g/L) Haptoglobin (g/L) Transferrin (g/L)
Concentration of Control
Coefficient of Variation
0.117 0.370 0.553 13.73 0.600 2.190 0.81 2.16 0.170 0.670 0.180 0.550 0.160 0.450 0.68 1.67 0.590 1.950 1.35 3.15
4.2 5.1 4.8 4.8 4.5 6.1 5.3 7.4 7.6 8.5 7.8 8.0 5.0 5.7 7.3 6.1 3.9 5.5 4.5 6.8
(RPPHS, designated lot 91/0619 by the College of American Pathologists). The data were examined graphically for breaks or trends based on age or sex. Ranges were determined for data t h a t exhibited normal distribution by using the means and 2 standard deviations. Outliers were removed according to the procedure of Hoffmann (8). Nonparametric statistical procedures were used to determine ranges encompassing 95% of the data for those analytes not exhibiting normal distribution
(9). Results A total of 469-533 patient data points were obtained for each analyte. Not all proteins were measured in each specimen due to the limited volumes available. We had some difficulty in gathering sufficient samples for the age range 1-12 months because there were both fewer patients and smaller sample volumes from these patients. We extended the study period to accumulate sufficient samples r e p r e s e n t a t i v e for this age group. We a n a l y z e d samples on 293 male and 272 female patients. We could not detect sex-related differences for any of the s t u d y a n a l y t e s and, consequently, combined the data as age-specific only. Table 2 shows the agespecific reference ranges for the 10 proteins. The Table presents age range, number of patients, the mean and range (95% confidence limits) for each of the proteins. For age-ranges in which we could not detect an age-related difference, we have combined the data. Thus, for the immunoglobulins A, G, and M there are clear age-related differences consistent with all previous data, whereas for proteins, such as 490
alpha-l-antitrypsin and haptoglobin, we could detect no such age-related differences. The levels of transferrin, prealbumin, ceruloplasmin, and complements C3 and C4 demonstrated some agerelated differences below 1 year of age but, in general, there was little difference beyond the age of 1 year. Consequently, for these proteins, data groups were combined when no age-related differences were detected.
Discussion We present the first pediatric reference ranges for 10 serum proteins t h a t are derived from an assay t h a t conforms to IFCC standardization. Previously, such ranges were derived from nonstandardized assays and, as such, were open to significant variability depending on the n a t u r e of the reagents being used in the assay. Our data are presented in an agerelated format, when there is an age-related difference. We could detect no sex-related differences. The patients whose samples were analyzed were carefully selected to exclude those with diseases t h a t might have affected protein levels and, within the confines of a hospital-based population, were as healthy as could be defined. Because it is unlikely t h a t sufficient data will ever be accrued from a truly healthy pediatric population, this patient selection probably reflects a population as close to normal as will be possible (4). In the study of multiple pediatric reference ranges for the Abbott IMx © analyzer, Soldin et al. (7) removed outliers by sequentially rejecting outliers. In this study, initial rejection was based on clinical criteria alone. We experienced difficulty in obtaining data for ages 1 month to 1 year. This was expected, because the reference intervals for this age group tends to be small, or missing, from almost every pediatric analyte for which a reference range is available (2). In comparing our IFCC-standardized data with the only other significant recent study of pediatric protein levels using nonstandardized materials (6), we noticed numerous differences, as outlined below. For IgA, we p r