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Technical Briefs |
1
Clinical Pathology,
2
Obstetrics, and
3
Pediatrics, College of Medicine, Inha University Hospital, 7-206, 3-ga, Shinheung-dong, Jung-gu, Inchon 400-103, Korea;
a author for correspondence: fax 82-32-890-2529, e-mail jwchoi{at}inha.ac.kr
The common laboratory tests for evaluating iron status are serum iron, total iron-binding capacity, transferrin saturation, and ferritin (1). However, ferritin is one of the acute phase reactants, and its concentration is influenced by various clinical conditions (2). Even mild upper respiratory infections are associated with an increase in serum ferritin (3). Examination of stainable iron in bone marrow is the gold standard for iron depletion; however, this procedure is invasive and is not feasible for the evaluation of all children suspected of iron deficiency.
Measurement of the soluble transferrin receptor (sTfR) recently has been introduced as a new diagnostic tool for the evaluation of iron status (2)(4). The sTfR concentration reflects the functional iron status of the body and the rate of erythropoiesis in bone marrow (4). Measurement of sTfR is valuable in physiologic conditions in which iron stores are relatively depleted, and such situations are encountered regularly in children and adolescents (5)(6).
Children are in a period of continuing growth; therefore, their reference intervals for many analytes are different from those for adults and may show age-related changes. Because comparative age-related data for sTfR in healthy individuals are limited, we investigated the age-related differences in sTfR from neonate to adult.
A total of 849 apparently healthy nonanemic subjects were investigated for sTfR and hematologic and iron markers. The subjects included neonates (n = 125), infants 4–24 months (n = 152), young children 3–7 years (n = 197), adolescents 14–19 years (n = 188), and adults 23–62 years (n = 187). For neonates, we examined cord blood samples obtained from healthy women who had experienced no complications during delivery. The 152 infants were divided into three groups according to age, i.e., infants 4–6 months, infants 7–12 months, and infants 13–24 months. Infants and adults were selected from individuals visiting the hospital for vaccination or routine health checks. To obtain the specimens of young children and adolescents, we visited elementary and high schools as well as kindergartens. This survey was explained and approved by both parents and directors at each educational center, and volunteers were included in the study population. Subjects were excluded if they had any diseases or had a history of blood transfusion, major surgery, or recent infections. We also excluded individuals with anemia or evidence of iron deficiency and neonates whose birth weight was <2500 g. Anemia was defined by WHO criteria (7), and all children with a hemoglobin <110 g/L were classified as having anemia. Diagnosis of iron deficiency was established according to the criteria of Dallman and Siimes (8).
Routine complete blood cell counts and red cell indices were measured with the electronic counter SE 9000 (Sysmex). Serum iron and total iron-binding capacity were assayed with the Hitachi 747 automatic chemical analyzer (Hitachi), and ferritin was measured by radioimmunoassay. Serum TfR was measured immunoenzymetrically using IDeATM sTfR kits (Orion Diagnostica). We diluted and reanalyzed any samples that had concentrations higher than the highest calibrators. All statistical analysis was performed using SAS 6.12 for Windows (SAS Institute). The nonparametric method was used to calculate the reference intervals for sTfR.
Changes in iron marker and sTfR concentrations in healthy
subjects are shown in Table 1
. The mean sTfR concentration varied according to age,
decreasing gradually from the neonatal period to adolescence. The sTfR
concentration in young children was significantly lower than that in
infants or neonates (P <0.01), and the mean sTfR
concentration in adolescents 14–16 years of age was significantly
higher than that of adolescents 17–19 years of age (P
<0.01). No significant differences in sTfR concentration were noted
between the adolescents 17–19 years of age and adults. Therefore, we
believe serum TfR concentrations reach adult concentrations after age
16.
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Our data for ferritin concentrations in neonates are in accord with another study showing that there is an active transfer of iron from the mother to the fetus (9). Compared with infants, neonates showed three- to sevenfold higher serum iron and ferritin concentrations. However, for sTfR, no statistically significant differences were observed between these two groups in our study. On the basis of these results, we believe that the sTfR concentration is more closely related to erythropoietic activity than iron depletion in the neonatal period.
It has been reported that there is no significant difference in sTfR
concentrations between men and women (10)(11).
Yeung and Zlotkin (10) found no sex difference in the sTfR
concentration in infants 9–15 months of age. Our results also showed
no significant differences in sTfR concentration between male and
female subjects except for infants 4–6 months of age. As shown in Fig. 1
, the sTfR concentration in male infants 4–6 months of age was
5.12 ± 0.94 mg/L, which was significantly higher than the
4.27 ± 0.86 mg/L in female infants in the same age group
(P <0.01). On the other hand, in infants 7–12 and 13–24
months of age, no statistical differences were observed between males
and females in the same age group (P = 0.265 and
P = 0.162, respectively). These results seem to
indicate that erythropoietic activity and the iron requirement in male
infants is greater than in female infants at this age.
