#1 In Scientific Dialogue With... Dr Sean Carter, Obstetrics & Gynaecology Senior Registrar at King Edward Memorial Hospital

Welcome to In Scientific Dialogue With. The Women and Infants Research Foundation’s (WIRF's) podcast series celebrating the pioneers shaping the future of women’s, maternal and newborn health.

This series spotlights incredible individuals driving innovation – medical researchers, clinicians, nurses, midwives, and professionals in allied health.

Each episode’s guest will discuss their innovative work and how it may transform maternal care and clinical practices from improving preterm birth outcomes to maternal mental health, gynaecology, and more.

So, sit back and join us for In Scientific Dialogue With.

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Welcome to Episode 1 of In Scientific Dialogue With...

I’m your host, Vicki Main. This month, I’m joined by Dr. Sean Carter, a John Monash Scholar and RANZCOG Senior Registrar in Obstetrics and Gynaecology at King Edward Memorial Hospital in Perth. He’s currently completing a PhD at the National University of Singapore, researching the molecular and pharmacological basis of fetal lung maturation to improve antenatal corticosteroid therapy and the management of preterm birth.

Sean has co-authored numerous peer-reviewed publications, holds several international research grants and scholarships, and has received multiple awards for his conference presentations.

Outside of research, he enjoys hiking, surfing, and sharing a whiskey with his PhD supervisor, Prof Matt Kemp.

Welcome, Dr. Sean Carter 

Transcript

Welcome to In Scientific Dialogue With, the Women and Infants Research Foundation’s (WIRF) podcast series celebrating the pioneers shaping the future of women’s, maternal, and newborn health.

This series spotlights incredible individuals driving innovation—medical researchers, clinicians, nurses, midwives, and other professionals in allied health. Each episode’s guest will discuss their innovative work and how it may transform maternal care and clinical practices, from improving preterm birth outcomes to maternal mental health, gynaecology, and more.

So, sit back and join us for In Scientific Dialogue With.

Welcome to Episode One of the In Scientific Dialogue With WIRF podcast. I'm your host, Vicki Main.

This month, I'm joined by Dr Sean Carter, a John Monash Scholar and RANZCOG Senior Registrar in Obstetrics and Gynaecology at King Edward Memorial Hospital in Perth. He's currently completing a PhD at the National University of Singapore, researching the molecular and pharmacological basis of fetal lung maturation to improve antenatal corticosteroid therapy and the management of preterm birth.

Sean has co-authored numerous peer-reviewed publications, holds several international research grants and scholarships, and has received multiple awards for his conference presentations. Outside of research, he enjoys hiking, surfing, and sharing a whisky or two with his PhD supervisor, Professor Matt Kemp.

Welcome, Dr Carter. May I call you Sean?

Dr Sean Carter – 1:41

Yeah, thank you very much, Vicki.

Vicki Main – 1:47

Can you share your journey into women's health research and what inspired you to pursue obstetrics and gynaecology?

Dr Sean Carter – 1:53

My journey into women's health and research began about 15 years ago, when I was a third-year medical student at the University of Western Australia. As part of my medical training, I needed to undertake a research project.

I'd never really been exposed to much research at all, and particularly So with regards to women's health. But I was quite fortunate that through some friends, I got introduced to the Werth team, the women's and infants Research Foundation team, and in particular Matthew Kemp, who's, of course, the current scientific director of worth and a professor in Singapore. But back then, he was a rather scruffy postdoctoral senior research fellow in the lab, and we quite quickly struck up a close friendship, which has continued for the last 15 years. And he took me under his wing and invited me to join the research that year. And so the next thing I really knew was I was walking into a corrugated iron sheep shed on a cold July winters morning here in Perth, and I was standing at an operating table learning to do a caesarean section for the first time on a sheep and deliver a pre term Land and from that moment on really this amazing research team, I got really passionate and enthusiastic about women's and infants research and particularly, of course, preterm birth research, and could see the translation from really what we were doing in that lab and in that sheep shed to really impactful research to try and change outcomes for preterm babies world, worldwide. And so that really led me to try and join the team at every opportunity I could. 

