Article Text

PDF

Newborns have unique confounding factors regarding the TfR-F ratio
  1. P REYNOLDS
  1. Immunology
  2. Imperial College
  3. Hammersmith Hospital, London, UK
  4. p.reynolds{at}ic.ac.uk
    1. H L HALLIDAY
    1. Department of Child Health
    2. The Queen's University of Belfast
    3. Belfast, Northern Ireland, UK
    4. h.halliday{at}qub.ac.uk
    5. Department of Haematology
      1. T R J LAPPIN
      1. Department of Child Health
      2. The Queen's University of Belfast
      3. Belfast, Northern Ireland, UK
      4. h.halliday{at}qub.ac.uk
      5. Department of Haematology

        Statistics from Altmetric.com

        Editor—Sweet et al investigated the serum transferrin receptor (STfR) and, for the first time in neonates, transferrin receptor-log ferritin (TfR-F) ratio in a prospective series of cord blood taken from term infants and their mothers. They are to be congratulated on completing another piece of the complex jigsaw that is fetal and neonatal iron metabolism.

        STfR and TfR-F were increased in iron deficient mothers, but not in their infants. The authors discussed at some length the translational (not transcriptional as stated in the discussion) control of intracellular ferritin synthesis.1 They measured serum ferritin, which is a glycosylated form of L-ferritin, and has been shown to correlate with intracellular iron in the absence of confounding factors.2 However, serum ferritin is secreted in response to a wide variety of other stimuli, including, for example, inflammation and shows gender differences in newborns.3Under these circumstances, serum ferritin may not accurately represent tissue iron stores.

        It has already been reported that STfR does not correlate with other measures of iron metabolism in the newborn,4 mainly because it is highly expressed by reticulocytes and other immature erythroid cells, with or without iron deficiency.

        The high sensitivity and specificity of the TfR-F ratio in adults is based upon their relationship in iron deficiency in the absence of factors that might otherwise elevate STfR levels.5 With both variables subject to these confounding factors in the neonate, I do not agree with the author's assertion that the TfR-F index “gives a measure of iron requirements in relation to iron availability” in this unique population.

        References

        Reply

        Editor—We thank Peter Reynolds, but feel that our use of the term post-transcriptional to describe the regulation of intracellular iron metabolism was correct. Iron regulatory elements (IREs) are stem cell loop structures of several key messenger RNA (mRNA) encoding proteins of iron metabolism. IREs can be located in the 5' region—for example, ferritin, or 3' region—for example, transferrin receptor, of the untranslated region of the mRNA. In relative iron deficiency, through interaction of the IREs with iron responsive proteins, transferrin uptake increases because the transferrin receptor mRNA is stabilised, whereas ferritin storage of iron decreases because translation of ferritin mRNA is blocked. These are clearly post-transcriptional, not post-translational events. The reciprocal regulation of the transferrin receptor and ferritin have recently been expertly reviewed by Hentze and Kuhn.1-1

        We agree that serum ferritin is increased in response to inflammation but the infants that we studied were born at term following normal pregnancies. All the babies were well at birth and did not require neonatal care. We think that it is unlikely that inflammation or other stimuli affected our serum ferritin values. Furthermore, in this study1-2 and in our previous study of preterm infants1-3 we found no gender differences in contrast to the results published by Tamura et al.1-4 Our figure for cord ferritin levels at term (listed first as mean +  SD) in female infants is almost identical to that of Tamura et al (164 + 106 μg/lv 166 + 110 μg/l), but our value for male infants is higher (160 +  97 μg/l v123 +  71 μg/l). We doubt if there are real gender differences in fetal ferritin levels. Therefore, we are still of the opinion that TfR-F index is a measure of iron requirements in relation to iron availability in the fetus and newborn as in adults and children.

        References

        1. 1-1.
        2. 1-2.
        3. 1-3.
        4. 1-4.
        View Abstract

        Request permissions

        If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.