The University of Alberta is leading a new, national partnership to coordinate more neonatal clinical trials in Canada and improve outcomes for premature babies and their families.

Known as PANDA, the Platform for Trials in Neonatal Care launched in 2024 under the leadership of U of A neonatologist Georg Schmӧlzer and with key support from WCHRI.

Thirteen of Canada’s 32 hospitals with comprehensive neonatal intensive care units have already joined the network, which allows researchers to collaborate on planning, funding and co-ordinating sites for randomized clinical trials. A steering committee ensures different sites don’t compete for the same funding.

Globally, complications from preterm birth are now the leading cause of death in children under five. In Canada, about 1,600 extremely premature babies are born at 28 weeks or less each year. Almost all of those born at 28 or 29 weeks survive, says Schmӧlzer, director of the Centre for the Studies of Asphyxia and Resuscitation, a leading neonatal research centre. But at 22 weeks, less than 40 per cent make it, often with long-term medical problems. The toll on them and their families is enormous, as are the costs to the health-care system.

“In neonatology, we don’t have answers for 80 per cent of the questions. We have no data. So there’s plenty of work to do,” he says.

Early intervention and clinical trials are key to improving the lives of preterm babies and their families, he says, drawing a clear line to WCHRI’s strategic priorities. These are areas identified by the institute where it can distinguish itself and draw on the strengths of its partnerships — in this case, with the Stollery Children’s Health Foundation — to drive forward high-impact research to benefit children and families in Alberta and beyond.

Schmӧlzer hopes PANDA will increase not only the number but also the diversity of babies involved in Canadian clinical trials, so researchers get better, more reliable data to improve treatments. Participation requires parental consent and many parents from racial and ethnic minority groups are reluctant, he says, largely because of historical mistrust of the medical and research communities. Education on this issue is one of the network’s goals.

Schmӧlzer has led and participated in more than 20 clinical trials since joining the U of A in 2012. While the number of neonatal researchers in Canada who want to do clinical trials is increasing, he says, there are still administrative and funding barriers, especially for early-career scientists.

He is leading PANDA’s first randomized clinical trial with $2.5 million in CIHR funding. The multi-site study will examine the optimal oxygen concentration for extremely premature babies. He plans to follow up with a similar study of babies born at 29 to 34 weeks.

Schmӧlzer also hopes to extend PANDA’s research umbrella to include near- or full-term babies and, eventually, pregnant people and those who have recently given birth.

“When we get fully up and running, I think we could create quite a lot of evidence on simple, important questions to improve the outcomes for moms as well as for babies.”

PANDA is also collaborating with the Canadian Premature Babies Foundation and Hope for HIE.

In Indigenous communities, the birth of a child is more than a medical event; it’s a sacred time for ceremonies that connect people to their culture and place. Yet for decades, expectant mothers from remote communities across Canada’s North have been required to leave their homes to give birth in distant medical facilities.

“The policy was put in place by the federal government with the intention of reducing infant mortality rates,” says Hennessey Chartier Ford, who planned her graduate research on the practice, known as birth evacuation, with support from WCHRI.

“But recent studies have shown that Indigenous women with low-risk pregnancies have better outcomes when birthing services are provided in their communities.”

In 2023, when she was a PhD student at the University of Alberta, Chartier Ford received a Patient and Community Engagement Training (PaCET) award to plan research into community-informed alternatives to birth evacuation, which is also common in other polar regions, including Greenland, Alaska and Norway. She could see that health-care systems have often been “designed without input from the Indigenous Peoples they serve, which had resulted in ineffective health services and policies.”

WCHRI issues at least four PaCET awards a year through its Graduate Studentship program to train candidates in participatory research, which engages patients, clinicians, community groups, government and non-government organizations as partners.

During her project, Chartier Ford lived in Yellowknife, NWT, and worked at the Institute for Circumpolar Health Research with Inuk Elder Rassi Nashalik and Inuk midwife Shelley O’Gorman. She also attended a conference in Denmark that brought together health researchers, Indigenous Elders and midwives from global polar regions to discuss maternal health issues.

She participated in a sharing circle where she learned that giving birth away from home carries cultural and emotional risks for community members, who view health and wellness through a holistic, culture-based lens. The importance of community engagement in research that involves maternal child health services in the Arctic became even clearer.

“I am proud to engage in research that recognizes the value of Indigenous knowledge and lived experiences and which positions community members as experts on their own health. I felt very honoured to get to learn from local Elders and other knowledge holders.”

Though Chartier Ford has since left her PhD program to study medicine at the University of Calgary, where she plans to specialize in obstetrics and gynecology, she remains committed to her research.

“I want to implement what I learned into my own medical practice,” she says. “I loved living in the North and I want to continue the research and do more work in partnership with the community.”