So every year, I would take some time away from medical school or my clinical training and come and join the team here, at worth to continue some of that research, and that eventually led me to undertake a PhD up in Singapore at the National University, under the supervision of Prof Matthew Kent and with the help of A John Monash scholarship. So that's really how I ended up falling into women's research and preterm birth research in particular. But it really was about the special team, the enthusiasm, the passion, and how translatable that research was that really drew me in from a clinical perspective. Of course, I started to get interested in women's health. Women's Health from doing the research and having some really close mentorships with some leaders in the field and obstetrics and gynecology. Through that, those connections, I did a couple of years of adult medicine and surgery and intensive care and. Um here in Perth, before coming across to King Edward Memorial Hospital, which is the only tertiary Center for Women's Health in Western Australia. And it was almost immediate that as I sort of got to know the team that I felt like I'd met my tribe, you know, I'd met my people, and knew from really quite quickly on the this was the specialty for me, for a number of different reasons. Obstetrics and gynecology became my my area of interest. It's a really unique area of medicine where our outcomes, that we aim for, particularly obstetrics, of course, are joy, and that's quite different to a lot of other areas of medicine that deal with, you know, relieving pain or treating chronic disease. So it was that really interesting aspect to the work that we were doing. The other thing I loved about it is that every single day is different in the life of an obstetrician gynecologist. You know, one day, I can be sitting in clinic doing medicine the next, or even that afternoon, we can be doing surgery and operating or doing ultrasounds. So radiology as well as dealing with a lot of critical care and very unwell patients, but a lot of it, as well, is dealing with patients that don't have disease, they're young, fit and healthy, but they are pregnant. So that's a really nice area of medicine that I like about it. It's also very patient centered, so the decision making process is very much around having discussions and educating patients and us coming up with a plan together, which I really enjoy about this specialty. And of course, we work in teams, so you're never really alone in obstetrics and gynecology. We have great working environments where they the work is also do with other members of other specialty teams and experts in their own fields, like midwifery and nursing staff, and that's quite unique to obstetrics in particular. So that really special connection that we have, particularly with midwives, is something that I really, really enjoy and some of my best friends, the midwives here at communities that have really taught me most of what I know through my training. There's another aspect to obstetrics, particularly on labor ward, that I enjoy, which is actually sounds a bit odd, but somewhat a lack of control, so you really don't know what's coming through the door every day, and that leads to a lot of excitement and a lot of adrenaline, which is actually really quite fun, makes makes for one fun workplace, especially with that team environment. So I'm very lucky to love my job. And no matter what kind of day I've had before or what kind of night I've had before. I always enjoy coming back into the hospital every day, so I'm very privileged to be able to have

Vicki Main-  1  8:06  

that fantastic so with approximately 15 million pre term babies born globally each year, and one in 10 babies are born pre term worldwide, what do you see as the most critical challenges in tackling preterm birth, both globally and regionally.

Dr Sean Carter -   8:26  

Yeah, look preterm birth. It's staggering. Those numbers for anyone listening. Preterm birth is when a baby's born too early or before 37 completed weeks of gestation. And depending on where you're around the world, that can be down to really the limits of viability, and that changes. But here at King Edwards, that's around 2223 weeks, depending on some factors. So this is a global health issue, and unfortunately, those numbers are probably from about 10 or 15 years ago, and they're only continue to rise. So even more babies are born prematurely every day around the world. And this is a disease that affects everyone. It's indiscriminate, but it certainly unfortunately affects the most vulnerable patients in our communities more so. So it's a really terrible disease. It's still the leading cause of death and disability for children under five worldwide, and that's not changing. There are lots of challenges around the management and the prevention of pre term birth, and this speaks to women's health in general, is that we know so little around preterm birth, but one of the challenges is that we don't understand normal labor at term, which is, I think is an obstetrician shocking, that we don't understand a normal process that every pregnant patient will go through. You know, we have some ideas around Labor and how that's initiated, but we don't fully understand the mechanisms in in women. And so when you don't understand normal, it's extremely difficult to understand a disease process or a pathology like preterm birth, because of we have no normal to compare it to. The other issue with preterm birth is it's the end result of a number of different conditions. So really it is an umbrella term for lots of different diseases in pregnancy that end up leading to premature birth. So we're not just dealing with one condition here. We're dealing with multiple and that makes it obviously more difficult to treat really, I think this is unfortunately about overall, there's a gross misrepresent or under representation of women's health and women's self research in the literature and in Public awareness, and I think that's actually the greatest challenge that we have, is that lack of research, that lack of awareness and that lack of funding for women's health research, and that's what we need more of. That's how we need to tackle this problem. Is that we need more awareness, we need more research, and to be able to do that, we need more funding. So overall, I think these are some of the general ways in which we can try and tackle this. Jim,

Vicki Main -   11:28  

Thank you for your insights there. So how does your research contribute to addressing these issues on both the local and global scale?

