#017 - Exploring the impact of dexamethasone on the PDA and cardiovascular function

Hello friends 👋

What does dexamethasone actually do to the preterm heart over time? In this episode of Rupa's Fellows Friday, Srirupa sits down with Phoenix Plessas-Azurduy, doctoral candidate at McGill University and researcher at the NeoCardioLab under Dr. Gabriel Altit. Phoenix shares her work on NORDIC-SPEC, a prospective longitudinal study using serial echocardiography to characterize the cardiovascular effects of dexamethasone in preterm infants. Her preliminary findings show a progressive reduction in PDA size and increasing ductal closure rates over time within a conservative management context. The conversation also covers mentorship, the value of cold emails, and what it looks like to build a research career from the ground up.

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Short Bio: Phoenix Plessas-Azurduy is a doctoral candidate in Clinical & Translational Research at McGill University, where she is currently fast-tracked into the PhD program following her first year in her Master's studies. She holds an Honours BSc in Physiology from McGill and conducts her research at the NeoCardioLab under the supervision of Dr.Gabriel Altit, within the Research Institute of the McGill University Health Centre (RI-MUHC) and the Montreal Children’s Hospital. Her doctoral research is supported by several prestigious and competitive funding sources, including: The Brain–Heart Interconnectome Doctoral Scholarship and several awards from McGill University and the Research Institute (including the McGill Graduate Excellence Award, the McCall MacBain Scholarship Finalist Award, the RI-MUHC Studentship and EDI Prizes for Academic Excellence). Beyond her primary research, Phoenix is a competitive youth soccer coach at CS St Laurent and founder of the ThinkSci Outreach Program.   In this episode, Phoenix Plesis Azurdi shares her groundbreaking research on the effects of dexamethasone on preterm infants' cardiovascular health, her experiences at PAS, and insights into mentorship and career development in neonatology.

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The transcript of today's episode can be found below 👇

Srirupa (00:00) Hello, everyone. Welcome to another fantastic episode of Rupa's Fellows Friday. I feel very excited and energized after returning from the Pediatric Academic Societies (PAS) meeting in Boston. I got to meet so many wonderful people, made a lot of new friends, and encountered so much science. I was just so fascinated with the people I met and the amazing work happening in their research worlds.

I am very excited to invite one of the friends I made at PAS — Phoenix Plessas-Azurduy. She is a doctoral candidate in Clinical and Translational Research at McGill University, currently in a fast-tracked pathway to the PhD program, and she is mentored by the great Dr. Gabriel Altit of the NeoCardioLab.

She conducts her research through the NeoCardioLab and works at the Research Institute of the McGill University Health Centre (RI-MUHC) and the Montreal Children's Hospital. Her research trajectory has been remarkable. Phoenix has been awarded multiple prestigious and competitive funding sources and grants, including the McGill Graduate Excellence Award and the McCall MacBain Scholarship Finalist Award. All of these are incredibly impressive, Phoenix.

I am so excited that we have the opportunity to get to know you a little better and to hear about the research you're doing at the NeoCardioLab. Welcome to the studio and welcome to our recording day.

Phoenix (01:35) Thank you so much for that intro, Rupa. I'm really excited to be here. Thank you so much for the opportunity.

Srirupa (01:41) So how did you feel about PAS? There was so much research happening — what was your takeaway?

Phoenix (01:50) It was a really fantastic experience. It was my first time at PAS. I've been to other smaller conferences, but this was unlike anything I've ever experienced. Being surrounded by giants in neonatology was just an amazing experience — being able to connect with current collaborators and meet so many of the people whose papers I've cited or whose work I've read so much about. It was truly a one-of-a-kind experience.

Srirupa (02:30) For sure. I remember my first PAS experience — it started with recognizing authors of books I was reading at that point as a neonatology fellow. And this time I just felt like there was a whole convergence of my citation manager — all of the people I cite in my papers were right in front of me. It was just amazing to see all of them in person.

PAS is just amazing and the networking is out of this world. And this time it was especially great talking and meeting with so many members of the NeoCardioLab as well. Fantastic.

I'm excited to highlight the project you are currently doing with Dr. Altit at the NeoCardioLab. I first want to understand the history behind the name NORDIC-SPEC, because it is such a stellar name. Let's start with that, and then we'll go over where your study currently stands.

Phoenix (03:32) Honestly, it is a fantastic acronym, but I cannot take any credit for it. My principal investigator (PI), Dr. Altit, is fantastic — being in the NeoCardioLab, you really come to appreciate the many acronyms he has to represent all of his studies, which makes for very effective use of time and resources in the lab.

NORDIC-SPEC is part of a larger program that Dr. Altit has built. NORDIC stands for Neonatal Outcomes Related to the Early Discovery of Impaired Cardiac Function. Within that, there are three larger ongoing projects. The first is NORDIC-PREM, focused on preterm infants. The second is NORDIC-SPEC, which looks specifically at the impacts of postnatal steroids. And the third is CDH — Congenital Diaphragmatic Hernia (CDH).

