Graduation Date

Spring 5-6-2017

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Health Promotion and Disease Prevention Research

First Advisor

Debora Barnes-Josiah, PhD

Second Advisor

Lorena Baccaglini, MD, PhD

Abstract

Preterm birth is a complex multifactorial process. Despite the well-known role of the placenta in supporting the fetal development and maternal-fetal tolerance, the placental epigenetic modifications and preterm birth (PTB) remains poorly understood and under investigated. Various maternal and environment factors can influence epigenetic programming during fetal development to affect the functioning and structures of organs, including the placenta, which can lead to adverse pregnancy outcomes, including PTB. The understanding of the placental epigenetic alterations and maternal determinants associated with PTB are apparently indispensable for the development of actual diagnosis and methods of prevention and treatment of premature labor. The purpose of this dissertation is to identify epigenetic factors and predictor risks contributing to PTB. To achieve this goal we conducted literature and systematic reviews to assess evidence from published, peer-reviewed epigenetic studies examining the association between human placenta epigenetic alterations and PTB. In addition, we conducted an epidemiological study of predictor risks of PTB. The review identified a few studies showing an association of epigenetic changes (DNA methylation, expression of miRNAs and mRNAs) with PTB. Although these studies have reported an association, their findings were not replicated across studies. Also, the results provide the evidence of methodological concerns and recommend the need for the use of standard quality reporting guidelines by journals, such as STROBE (STrengthening the Reporting of Observational Studies in Epidemiology) checklists to refine the quality under review. The epidemiological assessment of various risk predictors of PTB was conducted using de-identified data from the University of Hawaii Biorepository. The findings show an association between PTB and different predictor risks.

These results may help not only to understand the complexity of PTB, but also to standardize and to improve the quality of research related to placental epigenetic modifications and PTB. This dissertation provides an understanding of predictor risks and genes of causal importance in PTB. Moreover, further research is required to replicate and address the limitations of previous placental epigenetic studies. The finding of this epigenetic study lays the foundation of early stage screening and diagnostic of PTB, as well as suggesting therapeutic targets.

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