e s e n t d a t a b r o k e n down into smaller age groups and detected a rising t r e n d throughout the first year of life. Lockitch et al. presented an IgA range of 0-1.0 g/L for the 0-12-month age group (6). We have been able to further break down this first year of life to demonstrate a rising trend from 1 month of age to 1 year. Similar trends were observed within the first year of life for both IgG and IgM. IgM also demonstrated a quantitative difference t h a t we attribute to differences between IFCC-standardized and nonstandardized reagents. In our assay, the age group 4-19 years, for which we could see no trends and, therefore, combined the data, the reference range was 0.480-2.260 g/L. Combining the data for the 4-19-year-old subjects studied by Lockitch et al. produces a wider range of values of 0.230-3.870, almost doubling the upper limit. Differences also occur for C3, our range 1-19 years, 0.70-2.06 g/L (n = 338) vs 0.51-0.95 (n = 334); this CLINICALBIOCHEMISTRY,VOLUME29, OCTOBER 1996
PEDIATRIC REFERENCE RANGES TABLE 2 Pediatric Reference Intervals on the Beckman Array 360 Analyte
Age
# Subjects
Mean
Range
IgA (g/L)
0-1 month 1-4 months 4-12 months 1-2 years 2-3 years 3-4 years 4-5 years 5-6 years 6-7 years 7-10 years 10-13 years 13-19 years 0-3 months 3-24 months 2-4 years 4-19 years 0-2 months 2-12 months 1-4 years 4-19 years 0-2 months 2-12 months 1-19 years 0-3 months 3 m-19 years 0-1 month 1-6 months 6 m-19 years 0 - 1 month 1-6 months 6 m - 4 years 4-6 years 6-19 years 0-1 month 1-6 months 6 m-2 years 2-19 years 0-1 month I m-19 years 0-1 month 1-12 months 1-19 years
60 41 42 72 52 36 43 25 25 42 48 43 98 118 82 211 65 69 140 251 85 58 338 95 431 63 55 384 63 55 159 59 189 60 45 82 303 61 415 60 65 361
220 314 0.550 0.630 0.990 0.1420 0.1340 0.1360 0.1520 0.1540 0.1690 0.1880 6.10 7.54 10.40 11.81 0.560 0.627 0.960 0.1080 1.08 1.23 1.38 0.250 0.302 0.310 0.380 0.430 0.156 0.161 0.193 0.212 0.256 2.06 1.91 1.62 1.69 0.689 0.891 1.75 2.12 2.28
< 0.07-0.940 < 0.07-1.310 0.10-1.290 0.19-1.750 0.220-2.200 0.480-3.450 0.610-3.450 0.430-2.530 0.410-2.970 0.510-2.970 0.440-3.950 0.440-4.410 2.50-12.00 2.86-16.80 3.41-19.60 5.28-21.90 0.189-1.930 0.210-1.920 0.430-1.630 0.480-2.260 0.70-1.96 0.69-2.01 0.70-2.06 0.130-0.380 0.110-0.610 0.190-0.560 0.190-0.600 0.190-0.670 0.070-0.390 0.083-0.340 0.020-0.360 0.120-0.300 0.120-0.420 1.24-3.48 1.11-2.97 0.95-2.51 1.10-2.79 < 0.058-1.960 0.220-1.640 0.99-3.85 0.95-3.77 1.03-3.63
IgG (g/L)
IgM (g/L)
Comple:ment C3 (g/L) Complement C4 (g/L) Ceruloplasmin (g/L) Prealbumin (g/L)
Alpha -1-antitrypsin (g/L)
Haptog]obin (g/L) Transferrin (g/L)
is most likely a methodological difference because the method of Lockitch et al. measured C3c and our method analyzed total C3. For ceruloplasmin, our range 6 months to 19 years, 0.190-0.670 g/L v s 0.200.460. There are comparable values for C4, prealbumin, alpha-l-antitrypsin, haptoglobin, and transferrin between our series and that previously published (6). Our data for haptoglobin does not indicate a large difference between the newborn group and older children, in conl~rast to previously published d a t a (10). I t is possible t h a t t h e differences in r e f e r e n c e r a n g e s b e t w e e n o u r s t u d y a n d t h a t of Lockitch et al. were due to t h e p a t i e n t population. T h e d e m o g r a p h ics of a V a n c o u v e r pediatric p o p u l a t i o n a n d one in Dallas are different. However, we believe t h a t t h e m o s t likely e x p l a n a t i o n for a n y differences, o t h e r t h a n t h o s e for C3, r e l a t e s to I F C C s t a n d a r d i z a t i o n . CLINICAL BIOCHEMISTRY,VOLUME 29, OCTOBER 1996
Soon, all proprietary protein assays will likely be IFCC-standardized and the presentation of this data should provide a broad base for interpretation of such data in a pediatric population.
