Grant: Master's Award: Canada Graduate Scholarships

In Canada, approximately 8% of babies are born too early and while survival rates have improved dramatically, the risk of disability from brain injury remains high. Currently, when a mother is at risk for preterm birth (PTB) she is given magnesium sulphate (MgSO4) in an attempt to protect the baby’s brain. However, the evidence supporting this treatment is conflicting and its efficacy is modest at best as it only benefits a small number of premature babies. Without an effective treatment against PTB, there is a critical need to explore new therapies for protecting the brain from injury. A promising neuroprotective treatment is L-arginine, an amino acid that is important for healthy pregnancy. This proposal aims to understand how neuroprotective agents work by using a mouse model of maternal infection, the most common cause of PTB in humans. First, ultrasound will be used to determine any changes in placental or fetal blood flow and nuclear magnetic resonance will be used to study the effects on brain metabolism. The second aim of this proposal is to study the efficacy of L-arginine compared to that of MgSO4 in preventing brain injury. A series of behavioural testing and magnetic resonance imaging of the postnatal brain will be used to compare the long-term impacts of MgSO4 and L-arginine on brain development following PTB. While male sex is known to be a risk factor for poor outcomes following PTB, clinical studies of MgSO4 have yet to investigate the effect of sex on protection of the brain. We will investigate sex differences in response to the treatments to determine if fetal sex should be considered during clinical decision-making. By better understanding how neuroprotective agents work and exploring a new treatment, this work has potential to improve fetal health.