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Okay. Good morning, everyone. I'm Caroline Delahanty. I'm a pediatrician and neonatologist, and I've been chatting over the last few weeks on various topics. But, um, last week I talked about asthma and cystic fibrosis. So a pulmonary theme. I thought I would continue it this week with today with talking about lung disease in the neonate. And although the slide is entitled neonatal chronic lung disease, I'm going to talk about respiratory distress syndrome a little bit because they're linked together. Okay, So spiritually distressing room of the newborn. Everyone thinks about it as factor deficiency, which it is. But because we are resuscitate ing smaller and smaller babies, we're going to look at the embryology of the lung development because part what's really challenging neonatologists at the moment is that we're finding we're getting Embry a logical Pommery arrest when these babies are born at 22 to 26 weeks, because they basically don't have al viola development. But I have schematic diagrams to show you. So our problem is self acting deficiency, immature al viola development, and we then get this pathological deposition of highline membranes, which is why it also had the old name of Highline membrane disease we can have. It's not necessarily uniform disease. We can have parts of overdistension in the alveoli and eight electricity cysts. So when we're giving inflation pressures, what we're trying thing to do is actually recruit all Al Viola into play, including the basil areas of the lungs. So it's the same as in adults. We're trying to open up all gas exchange Al Viola. The theory is, we manage with oxygen and gentle respiratory support and surfactant replacement. Historically, Um, and I believe all of Europe has changed because there's certainly European respiratory guidelines and the consensus statement in place, which have been running since 2007. But the latest guideline update was 2019 is that we have moved away from intubating and ventilating as the primary mode of respiratory support and the method of giving surfactants the surfactant it's always been given down and the ET tube. It isn't anymore. It's now given by just passing a catheter, and that can be the same catheters that you use for nasogastric feeding. For example, it can be any catheter that you pass into the lungs. You still have to look unfortunately with the laryngoscope. We haven't managed to move to nebulize surfactant, which in a way would be the ideal. But the problem is it doesn't seem to be working unless we've gotten ET tube in place and it's not taken off. We then went through a phase after intubating and ventilation that we would intubate, give the baby a short period of ventilation, give them surfactant, and aim to extubate them within the first hour of life. But even that was causing ventilatory barrow trauma. So, you know, theoretical thinking and clinical evidence is moving on, and we're moving on two different techniques. So this is reviewed nationally and internationally. And here is the reference of the European consensus guideline on the management of respiratory distress syndrome. The 2019 update. America can vary. I don't think they can quite get together, but the American Academy of Pediatrics will give similar information, but they don't quite necessarily have a consensus. I think the most important thing, and we will talk about how to prime the lungs. The most important thing is antenatal steroids. You have to start with the preparation of the mother. You want to have antenatal steroids on board preferentially with 48 hours before the baby is delivered. I appreciate it's not always possible, but what that is doing is the antenatal betamethasone is stimulating through stimulating TSH thyroid stimulating hormone to mature the lung development. So we're trying to speed up and accelerate Al Viola development, bronchial development, and we're also stimulating surfactant production. So we're trying to get some X Ajan iss. Sorry, endogenous. I got that the wrong way. We're trying to get baby itself to develop al Viola cells and to produce surfactant. Obviously, the evidence based on this came from babies that were greater than 27 weeks that have Al Viola. And we have extrapolated that evidence based down to 22 to 26 weeks. But we don't actually have the evidence that anti nasal steroids A is going to embryologically speed them up. They don't have all viola type two cells, so, you know, maybe they have some, but they certainly don't have a lot for them to get, um, their own surfactant production. You want the mom and the baby in the correct place. You want them in the place where you have a neonatal intensive care unit that can deliver respiratory support for for babies. So in the UK and in a lot of Europe, there are centralized service models and they will move to the correct place. I think, uh, uh, Denmark lead the way with this. It was actually the Scandinavian countries that were very pro this but Germany in Brussels, France, the UK, the UK has probably been a bit slow to follow. It still has too many neonatal intensive care units. The aim is not to intubate and ventilate the baby. The aim is to give the baby some continuous positive airway pressure and allow the baby to self breathe and open it up. It's long. It's lungs with support. Ideally, there is a move, but an Australia have done a lot of research in this. So actually, before you even