Acknowledgements We would like to thank Beckman Instruments, Technical Marketing Department, Brea, CA for the provision of all reagents used in this study.
References 1. Meites S. Pediatric clinical chemistry: reference (normal) values. 3rd ed. Washington DC: American Association for Clinical Chemistry, Inc., 1989. 2. Soldin SJ, Hicks JM. Pediatric reference ranges. Washington DC: American Association for Clinical Chemistry, Inc, 1995. 491
DAVIS
3. Ross JW, Tetrault GA. How to select and verify reference intervals. CAP Today 1994; J u l y : 34-6. 4. Solberg HE. Using a hospitalized population to establish reference intervals: Pros and cons (editorial) Clin Chem 1994; 40: 2205-6. 5. Burritt MF, Slockbower JM, Forsman BS, et al. Pediatric reference intervals for 19 biologic variables in healthy children. Mayo Clinic Proc 1990; 65: 329-36. 6. Lockitch G, Halstead AC, Quigley G, et al. Age and sex specific reference intervals: study design and methods illustrated by measurement of serum proteins with the Behring LN Nephelometer. Clin Chem 1988; 34: 1618-21.
492
E T AL.
7. Soldin SJ, Morales A, Albalos F, Lenherr S, Rifai N. Pediatric reference ranges on the Abbott IMX for FSH, LH, Prolactin, TSH T4, T3, free T4, free T3, Tuptake, IgE and Ferritin. Clin Biochem 1995; 28: 603-6. 8. Hoffmann RG. Statistics in the practice of medicine. J Amer Med Assoc 1963; 185: 864-73. 9. Solberg HE. Establishment and use of reference values. In: Burtis CA, Ashwood ER., Eds. Tietz Textbook of Clinical Chemistry. Pp. 454-84. Philadelphia: WB Saunders, 1994. 10. Tietz NW. Clinical Guide to Laboratory Tests. 3rd ed. Philadelphia: WB Saunders, 1995.
CLINICAL BIOCHEMISTRY, VOLUME 29, OCTOBER 1996
SOOO9-9120(96)OOO46-X
IFCC-Standardized Pediatric Reference Intervals for 10 Serum Proteins Using the Beckman Array 360 System © MICHAEL L. DAVIS, CATHY AUSTIN, BETTE L. MESSMER, WENDI K. NICHOLS, ANDRI~ P. BONIN, and MICHAEL J. BENNETT Department of Clinical Chemistry, Children's Medical Center of Dallas, Dallas, TX, U.S.A., Department of Clinical Chemistry, Hopital Ste. Justine Montreal, Quebec, Canada, and Departments of Pathology and Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, U.S.A. Introduction
Samples and methods
Reference ranges in clinical chemistry are frequently established by analyzing samples remaining in excess of that required for normal clinical management, following the rejection of samples from clinically inappropriate patients. This process is difficult to replicate in pediatric practice because of the small sample volumes that are normally collected, and consequent: lack of excess material. Frequently, consensus ranges derived from previously published work are utilized in pediatrics (1,2). This practice is probably satisfactory when the analytical methods conform to iinternationally standardized procedures (3,4). Standardization is particularly important when different analytical systems and reagents are used to measure the analytes in question. This is particularly true for the assay of serum proteins by nephelometry, when the properties of the various proprietary an.tibodies used by the different manufacturers may vary considerably. To date, there have been very :Fewreports of pediatric reference ranges for serum proteins using nephelometry, and no reports using reagent systems that conform to international standards (5-7). We present here the results of age- and sexrelated reference values for 10 serum proteins that are standardized to IFCC recommendations, using the Beckman Array 360 Nephelometer, and compare this data to previously published nonstandardized data.
