When babies are born weeks – or even months – before their due date, they often face serious health challenges that are compounded by their immature immune systems and the risk of life-threatening infections.
Roughly eight per cent of babies in Canada are born before 37 weeks of pregnancy and infections are the leading cause of death in these fragile infants. The earlier a baby is born, the greater the risk: One in three babies born before 32 weeks of pregnancy and one in two born before 24 weeks in will get an infection.
Dr. Pascal Lavoie, neonatologist at BC Women’s Hospital + Health Centre and investigator at BC Children’s Hospital, has dedicated his research to finding ways to reduce the threat of infections in preterm babies to give these tiny patients the best possible chance to grow and thrive.
A recent study in Nature Communications from Dr. Lavoie and University of British Columbia (UBC) doctoral students Bernard Kan and Christina Michalski provides important insights into why preterm babies are more vulnerable to infections than babies born at term. This work could lead to the development of new treatments that jump-start their immune systems, lowering the risk of early-life infections that can lead to lifelong complications and death.
“We know that in preterm babies the dozens of immune receptors responsible for recognizing an infection are turned ‘off,’” said Dr. Lavoie, Associate Professor in Neonatology in the Department of Pediatrics in the Faculty of Medicine at UBC. “Through this research, we found out how that happens and identified a protein responsible for suppressing the immune system.”
Researchers have long known that fetuses have a limited ability to identify and respond to infections. This is likely because, in the womb, they are largely protected by their mom’s immune system and the placenta, and the inflammation involved in an immune response could damage developing tissue or cause preterm labour. When babies are born early, they’ve lost the benefits of being in womb, but their immune system is still developing.
“Infections in preterm babies are difficult to diagnose and often progress quickly,” said Dr. Lavoie. “Coupled with the fact that these babies are often born with complex health challenges, this means that infections are often life-threatening and can lead to serious complications.”
mTor, the protein identified through this new research, controls the energy supply required by the immune cells that are the first line of defense against infection. Significantly, researchers found that the earlier a baby is born, the lower the activity of mTOR. This lower activity starves these cells of the energy they need to launch an immune response. In the absence of mTOR, immune cells from preterm born earlier in pregnancy are paralyzed and unable to respond to infections.
According to researchers, mTOR is likely less active before birth to help fetal immune cells focus their energy on vital tasks, such as building strong organs and tissues. However, this becomes a problem when babies are born early, as it prevents their immune system from responding to infection.
“We’re excited about this discovery because it opens up the possibility of new therapies that could target this protein to turn ‘on’ a preterm baby’s ability to recognize and respond to infections,” said Dr. Lavoie. “For the first time, we now have a key to how immune cells are broadly turned off all across the board in preterm babies, leaving them extremely vulnerable. Our discovery brings us one step closer to helping us prevent infections in these babies, allowing caregivers in the NICU to focus on treating and managing other complex health needs, preventing unnecessary complications and giving them a better start in life.”
Currently, there are already drugs in use in adults that have been shown to boost the energetic capacity of immune cells, enabling them to fight infection. Dr. Lavoie’s new research points to the potential these medications hold for preterm babies, but more research is needed.
Dr. Pascal Lavoie is an Associate Professor, Partner Institute, Division of Neonatology, Department of Pediatrics, Faculty of Medicine, University of British Columbia.
Bernard Kan and Christina Michalski are UBC doctoral students supervised by Dr. Lavoie at BC Children’s Hospital Research Institute.
This research was funded by the Canadian Institutes of Health Research, the Michael Smith Foundation for Health Research and BC Children’s Hospital Foundation. The research team would like to thank all of the families who donated cord blood for this project and BC Women’s Hospital Preemie Biobank, supported by the BC Children’s Hospital Biobank and BC Women’s, for their assistance collecting biological samples for this study.
BC Women’s Hospital + Health Centre and BC Children’s Hospital are programs of the Provincial Health Services Authority.