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#203 - The Giants of Neonatology - Fighting for Air (Pr. Ola Didrik Saugstad)



Hello friends 👋

Hey everyone, it's Ben here. In our latest episode of The Incubator podcast, Daphna and I had the privilege of interviewing Professor Ola Didrik Saugstad, a true giant in the field of neonatology. Professor Saugstad took us on a fascinating journey, sharing his groundbreaking research on hypoxanthine as a marker for asphyxia in newborns and his pioneering work on resuscitating babies with room air instead of pure oxygen. It was incredible to learn how he challenged the long-standing dogma of using 100% oxygen for resuscitation, despite facing initial skepticism from the medical community. Through his unwavering determination and collaborative efforts with researchers worldwide, Professor Saugstad's findings ultimately led to a paradigm shift in neonatal resuscitation guidelines. He emphasized the importance of being receptive to new ideas, conducting rigorous studies, and promoting teamwork in research. We also discussed the challenges of conducting clinical trials in an increasingly complex era and the crucial role of ongoing international collaboration in addressing the remaining questions in neonatology, especially concerning optimal oxygen use in preterm infants. Professor Saugstad's inspiring story showcases the remarkable impact that dedicated researchers can have on enhancing care for our most vulnerable patients.

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Short Bio: Ola Didrik Saugstad (born 1947) earned his MD (1973) and PhD (1977) from University of Oslo, Norway. In 1980–81 he was post doc with a Fogarty grant from National Institutes of Health at Division of Neonatology, Department of Pediatrics, School of Medicine, University of California, San Diego. From 1986–2017 he was senior consultant of Neonatology at Oslo University Hospital and from 1991–2017 professor and Director of Department of Pediatric Research, University of Oslo. He was visiting research associate at the Cardiovascular Research Institute at University of San Francisco 1986 and from 2018 Adjunct Professor of Pediatrics, (Neonatology) at Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Chicago Illinois. His research in Sweden and Oslo, and how this changed the present concept that newborns in need of resuscitation at birth instead of given pure oxygen should be given air. This discovery resulted in new international guidelines, improved resuscitation routines, and prevented the death of several hundred thousand newborns each year. Saugstad has traveled all over the world giving lectures about newborn resuscitation and health. He has been given numerous international and national awards, such as the Landmark Award by American Academy of Pediatrics (Perinatal section). He is an appointed honorary member of a number of national associations and an honorary doctor and professor at international institutions. In addition to his engagement for the smallest among us, Saugstad has been involved in the debate about Biotechnology and Chronic Fatigue syndrome.


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Here are some of Pr Saugstad's many publications:


Aasen AO, Saugstad OD.Circ Shock. 1979;6(3):277-83.PMID: 498432

 

Meberg A, Saugstad OD.Scand J Clin Lab Invest. 1978 Sep;38(5):437-40. doi: 10.1080/00365517809108448.PMID: 705228

 

Saugstad OD, Bo G, Ostrem T, Aasen AO.Eur Surg Res. 1977;9(1):23-33. doi: 10.1159/000127922.PMID: 14834

 

Saugstad OD, Aasen AO, Hetland O.Eur Surg Res. 1978;10(5):314-21. doi: 10.1159/000128021.PMID: 30633

 

Saugstad OD, Ostrem T.Eur Surg Res. 1977;9(1):48-56. doi: 10.1159/000127924.PMID: 844465

 

Saugstad OD.J Oslo City Hosp. 1977 Mar;27(3):29-40.PMID: 845718 No abstract available.

 

Saugstad OD, Schrader H, Aasen AO.Brain Res. 1976 Aug 6;112(1):188-9. doi: 10.1016/0006-8993(76)90349-8.PMID: 947488 No abstract available.

 

Saugstad OD.Pediatr Res. 1975 Apr;9(4):158-61. doi: 10.1203/00006450-197504000-00002.PMID: 1143950

 

Saugstad OD.Pediatr Res. 1975 Jul;9(7):575-9. doi: 10.1203/00006450-197507000-00004.PMID: 1161346

 

Saugstad OD, Hallman M, Abraham JL, Epstein B, Cochrane C, Gluck L.Pediatr Res. 1984 Jun;18(6):501-4. doi: 10.1203/00006450-198406000-00002.PMID: 6610852

 

Saugstad OD, Rootwelt T, Aalen O.Pediatrics. 1998 Jul;102(1):e1. doi: 10.1542/peds.102.1.e1.PMID: 9651453 Clinical Trial.

 

Saugstad OD, Kroese A, Myhre HO, Andersen R.Scand J Clin Lab Invest. 1977 Oct;37(6):517-20. doi: 10.3109/00365517709101840.PMID: 10733408

 

Saugstad OD, Ramji S, Irani SF, El-Meneza S, Hernandez EA, Vento M, Talvik T, Solberg R, Rootwelt T, Aalen OO.Pediatrics. 2003 Aug;112(2):296-300. doi: 10.1542/peds.112.2.296.PMID: 12897277 Clinical Trial.