From infertility to painful, erratic periods and weight gain, polycystic ovary syndrome — or PCOS — has plagued Paula de Gannes-Beckles for most of her life.

Diagnosed as a pre-teen, she’s now a patient partner on a University of Alberta research team with a mission to reduce the risks of serious, long-term health effects on young women with the hormonal disorder.

“This is so important to our wellness,” says de Gannes-Beckles. “A lot of women with PCOS do not know about the cardiac risks. And it’s fearful! It’s so scary.”

She monitors her heart health and has made lifestyle, exercise and diet changes with the help of researcher Donna Vine, who leads the study into the progression of heart disease in young women with PCOS, which affects up to 15 per cent of people with ovaries.

People with PCOS can have enlarged follicles in the ovary that appear like cysts. It affects ovulation and menstrual function, causing problems with fertility as well as acne or hair growth on the face or body. It’s also associated with other health issues, such as weight gain, diabetes and heart disease.

With funding from WCHRI and the University of Alberta Hospital, Vine and co-investigator Mahua Ghosh, an endocrinologist, worked with the Alberta Health Services Pathway Unit, clinicians and patient partners to create a PCOS diagnostic tool for doctors and a guide for patients on My Health Alberta.

“If we can detect it early and intervene, we could be protecting women in their 30s and 40s from heart disease,” says Vine, a professor in the Faculty of Agricultural, Life and Environmental Sciences and founder of PCOS Together, a patient support and research program. “This disease impacts their family life and their ability to work and study, due to the symptoms. And on top of that, you’ve got the increased risk of several chronic diseases.”

Vine’s research has found that Alberta women with PCOS have a two-fold higher incidence of heart disease compared to other women and three to four times the rate of obesity and diabetes. They are also more prone to eating disorders, certain cancers, mental health issues and respiratory disorders.

Her team studied 90 women in their 20s and 30s. About half had PCOS, and the other half were a similar age and size. They found that those with PCOS showed many more signs of early heart problems than the other group, including narrowing of the arteries in the neck, which increases the risk of stroke or heart attack.

Thanks to a WCHRI Innovation Grant, Vine was able to follow up with the same group a year later. She discovered progressive narrowing of the arteries and other risk factors in about a quarter of those with PCOS, and sent them for more checkups with heart and hormone specialists. Study participants with heart issues were offered help with nutrition and healthy lifestyle choices, as well as medicine for blood pressure, diabetes or weight, if necessary.

Vine hopes her research will provide the basis for a national, long-term study of young women with PCOS and others at higher risk for heart problems, and lead to improvements in the prevention of heart disease. To participate, contact PCOSTogether@ualberta.ca.

A Type 1 diabetes diagnosis at 15 didn’t stop Saru Toor from playing competitive handball. But figuring out how to adjust her insulin before games and practices was stressful, she says. There was always a risk that her blood sugar would bottom out.

So, she jumped at the chance to take part in a study on how to help menstruating women manage the risks of developing low blood glucose levels during exercise. If not managed properly, the condition — called hypoglycemia — can lead to coma or even death.

“I want there to be more knowledge about all of this for other Type 1 diabetics, especially those who experience having a menstrual cycle and what that does to their blood sugar,” says Toor. Now 22 and a lab assistant at the University of Alberta, she still exercises regularly but avoids certain days of her cycle.

About five to 10 per cent of the 1.6 million women in Canada who live with diabetes have Type 1, which happens when the pancreas stops producing insulin.

The study, funded by a WCHRI Innovation Grant, was the first to examine the effect on blood sugar during exercise throughout the menstrual cycle of women with Type 1 diabetes. It was led by Jane Yardley, an adjunct kinesiology professor at the U of A and director of the research unit in physical activity and diabetes at the Montreal Clinical Research Institute.

Yardley doesn’t want fear of hypoglycemia to stop women from exercising. So, her research is focused on developing more precise recommendations for adjusting insulin.

Guidelines exist, but they’re based on data from studies on young, fit men, she says. “Women have been completely neglected in this field.”

Exercise is important for people with Type 1 diabetes, which requires insulin therapy for life. It can prevent or delay the progression of some diabetes-related complications, and studies show that those who exercise regularly live several years longer than those who don’t. But it’s especially crucial for women with the life-altering autoimmune disease, because they lose more muscle mass and bone density after menopause and suffer up to four times the risk of fractures than women without diabetes.

In a second project, initially supported by a WCHRI Bridge Grant and now funded by Diabetes Canada, Yardley is looking at how to manage the risks of developing low blood sugar during exercise in post-menopausal women with Type 1 diabetes.

Her studies began when she was based at the U of A and continued in Montreal after she moved there in 2023.