cut the cord while this baby is still receiving oxygen from its mum, which will be supporting from the center supporting the heart rate supporting the fetal breathing. Remember, babies breathe in the womb, there is fetal breathing. Um, while they do that, if you can get seep up on, it's quite difficult sometimes because if this is a section you're going into a sterile environment. If it's a vaginal delivery, it's very busy down there with the midwife delivering the baby and then the neonatologists, trying to get in to put a face mask on seat. Give CPAP delivery. There's a lot of equipment being moved, and you're trying to keep the baby warm. So you're trying to get them on a heated mattress at that point or radiant overheat with the plan plastic bag around the baby. Next week, I'm going to talk about that transitional adaptation, but the transition is really important that you get seep up on straight away so you don't go straight to put in et tube in. When I started, I would go straight away to enter keel to you. Now I have to go straight away to put in CPAP on. We know oxygen, remember is damaging and even high oxygen for a short period is damaging. It damages the brain, okay, but it damages the lungs as well. So you want to start a G. We're not sure where to start, so in turn, babies and babies over 34 weeks you start in air and you titrate up in preterm babies were saying starting 30%. But that is a guess. We don't actually have the evidence for it. It's just the consensus, or will they tend to need a bit of oxygen because they haven't got very good gas exchange, So let's start at 30%. But you want to put a saturation monitor on the baby. I'm going to talk in more detail about this next week so that you are titrating to their saturations and accepting that they're going to take five minutes to come up to 92%. They start at 60. So you know, so to be 60% at one minute is normal. Remember, they've been used in utero hypoxia. So the preparation is all about having oxygen with a blender, so have an oxygen air mix and having the ability to put a saturation monitor on, we like delayed cord clamping. Not only does it give us more time, remember, it reduces the incidence of intraventricular brain hemorrhage and the incidence of babies having the need for additional transfusions. We want them to have blood coming in for storing during that period that the mom gives them blood, and we also know we use We have less problems with BP if we use delayed cord clamping. But the big thing is we don't damage the brain. Okay, All this is about brain. Really? Actually, because you want a baby with a normal neurodevelopmental outcome, I'm going to talk about Lisa, which stands for less invasive surfactant administration. Remember, we don't have this intratracheal tube down, and Lisa is absolutely recommended. If you need greater than 30% oxygen. Okay, do. It's come into place initially. Theoretically, because we couldn't seem to get nebulized the fact and administration to be effective. We don't want to put that endotracheal tube in because we know that even short periods of ventilation cause trauma and fracture of the capillary Alvey ola bed. So we want to put So when the baby is still on CPAP still breathing itself, some units will give them a mild sedative which doesn't stop respiration. Just something to relax them. Some units will actually do it with nothing, and we'll actually do it just with sucrose because the baby responds the to taste to sweetness because their comfort is actually human breast milk. So, baby, it gets it's comfort from human breast milk, and some of that is actually the sweetness effect, which is pacifying a baby and calm in them. So actually, quite often we'll use sucrose syrup as part of our package when we will put a soft catheter down the trachea. So, unfortunately, you still have to put the baby through the process of have another ring a scope in the McGill's forceps. If you can put in it's mouth, there's very much a building evidence base. And I'm going to show you some funnel charts that you get less bronchopulmonary dysplasia, so less chronic lung disease, and you certainly get less pneumothorax. And all these things are leaving, leading to less chronic lung disease, which is important for your childhood and adult life. And we'll come on to discuss why we really want to get rid of chronic lung disease. So this is a picture. What I want you to look at is it still needs equipment in a MB, this baby who is on CPAP Okay, so this baby has the continuous positive airway pressure, but the baby is self ventilating. It does not have an endotracheal tube down, it's breathing on its own, and it's just taken some pressure when it breathes to support maintaining al Viola recruitment. The catheter is put down and you can see it's a very soft, fine catheter. And then this is a factor will be stringent in when the baby's breathing. You don't want to flood the baby. Okay, you don't want to, because it's remember it's volume. You're putting water down into that. You know a liquid down into the lungs so the baby doesn't want to feel as if it's drowned in, so you try to do it gently over a five minute period. We're normally talking about 1.5 mils of liquid going down, but there is now. There are no studies taking place when we may want to put higher volume down to see if that stops the fade out of stuff. Acting. Remember, surfactant is recycled in the body and that the baby won't be very