Document Type

Dissertation

Date of Degree

Fall 2015

Degree Name

PhD (Doctor of Philosophy)

Degree In

Pharmaceutical Sciences and Experimental Therapeutics

First Advisor

Peter Veng-Pedersen

Abstract

Anemia of prematurity is characterized by a progressive decline in hemoglobin level during the first month of life. Unlike term newborns, preterm infants become anemic and often require red blood cell transfusions. Various factors contribute to the development of this anemia. These include short infant red blood cell (RBC) lifespan, decline in erythropoiesis rate after birth, and blood losses caused by repeated phlebotomies.

The objectives of this work were to develop novel models to evaluate fetal and neonatal erythropoiesis, and to study in vivo adult and neonatal RBC survival in low birth weight preterm anemic infants. The model developed to evaluate fetal erythropoiesis was based on the in utero growth of the fetus over time. Neonatal erythropoiesis rate was estimated using a hemoglobin (Hb) mass-balance based method that 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 to quantify the amount of Hb produced and the Hb production rate during the first month of life. To study RBC survival, two separate models, one describing the elimination of neonatal RBCs produced under non-steady state conditions, and the second describing the elimination of adult RBCs produced under steady state conditions were developed and applied to the RBC survival data obtained from low birth weight anemic preterm infants. The proposed mathematical models and its implementation provides a flexible framework to study both in utero non-steady state (non-SS) fetal erythropoiesis and neonatal erythropoiesis in newborn infants.

Public Abstract

Anemia of prematurity (AOP) is an exaggerated, pathologic response of the preterm infant to the transition from a relatively hypoxic state before birth to a relatively hyperoxic state with increased tissue oxygenation after birth that leads to a decline in erythropoietin (EPO) concentration. Three basic mechanisms are responsible for the development of AOP, (1) inadequate RBC production, (2) shortened RBC life span, and (3) blood loss.

The objectives of this work were to develop and evaluate novel mathematical models to evaluate fetal and neonatal erythropoiesis, and to study in vivo adult and neonatal RBC survival in low birth weight preterm anemic infants. The proposed models and its implementation provide a flexible framework to study both non-steady state (non-SS) fetal erythropoiesis and neonatal erythropoiesis in anemic newborn infants.

Keywords

publicabstract, Erythropoiesis, Red blood cell

Pages

xv, 146

Bibliography

141-146

Copyright

Copyright 2015 Denison John Kuruvilla

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