The specimens used in this study were comprised of serum in excess of that required for normal clinical management, collected prospectively in a series of patients admitted to, or attending, outpatient clinics at The Children's Medical Center of Dallas (CMC). Samples from patients with conditions likely to result in abnormal plasma protein levels (i.e., those with impaired hematologic, hepatic, renal, or immune functions) were rejected from the study. Samples accepted for the study were coded for patient age and sex only, to maintain anonymity. This study was approved by the Institutional Review Board of The University of Texas Southwestern Medical Center at Dallas. The demographics of the patient population at CMC are as follows: 57% Caucasian, 20% Hispanic, 18% African American, 1% Asian, 4% other. The goal was to identify a minimum of 40 samples in each of the age ranges: 0-1 month, 1-2 months, 2-3 months, 3-4 months, 4-5 months, 5-6 months, 6-7 months, 7-8 months, 8-9 months, 9-10 months, 10-11 months, 11-12 months, 1-2 years, 2-3 years, 4-5 years, 5-6 years, and 6-18 years. Upon acceptance into the study, the samples were immediately stored frozen at -20 °C prior to batch analysis. Samples were typically stored for 1-2 weeks. Upon thawing for analysis, all tests were performed and no samples were refrozen. Samples were analyzed for immunoglobulins G, A, and M, prealbumin (transthyretin), ceruloplasmin, alpha-l-antitrypsin, haptoglobin, transferrin, and complements C3 (total C3) and C4 using the standard protocols developed by Beckman for use with the Array System, with no modifications. Betweenbatch performance data is presented in Table 1. These analytes have been standardized to the International Federation of Clinical Chemistry (IFCC) reference preparation for proteins in human serum
Correspondence: Dr. Michael J. Bennett, D e p a r t m e n t of Pathology, Children's Medical C e n t e r of Dallas, 1935 Motor Street, Dallas TX 75235, U.S.A. M a n u s c r i p t received F e b r u a r y 7, 1996; revised M ar ch 18, 1996; accepted Marc:h 21, 1996. CLINICAL BIOCHEMISTRY, VOLUME 29, OCTOBER 1996
489
DAVIS ET AL. TABLE 1 Between Batch Precision of IFCC Standardized Protein Assays on Beckman Array Analyte IgA (g/L) IgG (g/L) IgM (g/L) Complement C3 (g/L) Complement C4 (g/L) Ceruloplasmin (g/L) Prealbumin (g/L) Alpha-l-antitrypsin (g/L) Haptoglobin (g/L) Transferrin (g/L)
Concentration of Control
Coefficient of Variation
0.117 0.370 0.553 13.73 0.600 2.190 0.81 2.16 0.170 0.670 0.180 0.550 0.160 0.450 0.68 1.67 0.590 1.950 1.35 3.15
4.2 5.1 4.8 4.8 4.5 6.1 5.3 7.4 7.6 8.5 7.8 8.0 5.0 5.7 7.3 6.1 3.9 5.5 4.5 6.8
(RPPHS, designated lot 91/0619 by the College of American Pathologists). The data were examined graphically for breaks or trends based on age or sex. Ranges were determined for data t h a t exhibited normal distribution by using the means and 2 standard deviations. Outliers were removed according to the procedure of Hoffmann (8). Nonparametric statistical procedures were used to determine ranges encompassing 95% of the data for those analytes not exhibiting normal distribution
(9). Results A total of 469-533 patient data points were obtained for each analyte. Not all proteins were measured in each specimen due to the limited volumes available. We had some difficulty in gathering sufficient samples for the age range 1-12 months because there were both fewer patients and smaller sample volumes from these patients. We extended the study period to accumulate sufficient samples r e p r e s e n t a t i v e for this age group. We a n a l y z e d samples on 293 male and 272 female patients. We could not detect sex-related differences for any of the s t u d y a n a l y t e s and, consequently, combined the data as age-specific only. Table 2 shows the agespecific reference ranges for the 10 proteins. The Table presents age range, number of patients, the mean and range (95% confidence limits) for each of the proteins. For age-ranges in which we could not detect an age-related difference, we have combined the data. Thus, for the immunoglobulins A, G, and M there are clear age-related differences consistent with all previous data, whereas for proteins, such as 490
alpha-l-antitrypsin and haptoglobin, we could detect no such age-related differences. The levels of transferrin, prealbumin, ceruloplasmin, and complements C3 and C4 demonstrated some agerelated differences below 1 year of age but, in general, there was little difference beyond the age of 1 year. Consequently, for these proteins, data groups were combined when no age-related differences were detected.