good at recycling factor. It's an energy dependent process. It again requires the are viola cells. So these are the studies. Um, a lot of this was done in Germany, actually, um, so the latest data has come from 2019 and 2020 So it's all very recent and what we're seeing. Although the numbers look small. We're seeing that with Lisa. If you take your one line, hang on. If I take my one line if you look at number one on the horizontal chart, if you swing to the left as you're looking at your screen, it's favoring Lisa. If you swing to the right, it's favoring conventional treatment, which was to intubate the baby and gives a fact and via an ET tube to involve in having a baby on a ventilator and what we're seeing that the need for mechanical ventilation within 72 hours. So if we did nothing and just put the baby on CPAP, which we used to do as well and see if they fail if we know if they're in 30% oxygen, give them some surfactant via the soft capita. They will not fail within 72 hours because what's been happening historically is that we've had failure. As as I can see that you have your hand up. Yes, I had a question. Uh, I think, uh, does the chances of getting a, uh what we call, uh, hospital acquired pneumonia or Mercer or any other stuff is more in the conventional or more in the Lisa. Uh, both have the same outcome that the percentage of the risk can have better infant work. Acquire, uh, hospital acquired pneumonia or, uh, ventilator. Pneumonia. So Okay, so hospital acquired ventilator required pneumonia is more common in babies that have an et tube in and that have ventilation. Now, some of that. A lot of hospital acquired pneumonia. You wouldn't necessarily grow flora from a lot of it can be the mechanical problems. I appreciate. Babies don't don't necessarily cough, but even put in an et tube down and a having to do et suction that destroys celery movement, which is sweeping the mucus up. And what babies and Children do is and what we do. We don't realize we're doing it. We're swallowing mucous all the time that are sillier in our lungs are beated up into our oropharynx. So if you have an et tube down, you will be damaging those sillier. Okay? And if you do suction, you will be damaging the sillier. So it used to be that, uh so I keep going about how it used to be, but I think there's a huge evidence based around neonatal medicine. I think it's a very dynamic specialty. Um, it used to be that the nursing team would be section in babies every four hours. Um, what they called with their cares. Whereas now that they only suction if they think the chest doesn't sound clear. But hospital acquired pneumonia is basically associated with ventilation. You will still get eight electrolysis on CPAP. So one of the reasons that you want to look at your CPAP pressures and I put six centimeters on that slide Uh uh, We will go up to eight. We will go up to nine Australia, Melbourne, do a lot of research. Australia did a randomized controlled trial of using 10 centimeters versus six centimeters to see if it would recruit morale viola I and prevent chronic lung disease because we know eight electrolysis is bad. But what they found is they increased their risks of pneumothorax. So people are very nervous about 10 centimeters, But we're not nervous about eight centimeters, but we start at six, and then we move up. Uh, compared to the, uh, conventional way, uh, the lisa has, uh, less likely to cause, uh, it's susceptible to the pneumonia. Or compared to this, like okay, it's less likely compared to conventional. So Lisa is better. You get less pneumonia because you don't you're not interrupting the sillier that are bringing the mucus up, so it's less likely we're also seeing in this slide that Broncho pulmonary dysplasia, although I appreciate there's a range is moving towards being less less bronchopulmonary dysplasia if you look at where your midpoint of your points are. That 2019 study with a bigger number of babies 16 24 did cross and have a wide range. So I there's still work to be done because ideally, what you want is an adequately powered study. But certainly the data coming through is suggesting this is better and it's been accepted by the European consensus. So if we talk about, go on to talk about bronchopulmonary dysplasia and I'm suddenly realized, I've been talking too much. It's the commonest form of chronic lung disease in infancy. It's big business in infancy, first reported in 1967 and the instances varying across Europe between about 25 55%. Um, it's the C quickly of respiratory distressing homes factor deficiency Highline membrane disease. What should also have there is security suck really of Al Viola development arrest. Okay, so we've got a clinical symptom that's disrupting Alvey your ization and microvascular development leading to abnormal gas exchange and lung mechanics. So although we talk about the viola development, you also need to have the capillary bed vascular development. And remember, these babies naturally have pulmonary hypertension, and they don't want to put the lung, the blood into the lungs. They naturally want to stay in a fetal circulation because these if these lungs are not open, they're not a low pressure environment. And they're not low pressure vascular environment. It's associated. Be term infants. You require mechanical ventilation on oxygen therapy for respiratory distress syndrome. Your textbooks will tell you that you can have a genetic condition