Grant: CIHR Fellowship

Preterm birth (PTB), delivery prior to 37 weeks gestation, is the leading direct cause of neonatal mortality and the second leading cause of death in children under the age of five. PTB can have lifelong consequences including growth delay, neurodevelopmental impairment, cerebral palsy and increased risk of chronic disease in adulthood. There is an urgent need to improve our understanding of the underlying pathophysiology, to enhance our identification of pregnancies at risk and to identify safe and effective intervention strategies. Successful pregnancy requires healthy development in the placenta, which relies on a tightly regulated balance of pro- and anti-angiogenic factors. Recent research suggests that dysregulation of angiogenic pathways, early in pregnancy, may result in placental vascular insufficiency and inability of the placenta to support normal fetal growth and development. We hypothesize that circulating levels of pro- and anti-angiogenic factors will be dysregulated, early in pregnancy, in women who subsequently deliver preterm, and that these biomarkers will predict pregnancies at risk of PTB and identify novel targets for interventions to improve outcomes. In preliminary studies we have identified candidate genes and pathways involved in inflammatory and angiogenic processes in the pathobiology of PTB. We now plan to validate and extend these findings in well-characterized patient populations of pregnant women in Tanzania and Malawi. From these results we will refine a panel of biomarkers and begin to develop and evaluate predictive models of PTB and assess potential targets for therapeutic intervention strategies using relevant animal models. Collectively this approach will address critical knowledge gaps in our understanding of the pathophysiology of PM and establish a rational basis for effective interventions for this global health priority.