 Dr Sean Carter - 11:38  

So our team, and particularly my PhD is focusing on one of the main treatments that we give to women at risk of preterm birth being antenatal steroids. So any woman that comes in that's at risk of preterm birth around the world will be administered these drugs, and they primarily work by maturing the fetal lung. The biggest hurdle that primary babies have to life is breathing, because their lungs are too stiff. They can't perform gas exchange. So these babies really struggle to breathe. So we've known for the last 50 years or so the antenatal steroids improve breathing, and because of that, they improve survival. So you know, however, despite using these drugs for 50 years, we are increasingly finding that there's many potential issues with antenatal steroids. Firstly, no one around the world, despite 50 years of use, can agree on the drug to use, the way or the dosage of which drug we use, and the way we thought we'd give it in the particular regime, which is pretty surprising, because these are some of the most widely prescribed drugs in Pregnancy. Wow, yeah, so part of our research is trying to address that issue in terms of which drug we should use and which dose and regime we should use. The other aspects to our research is starting to investigate some of the off target or adverse effects of these drugs, particularly on other organs. So obviously we're using these drugs to mature the lung, but we are increasingly finding that these drugs affect every single other developing organ in the fetus, and some of them are particularly troubling, particularly with regards to brain development and things like that. So part of my research is about optimising this important therapy. We know these drugs are great benefit when they're given to the right patient at the right time, but we're trying to improve how they're given and to which patients they're given to, and really trying to understand how these drugs work on a molecular basis, because hopefully in the future, we can understand that better and come up with more targeted therapies to improve the outcome so the benefits from these drugs in terms of survival and lung maturation, but without some of those off target potentially damaging effects.

Vicki Main -   14:19  

Thank you. That's fascinating. How have your experiences at King Edward Memorial Hospital shaped your research in this area?

 Dr Sean Carter -   14:29  

Yeah, well, so King Edwards is the, as I said, the only tertiary unit right now in Western Australia. What that means is that all women at risk of having extreme preterm birth, particularly under 30 weeks, or particularly under 28 weeks, will be transferred to King Edwards from around the state, so that can be as far as you know, Broome kananara, or further south as Esperance. Say, you know, or even further, so we have a centralization of all of these women risk of extreme preterm birth, and from that, we do all of these difficult, extreme preterm deliveries. So as a trainer, you get a unfortunately, well, whichever way you look at it, you get a large amount of experience in dealing with preterm birth, and that has an effect. So you know, it's not uncommon to be having to do an emergency cesarean section on a patient at King Edwards that's 23 or 2425 weeks, and delivering babies that fit in the palm of your hand, that see through, that are not breathing and delivering that baby and handing it to our colleagues, the neonatologists, that are in the operating room right behind you. It's an interesting situation that operating room, we turn the heat up because of these babies can't control their temperature, so it's very, very hot in that operating room. And when we there's a lot of people there, obviously there's Midwifery, nursing staff, multiple neonatologists, and, of course, the obstetric team and the anesthetists. There's a lot of people there. And when we deliver these babies, we hand them to the neonatologist, and you can hear them behind you working on these babies on the neonatal cots, as we still have to operate and take care of the mother. And that's a really emotional experience hearing these things in the background and trying to resuscitate these babies as you're still having to operate on a mother. It's then that, you know, after the operation, that we go and see the families and we counsel them as a team, and just seeing the impacts of that extreme preterm birth, and really most preterm birth has on patients, on families, was a huge motivation for me to try and change this, this disease and the outcomes that we have for primary babies.

 Vicki Main -   17:15  

You're currently completing your PhD at the National University of Singapore on the optimisation of antenatal steroids. Can you tell us more about these drugs and what they are used for and what challenges remain in addressing the long term health of preterm infants?