where you can have, um, efficiency of surfactant production. I have never seen it. It's extremely rare. But if you have a term baby with significant respiratory distress syndrome and you've gone through infection, pneumonia, all these things, um you're actually then thinking well, actually, if they've been born and if you can't get them off the ventilator. If they seem to be ventilated dependent and it's not a new a muscular condition, do they have a genetics fact in deficiency? Okay, how do we define it? So it was oxygen requirement at 28 days previously. But the problem is, if you're born at 22 weeks and you're 28 days old, you're only 26 weeks. So we've moved internationally, and a lot of this is for research and for monitoring to a definition at 36 weeks. Corrected gestational age, which is a better predictor of lung function at two years. So if you can get that baby out of oxygen by 36 weeks, they're going to have better lung quality, and we define it into whether it's mild, moderate or severe. Okay, so you you want babies, do break. The cohort were very closely monitored. We have to report everything less than 32 weeks greater than 32 weeks because your risks are greater if you're less than 32 weeks. If you have it greater than 32 weeks, you're pretty unlucky, actually. But it's all about 36 weeks post mental, post menstrual age or discharge for the time of assessment and you want to know we also can collect data on Were you treated for 28 days with oxygen for greater than that? But mild is okay. You're 28 days of oxygen, but you're in room air at 36 weeks and I've got the definitions across the board. I'm going to speed up a little bit. Actually, severe bpd, which are the ones that we really worry about, are the ones that actually are in greater than 30% oxygen and are still requiring some pressure to keep their al viola open. So these are babies that we cannot wean of what we call high flow, where we are giving them pressure or of continuous positive airway pressure informer CPAP So they are still needing respiratory support out with oxygen. They'll have oxygen as well, but they need in dual therapy. This is reporting to the National Neonatal Audit Program, which is UK based. Um, there are various programs across Europe and there are international programs in something called the Vermont Oxford Network Database that we record too. So in the UK, the national rate for bpd is down the bottom at 37%. So we're we're in that range. Our unit. We were sitting at 43 but one or two babies can skew it. What I want you to take from this slide is that if you're born at 23 weeks, obviously we've got small numbers. We are. When we looked at this six month co heart, we only had four. But we're monitoring all the time. So this snapshot, um and it may even have been a four month period. We can see we look at their intervention for hemorrhage rate. We look at necrotizing enterocolitis. We look at BP. D. And we look at retinopathy of prematurity treatment, so come into threshold, come into treatment. So if we look at our 23 24 weekers, what I want you to see is that all of the 23 24 weekers are getting bpd. Okay, We can't seem to get these very small 22 23 24 weekers through without still needing respiratory support at 36 weeks. Okay. As you go up, Gestations, you start to see that you may get 1 25 weaker out of your cohort through, but as you get to 26 weeks, they get much better. And as you get 27 28 29 they're much better again. So our problem is really these 22 to 26 weeks. So let's take that to then talk about the pathophysiology. Why are these 22 to 26 weeks so bad? We give them surfactant. We give them antenatal steroids to stimulate their lung maturity and to stimulate their own Al Viola Type two cells. Fact, um, production. We give them nutrition, we support them. We try to prevent Path of eight Alexis, but we still got a problem. And it's all about the embryology and really, the development of the Al Viola Type two cells. Brits. More than that, it's also it's about this fact and production. But it's also about the capillary bed. Okay, so I want you to go back to embryology now. I'm always very impressed with medical school's out with UK, and they're embryology teaching. I don't think we do it as well as what a lot of other European medical school do. So I'm hoping this is a little bit familiar to you. So at 3 to 6 weeks. All you have is an embryonic lung. But you need to follow my slide across. I'm starting here. Then at 6 to 8. 16 weeks that bud starts to branch. It starts to bifurcate, and it starts to develop what we call the ace in our blood. Okay, then we go into what we call canonical ization. So they start to become tubes, they start to open up, so they're getting ready to take a right. Okay, that's 16 to 26 weeks. So at least now they're not solid. They've actually got cuniculus. They've got tubes forming and they start to branch. And what you see down the bottom is you start to get secretary cells, which are going to secrete mucus. To keep the airways moist and lubricant. You start to see sillier coming in. So that's good. Oh, I've lost my slide. Right. So I'm starting to see sillier. I like cilia cause cilia are going to beat and keep my airway clear. Okay. I am starting to see a capillary coming in a blood vessel. Come in so I can pick up oxygen because no point putting in, um, oxygen and ventilation. If you haven't got a way of picking up and gas exchange. So I'm starting to