Discussion We present the first pediatric reference ranges for 10 serum proteins t h a t are derived from an assay t h a t conforms to IFCC standardization. Previously, such ranges were derived from nonstandardized assays and, as such, were open to significant variability depending on the n a t u r e of the reagents being used in the assay. Our data are presented in an agerelated format, when there is an age-related difference. We could detect no sex-related differences. The patients whose samples were analyzed were carefully selected to exclude those with diseases t h a t might have affected protein levels and, within the confines of a hospital-based population, were as healthy as could be defined. Because it is unlikely t h a t sufficient data will ever be accrued from a truly healthy pediatric population, this patient selection probably reflects a population as close to normal as will be possible (4). In the study of multiple pediatric reference ranges for the Abbott IMx © analyzer, Soldin et al. (7) removed outliers by sequentially rejecting outliers. In this study, initial rejection was based on clinical criteria alone. We experienced difficulty in obtaining data for ages 1 month to 1 year. This was expected, because the reference intervals for this age group tends to be small, or missing, from almost every pediatric analyte for which a reference range is available (2). In comparing our IFCC-standardized data with the only other significant recent study of pediatric protein levels using nonstandardized materials (6), we noticed numerous differences, as outlined below. For IgA, we p r e s e n t d a t a b r o k e n down into smaller age groups and detected a rising t r e n d throughout the first year of life. Lockitch et al. presented an IgA range of 0-1.0 g/L for the 0-12-month age group (6). We have been able to further break down this first year of life to demonstrate a rising trend from 1 month of age to 1 year. Similar trends were observed within the first year of life for both IgG and IgM. IgM also demonstrated a quantitative difference t h a t we attribute to differences between IFCC-standardized and nonstandardized reagents. In our assay, the age group 4-19 years, for which we could see no trends and, therefore, combined the data, the reference range was 0.480-2.260 g/L. Combining the data for the 4-19-year-old subjects studied by Lockitch et al. produces a wider range of values of 0.230-3.870, almost doubling the upper limit. Differences also occur for C3, our range 1-19 years, 0.70-2.06 g/L (n = 338) vs 0.51-0.95 (n = 334); this CLINICALBIOCHEMISTRY,VOLUME29, OCTOBER 1996
PEDIATRIC REFERENCE RANGES TABLE 2 Pediatric Reference Intervals on the Beckman Array 360 Analyte
Age
# Subjects
Mean
Range
IgA (g/L)
0-1 month 1-4 months 4-12 months 1-2 years 2-3 years 3-4 years 4-5 years 5-6 years 6-7 years 7-10 years 10-13 years 13-19 years 0-3 months 3-24 months 2-4 years 4-19 years 0-2 months 2-12 months 1-4 years 4-19 years 0-2 months 2-12 months 1-19 years 0-3 months 3 m-19 years 0-1 month 1-6 months 6 m-19 years 0 - 1 month 1-6 months 6 m - 4 years 4-6 years 6-19 years 0-1 month 1-6 months 6 m-2 years 2-19 years 0-1 month I m-19 years 0-1 month 1-12 months 1-19 years
60 41 42 72 52 36 43 25 25 42 48 43 98 118 82 211 65 69 140 251 85 58 338 95 431 63 55 384 63 55 159 59 189 60 45 82 303 61 415 60 65 361
220 314 0.550 0.630 0.990 0.1420 0.1340 0.1360 0.1520 0.1540 0.1690 0.1880 6.10 7.54 10.40 11.81 0.560 0.627 0.960 0.1080 1.08 1.23 1.38 0.250 0.302 0.310 0.380 0.430 0.156 0.161 0.193 0.212 0.256 2.06 1.91 1.62 1.69 0.689 0.891 1.75 2.12 2.28