 Dr Sean Carter - 17:33  

Yeah, absolutely. So. Firstly, one of the biggest hurdles to life that premature babies face is breathing because of their lungs are too immature. They're they're too stiff and they're they're not mature enough to undertake gas exchange. So luckily, we have a treatment that we give to any women there, or any woman that is at risk of preterm birth around the world in antenatal steroids. And these are drugs that were first developed or first discovered, sorry, back in the 70s in New Zealand. And we know from a lot of clinical trials that over the last 50 years, these drugs very work very well to mature the fetal lung, and because of that, they improve that baby's ability to breathe and then, therefore survival. It's really interesting though, that despite 50 years of clinical use, no one around the world can decide on which is the best antenatal steroids to use. So there's a number of different drugs that come under the term antenatal steroids. We don't know which is the best dose to use and which is the best regime to use. So there's a lot of wide variation around the use of these drugs, despite them being one of the most commonly used drugs in obstetric practice around the world. So that's one of the sort of interesting things in which we are trying to look at advising and discovering or investigating what is the best drug and what is the best or the safest dosage to use. The other issue with these drugs is that in obstetric practice, we are not, unfortunately, very good at deciding which women are at risk of preterm birth and are going to then go on and deliver preterm versus those that might come into hospital contracting or with ruptured membranes. And we think are at risk of preterm birth, but actually stay pregnant up until term. So if you look at the trials, we actually get this wrong about half or up to half of the time. And so in that case, we're potentially exposing women, or up to half of the women at risk of preterm birth, of giving them steroids with no real benefit. Yeah, and that's an issue, because we're increasingly finding with steroids that there are many off target, potentially adverse effects from these drugs. So we know that they work very well when given to the right patient at the right time in terms of improving survival and lung maturation. But we also are increasingly finding that there is some off target effects on particularly things like brain development, that we really need to understand further and have some more nuanced discussions around with patients before we give these so a lot of our research is looking into some of those aspects.

 Vicki Main -   20:41  

Yeah, can you tell us a bit more about how your research might contribute to the developing more targeted, safer antenatal steroid treatment protocols for preterm births?

 Dr Sean Carter -   20:53  

Yeah, absolutely so. Part of my research is looking at how these drugs work on a cellular level, molecular level, which is sort of surprising, because, as I said, we've been giving these drugs for 50 years, and we don't understand, really on a deep level, how they work to mature the fetal lungs. So part of our research is trying to do that, to try and deep, do a deep dive into how they work on a cellular level, so that we can understand and then hopefully, in the future, come up with a targeted therapy that only matures the lung but doesn't have some of these off target effects. So that's some of the work that we are quite excited about and looking forward to completing into the future. Yeah,

 Vicki Main  21:38  

thank you, and you recently published a paper investigating the use of antenatal steroids in Singapore. Can you tell us more about this research?

 Dr Sean Carter -  21:50  

Yeah, so Singapore is a great place to do research. It's great place to eat pepper crab and drink ice cold Tiger beers. But it's also it's really interesting to study steroids there, because they have, as a nation, a very unique dose of antenatal steroids that they give to women there. It's a quite high dose compared to other areas of the world, given over a relatively short duration, compared to places like Australia and New Zealand, the that regime has never been studied in large clinical trials, so we undertook a study investigating that, and we're interestingly able to show that the particular antenatal steroid that they use, dexamethasone is potentially not as effective at maturing the fetal lung as the drug of choice that we use in Australia, which is beta methasone at that dose that they're using. So in this paper, we were able to show that a reduced dose of antenatal steroids, and particularly using beta methasone Rather than dexamethasone, maybe best for lung maturation. But we also looked at brain development, and we were able to show that, again, a lower dose of betamethasone used in Australia is potentially much safer for brain development and neurodevelopment for these preterm babies, as opposed to the very high dose of dexametha Dexamethasone that they were using in Singapore today.

 Vicki Main -   23:29  

Wow, that's fascinating. And what has been the wider research community's response to your findings on antenatal steroids, and particularly regarding the long term risks.

 Dr Sean Carter-   23:42  

Yeah. So, you know, medicine is always slow to change, so there was a lot of talk about this paper when it came out in Singapore, but I'm very pleased to say that there has been a lot of enthusiasm about changing the way that they're giving antenatal steroids in Singapore as a result of this paper, and that's led to a another paper that we've written as a consensus statement on changing these drugs and the way in which they're given in Singapore to be more in line with a lot of the rest of the world, in particular with Australia and New Zealand. So we're very pleased to be able to say that it looks like there will be a drug change and a dose change in Singapore to potentially a more effective and safer regime of adenosine asteroids use there.