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


Ben Courchia MD (00:01.222)

Hello everybody. Welcome back to the incubator podcast. We are back today with a new episode from our series, the giants of neonatology. We have the pleasure of having on with us, Professor Ola Sokstad from Norway, Daphne Hawe this morning.

 

Daphna Yasova Barbeau, MD (00:16.931)

I'm doing well. We love the Giants series and we certainly have a giant in the studio with us today, don't we?

 

Ben Courchia MD (00:24.922)

Absolutely. Dr. Sokstad, thank you so much for making the time to be on with us today.

 

ola Saugstad (00:29.582)

Thank you so much for having me. It's a great honor and a pleasure to be here as your guest.

 

Ben Courchia MD (00:36.354)

The pleasure is all ours. I'm gonna introduce Your I could I could spend the hour reading your bio so I'm gonna try to give a Cursory version of your bio so that people can actually get a glimpse as to the work that you've done and the impact that You've had on the field You earned your medical degree in 1973 and your PhD in 1970 1977 from the University of Oslo and you went in 1980 to get your postdoc

 

Daphna Yasova Barbeau, MD (00:42.191)

That's right.

 

Ben Courchia MD (01:04.694)

with a Fogarty grant from the National Institutes of Health at Division of Neonatology Department of Pediatrics in the University of California in San Diego. You have done tremendous work when it comes to neonatal resuscitation. Your research in Sweden and Oslo has really changed the concept that newborn need resuscitation at birth with pure oxygen.

 

And maybe you've allowed this transition to happen where we actually perform neonatal resuscitation with much less oxygen and more closer to room air. You have traveled all over the world. You've given lectures about newborn resuscitation and health. You've been given numerous international and national awards, such as the landmark award by the American Academy of Pediatrics. You have

 

You're an appointed honorary member of a number of national associations and an honorary doctor and professor of international institutions. Dr. Sokstad, thank you so much for taking the time to be with us this morning. I wanted to begin this conversation by talking about the early stages of your life. You grew up in a very academic environment. Your your father was a psychologist. Your mother was in education.

 

Can you tell us a little bit what it was like to grow in this and to grow up in this environment?

 

ola Saugstad (02:26.766)

Well, I think it was basically it was very stimulating, but you know, when I was a boy, I didn't think about it. But I have to mention also that which you didn't mention, I spent two years in Chicago when I was a small boy from three to five years because my father took his PhD.

 

Ben Courchia MD (02:46.371)

That's right, because your father was... Did that have any remaining lasting impact on you?

 

ola Saugstad (02:50.758)

Yeah, so my father took his PhD in psychology.

 

Yeah, I think so, because I always felt I had a very close relation emotionally to the United States. And of course, at that time, although I was only five years, I spoke fluent American, and then I forgot it. But I always felt the kind of US is my second home country. And of course, when I grew older, I realized I was brought up in a

 

Ben Courchia MD (03:11.478)

Mm-hmm.

 

ola Saugstad (03:25.262)

perhaps a special family. My father was a professor, I had two uncles who were professors, and my grandfather was a professor and director of the University of Oslo. To go back to my mother's family, there are academicians and priests for 200 years. So, of course, now when I'm older, I...

 

I appreciate that background more and understand it was a privilege to be raised in such an environment.

 

Ben Courchia MD (04:08.062)

Considering the quality of the work that your parents have accomplished, did they look down on your decision to pursue a career in medicine?

 

Daphna Yasova Barbeau, MD (04:18.807)

Hahaha!

 

ola Saugstad (04:20.382)

No, no, I think you well, you know, I am I was very determined. I from I was 12 years old. I decided I want to be a doctor and there was no discussion about it. And no, I think they I mean, and one of my privileges was that I learned very early in life that you should follow your kind of your calling, your interests. And if young people.

 

Daphna Yasova Barbeau, MD (04:29.925)

Hmm.

 

Ben Courchia MD (04:32.094)

Mmm.

 

ola Saugstad (04:50.402)

come up to me and ask for advice, I say the same. Follow your interest. And I think that's the most important.

 

Ben Courchia MD (05:01.999)

Was there an experience that prompted you at the age of 12 to fall in love with healthcare, with medicine?

 

ola Saugstad (05:09.178)

No, I don't think there was anything special. I actually, I was very, I also want to be, become an archeologist, but for a brief period of my life, but then I decided to become a doctor. So, no, I don't know. I had two uncles who are doctors. So, but I found, you know, I was interested in, in

 

Daphna Yasova Barbeau, MD (05:19.939)

Hehehehehehe

 

Ben Courchia MD (05:31.733)

Mmm.

 

ola Saugstad (05:36.558)

humans but I was interested in science so I found this was a kind of a unique combination medicine and at that time I was not thinking about it.

 

Daphna Yasova Barbeau, MD (05:50.328)

You know, I wonder.

