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Effect of a Mild Infection on Serum Ferritin Concentrationð Clinical and Epidemiological Implications

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Effect of a Mild Infection on Serum Ferritin Concentrationð Clinical and Epidemiological Implications European Journal of Clinical Nutrition (1998) 52, 376±379 ß 1998 Stockton Press. All rights reserved 0954±3007/98 $12.00 http://www.stockton-press.co.uk/ejcn Effect of a mild infection on serum ferritin concentrationÐ clinical and epidemiological implications L HultheÂn, G Lindstedt, P-A Lundberg and L Hallberg Department of Clinical Nutrition, Institute of Internal Medicine, and Department of Clinical Chemistry, University of GoÈteborg, Sahlgrenska University Hospital, GoÈteborg, Sweden Objectives: To study the distribution of serum ferritin concentration in adolescent boys and girls with and without a preceding mild infection. Design: The prevalence of iron de®ciency was studied in two representative samples. The ®rst sample from 1990 comprised 207 boys and 220 girls. The second sample from 1994 included 620 boys and 624 girls. In total 1675 adolescents, 15±16 y old, 827 boys and 844 girls were studied. Results: A signi®cant shift of serum ferritin concentration towards higher values was observed in those who reported an upper respiratory infection with fever during the preceding month (P < 0.001). Signi®cant differences were found between serum ferritin values in healthy, not infected adolescents and serum ferritin values in those with ongoing infection, both in boys and girls in the two materials (P < 0.01), and in those with a mild infection during the preceding three weeks. Conclusions: The prevalence of recent infection should be included as information when trying to assess the prevalence of iron de®ciency on the basis of serum ferritin measurements and when examining relationships between iron status and composition of the diet. The ®ndings imply that differences in prevalence of iron de®ciency between different studies might partly be explained by differences in prevalence of simple respiratory infections. The diagnostic sensitivity of the serum ferritin assay for iron de®ciency, using conventional reference limits, decreases for subjects with recent such infections; similarly, there will be a decrease in the diagnostic speci®city for haemochromatosis. Sponsorship: Swedish Medical Research Council (project B9519X-04721-20B) and Swedish Dairy Association, Stockholm. Descriptors: serum ferritin concentration; mild infection; adolescents; prevalence of iron de®ciency; diagnostic sensitivity and speci®city=iron de®ciency; iron overload Introduction Some years ago, we made the unexpected observation that even a sore throat combined with fever for a few days The evaluation of iron status requires the use of reliable had a dramatic in¯uence on serum ferritin with an increase indicators. Early studies suggested that the concentration of which remained high for a long time. At our laboratory a serum ferritin was related to the amounts of stored iron nurse on our staff with an iron de®ciency due to heavy (Walters et al, 1973). Formulas have been devised to menstrual bleedings participated in a study to reduce the estimate iron stores from concentrations of serum ferritin bleedings. Her serum ferritin was followed monthly for in healthy individuals (Cook & Finch, 1979; Cook et al, three months and was in the range 10±12 mg/L. One week 1986). The introduction of serum ferritin for the evaluation after the start of her infection combined with fever for some of the iron status (Addison et al, 1972; Jacobs et al, 1972) days, her serum ferritin increased to 75 mg/L. At that time was a marked diagnostic improvement since low serum she was afebrile, clinically well and back to work. There- ferritin concentrations are only seen in iron de®ciency, after serum ferritin was followed weekly and remained indicating an absence of iron stores. Low serum ferritin is elevated for eight weeks. Serum ferritin then turned back to not associated with any other known condition (Walters et the initially low value, 11 mg/L. This observation suggested al, 1973). On the other hand, it is well-known that, for that even a rather mild infection with fever may markedly example, severe infections, in¯ammatory conditions, liver increase serum ferritin and may remain elevated for several diseases, starvation and heavy ethanol intake, could weeks. In our recent studies on adolescents we used serum increase serum ferritin also in iron de®cient subjects, ferritin as a main marker of iron status. Our observation (BirgegaÊrd et al, 1978; Worwood, 1979; Lundberg et al, above suggested that even a mild infection might in¯uence 1984; Lundin et al, 1981; Meyer et al, 1984). the level of serum ferritin. An effect of mild infections on serum ferritin, however, The purpose of this present study was to examine the has not been examined. Such an effect on the prevalence of effect of a preceding mild infection on serum ferritin iron de®ciency in population