 Vicki Main-   24:37  

Brilliant, brilliant work. Well done. Following on from this, I understand that you've developed, recently developed, a maternal blood test to predict fetal lung maturation. Can you tell us more about the important study and how it might be used clinically?

Dr Sean Carter-   24:55  

Yeah. So as I was saying, one of the issues with antenatal steroids is that. And we often expose, you know, up to half of the women that we think are at risk of preterm birth to steroids when they don't need it. And we know these drugs work less effectively the closer you get to terms. So the benefits really drop off after sort of 3435 weeks of gestation. And that's, you know, presumably, because of a lot of these babies already have mature lungs at that gestation. So there really isn't a great deal of benefit, we would argue, in those late pre term births, sort of over 3435 weeks. But unfortunately, in clinical practice, we don't have any minimally invasive or non invasive way of deciding whether or not a baby has mature lungs or not when they're still in utero. And because of that, we wanted to develop a minimally invasive or blood test, a maternal blood test, that could predict fetal lung maturation and give us some understanding about that, so that we could then use that result to decide whether or not a particular patient needed steroids or not. So really, we're trying to use this to optimize patient selection for steroids. This test, in some ways, is a biomarker into into the womb, so it gives us information about how a baby is maturing, particularly, of course, lung maturation. So it's a new sort of it's a new window into intra uterine development. And hopefully we can develop more tests the looking at other organ development, so it doesn't have to just necessarily be about lungs, but we can also look at other organ development depending on the situation,

 Vicki Main-   26:46  

moving on to intrauterine infections, these are the leading cause of preterm birth. And can you share more about this and how, with regard to your research, what role do early inflammatory markers play in the tiny detection and prevention of this condition, and how might these findings inform current clinical practices?

 Dr Sean Carter -   27:08  

Yeah, sure. So intrauterine infection and inflammation, or Coronavirus, as you said, is is a leading cause of preterm birth, so naturally, we got quite interested in looking at this condition, and it's very interesting, when you look at the current clinical tests for how we decide whether or not a patient has intrauterine infection and inflammation, they actually perform really, really poorly. So we're not good at actually deciding which patient has this condition and which patients don't. A lot of the criteria that we use currently rely on things like a mother's temperature going up, or her respiratory rate, so how quickly she's breathing, or her heart rate, so the maternal heart rate, or even the fetal heart rate, and a lot of these things can go up for reasons that aren't related to infection or inflammation. So really, we don't have good markers at present, even blood tests are not very accurate in diagnosing this condition. And the best treatment that we have, or sorry, best test that we have is amniocentesis, which involves putting a needle into the abdomen, which is obviously quite invasive and can be potentially painful, obviously to the patient, which is not often done. And there's a number of issues around not having a good test for injury and inflammation and infection. One is that we don't have good treatments for this condition, so if we suspect it, the only thing that we can do is administer antibiotics rapidly to the mother and then precipitate an urgent delivery of the fetus, because if this baby is infected, we know that this can lead to brain damage, so the only treatment we have is is delivering. The problem is, if we don't have a good test, we often deliver babies incorrectly, potentially that don't have infection, and we expose them and the mother to antibiotics. The flip side as well is that we often miss babies that have infection, and that's a subclinical infection, so we don't see it until that baby is very, very unwell. So there's a missed opportunity there. So we got interested in trying to improve these tests to increase the accuracy so that we could pick the babies that do need delivery and treatment, as opposed to those babies that we can potentially monitor and avoid delivery.

Vicki Main - 29:55  

Yeah, that's fantastic. And I know when I was doing my own background research. Into the whole notion of intrauterine infections. It seems that there was, you know, things like, as you mentioned, brain damage, sectors and cerebral palsy, and there was various, various knock on effects of these things. So it's such important the research that you're doing, Sean, in this area. It's fantastic given the significant neonatal risks associated with coronaviruses such as brain disease and SEPTA. So how does your research in early detection and inflammation aim to improve neonatal neonatal care strategies, particularly for extremely pre term infants?