 

Daphna Yasova Barbeau, MD (05:55.151)

No, I was wondering, a lot of us in medicine, we have children, right? And we talk a lot about, are our kids gonna go in to medicine or how do we balance wanting our kids to be successful but not too much pressure? That's a big conversation, I think, for parents these days. And it sounds like you had quite a supportive family despite this kind of academic pedigree. And so.

 

I wonder if there were any particular things that were really supportive in your childhood, your kind of young adulthood, adolescence that helped kind of set you on this path. I think one that was quite academically rigorous, but I think in terms of science and thinking of new solutions, we really have to.

 

foster this kind of creativity in our rising scientists so that their minds stay open to new opportunities.

 

ola Saugstad (06:55.398)

Yeah, that's true. I said, I think nobody really questioned my wish to become a doctor when I grew up, because I didn't discuss it with anyone. I just decided I want to do that. I changed, when I went into high school, I changed school to get, because it was very competitive to get into medical school in Oslo. So I had from early

 

In high school, I had to really get good grades. And so I changed school and I was very determined. But I had another interest, which was as strong as my interest for medicine, that was soccer. I was a passionate soccer player from I was eight, nine years old and I was very ambitious. So I tried to combine that with medical students and

 

Ben Courchia MD (07:27.94)

Mm-hmm.

 

Daphna Yasova Barbeau, MD (07:40.789)

Hmm. Mm-hmm.

 

ola Saugstad (07:52.778)

studies and Yeah, so I had two passions

 

Ben Courchia MD (08:00.03)

I'll have more questions about your perspective on football afterwards. Cause as a Frenchman myself, I cannot say soccer. I'm so sorry. We'll, we'll, we'll have to, we'll have to stick with football. But why in unitology then? I was looking at your, at your family history and I thought for sure psychiatry was in line for you with a family dedicated to education and the father who was a prominent psychologist. At what point do you say, I want to treat children, I want to help.

 

ola Saugstad (08:04.233)

Okay.

 

Oh, yeah.

 

ola Saugstad (08:12.18)

Yeah.

 

Ben Courchia MD (08:28.882)

kids and babies.

 

ola Saugstad (08:31.306)

Well, that was during my medical studies, medical school, because I was extremely interested in biochemistry, for instance. And I also, from when I was young, I had written about that in my biography. When I always felt I got contact with children, I felt that children needed protection.

 

And then I found this unique combination of children in biochemistry in pediatrics. And I didn't have any clear, you know, wish or wish to go into neonatology, but I just by my chance, I would say I got this offer at my last year in medical school in Oslo to go to Sweden.

 

and start research on pyrenic asphyxia with the famous professor of pyrenic medicine, Jostar Hult. So that was serendipitous, I think. But then I decided this is what I want to do. And I want to dedicate my life, at least my professional life, to new ones.

 

Ben Courchia MD (09:59.966)

Mm-hmm. Your research work is obviously something that we wanted to talk to you about. You have truly made an impact on how we resuscitate babies at birth by moving us away from using 100% oxygen on babies who were suffering from asphyxia, hypoxemia. I think there's an interesting story between neonatology and oxygen. I think we've...

 

learn, we used to love oxygen, then we learned to hate oxygen, then we sort of recently have come to this sort of middle ground or this marital status where we're like, we understand that too much is probably not good and not enough is probably not as good either. Can you tell us a little bit when you're embarking on this work, looking at oxidative stress and so on, is that something that is in vogue? Is that something that's the trend at the time to try to really look at?

 

ola Saugstad (10:27.715)

Yes.

 

Ben Courchia MD (10:55.366)

the effects of oxygen or are you feeling like you're taking an unusual path in neonatal research?

 

ola Saugstad (11:04.322)

Well, yeah, it's true. I mean, the history of oxygen in neontology is fascinating and quite dramatic, as you know. And I was not, I was not interested in, in oxygen per se. When I, when I started my research, I, I was interested in asphyxia. And the aim of my, my doctoral thesis, which I started in Sweden in Uppsala, was to

 

Daphna Yasova Barbeau, MD (11:27.044)

Mm-hmm.

 

ola Saugstad (11:34.926)

find a biochemical indicator of asphyxia. At that time, we had APTAR score and we had acid-base balance, but not more than that. So my supervisor, he had very high ambitions and I was just finished medical school, but he had high ambitions that all are you, you have to...

 

you have to kind of invent or find a biochemical APCA score. So I embarked on that and I started to measure this metabolite, which is called hyposanthin. And hyposanthin is a purine metabolite. It's a breakdown product from ATP. So I was thinking that if we can measure

 

Daphna Yasova Barbeau, MD (12:08.645)

Hmm.

 

Ben Courchia MD (12:21.732)

Mm-hmm.

 

ola Saugstad (12:30.894)

hyposanthine in body fluids you kind of get an estimation of the energy status of the cell because you know the ATP is intracellular so we cannot measure that in body fluids so I thought that maybe hyposanthine kind of could reflect the ATP level.