Although results are not yet published, Yardley is already talking to diabetes educators and nurses about adjusting insulin differently depending on where a woman is in her menstrual cycle. Early results indicate some have a higher risk of hypoglycemia during the luteal phase, a week or so before bleeding. But that doesn’t mean they should avoid exercise, Yardley says.

“I would never say that,” she laughs. “I would say, ‘pay more attention’… If you’re aware, you can pre-empt.”

When two siblings came to the Stollery Children’s Hospital with developmental delays and unusual facial features, doctors suspected a rare genetic disorder called Alazami Syndrome. Standard genetic tests failed to confirm the diagnosis, however, so they turned to the Translational Genomics Hub for help.

Part of the Women and Children’s Health Research Institute, the hub — or TGH — brings together experts from different areas of biology and genetics to solve genetic mysteries. The team evaluates the results of sophisticated gene-sequencing tests performed in the clinic. They do experiments in the lab to verify the findings in the hopes of identifying new genetic disorders, or variants of existing ones, to provide a diagnosis.

“It offers an extra layer of possibilities — both for clinicians and researchers — to complete those complex genetic investigations,” says Oana Caluseriu, a clinical geneticist and associate professor in the Department of Medical Genetics. She leads the TGH in tandem with Todd Alexander, chair of the Department of Pediatrics.

The mystery of the siblings — aged 9 and 17 — was ultimately solved by medical geneticist Saadet Andrews. She determined they have Alazami Syndrome from a gene variant not yet recorded in the medical literature.

Once her findings are reviewed and published, she will be able to confirm her diagnosis for the family and update the specific variant in a public database to help medical geneticists all over the world.

For those who have waited decades for answers, a genetic diagnosis comes as a relief, even if no treatment is available. It may allow families to access community supports for their loved ones, or prevent the disorder from recurring in their family tree.

To date, about 7,000 genetic disorders have been clinically described globally, but not all have a gene attached or a cause established. “There is still a lot of work to do, and all of us are just adding one little brick at a time,” Caluseriu says.

In the three years since it launched, the TGH has expanded the repertoire of tests it offers. This is good news for those still waiting for answers — like the large family with whom Caluseriu has been working to identify a fatal, genetic disorder that has afflicted five generations. After identifying a promising gene, she used an online platform — “kind of a dating app for researchers” — that matched her with colleagues from around the world who have found the same gene in their patients. She swiped right on a research group in Australia and a scientist in Calgary, and a fruitful collaboration ensued.

“It has taken years and a lot of effort, but we are now getting ready to write the manuscript and describe a new genetic disorder,” she says. “It’s a very complex process, but once we convincingly demonstrate our findings, we will be able to work with the family to avoid the devastating outcomes that have ravaged so many lives. And the same will happen for any other family carrying the same faulty gene anywhere in the world who accesses a genetic service.”

Adam Purificati-Fuñe didn’t expect to learn to better appreciate his Filipino heritage from a support group for Nêhiyaw (Cree) men.

As research for his graduate degree from the Faculty of Agricultural, Life & Environmental Sciences, he took part in a community-led program for Nêhiyaw fathers in Maskwacîs, a Central Alberta community of four First Nations. Called the Deadly Dads Support Society, its purpose was to support them as parents and to help them reconnect with traditional spiritual practices.

“I’m not a father, and I’m not Nêhiyaw,” he says, “but I’ve used the skills I learned in Maskwacîs to start my own journey to reconnect with my culture and community.”

The Deadly Dads group was born from a long-standing partnership between the local community and U of A researchers that honours Nêhiyaw ways of knowing. Guided by a community advisory committee including Elders and researchers, the group of fathers, uncles and grandfathers met regularly from August 2021 to January 2023 for sweat ceremonies, sharing circles, a family camp, a round dance and activities including bowling, golf, pool, paintball and firearm safety training.

“It really evolved with the input of people in the community,” explains Purificati-Fuñe, whose research was supported by a WCHRI Patient and Community Engagement Training award. “We worked in partnership to implement a strategy for men to strengthen their traditional relationship, parenting and kinship roles. We also worked with the community to evaluate the impact of this strategy on family and community well-being.”

Participants reported feeling a stronger sense of belonging, connection to culture, motivation to better their lives and appreciation of the wisdom of Elders, notes Purificati-Fuñe. The most important outcome was the relationships that developed.

The Deadly Dads is important for men’s mental health, and by extension, their families’, says Sonny Lightning, a Maskwacîs community member who continues to lead the group. “Adam was a big part of this group becoming a non-profit organization. We still get together, and we have an open-door policy. The people who show up want to be there for a good reason: to connect and to support each other.”

In his thesis, Purificati-Fuñe said the knowledge to support healthy families already existed in Maskwacîs and Nêhiyaw culture, and his time with the Deadly Dads changed his perspective on the role of researchers.

