A Mass Balance-Based Semiparametric Approach to Evaluate Neonatal Erythropoiesis.
Postnatal hemoglobin (Hb) production in anemic preterm infants is determined by several factors including the endogenous erythropoietin levels, allogeneic RBC transfusions administered to treat anemia, and developmental age. As a result, their postnatal Hb production rate can vary considerably. This work introduces a novel Hb mass balance-based semiparametric approach that utilizes infant blood concentrations of Hb from the first 30 postnatal days to estimate the amount of Hb produced and the erythropoiesis rate in newborn infants. The proposed method has the advantage of not relying on specific structural pharmacodynamic model assumptions to describe the Hb production, but instead utilizes simple mass balance principles and nonparametric regression analysis. The developed method was applied to the Hb data from 79 critically ill anemic very low birth weight preterm infants to evaluate the dynamic changes in erythropoiesis during the first month of life and to determine the inter-subject variability in Hb production. The estimated mean (±SD) cumulative amount of Hb produced by the infants over the first month of life was 6.6 ± 3.4 g (mean body weight, 0.768 kg), and the mean estimated body weight-scaled Hb production rate over the same period was 0.23 ± 0.12 g/day/kg. A significant positive correlation was observed between infant gestational age and the mean body weight-scaled Hb production rate over the first month of life (P < 0.05). We conclude that the proposed mathematical approach and its implementation provide a flexible framework to evaluate postnatal erythropoiesis in newborn infants.
Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, 115 S. Grand Ave. S227, Iowa City, Iowa, 52242, USA.
Denison J
DJ
Kuruvilla
Department of Pediatrics, College of Medicine, University of Iowa, Iowa City, Iowa, USA.
John A
JA
Widness
Department of Pediatrics, College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Demet
D
Nalbant
Department of Pediatrics, College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Robert L
RL
Schmidt
Departments of Biochemistry & Molecular Biology and Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Donald M
DM
Mock
Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, 115 S. Grand Ave. S227, Iowa City, Iowa, 52242, USA. veng@uiowa.edu.
Peter
P
Veng-Pedersen
D000465:Algorithms; D000740:Anemia / Q000097:blood / Q000628:therapy; D001835:Body Weight; D017707:Erythrocyte Transfusion; D004920:Erythropoiesis / Q000187:drug effects*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D019102:Infant, Very Low Birth Weight; D008297:Male; D008962:Models, Theoretical; D018962:Phlebotomy
D006454:Hemoglobins
anemic preterm infants; neonatal erythropoiesis; pharmacodynamic; postnatal hemoglobin production; very low birth weight