 

Ben Courchia MD (12:52.902)

Mm-hmm.

 

Daphna Yasova Barbeau, MD (12:58.907)

Thanks for watching!

 

ola Saugstad (13:01.038)

Now the problem was that there was no methods to measure hyposanthine at that time in butterflies. So my supervisor who was an expert on PO2 electrodes and he suggested that we should measure the oxygen consumption when hyposanthine is oxidized to uric acid in the presence of the enzyme santhine oxidase.

 

I started to work on that and I was able to actually to establish this method to measure hypersentin in plasma of newborn babies and I needed only 0.2 milliliter of plasma and I was able to measure this very fast. So that was the starting point and then I...

 

I started to measure hypersentin in an umbilical cord of newborn babies who had suffered asphyxia compared with controls on asphyctic babies and found that asphyctic babies had significantly higher, actually almost fivefold higher, hypersentin levels. So that was the start and that was my starting point to work with asphyxia and to find an

 

indicator of asphyxia, biochemical indicator of asphyxia.

 

Daphna Yasova Barbeau, MD (14:35.783)

I think it's such a good reminder of how far neonatology has come. I mean, really what you were doing in the fact that you mentioned it was 0.2 MLs, right? We're so judicious about how much blood we take from babies, but this was really a time where, I mean, frequent labs were not a part of the routine management. We just didn't, you know, have those opportunities. Um, so it's just so interesting that that's, uh, you know, how your career started. Um,

 

I wonder if you can speak a little bit then to how did you get more involved with the resuscitation side of things.

 

ola Saugstad (15:12.118)

Yes. Yeah. So I went back to Oslo and I wanted to kind of pursue this, follow up this new observation about hyposentine. So I got a position as a research fellow at the Institute for Surgical Research at the University of Oslo. And there I started to...

 

experimental studies. So I measured hyposanthin in animals, for instance, pigs, piglets during hypoxia and was able to show that hyposanthin is increased. And then we did a study which was for me very important. We measured hyposanthin during recitation of, we had animals with endotoxic shock.

 

and we resuscitated them and we were actually measuring something completely different. We were measuring proteolytic enzymes. So this was a colleague of mine, but I was helping him and I said, do you mind if we resuscitate the animals at the end of the experiments and I take some

 

And we did and what I saw was that hyposanthine increases exponentially during the first 10-12 minutes. Very rapid increase in hyposanthine. At the same time I read the paper of Friedrich and McCord from the US showing that

 

is an oxygen radical generator when sentin is oxidized to uric acid oxygen radicals are generated and hypersentin is the step for hypersentin so then I of course it was quite easy to understand that if hypersentin is oxidized to uric acid it generates free radicals

 

ola Saugstad (17:41.842)

So of course if you have a very high hypersanthine concentration in the body fluids or in the tissues and you then give oxygen then I understood that this might be detrimental because the more hypersanthine you have the more free radicals will be generated. So this we published this in 1979 and in 1980.

 

I suggested this in another study. So that was kind of the first time we suggested that the combination of hypersanthin and oxyfin might be detrimental. And then, yeah.

 

Ben Courchia MD (18:27.089)

I was going to disagree with you because it doesn't seem that straightforward. I think the connections you were... But because I think what you're describing...

 

Daphna Yasova Barbeau, MD (18:32.479)

It doesn't seem easy at all.

 

ola Saugstad (18:34.594)

Okay. Well, I then I have to tell you, I, yeah, I had studied some biochemistry in addition to medical school. So maybe it was easier for me to grasp this.

 

Ben Courchia MD (18:44.734)

Mm-hmm.

 

Ben Courchia MD (18:51.552)

Because I think that's interesting that you're looking for this marker of hypoxia, but then to make the connection that this element, the hypoxanthine, could actually be a source of oxygen radicals. And to be clear, you're talking about the hypo oxidase system. I think it doesn't feel like it would be logical for the marker of hypoxia to then be able to generate...

 

to generate this amount of radical. So I think it's quite impressive that you were able to see this disconnection between the two. But I wanted to let you finish maybe from, once you realize that hypoxanthine is a marker of hypoxia but that there's this explosive generation, as you mentioned, of oxygen radicals by the, in the post hypoxic reoxygenation phase,

 

What exactly, when exactly do you make that connection? And when do you clearly see, hey, we need to use then less oxygen at resuscitation.

 

ola Saugstad (19:58.662)

Yeah, well, so this was in 1980. I started my research. I finished medical school in 1973. So this took seven years, but in between I, I had to do my internship. And I started my specialization in pediatrics in 1979. So I was not so active in experimental research for some years, but I had this in the back of my head during these years. And then I, I was able to get

 

grants from the end of the 80s, 86, 87. I got my first grants, I got my PhD fellows. So I recruited two or three PhD fellows and I was interested in testing out the effect of hyper-scientist on the circulation. I have to mention I spent also a semester in San Francisco.