see, uh, blood vessels coming in. And then by the time I get 26 to 36 weeks, I want to keep losing this right. What I'm really starting to say is the valve Eola type one cells and the alvie Ola type two cells because, look, they were missing before 26 weeks. We had a basil cell coming in that blue sell that was going to differentiate. But what I didn't have was differentiated cells. And as we get older, the capillary gets much better forms. We've got the mellow bodies we've got. We've got energy efficient cells that can do all this ATP production surfactant requires energy. So it's all in the embryology. So you can see from this why we're really struggling with less than 26 weeks. So then we need to think of what we do to change it. So what we can do is we can think about, uh, I'm going to. So obviously, pregnancy abnormalities and fetal exposures may damage the foetus, and that's retail development. We're talking about alcohol were talking about smoking in particular because smoking in peace percentile function and actually makes babies small. And they maybe embryologically a little bit smaller than what you would ideally want them to be. So we don't like smoking. Smoking causes premature delivery, causes placental hypoxia and causes fetal compromise, particularly with growth but also Embry a logical development. You then want to think about what can you do to modulate a baby coming up to delivery? And really, what we have for lungs is, um, steroids. Magnesium sulfate, which is given, is to actually prevent hypoxic damage and to reduce the incidence of cerebral palsy. It's not particularly to help the lungs, although obviously, if you're less hypoxic, you're going to have less respiratory distress so your respiratory distress will have a bigger cytokine inflammatory response. If you've had hypoxia, it will also have a huge response. Inflammatory response. If you've had maternal infection in the womb in the form of chorioamnionitis this so all these drive inflammation and site kinds and that inflammation affects the lungs and in flex where we are. But obviously postnatally, we need to think about what we can do to support lung development, how we can optimize lung development, keep those al Viola open If they're, they're keep the ace and open and we can think about how we can repair, which is where we come in to postnatal steroids to damp down the inflammatory risk cascade that's going on. And then as you go further along our arrow, obviously there is remodeling and growth as the child grows and we normally say that by two we should have some remodeling. But growth of lungs continues throughout childhood. I just want to show these two X rays What? We're not seeing so much, probably because we're not ventilating. We're not seeing the old BP D X ray where we're seeing a lot of, uh, scarring and fibrosis. So radiologically it has changed. We're not seeing the hyperinflation, the emphysema and the scarring. You can see that these lungs are overinflated. So they've got overdistended al Viola because we have overdistended them with the ventilation and then we've caused them to scar and fibro s Okay, I think I've actually spoken about this so priest of fact. And they were older Children. Um, I'm going to go on the new DPT, and I appreciate I'm repeating myself, and I'm going to look at the time, right? Okay, so we're treating them so the lung is more immature at the time of injury is our big problem because we're resuscitating smaller babies and they're really the ones we're struggling with. So it's the babies less than 28 weeks, Really. It's more the babies less than 27 with the birth rate of less than a kilo, 1000 g, we've treated them as surfactant. We're not necrotizing. We're not setting up that necrotizing bronculitis, so we don't see that which we saw before. But what we've got is immature, a viola damaged in a uniform fashion. So it seems to be a widespread. We're not necessarily getting patchy necrosis. The primary injury seems to be our thinking is that it's more an arrest of all of the other development. And we've got a simple are viola space, which isn't mature with it's type two. No matter sites. It's not mature with its mitochondria, intra Salalah, and it's 80 p generation. The fibrosis just do diffuse, but we're seeing on X ray that it's often mild injury but homogeneous, but it's still significant prematurity. Very low birth weight in a male, um so If you get twin boys, it's normally you know, they're going to have bad lungs. Though the girls do better. It's all to do with estrogen driving, thyroid function, driving steroid production, um, as a mechanical ventilation we don't like. But what we find is that they deteriorate pulmonary wise in the first month of life. So we have what we call the honeymoon phase because we do actually call it honeymoon phase. They seem to be really great in the first week. Then after that, everything kicks in, which is actually the cytokine inflammatory effect kicking in. We do know that oxygen is toxic. Okay, we've known that since the sixties. Remember it cause blindness, but it also caused lung disease, chronic lung disease of infants. And we know that the free radical generation from oxidative stress injures the LVO lie and even brief exposures, which is why we want a saturation monitor on and why we don't start in 100% oxygen can result in long term changes. That evidence base is there. A lot of that came out of Egypt, actually, because they