Characterization and differentiation of iron status in anemic very low birth weight infants using a diagnostic nomogram

Abstract

Background: In the early weeks of life, very low birth weight (VLBW) infants experience intense laboratory blood sampling leading to clinically significant anemia and the need for red blood cell transfusion. Although controversial, treatment with recombinant human erythropoietin (EPO) and iron has been recommended to stimulate erythropoiesis; optimal dosing of EPO and iron is still uncertain.

Objectives: To assess the validity of a four-quadrant diagnostic plot of iron availability (ferritin index) versus iron demand for erythropoiesis (reticulocyte hemoglobin content, CHr) for differentiating iron status in anemic VLBW infants.

Methods: Study subjects were enrolled in a previously reported randomized controlled trial of clinically stable VLBW infants <31 weeks' gestation and <1,300 g at birth to receive 18 days of treatment with: group 1: oral iron; group 2: EPO + oral iron, and group 3: EPO + intravenous + oral iron.

Results: At the end of treatment the ferritin index was significantly higher in both EPO groups compared to the control group. By day 18, CHr of the control group declined into the quadrant of the diagnostic plot characteristic of functional iron deficiency and anemia of chronic disease. Both EPO groups ended in the quadrants that are characteristic for latent iron deficiency and iron deficiency anemia, respectively.

Conclusions: The diagnostic plot for differentiating anemia in VLBW infants may be an informative, clinically useful tool for iron status assessment under different physiologic and therapeutic erythropoietic states. Larger additional studies in difficult patient populations are needed before the clinical utility of this diagnostic procedure can be unequivocally confirmed.

Fig. 1

Diagnostic plot for identifying the different erythropoietic states with therapeutical implications for the treatment of different phases of iron deficiency adapted from Thomas et al. [11]. ^aTherapeutic implications for the treatment of different phases of iron deficiency according to Thomas et al. [11]

Fig. 2

Change in sTfR (a), ferritin index (b) and CHr (c) during the treatment by study group. Data are shown as mean ± SEM. Post hoc statistical significance compared with group 1 is indicated by the asterisk(s): * p < 0.05; ** p < 0.01; ns = not significant.

Fig. 3

Diagnostic plot for identifying the different erythropoietic states. The course of each group is plotted from the 3-day run-in baseline period (day = −3) through the start of treatment (day = 0) continuing on to the end of treatment (day = 18). The x-axis represents the biochemical indicators for iron supply (sTfR/log ferritin, i.e., ferritin index) and the y-axis represents the hematological indicator for iron demand by erythropoiesis (CHr). Q1-4 indicates quadrants 1 to 4.