My project, NORDIC-SPEC — where SPEC stands for Surveillance of Postnatal Steroids Effects on Cardiovascular Function in Preterm Infants — is my thesis project. What we do is a prospective observational longitudinal study using serial echocardiography at different time points within administration of specifically dexamethasone (DEXA) to look at different parameters of cardiovascular function. We perform echos at day zero, day three, day seven, and day 14 on DEXA, as well as one and two weeks post-cessation of DEXA, and then at 36 weeks post-menstrual age.

Along with each echo, we also do a lung ultrasound to see if there are correlates between mechanical ventilation weaning and our lung ultrasound scores. We also perform an electrocardiogram (ECG) at each time point to look at heart rate variability (HRV) and autonomic regulation. And specifically what I'm looking at is characterizing the profile of the patent ductus arteriosus (PDA) and left ventricular (LV) function — using speckle tracking echocardiography to look at hypertrophy and other parameters of LV function.

Srirupa (05:55) That's awesome. And this is a prospective study, which is itself pretty remarkable given the well-known challenges with recruitment and consent in neonatology. It's wonderful that you're looking at the effects of a medication that is so commonly and so variably used in our world.

This is going to add such significant impact to the existing literature. There are so many unanswered questions about dexamethasone, and it's such an interesting approach to look at its longitudinal effects on cardiovascular function. I'm curious — what have you found so far? Would you mind sharing some preliminary results?

Phoenix (06:41) Yes, of course. And exactly as you said, many unanswered questions remain — not only around dexamethasone but hydrocortisone as well. You're right that there's variability in practice, not only across countries but between units within the same city. I didn't realize how contentious the topic was until I really started diving deeper into the literature.

The NORDIC program began in 2019, and we began recruitment for NORDIC-SPEC in June 2021. We actually just closed recruitment last month with 60 patients included in the SPEC study. And just a quick shout out — as you said, recruitment is very difficult in this specific population, but we have a fantastic team at the NeoCardioLab. Not only Dr. Altit, but also a fantastic project manager, Daniela Villegas-Martinez, who does an amazing job recruiting these patients. This project would simply not be possible without her and the team.

For the preliminary analysis I had the opportunity to present at PAS, I looked at evaluation of the trajectory of PDA size and closure rates. As I mentioned, we take echos at defined time points. I looked at different parameters — PDA size, but also other echo indicators including shunt direction, velocity time integral (VTI), systolic and diastolic velocity, and more.

We had 53 patients included in this PDA preliminary analysis, as some babies either didn't have a day zero scan or had spontaneous closure prior to DEXA administration.

One interesting aspect of this study is that all babies included were started on dexamethasone after the first postnatal week of life, and only five received some type of treatment specifically for the PDA — one was ligation much later in the course, and the other four received another agent, also later. This is different from some centers because of the large variability in practice. What this cohort brings is a description of the PDA trajectory within a conservative management policy.

In the end, with those 53 patients, we characterized the PDA profile across time points. We saw 95% with an unrestricted PDA at DEXA start that had complete closure or a restrictive pattern by 36 weeks post-menstrual age. Our median PDA size reached zero at day 14 on DEXA. Of the 13 ducts that remained open throughout the study, size decreased from a median of 2.3 to 1.4 millimeters at 36 weeks post-menstrual age. We also saw an average PDA size reduction across time points. We ran a few statistical models, including generalized estimating equations and a random effects model, both of which showed a significant increase in the likelihood of PDA closure over time and a decrease in PDA size of 0.21 millimeters per time point.

As I mentioned, this is a cohort exposed to a conservative management policy, prospective in design, with echo scans blinded to patient status at the time of echo. Limitations include that it's a single-center study with a smaller sample size, we have no long-term data past 36 weeks, and due to the inherent study design there is no control group.

In conclusion, in preterm infants receiving DEXA for evolving bronchopulmonary dysplasia (BPD), serial echocardiography showed a progressive reduction in PDA size and increasing rates of ductal closure over time — reflecting a temporal pattern of ductal constriction within this conservative management context.

Srirupa (11:57) This is so interesting. One thing we don't always think about is how significant variability can impact all of these functions. And I always keep in mind that it's not just DEXA these babies are getting — they might be on antibiotics, different therapies, multiple interventions at once. Were other concurrent medications stratified as well? How did you account for those that might also affect the PDA?

Phoenix (12:34) 100% — you bring up an excellent point. There is variability not only in DEXA use but also in practices around fluid management, prostaglandin, and many other factors. I'm currently in the process of collecting exactly that clinical data to see if we can stratify by these different parameters. Not yet, but that's definitely to come. You make an excellent point.