didn't have such good access to oxygen. Um, and, uh, two blenders. Sorry, they didn't have oxygen air blenders. They were resuscitating 100% oxygen. Um, you know, anything that sets up inflammation in the boom? Inflammation in the fetus is not good. So chorioamnionitis has more severe bpd. You may get decreased respiratory distress syndrome at the beginning because the stress effect of that matures the baby because it knows it needs to come out. It's got to come out or die. Um, so it stimulates, um, surfactant production. And the same thing happens with growth restriction, actually. So this in uterine growth restriction. So the placental stress stimulates the baby to have less respiratory distress syndrome, but they have more BP d. Because that inflammatory burden carries on post Nate Italy and everything that we need to do is to reduce the inflammatory burden postnatally with postnatal sexist as well. If you get a baby that gets infection, including ventilator required pneumonia, you are setting up inflammation in the lungs and that then drives al Viola star in that everything is about prevention. Okay, so you don't want them to get infected. You don't want them to have you want them to come out quickly. If there's chorioamni, I just get them out of that environment. And if they're failing to thrive, that's an indication for delivery. So percentile dysfunction is an indication for delivery. So we've talked about this. Talked about the ventilation strategies. If you do have to ventilate them, you want to use low volume so that you don't over distend and we target. The volume were given between 3 to 5 mils. So it's very low, much lower than adults ventilators. And we allow carbon dioxide to be high actually, so we accept carbon dioxide's of less than age. We don't want them 5 to 6 on the blood gas. So we're very different from adult anesthetics and gas exchange because we know they tolerate it. And it does doesn't cause intraventricular hemorrhage if we allow them to go too low. What happens is the blood vessels to the brain basic constrict, and then because they can't control it, they get a reactive base of dilatations and they bleed so we don't like low carbon dioxide. We see a calm dioxide of 5.5 on a blood gas. That is really bad news. Honestly, you just you run to the ventilator to change it. We target oxygen because we know high oxygen is damaging. People have looked at low oxygen and found it wasn't very good. You actually had more death because you've got more pulmonary hypertension. Um, and you had poor growth. We've talked. I'm going to talk a little bit about Costco steroids. But I think one of the things that has come through in the last few years is that giving babies caffeine actually is good even if they're not having apneas of prematurity. So we were always given it to stimulate the breathing, but if they were breathing normally, we didn't give it. But now we give it because what we know is and it it'll be through. Caffeine actually works on a T. P. So it drives cyclic a M MP back to 80 p. Adenosine phosphate, Trans paralyzed. Probably got that wrong, but ATP, So it's an energy driver. It gives the baby energy in its cells. And it is a fact it is an energy dependent process. So we found actually that given caffeine is something called the cap trial. We weren't particularly looking for it. No, we were actually sorry. It had a lower instants of bronchopulmonary dysplasia. And some of that may be that coffee Coffee Not only is sporting energy is actually a mild diuretic, so you may just be keeping lungs slightly drier. Everything is aimed at minimizing harm. And these are things that have been tried over the years. Bronchodilators we know don't work. They don't have the smooth muscle receptors to dilate up. You may use it when they're one. If they get recurrent weaves and give it a trial, it doesn't work in the newborn period. Sorry, The screen is not showing itself of blank. Oh, right, I'll go into the next one. Is that one Joe? Full snappers like post nasal steroids. Can you see that? Yes. Yes. OK, so I mentioned briefly. Broncho dilators don't work. Actually, there's interest in stem cells because if you could somehow keep stems, get stem cells into that baby from the percenter, which is a huge resource of stem cells. Because if you could keep that embryology developing, that's what really what you want to do. So I don't know if the future is stem cell therapy to keep that al viola development, but let's talk about postnatal steroids. I know I'm running a bit late, but I'll keep going with this, actually, and then I skip purse Natal steroids has been one of the mainstays of we used it to take the inflammation down. It does two things, right? We would give babies dexamethasone. It took the inflammation down its anti inflammatory, very powerful anti inflammatory. So you're suppressing the cytokines inflammation, and like, it definitely works. And you. So what we would do historically is we would do is if the baby was stuck on the ventilator. We then thought, and it's to facilitate excavation and personal steroids are absolutely recommended for facilitating excavation. Okay, Day 10, currently, we take them off. Unfortunately, what we've done in the past is give them very high doses. Um, you don't know what you're doing. And it was only when they got two, um, two years of age, we realized that we were increasing the risk of cerebral palsy. Okay, so we were causing