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Other investigators have reported reference intervals for sTfR for healthy infants and adults (10)(12). Yeung and Zlotkin (10) found a mean sTfR concentration of 4.4 ± 1.1 mg/L in healthy infants 9–15 months of age. Our results for sTfR in infants were slightly higher than those of Yeung and Zlotkin (10), possibly because we included infants 4–6 and 13–24 months of age, who had relatively high sTfR concentrations. Our results for mean sTfR in adults were similar to those of Suominen et al. (12). In our study, the intraassay CVs (n = 20) for three samples (mean sTfR, 1.2–6.3 mg/L) were 3.9–6.5%; the interassay CVs calculated from duplicate results in 10 subsequent assays were 4.2–6.9%. The mean concentrations and reference intervals for sTfR appear to vary by authors and analytical methods. Therefore, it is necessary for individual laboratories to establish their own reference values.
In conclusion, we found that sTfR concentrations showed age- and sex-related differences. sTfR in childhood declines with age and appears to reach the adult concentration at 17 years of age. In early infancy, an increased need for iron seems to be more closely associated with male infants.
References
The following articles in journals at HighWire Press have cited this article:
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  G. Hay, H. Refsum, A. Whitelaw, E. L. Melbye, E. Haug, and B. Borch-Iohnsen Predictors of serum ferritin and serum soluble transferrin receptor in newborns and their associations with iron status during the first 2 y of life Am. J. Clinical Nutrition, July 1, 2007; 86(1): 64 - 73. [Abstract] [Full Text] [PDF]
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 R. Crowell, A. M. Ferris, R. J. Wood, P. Joyce, and H. Slivka Comparative Effectiveness of Zinc Protoporphyrin and Hemoglobin Concentrations in Identifying Iron Deficiency in a Group of Low-Income, Preschool-Aged Children: Practical Implications of Recent Illness Pediatrics, July 1, 2006; 118(1): 224 - 232. [Abstract] [Full Text] [PDF]
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 J. W. Choi Combination of Serum Transferrin Receptor and Red Cell Distribution Width for Assessing Anemia in Patients with Chronic Diseases Ann. Clin. Lab. Sci., January 1, 2006; 36(3): 356 - 358. [Full Text] [PDF]
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J. M Schneider, M. L Fujii, C. L Lamp, B. Lonnerdal, K. G Dewey, and S. Zidenberg-Cherr Anemia, iron deficiency, and iron deficiency anemia in 12-36-mo-old children from low-income families Am. J. Clinical Nutrition, December 1, 2005; 82(6): 1269 - 1275. [Abstract] [Full Text] [PDF]
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J. W. Choi Sensitivity, Specificity, and Predictive Value of Serum Soluble Transferrin Receptor at Different Stages of Iron Deficiency Ann. Clin. Lab. Sci., October 1, 2005; 35(4): 435 - 439. [Abstract] [Full Text] [PDF]
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M. Domellof, B. Lonnerdal, K. G. Dewey, R. J. Cohen, L. L. Rivera, and O. Hernell Sex Differences in Iron Status During Infancy Pediatrics, September 1, 2002; 110(3): 545 - 552. [Abstract] [Full Text] [PDF]
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 A. Akesson, P. Bjellerup, M. Berglund, K. Bremme, and M. Vahter Soluble Transferrin Receptor: Longitudinal Assessment From Pregnancy to Postlactation Obstet. Gynecol., February 1, 2002; 99(2): 260 - 266. [Abstract] [Full Text] [PDF]
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 P. Suominen, A. Virtanen, M. Lehtonen-Veromaa, O. J. Heinonen, T. T. Salmi, M. Alanen, T. Mottonen, A. Rajamaki, and K. Irjala Regression-based Reference Limits for Serum Transferrin Receptor in Children 6 Months to 16 Years of Age Clin. Chem., May 1, 2001; 47(5): 935 - 937. [Full Text] [PDF]
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M. Olivares, T. Walter, J. D Cook, E. Hertrampf, and F. Pizarro Usefulness of serum transferrin receptor and serum ferritin in diagnosis of iron deficiency in infancy Am. J. Clinical Nutrition, November 1, 2000; 72(5): 1191 - 1195. [Abstract] [Full Text] [PDF]
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J. W. Choi, M. W. Im, and S. H. Pai Serum Transferrin Receptor Concentrations during Normal Pregnancy Clin. Chem., May 1, 2000; 46(5): 725 - 727. [Full Text] [PDF]
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