The dynamics of red blood cells and iron status during infancy

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 dynamics in infants after extremely preterm birth (Paper Ⅳ).The first three studies defined reference intervals at four time points during thefirst year of life. Paper Ⅰ investigated ferritin as a biomarker of iron stores andpresented 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 theseendogenous RBCs and the development of infant morbidities after extremelypreterm birth.