 

at the Institute for Cardiovascular Research in 1986. So I became interested in the perinatal circulation and regulation of the perinatal circulation. I was with the now late Ebran Rudolph, who was an extraordinary man.

 

ola Saugstad (21:18.95)

So then we started to do again some animal experiments with pigs and then piglets and they were not so successful. So I had this in the back of my head that perhaps one should resuscitate with lower oxygen concentrations. But I had not really... I was not so determined that I should...

 

tested out. But then one of my fellows, he had problems with his experiments. We didn't get good results. Then I suggested, why not try to see if he can resuscitate with air. And he did. And it went very well. So we looked at hemodynamic markers and acid-base balance and

 

They did as well with air as with 100% oxygen. And this was the end of the 80s. So in 1991, we published or we presented our first results with newborn piglets resuscitated with air versus 100% oxygen. And I still remember.

 

This was my fellow presented at the European Society for Pediatric Research. It was in Zurich in Switzerland and it was a packed auditorium. And I never forget the reaction because people were so enthusiastic when we presented that. I think people understood that this was a kind of change in a paradigm.

 

So we were able to show that it is possible to resuscitate with air. And then we went on and I realized I had to do some clinical studies. And how could I do that? I talked to my old boss in Sweden, Justar Ruten, and said we have to do clinical studies also. And I didn't have any experience with clinical studies at that time. I had done a lot of...

 

ola Saugstad (23:44.73)

animal experiments, but no clinical studies. So he said, well, I just, I was in contact with, um, a guy in New Delhi, in India, Siddharth Ramji, and he's running a big unit in Delhi. So maybe we can ask him if we want to join us, make a project. So we did, I wrote up a protocol and Siddharth said, yes, he would like to do that.

 

And very quickly he had resuscitated 84 newborn babies with either air or 100% oxygen. And again we were able to show that outcome was more or less similar between these groups. And we published that. Again we went to the European Society of Pediatric Research.

 

Daphna Yasova Barbeau, MD (24:30.037)

Mm-hmm.

 

ola Saugstad (24:44.134)

That was in 1992 now. It was in Sweden. And again, there was a very, very positive reaction from the audience. And we published that in those data in 1993 in pediatric research. And then I was thinking, well, this was only a pilot study. We need a bigger study. So then I started to organize.

 

what is called the RESSR2 study, which was a multi-center study. We recruited 10 centers from six different countries, from India, Philippines, Egypt, Spain, Estonia, Norway, and we got approximately 600 babies who needed resuscitation. And again, we were able to show that

 

those babies have been resuscitated with air did as well as those who had received 100% oxygen and it was a tendency to better outcome in the air resuscitated babies but it was not significant and now and this was published in 1998 and then several other started

 

to test it out. For instance, Max Vento from Valencia. He did some big studies and did more studies in India. So around 2003, 2004, I had sabbatical. I spent that in Spain with Max Vento. And we wrote up meta-analysis. And then we were able to show that...

 

Ben Courchia MD (26:18.567)

Mm-hmm.

 

ola Saugstad (26:42.546)

the mortality was lower in babies resuscitate with air. And that was for me also surprised because I hadn't expected that. I thought that maybe we can show that you can do as well with air as with hand vasoxone. But now we show that there was a 30% reduction in mortality. So that was really a surprise. And now we are...

 

Daphna Yasova Barbeau, MD (27:00.815)

Mm.

 

Ben Courchia MD (27:09.629)

Mm-hmm.

 

ola Saugstad (27:10.73)

And then the first Cochrane review came also in 2004, showing the same. So this, yeah.

 

Ben Courchia MD (27:23.234)

There's actually a very nice article by Max Vento in Neo Reviews in a historical perspective that talks a little bit about this journey that you embarked on. In there, he mentions that the response to the initial results was not always very positive. He even mentions that in 1997, when you were giving a lecture at the European Society for Pediatric Research in Hungary, somebody...

 

ola Saugstad (27:34.166)

Yeah.

 

Daphna Yasova Barbeau, MD (27:38.715)

Mm-hmm.

 

ola Saugstad (27:41.559)

No.

 

Ben Courchia MD (27:50.874)

like stood up and shouted at you because they were not particularly negative. Can you tell us a little bit about what was it like dealing with a portion of the community not thinking that this was the right path for neonatology?

 

ola Saugstad (27:53.442)

Yeah, I see.

 

ola Saugstad (28:09.142)

Well, many people said I was crazy. And yeah, and I, I remember this woman. I was, I had the honor to give the opening lecture of this, this European Congress in Hungary. And she stood up and shouted at me that it was unethical. And my answer was, but it's.

 

You know, use oxygen has never been tested out in a randomized study before. So, so that is, if it's unethical, that is also unethical. Um, so I got some, some such reactions, but mostly people said this was a stupid idea or I was crazy, uh, but then we got more and more results and, um,

 

Daphna Yasova Barbeau, MD (28:43.279)

Mm-hmm.

