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The dynamics of red blood cells and iron status during infancy

Larsson, Marie LU (2023) In Lund University, Faculty of Medicine Doctoral Dissertation Series
Abstract
Red blood cell (RBC) and iron status biomarkers are commonly used in clinical diagnostics. However, interpretations of infant test results are inherently challenging. Modern well-defined comparative data based on presumably healthy term-born infants have mainly been lacking and interpretations could be further complicated by interference from frequent infections. Moreover, the trends that follow with transition from fetal life and rapid growth are dynamic. The processes, which are also dependent on gestational age at birth, need to be better understood.
This dissertation includes three retrospective reference interval studies of termborn presumably healthy infants (Papers Ⅰ, Ⅱ, Ⅲ) followed by one prospective study investigating RBC... (More)
Red blood cell (RBC) and iron status biomarkers are commonly used in clinical diagnostics. However, interpretations of infant test results are inherently challenging. Modern well-defined comparative data based on presumably healthy term-born infants have mainly been lacking and interpretations could be further complicated by interference from frequent infections. Moreover, the trends that follow with transition from fetal life and rapid growth are dynamic. The processes, which are also dependent on gestational age at birth, need to be better understood.
This dissertation includes three retrospective reference interval studies of termborn presumably healthy infants (Papers Ⅰ, Ⅱ, Ⅲ) followed by one prospective study investigating RBC dynamics in infants after extremely preterm birth (Paper Ⅳ).
The first three studies defined reference intervals at four time points during the
first year of life. Paper Ⅰ investigated ferritin as a biomarker of iron stores and
presented reference intervals divided into subgroups by age and sex. In Paper Ⅱ the biomarker soluble transferrin receptor (sTfR) was studied. Age dynamics in the first year of life were established, where the upper reference limits were higher compared with adults even in iron-replete infants. Influence from the acute phase response was not demonstrated as sTfR concentrations did not co-vary with CRP concentrations except in samples 48‐96 hours after birth. This association could hypothetically be due to the triggering of transferrin receptor expression following the fluctuations in oxygenation during normal labor. In Paper Ⅲ, hemoglobin (Hb) and RBC biomarkers were studied. The reference interval widths found were mainly narrower compared with other studies. In addition, adherence to the World Health Organization threshold of Hb 49 pg/cell) rapidly decreased during the first weeks in life.
In conclusion, this work presents opportunities for improvements to the interpretation of infant test results. As reference data are also required for epidemiological studies, the disagreement with the WHO classification for Hb despite seemingly favorable conditions in infancy needs further investigation. The insights from studying the RBC dynamics after extremely preterm birth underline the unique characteristics of their peripheral RBC population and further reveal a potential biomarker, Hyper-He, for studying postnatal erythropoietic transitions.
Future research is needed to investigate the potential role of the loss of these
endogenous RBCs and the development of infant morbidities after extremely
preterm birth. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • professor dr Lopriore, Enrico, Leiden University Medical Center, Leiden, The Netherlands
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Barnreferensintervall, Röda blodkroppar, Erytrocyter, Extremt för tidig födsel, Erytropoes, Klinisk kemi, Järnstatus, Ferritin, sTfR, Neonatologi, Pediatrik, Fetal tillväxthämning, Referensintervall, Pediatric reference intervals, Reference limits, Extremely preterm birth, Fetal growth restriction, Clinical chemistry, Iron status, Red blood cells, Erythrocyte, Transfusion, Ferritin, sTfR, Hemoglobin, Neonatal, Reference intervals, Umbilical cord blood, Infancy, Iron deficiency, Anemia, Acute phase response, soluble Transferrin receptor, Neonatal intensive care, Erythropoiesis, Birth, Infant
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
issue
2023:111
pages
73 pages
publisher
Lund University, Faculty of Medicine
defense location
Segerfalksalen, BMC A10, Sölvegatan 17 i Lund
defense date
2023-10-06 13:00:00
ISSN
1652-8220
ISBN
978-91-8021-450-6
language
English
LU publication?
yes
id
3412afbb-6487-47c4-8fa7-9bff614c9e56
date added to LUP
2023-09-12 11:29:54
date last changed
2023-09-26 09:31:18
@phdthesis{3412afbb-6487-47c4-8fa7-9bff614c9e56,
  abstract     = {{Red blood cell (RBC) and iron status biomarkers are commonly used in clinical diagnostics. However, interpretations of infant test results are inherently challenging. Modern well-defined comparative data based on presumably healthy term-born infants have mainly been lacking and interpretations could be further complicated by interference from frequent infections. Moreover, the trends that follow with transition from fetal life and rapid growth are dynamic. The processes, which are also dependent on gestational age at birth, need to be better understood.<br/>This dissertation includes three retrospective reference interval studies of termborn presumably healthy infants (Papers Ⅰ, Ⅱ, Ⅲ) followed by one prospective study investigating RBC dynamics in infants after extremely preterm birth (Paper Ⅳ).<br/>The first three studies defined reference intervals at four time points during the<br/>first year of life. Paper Ⅰ investigated ferritin as a biomarker of iron stores and<br/>presented reference intervals divided into subgroups by age and sex. In Paper Ⅱ the biomarker soluble transferrin receptor (sTfR) was studied. Age dynamics in the first year of life were established, where the upper reference limits were higher compared with adults even in iron-replete infants. Influence from the acute phase response was not demonstrated as sTfR concentrations did not co-vary with CRP concentrations except in samples 48‐96 hours after birth. This association could hypothetically be due to the triggering of transferrin receptor expression following the fluctuations in oxygenation during normal labor. In Paper Ⅲ, hemoglobin (Hb) and RBC biomarkers were studied. The reference interval widths found were mainly narrower compared with other studies. In addition, adherence to the World Health Organization threshold of Hb 49 pg/cell) rapidly decreased during the first weeks in life.<br/>In conclusion, this work presents opportunities for improvements to the interpretation of infant test results. As reference data are also required for epidemiological studies, the disagreement with the WHO classification for Hb despite seemingly favorable conditions in infancy needs further investigation. The insights from studying the RBC dynamics after extremely preterm birth underline the unique characteristics of their peripheral RBC population and further reveal a potential biomarker, Hyper-He, for studying postnatal erythropoietic transitions.<br/>Future research is needed to investigate the potential role of the loss of these<br/>endogenous RBCs and the development of infant morbidities after extremely<br/>preterm birth.}},
  author       = {{Larsson, Marie}},
  isbn         = {{978-91-8021-450-6}},
  issn         = {{1652-8220}},
  keywords     = {{Barnreferensintervall; Röda blodkroppar; Erytrocyter; Extremt för tidig födsel; Erytropoes; Klinisk kemi; Järnstatus; Ferritin; sTfR; Neonatologi; Pediatrik; Fetal tillväxthämning; Referensintervall; Pediatric reference intervals; Reference limits; Extremely preterm birth; Fetal growth restriction; Clinical chemistry; Iron status; Red blood cells; Erythrocyte; Transfusion; Ferritin; sTfR; Hemoglobin; Neonatal; Reference intervals; Umbilical cord blood; Infancy; Iron deficiency; Anemia; Acute phase response; soluble Transferrin receptor; Neonatal intensive care; Erythropoiesis; Birth; Infant}},
  language     = {{eng}},
  number       = {{2023:111}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{The dynamics of red blood cells and iron status during infancy}},
  url          = {{https://lup.lub.lu.se/search/files/159539713/MarieLarsson_PhDthesis_web.pdf}},
  year         = {{2023}},
}