Pregnancy and delivery complications are remarkably common and put both the mother and the neonate at increased risk for both acute and chronic adverse health outcomes. Despite these well-known risks, the underlying etiology of most pregnancy and delivery complications is not clear. The first step in understanding these etiologies is to examine changes over uncomplicated, full term pregnancies. We identify patterns of gene expression changes over pregnancy that are consistent with physiological changes, including changes in oxygen transport, immune factors, and response to microbes. In complicated pregnancies, we identify DNA methylation changes predictive of fetal intolerance of labor, a common pregnancy complication that may indicate the need for a Cesarean section. Thus, understanding the gene expression and gene regulatory changes associated with pregnancy can allow for better prediction of maternal risk.
In addition to maternal DNA methylation changes, neonatal DNA methylation can also serve as a proxy for neonatal risk. We developed a predictor of gestational age at birth based on DNA methylation data from neonatal blood spots and cord blood. The difference between predicted age and clinically estimated gestational age, termed gestational age acceleration, is associated with a variety of factors related to developmental maturity. We show that neonates requiring oxygen, steroids, and surfactant in the neonatal intensive care unit have a lower developmental maturity than those who do not. Additionally, neonates with a lower developmental maturity are more likely to develop bronchopulmonary dysplasia. Gestational age acceleration, therefore, is a useful tool for both clinical and research applications to better quantify neonatal risk.
Table of Contents
Chapter 1: Maternal and Neonatal Risk Associated with Pregnancy 1
Physiological Changes Over Pregnancy 2
Adverse Health Outcomes Associated with Pregnancy Complications 4
Genetic, Epigenetic, and Transcriptomic Signatures of Pregnancy Complications 6
Chapter 2: Characterization of Gene Expression Changes Over Healthy Term Pregnancies 34
Chapter 3: SLC9B1 Methylation Predicts Fetal Intolerance of Labor 60
Chapter 4: Predicting Neonatal Gestational Age Using DNA Methylation 88
Chapter 5: Predicting Perinatal Risk Using DNA Methylation 137
Chapter 6: Conclusions and Recommendations for Future Studies 163
About this Dissertation
|Committee Chair / Thesis Advisor|
|Epigenetic and Transcriptomic Signatures of Maternal and Neonatal Risk for Adverse Pregnancy Outcomes ()||2018-12-14||