 

ola Saugstad (29:06.266)

I think people change their attitude. So in 2006, in 2000, I was invited to be part of the panel making the new international guidelines, the ILKOR guidelines. And we met in Dallas. And at that time, I didn't feel we had enough data to say that you should start with air.

 

Daphna Yasova Barbeau, MD (29:07.105)

Mm-hmm.

 

Daphna Yasova Barbeau, MD (29:25.936)

Mm-hmm.

 

ola Saugstad (29:36.918)

it was said that if you don't have oxygen, you may start with air, which I think was a progress. And then in 2005, 2006, new Ilkor guidelines were published and they said that you can choose whether you would use 100% oxygen or air. And then some countries quickly

 

changed their national guidelines. And the first country which changed was Canada. I was in Canada in 2006 and gave a lecture at their national meeting. And then I went to Australia some months later, and Australia changed also. So these were the two first countries who changed from oxygen to air. And many other countries, including my own, were hesitating.

 

Ben Courchia MD (30:29.63)

Mm-hmm.

 

ola Saugstad (30:33.698)

And some said maybe we should pick something in between 40%. But you know, we hadn't tested out 40%. We hadn't tested out 60%. But then more and more countries changed. And actually, US was one of the last countries to change. Not because people are not interested, because many people are interested. I got a lot of support, a lot of interest. I was invited to the United States. I think it was for legal reasons. People were...

 

Daphna Yasova Barbeau, MD (30:40.182)

Mm.

 

ola Saugstad (31:03.254)

didn't dare to do changes and to deviate from what was considered as the standard practice of care. So, but then more and more, you know, I think centers also in US switched to air. And in 2010, Ilkor changed and said that you should start with air for babies.

 

Daphna Yasova Barbeau, MD (31:03.619)

Mm-hmm.

 

ola Saugstad (31:31.578)

only babies term or near term babies. We hadn't really tested this out in preterm babies.

 

So that's the story.

 

Daphna Yasova Barbeau, MD (31:41.091)

Yeah, it's interesting. It's a long history and I really appreciate, I really valued you walking us through that. You're right, in 2010 they said we can start with Roomer, but it was actually not until 2015 where they recommended, Ilcor recommended against hyperoxia starting with 65 to 100%. We talk about this a lot on the podcast.

 

how long it takes from the initial studies that show benefit to getting things to the bedside. This was a perfect example of that. I wonder what are some of your recommendations? How can we shorten the lead time from... I respect that everybody wanted to make sure that you were right, obviously. What do you think is some of the tips to shortening the time from...

 

ola Saugstad (32:12.002)

Well.

 

Ben Courchia MD (32:28.99)

Thanks for watching!

 

Daphna Yasova Barbeau, MD (32:40.269)

you know, bench studies to clinical studies and then being able to get things to the patients.

 

ola Saugstad (32:46.758)

Yeah, well, I often was told that, Ola, you have to be more aggressive. You have to promote this. But, you know, I didn't feel it was my role to promote the Rumei recitation. My role was to present data. And I think that those who present data should not be the same making the changes. So because, so that was very important for me. And then I was also thinking.

 

during these 30 years because it took 30 years to change. That, well, maybe something is wrong with my reasoning here, maybe. And it could be subgroups, could be subgroups, or babies who need oxygen. So I was not so keen to stand up and say that we have to change. Kind of appreciated it took time and that it was more and more.

 

Daphna Yasova Barbeau, MD (33:29.595)

So humble.

 

ola Saugstad (33:45.326)

I knew other studies confirming what we found also. But of course 30 years was too much. And I think we had evidence 10 years earlier or close to 10 years earlier. So yeah.

 

Daphna Yasova Barbeau, MD (34:09.147)

I was just gonna say, we just reviewed a paper this last week on our journal club about the use of hyperoxia in babies undergoing therapeutic hypothermia with HIE. And we're still learning about how potentially detrimental, free radicals can be. But as Ben mentioned, this was kind of revolutionary at the time that you were studying it, not just in neotitinatology, but across.

 

ola Saugstad (34:24.048)

Thank you.

 

Daphna Yasova Barbeau, MD (34:36.376)

And you actually, you wrote a book, The War Over Oxygen. And it says here you describe it as one of the greatest scandals in the history of medicine. Can you speak a little bit to that?

 

ola Saugstad (34:47.926)

Yeah, I think so. I mean, because, you know, there was a dogma. It was a dogma from the end of the 18th century. You know, oxygen was described as an element in 1792 or from Sweden or 1794 by Priestley. And very quickly, they started to use oxygen, treat newborn babies with oxygen. And it was...

 

not much questioning about using 100% oxygen. Michael O'Bladden, the German Neonatologist, he has summarized the history of that and said that for 200 years there was no one really questioning the use of 100% oxygen. And American Heart Association in their Guidelines for Newborn Resuscitation in 1992 said that there is no reason to be concerned giving 100% oxygen

 

during the very brief period of newborn recitation. So that was in 1992. However, in 1998, I was invited to the Hot Topics in Washington for the first time and presented my data. I was very nervous because I knew that there were many critical.

