Document Type

Dissertation

Date of Degree

Spring 2014

Degree Name

PhD (Doctor of Philosophy)

Degree In

Translational Biomedicine

First Advisor

Jeffrey C. Murray

Abstract

Preterm birth (PTB) is defined as birth before 37 weeks gestational age. PTB is a common outcome and one that may be increasing in prevalence with serious individual and public health implications both immediately and long term. While PTB is a pregnancy specific outcome it is more appropriately viewed as the culmination of risk factors present both before pregnancy and possibly in past generations. This thesis attempts to review the implications, risk factors and current prevention strategies directed at PTB while placing it in an intergenerational and life cycle context. Three novel investigations are presented and their consequences are discussed. These investigations cover the lifespan and relate to identifying PTB and treating its immediate health outcomes. The first examines mitochondrial genetics and it's relation to PTB. There is a strong a priori hypothesis that mitochondrial genetics, being maternally inherited, may contribute to an individual's risk for PTB. However, in two genome wide association studies, no evidence is found for any mitochondrial polymorphisms being related to PTB. The second investigation reports an attempt to identify women at risk for PTB within a given pregnancy. Using routinely collected maternal information and serum screening data a potentially useful screening method is derived. While the algorithm does not have ideal performance characteristics it compares favorably to other population wide screening techniques and could be improved through future validation and data collection. The third and final investigation attempts to address quality of care for infants born preterm. In a network of neonatal intensive care units, wide variations in mortality outcomes are observed. Intensity of medical intervention appears to be an important predictor of mortality for the lowest gestational age infants. However, this intensity of intervention does not fully explain the observed differences in mortality outcomes. Finally, these study are discussed in context with one another and a new framework for considering PTB is presented that may help to guide future investigation into predicting, preventing and caring for those at risk for or experiencing a PTB.

Keywords

low birth weight, neonatology, prediction, preterm birth, prevention

Pages

viii, 141 pages

Bibliography

Includes bibliographical references (pages 111-141).

Copyright

Copyright 2014 Brandon Wesley Alleman

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