Srirupa (13:03) Yeah, these are the unanswered questions. DEXA is one of the most commonly used medications in our community, and you have units that are either PDA believers or PDA non-believers. DEXA courses vary depending on what your unit believes about the duct. And it's interesting — this work is definitely going to add to the evidence that these factors may be working in concert in ways we haven't fully appreciated.

I ask this question to all of my guests: how do you plan on taking this forward in terms of your career trajectory? This is such a significant study, and kudos to you. And another shout out to Daniela for doing such a wonderful job supporting the program — consenting in neonatology is genuinely hard, especially when babies can be quite sick at the outset. With your involvement in a study of this magnitude, how do you envision your career path going forward?

Phoenix (14:29) That's a fantastic question. There is no "I" in team — the study began in 2020 and I only came on board in 2024, so I've been here for the tail end of recruitment. But there's a tremendous amount of work that has gone into this.

In terms of next steps, there is a lot of data ahead. We will be analyzing the 2D conventional echo measures and also using strain to look at LV function. I think the logical next steps are: finalizing the PDA data, then looking at lung ultrasound scores, then characterizing LV function at each time point — because that's a major clinical concern: hypertrophy, alternate impacts on the heart. And then looking at HRV and autonomic regulation.

For me personally, the NeoCardioLab and Dr. Altit have shaped a lot of my trajectory so far. I started as a master's student, absolutely loved the people around me and the work I was doing, and decided to fast track to the PhD program — and I've really loved it. Right now it's definitely one of the things that feeds me.

I think I would see a career in this space. I did my bachelor's in physiology, so everything related to hemodynamics is very interesting to me. I'm particularly drawn to how echocardiography can inform acute management. I'll acknowledge that there may be some confirmation bias since I'm immersed in it every day, but I'm surrounded by really fantastic mentors who do an amazing job at what they do. And I'm convinced that wherever this project takes me, it'll be somewhere good.

Srirupa (17:01) That's fantastic. From what I've heard, Dr. Altit is an amazing mentor, and that clearly shows in your dedication to your work. I strongly believe your mentor shapes and guides your future. I ask this question for our listeners who are early in their careers, trying to seek out mentorship and understand what a normal mentor-mentee relationship looks like. How has that worked in your experience?

Phoenix (17:41) These are fantastic questions. To give a bit of insight into Dr. Altit — and you know him well — every single time a speaker comes to the hospital or gives a presentation with a stellar career in neonatology or any related field, his first or last question is always: "What do you think it takes to be a good mentor?" or "How are you able to mentor in X area?" I think that speaks volumes to the type of mentor he is. He really centers every decision around our individual trajectories. He has what we call an army of students, and yet he gives such personalized attention to each of us because he genuinely sees the value — in French, valorisant — in what we do and what we each want out of our experiences.

I'll give a bit of background on how I got into the position I'm in now. I've been in the NeoCardioLab for quite a while — I joined during my undergrad. It was the summer after my first year, and I was sending cold emails as undergrads do. I got a reply back in late April from Dr. Altit saying: "I'm not sure I have any funding, but I would love to have a student." I replied — and I think I can still find the email — saying something like: "No worries about the funding — I would compare different lab coat textures if that's what you need." And that kind of started the journey with the NeoCardioLab, which I stuck with all throughout my undergrad. When the opportunity came up to do graduate school with Dr. Altit, I jumped at it.

I think how you shape a mentor-mentee relationship is really important. As a mentee, being organized, motivated, and disciplined is a big part of it. But equally important is finding a mentor whose values and vision align with yours. That takes time. And what I always say — and I think these conversations are important to have with the next generation — is that so many people think research positions are scarce and they just have to jump at the first opportunity. But the reality is: research is endless. There are so many questions to be answered. Do your interviews, get informed, see what's out there, ask the right questions, and then decide. There's no lack of opportunity — you just have to wait until the right one comes along.

I should also acknowledge that this comes from a privileged standpoint. I had the opportunity to work part-time unpaid with Dr. Altit, which not everyone can afford. But within your own reality, try your best to find something that truly aligns with your values.

Srirupa (21:23) Yeah, I can relate to the cold emails — been there, done that. But the relationships that come out of cold emails are just fantastic. It might feel a little like sending a random message into the void, but it shows your interest. And if you get a reply back, it shows that person is interested in helping shape your career. So to any early-career neonatology fellows or graduate students listening — cold emailing is a good habit. You're going to meet people who would never have been in your life if you hadn't taken that first step. That's fantastic. I'm very appreciative of the time you've spent with us today. It's been great talking about your amazing project and your next steps, and visualizing what this work is going to look like going forward. I wish you all the best — there are amazing things in store for you.

Phoenix (22:45) Thank you so much for your time, Rupa. I've really appreciated it, and good luck to you in season two.

Srirupa (22:53) Thank you. Bye-bye.

Phoenix (22:55) Bye.