 

persons in the audience and you know all the kind of elite of American nanotoologists were there. So but I gave my lecture and there was a long I've written about that in my book that is a long line of people coming up to queuing up for to the microphone but Mary Allen Avery stood up and she supported me.

 

And she said, I always been concerned about using huntin' was an oxygen. And that was so important. I got the support from the queen of neontology at that time, Mireille Nivry. I will never forget that. And we became good friends till she died some years ago now.

 

Ben Courchia MD (37:06.65)

That's so interesting how maybe sometimes when we have the incentive to speak up, this can have a big impact. So thank you. Thank you for sharing that. Did anybody who did any of the naysayers who didn't think that a roommate resuscitation was a good idea eventually turn around and came to apologize to say, Hey, we were wrong. Sorry for making your life difficult.

 

Daphna Yasova Barbeau, MD (37:13.949)

Mm-hmm.

 

ola Saugstad (37:30.346)

No, no, I don't think so. But you know, I, you know, when it changed, it changed quickly. And I felt really, I was kind of a celebrity very quickly. And I came to Australia in 2007 and I was a cheer as a champion, you know? So I cannot complain. I think, I mean, I think that.

 

Ben Courchia MD (37:32.877)

Hahaha!

 

Daphna Yasova Barbeau, MD (37:37.173)

Yeah.

 

Ben Courchia MD (37:39.751)

Mm-hmm.

 

Daphna Yasova Barbeau, MD (37:45.403)

Mmm.

 

ola Saugstad (37:58.834)

It is important that people have criticism and objections to new ideas. I was fortunate because you mentioned Max Svento, and of course he was a very important part of this. Because he so quickly started to study the same. So we have been very close.

 

Ben Courchia MD (38:07.046)

Mm-hmm. Yeah.

 

ola Saugstad (38:27.79)

collaborators and friends for more than 30 years.

 

Daphna Yasova Barbeau, MD (38:37.467)

I think yours is one really of the perseverance needed for science. And I wonder, you know, there's so many things in neonatology specifically that we take as dogma. We've used that word a few times. And I wonder how do we not make kind of some of these same mistakes when we have somebody in the community who wants to revisit old practices, you know, and say, well, we haven't thought about it from this.

 

side before. How do we promote people looking at practices that haven't been well studied in neonatology?

 

ola Saugstad (39:15.97)

Well, I think that first of all, we have to be open to new ideas. And I think that if we want to say that you want to change practice, or you think your question established routines, you have to study it in a proper way by randomized studies and pilot studies, animal studies first, if possible.

 

which I think is what we want to do and then to do it in a proper way and do randomized studies and multi-center studies. I think that's the only way to do that.

 

Ben Courchia MD (40:05.094)

Ola, we had the pleasure of having at the Delphi conference this year, Professor Atli Mohen, who you know very well, who spoke to us a little bit about how the field of neonatology has reached the era of complexity. And I am wondering if you can talk to us a little bit about how challenging it is becoming to continue to do these randomized control trials as we're just bringing up in the current climate where there are so many variables.

 

The patients are so complex. There's a lot of differences between babies of various gestational ages. How do you feel that research and investigative work in neonatology has changed? And where do you see it go in the next 10 to 15 years?

 

ola Saugstad (40:51.53)

Yeah, well, that's a very big question, of course. And I think Atle Mone, who was one of my first PhD fellows, is a better man to answer these questions. But I think that, you know, yeah, it's true. You have so many complex situations. And again, I think that you have to.

 

You have to make very strict protocols. And but of course, it's more complex now than when I started my clinical studies 30 years ago, or more than 30 years ago. But I think the basis is the same, that you have to, when you do.

 

randomized studies and you have to...

 

ola Saugstad (41:57.258)

Be sure that you have enough power. I've seen so many studies, also animal studies, which do not have power. And then I think it's waste of time and money and it is unethical to do that. Because if you do a study and you can't get an answer from that study, it's waste of time and money and resources. And...

 

So that's one thing, it has to be done in a decent way. And I think I am now, the last years I've been part of a large international group. We are kind of pursuing this, all these questions about oxygen, because there are lots of unanswered questions. And I think in this group with international experts, I think...

 

I think also that's one way to collaborate because we are kind of discussing together and we're trying with first of all we have to identify weaknesses of our own protocols and again we have to do it in a proper way that we have sufficient power and of course we have to adjust.

 

for confounding factors and all these things. I don't know if this is a very good answer to your important question. And

 

Ben Courchia MD (43:35.022)

I think it is. I think what I'm gathering from your answer is that complexity should not deter us from continuing to strive for the type of rigorousness that we've always aimed to achieve in clinical and basic science research. I was talking to people that have worked with you in the past and they mentioned a few things like you set the bar very high, you're very competitive, so I'm not very surprised.