studies as well as on its values. This was made both by comparing the distribution diagnostic sensitivity and speci®city for abnormal iron of serum ferritin in those with and without a preceding stores, has not been examined. infection in the last month and by examining the difference in serum ferritin as above but in relation to the interval Correspondence: Dr L HultheÂn. Received 20 December 1997; revised 4 February 1998; accepted between the examination of serum ferritin and the time of 28 February 1998 the infection. Effect of a mild infection on serum ferritin concentration L HultheÂn et al 377 Material and methods De®nition of infection was based on an examination and on a medical history, taken by a specially trained nurse, the Two samples of 15 to 16 y old boys and girls in GoÈteborg same for both the studies. In the questionnaire used, were studied. The ®rst study was performed in 1990 in questions were raised about the present state of health early spring when the incidence of infections is usually and about recent disorders. A speci®c question was raised low. This study comprised four schools and the sample about recent infection and if so, the time for the infection represented 1 out of 10 of all pupils in the 9th grade that was registered as well as its severity (fever for a certain year in GoÈteborg. Written information was sent via all the number of days, symptoms and treatment). pupils to their parents, who had to give written approval for drawing of blood samples. Permission was granted for 220 girls (86% of those invited in the original sample) and 207 Statistics All statistical analyses were made using a Stat- boys (80% of those invited in the original sample). view IV computer program (Abacus Concepts Inc., Ber- The ®rst study was a pilot study, comprising different kely, CA). Mean values were compared using the t-test. socioeconomic groups. Due to its size, moreover, the The project was approved by the Ethical Committee of sample was less representative of the general population. the Medical Faculty of the University of GoÈteborg. In the second study greater efforts were made, in cooperation with the epidemiological unit of the town council, to get a representative sample, covering different Results socioeconomic and living conditions. The second study was In the ®rst study, made during March±April 1990, 21.7% of performed in October±December 1994, and included 624 the 207 boys and 20.5% of the 220 girls reported an upper girls (90% of those invited to the study) and 620 boys (89% repiratory infection with fever during the preceding month. of those invited). This second study was more comprehen- The infection rate was signifcantly higher among those sive, and comprised 13 schools chosen to represent areas with a high serum ferritin (P < 0.001), suggesting that a with different socioeconomic and living conditions. All preceding infection may have shifted serum ferritin toward adolescents in grade nine at these schools were invited to higher values. Among the girls with no history of infection participate. The participants represented 24.8% of the total (N 175) 43.9% had serum ferritin, 15 mgL vs 25.5% number of adolescent students in this age group in GoÈte- among those with a history of infection (N 45). For the borg that year. GoÈteborg is the second largest city in boys with no history of infection (N 162) 17.0% had Sweden with about 430 000 inhabitants. serum ferritin 15 mg/L vs 4.8% among those with a This study was carried out to get knowledge about the history of infection (N 45). baseline iron status situation in adolescents in Sweden In the second study, performed during October±Decem- before the general iron forti®cation of white wheat ¯our ber 1994, 19.8% of the 620 boys and 21.8% of the 627 girls was stopped (31 December 1994). To study the effect of reported an upper respiratory infection during the preceding withdrawal a new study is planned for 1998. month. We found a marked shift of serum ferritin towards higher values in those who reported an upper respiratory Serum ferritin used in the two studies was determined by a infection during the preceding month (P < 0.001). Among double-antibody polyethylenglycol RIA (Diagnostic Pro- the girls with no history of infection (N 501) we found ducts Corp. Los Angeles, CA). The assay was calibrated 39.6% with serum ferritin 15 mg/L vs 16% among those against World Health Organization 1st International Stan- with a history of infection (N 140). For the boys with no dard, IS80/602 (Worwood, 1979). history of infection (N 491) we found 24.7% with serum Table 1 Prevalence of iron de®ciency, serum ferritin 15 mg=L. With and without reported preceding mild infection Without preceding infection*** With preceding infection*** The total material (no) (%) (no) (%) (no) (%) Boys* 1990 28=165 17.0 2=42 4.8 3 0=207 14.5 Boys* 1994 121=489 24.7 1 0=131 7.6 13 1=620 21.1 Girls** 1990 76=173 43.9 1 2=47 25.5 8 8=220 40.0 Girls** 1994 197=498 39.6 2 7=125 16 22 4=623 35.9 *P < 0.05 (1990 vs 1994).
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