Investigating Genetic Markers Associated with Spontaneous Preterm Birth in Low-Risk Pregnancies

Abstract

Preterm birth is the leading cause of infant mortality worldwide and is a strong risk factor for serious short and long-term health concerns for the child. However, the cause of many preterm births is unknown. Two-thirds of preterm births occur spontaneously, and half of those occur in low-risk pregnancies. Commonly implicated pathways to preterm birth include infection or inflammation, stress, and uterine overdistention. Many studies attempting to target idiopathic spontaneous preterm birth fail to account for confounding maternal medical conditions that can lead to premature labour and delivery, therefore conflating idiopathic cases with those driven by known risk factors. This meta-analysis identified genetic associations with idiopathic spontaneous preterm birth by ruling out genetic loci associated with the high-risk pregnancy conditions of preeclampsia, gestational diabetes mellitus, hypertension, type I diabetes, and placental abruption. The implicated gene loci were subjected to a gene ontology and pathway analysis, revealing three overrepresented functional groupings: neuronal synapses, calcium and ion homeostasis, and metabolism and endocrine signaling. Analysis of these functional groupings and the implicated genes indicates that the placental environment; calcium dysregulation in the myometrium; and possibly maternal mental health contribute to spontaneous preterm birth. Additionally, this thesis highlights the significance of immune biomolecules in the sequence of events that lead to preterm labor. Overall, this thesis represents a novel approach to understanding the pathology of idiopathic spontaneous preterm birth and establishes associations that should be further investigated. The results of this study identify potential diagnostic biomarkers that may help reduce the rates of preterm birth through early detection and intervention.