 

by the answer that you've given us about complexity, which leads me to my last question. I'll let Daphna close out the show afterwards. But speaking to people who have worked with you, they mentioned a few themes that I think relate to something you spoke to us about earlier in the episode where you talked to us about your passion for football. I think people who've worked with you said that you're very competitive and that you, they always feel like they're part of the team. They're always...

 

Daphna Yasova Barbeau, MD (44:06.971)

Ha ha ha!

 

Ben Courchia MD (44:33.158)

feel like they are part of a larger body, a group of people. Do you draw a lot from the themes of soccer, football, to in how you manage a research group or a research team? And can you tell us a little bit more about that?

 

ola Saugstad (44:49.518)

Well, I think that's a very good and interesting question because I think we can learn a lot from team sport, soccer, football, European football, because you have to be a team and you have to accept that your teammates do mistakes, but you also have to accept that you do mistakes yourself. And then of course, if you are a good team, you see that you achieve

 

so much more than if you are kind of trying to do everything alone. And actually, when I became a professor, I became head of the Department of Pediatric Research in Oslo. Our national soccer team, which had been very poor at that time, we got a new coach and our soccer team.

 

kind of accelerated and it was at the time ranked as number two in the world, which was incredible because Norway had never had a good soccer team. So I said that if they're able to do that with soccer in Norway, we can do it also in research. So that was really inspiring me. And this coach, I had actually played against him when I was younger. So I knew him a little bit.

 

Daphna Yasova Barbeau, MD (45:52.367)

Hmm.

 

Daphna Yasova Barbeau, MD (46:06.058)

Hmm.

 

Mm-hmm.

 

ola Saugstad (46:18.478)

He was a very good player. So it's true, I think we can learn from sport and we can learn from many other parts of society. And yeah, I'm very happy that because I have been dependent on having a big group around me. I have had 50 PhD fellows totally.

 

My group was the biggest. I had 15 PhD fellows in the group. And it made us very efficient. We published a lot. And people were enthusiastic. And I think people understood that we were kind of also working. We were pioneers in our field. So that was, of course, an advantage for us.

 

Daphna Yasova Barbeau, MD (47:02.014)

Mm-hmm.

 

Ben Courchia MD (47:14.962)

Hmph.

 

Daphna Yasova Barbeau, MD (47:17.207)

Yeah, I love that story about, you know, leadership and really teamwork being a key feature. But one of the other things I took from your answer about, you know, managing the complexity is that collaboration is important. And actually, I mean, you were really a role model in international collaboration before it was so easy to just hop on a zoom call, right? And do this extensive international collaboration.

 

And I think we see that even now in neonatology, we've got amazing groups working on the same things across the globe. And I'm hoping you can give some guidance about how important collaboration across research teams and across international lines will help kind of move the field forward.

 

ola Saugstad (48:11.903)

Coming from a small country, Norway, I very early in my career realized that I need to collaborate with foreign groups in order to achieve what I wanted to. So that was one important understanding. But then I think what is also very important is that

 

some people are following the same track, not only for three years or five years or 10 years, but for 20 years, 30 years, 40 years, and to kind of know the history, and maybe also then it's easier to see where the future direction should go. And I have been privileged because I followed one idea from

 

When I started research till today, basically, follow one idea which I have developed.

 

Daphna Yasova Barbeau, MD (49:19.475)

My last question then is you've really, like you said, seen the whole history of oxygen and neonatology as it stands. Where do we go from here? What are the holes still in the story for oxygen and our work in the NICU?

 

ola Saugstad (49:41.098)

Yeah, so there was some technical problems. Could you repeat that?

 

Daphna Yasova Barbeau, MD (49:47.947)

It cut off. Sure. I said, you know, you've seen the entire history really of oxygen and its use in neonates. And so where do we go from here? Where are the holes in the story of oxygen in the NICU?

 

ola Saugstad (50:03.246)

Well, yeah, we have still many unanswered questions. And first of all, I think it's for the premise, especially those immature babies, less than 28 weeks. We don't know really what the optimal initial FIO2 is for these babies. And we have a lot of discussion about that.

 

And what we know for sure that the most immature babies, they probably need some oxygen initially. We shouldn't start with air for these babies, but we don't know how much we should give them. And we have so far suggested that we should start with 30% oxygen and titrate according to the clinical development heart rate, et cetera. But.

 

But it might be that we need higher to start higher. So this is one unanswered question. And the international group, I'm a part of. We are working on this. But I don't think we have the final answer yet.

 

Ben Courchia MD (51:24.07)

Dr. Saukstad, this was a great place for us to end on, really a tremendous conversation. I've clipped so many things that you've said along this interesting hour, and I think our audience will really enjoy listening to this conversation. Thank you so much for making the time to be on with us this morning, this evening for you. And thank you for sharing your knowledge with us.

 

ola Saugstad (51:50.006)

Well, thank you. Thank you for very interesting questions and for this nice discussion and communication. Thank you so much for inviting me.

 

Daphna Yasova Barbeau, MD (52:02.399)

Our pleasure.

  

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