< 0.07-0.940 < 0.07-1.310 0.10-1.290 0.19-1.750 0.220-2.200 0.480-3.450 0.610-3.450 0.430-2.530 0.410-2.970 0.510-2.970 0.440-3.950 0.440-4.410 2.50-12.00 2.86-16.80 3.41-19.60 5.28-21.90 0.189-1.930 0.210-1.920 0.430-1.630 0.480-2.260 0.70-1.96 0.69-2.01 0.70-2.06 0.130-0.380 0.110-0.610 0.190-0.560 0.190-0.600 0.190-0.670 0.070-0.390 0.083-0.340 0.020-0.360 0.120-0.300 0.120-0.420 1.24-3.48 1.11-2.97 0.95-2.51 1.10-2.79 < 0.058-1.960 0.220-1.640 0.99-3.85 0.95-3.77 1.03-3.63
IgG (g/L)
IgM (g/L)
Comple:ment C3 (g/L) Complement C4 (g/L) Ceruloplasmin (g/L) Prealbumin (g/L)
Alpha -1-antitrypsin (g/L)
Haptog]obin (g/L) Transferrin (g/L)
is most likely a methodological difference because the method of Lockitch et al. measured C3c and our method analyzed total C3. For ceruloplasmin, our range 6 months to 19 years, 0.190-0.670 g/L v s 0.200.460. There are comparable values for C4, prealbumin, alpha-l-antitrypsin, haptoglobin, and transferrin between our series and that previously published (6). Our data for haptoglobin does not indicate a large difference between the newborn group and older children, in conl~rast to previously published d a t a (10). I t is possible t h a t t h e differences in r e f e r e n c e r a n g e s b e t w e e n o u r s t u d y a n d t h a t of Lockitch et al. were due to t h e p a t i e n t population. T h e d e m o g r a p h ics of a V a n c o u v e r pediatric p o p u l a t i o n a n d one in Dallas are different. However, we believe t h a t t h e m o s t likely e x p l a n a t i o n for a n y differences, o t h e r t h a n t h o s e for C3, r e l a t e s to I F C C s t a n d a r d i z a t i o n . CLINICAL BIOCHEMISTRY,VOLUME 29, OCTOBER 1996
Soon, all proprietary protein assays will likely be IFCC-standardized and the presentation of this data should provide a broad base for interpretation of such data in a pediatric population.
Acknowledgements We would like to thank Beckman Instruments, Technical Marketing Department, Brea, CA for the provision of all reagents used in this study.
References 1. Meites S. Pediatric clinical chemistry: reference (normal) values. 3rd ed. Washington DC: American Association for Clinical Chemistry, Inc., 1989. 2. Soldin SJ, Hicks JM. Pediatric reference ranges. Washington DC: American Association for Clinical Chemistry, Inc, 1995. 491
DAVIS
3. Ross JW, Tetrault GA. How to select and verify reference intervals. CAP Today 1994; J u l y : 34-6. 4. Solberg HE. Using a hospitalized population to establish reference intervals: Pros and cons (editorial) Clin Chem 1994; 40: 2205-6. 5. Burritt MF, Slockbower JM, Forsman BS, et al. Pediatric reference intervals for 19 biologic variables in healthy children. Mayo Clinic Proc 1990; 65: 329-36. 6. Lockitch G, Halstead AC, Quigley G, et al. Age and sex specific reference intervals: study design and methods illustrated by measurement of serum proteins with the Behring LN Nephelometer. Clin Chem 1988; 34: 1618-21.
492
E T AL.
7. Soldin SJ, Morales A, Albalos F, Lenherr S, Rifai N. Pediatric reference ranges on the Abbott IMX for FSH, LH, Prolactin, TSH T4, T3, free T4, free T3, Tuptake, IgE and Ferritin. Clin Biochem 1995; 28: 603-6. 8. Hoffmann RG. Statistics in the practice of medicine. J Amer Med Assoc 1963; 185: 864-73. 9. Solberg HE. Establishment and use of reference values. In: Burtis CA, Ashwood ER., Eds. Tietz Textbook of Clinical Chemistry. Pp. 454-84. Philadelphia: WB Saunders, 1994. 10. Tietz NW. Clinical Guide to Laboratory Tests. 3rd ed. Philadelphia: WB Saunders, 1995.
CLINICAL BIOCHEMISTRY, VOLUME 29, OCTOBER 1996