“I received a lot of encouragement to learn about my own history, to develop my own identity, and to love all parts of who I am, especially in ceremony and through the examples given by Mosoms (grandfathers), Kokoms (grandmothers) and many of the dads. I’ve never been in a space where people loved so deeply who they are, who their ancestors are, and who their next generation will be.

“It is our responsibility as researchers, and as human beings, to look at ourselves, understand ourselves, and heal ourselves, rather than imposing our knowledge onto others, so we can be better partners in the pursuit of a good future for the generations coming after us.”

With support from WCHRI, an international research project has been tracking Edmonton families since 2011, seeking the best treatment for women with diabetes in pregnancy and their children.

The study recruited 500 pregnant women with diabetes at four centres in Australia and 25 in Canada, including two in Edmonton, where the research is coordinated by WCHRI’s study management and clinical trials support services. The first phase of MiTy — or Metformin in women with type 2 diabetes in pregnancy — compared treatment with insulin alone and insulin with metformin on the women; the second gathered data on their babies; and the third on the now-school-aged children.

Diabetes-in-pregnancy rates have more than doubled since 2000, and continue to rise. The disease causes high blood sugar levels, which increase the risks of preeclampsia, a form of high blood pressure in pregnancy, as well as preterm birth, birth trauma and C-section, because the baby grows too large for a vaginal birth. Both mother and child are also more likely to develop Type 2 diabetes and heart disease later in life.

MiTy’s first phase showed metformin has some clear benefits: women gained less weight during pregnancy and had babies with lower birth weights than those in the placebo group. “But there have been some concerns about the drug crossing the placenta and its effects on offspring, both during and after the pregnancy,” says Andrea Haqq, a pediatric endocrinologist and professor of pediatrics at the University of Alberta.

Haqq oversaw the second and third phases of the Edmonton trials. The second, MiTy Kids, studied 283 of the babies born to the MiTy moms through to age two. It found that exposure to metformin in utero didn’t seem to affect their weight gain. The third, MiTy Tykes, is following 220 of the MiTy Kids from ages four to 11 to measure weight gain and social and cognitive development. Those results aren’t yet published.

MiTy is an example of what excellent health research looks like, Haqq says. “In my field, our highest-impact publications have come out of national and international collaboration. It’s really a team effort. When you work in a silo, you can’t do anything as impactful.”

WCHRI clinical research coordinator Heather Rylance was a constant presence through every phase of the MiTy project. Rylance saw the women once a month during their pregnancies and did home visits to collect blood samples and body measurements from their babies. The study was double-blind, meaning neither the participants nor Rylance and the researchers knew who received metformin and who was given the placebo, which helps to eliminate bias.

A long-time diabetes nurse, Rylance is very familiar with the risks of untreated diabetes. “Type 2 diabetes carries a lot of contraindications, like high blood pressure,” she says. “We want to help the mom as well as the baby stay healthy.”

Brain injuries can affect anyone, but infants and their rapidly developing brains are particularly vulnerable. On a cellular level, they respond differently to damage than those of older people, but it’s not clear why.

Maria Ioannou, a University of Alberta professor of cell biology, is on a research journey to discover ways to improve outcomes following neonatal brain injury. She suspects some answers might lie with the lipids in infant brain cells.

Lipids are a group of biological molecules best known as fat. They have many functions throughout the body, including energy storage and communication between cells. Lipids can also be stored in globules — called lipid droplets.

With support from a WCHRI Innovation Grant, Ioannou and her team set out to explore how stress affects the formation of lipid droplets within neonatal brain cells. They focused on a form of stress called excitotoxicity, which occurs when nerve cells are overwhelmed by very high levels of neurotransmitters (chemical messengers in the brain).

“We found that if you induce cellular stress, you start to see lipid droplets form,” says Ioannou, who holds the Canada Research Chair in brain liquid cell biology. The droplets seem to minimize the damage of cellular stress, as the team hypothesized, but it isn’t clear why.

It’s also uncertain whether the protective benefits of lipid droplets cease once they exceed a certain threshold. And why do lipid droplets form most frequently in microglia, the brain’s immune cells, which account for just 10 to 15 per cent of all brain cells? That’s not clear either.

“We’re in the process of writing up the findings, though there is still much that remains to be studied,” she says. That’s the fate of discovery scientists like her: the more experiments they do, the more follow-up questions emerge.

She hopes clarity will come with future studies of lipid droplets. In time, she plans to pivot to research on lipid-based therapies for the treatment of neonatal brain injury.

“At the end of the day, WCHRI’s mandate is to improve the health outcomes of women and children,” she says. “Even though this is a discovery project, I think it has a lot of potential to do just that.”