neurodevelopmental harm. And that was from international meta analysis of pooling results of all the babies born so post at a Stewart's steroids then became avoided. But the problem is, we need them. So we have cut to something called the Dart regime, which is right down the bottom of the slide, which is low dose 10 day called course because initially it came out of Australia. They didn't power this study enough for neurodevelopmental outcomes, because really you need international data sets for that. But over time, because Dart has been around, I think now, since 2010, we don't think we are doing any harm, and we think it's the total dose that's important. So if you've got a baby that you've got a pulse several times for survival and your options at this point our survival or death and parents will choose survival, we cancel them. Um, we know it's the total dose. That's the problem. So you want a shorter course as possible and minimal courses. But it's very difficult to manage these 22 to 25 weekers without postnatal steroids. Okay, we tried early steroids that didn't work. We've tried everything, believe it or not, And there's still a lot of debate about steroids, So currently there's a meta analysis analysis out there of 20 randomized controlled trials from around the world. The baseline risk of BPT is if it's less than 35%. You've got increased chance. Actually, I think that's right. So if your risk is less than 35% we don't want to give early steroids. But if we've got a high risk, what we know is given steroids. If your BP D risk is greater than 65% and there are calculators which look at your ventilatory requirements, they look at your gestation, your birth weight, and they look at how much oxygen you're given. It's a simple calculation, and then your bpd risk is given to you. And if you come in at greater than 65% if you got, if you give steroids, you reduce your risk, and that's when we sort of want to give it or if we can't get baby off the ventilator. So there's a debate about what to do with the baby on CPAP, who's sitting in 40% oxygen on data and you know they get there 24 weeks. You know they're going to go on to get B B D. So we run them through a calculator to know whether we should give it. Hydrocortisone has become very topical because it's a different steroid. So one of the problems with dexamethasone on animal studies we think it's the carrier molecule, the sulfa inner urea that is actually what is toxic to the neuronal cell. So everyone has thought, Well, let's try a different steroid. So there are hydrocortisone studies that have taken place. And should we give it prophylactically of high risk patient. So you've got your 24 weaker. Should you give it by Day five? And there's been the premier lot study. One of the problems is there's a lot of debate still about the neurodevelopmental outcomes. So although we can get quick data on what's happening to the lungs, because we can get that, probably by discharge, can we discharge them without oxygen, right? It's a simple measure at term. Why? Where are they at 36 weeks? You're really problem is what about their cognitive function as they enter school? What about their motor? And they're Bailey scores when they're aged, too. I've got a big slide on data that's been collected, but I think I'm actually taking too much time. But I want to take go down to hydrocortisone. So the rationale is you don't have this toxic sulfonylurea in dexamethasone. So is it a better choice of steroid? Okay, Will it avoid the adverse neurodevelopmental effects dexamethasone? There's a moderate quality, small, randomized controlled trials. Um, the feeling is it's promising, but more research is into neurodevelopmental outcome is required. We certainly seem to avoid the high BP effects of steroids. But remember, steroids will cause one of the big problems. And one of the reasons a lot units sit stare away about it is that steroids cause gastric perforation, and we see it. So we give them steroids for their lungs, estimating that they're going to have bronchopulmonary dysplasia. But we go and perforate their stomach or their bowel, and they end up with a colostomy and an inflammatory response. Remember, we don't like side kinds. They end up with gastric perforation. So everyone's nervous. We're still nervous, and it's not being rolled out internationally. I want to talk briefly about morbidity. Why does bpd matter? It matters because you're more likely to be hospitalized in the first two years of life. You're more likely to go back to pediatric intensive care. You don't have any reserve. Okay? You also have a decline in lung function with age. Are we leading you on to get pulmonary hypertension? As a 40 year old and chronic obstructive airways disease as a 40 year old, what we do know is, if we did spyrometry on these Children, they've got reduced function. Okay? They've got reactive airways disease. They're going to need bronchodilators as a child. It's a little bit different from asthma, but they manage like asthmatics, and they're going to potentially develop pulmonary hypertension. Corporal Manali, where they eventually go into heart failure. So it matters. This is it graphically showing you a normal individual. Your lung function actually falls as you get older anyway. Okay, But if you've been born prematurely and the more premature your lung function falls more dramatically, remember this all on old data. We don't know what's going to happen to our 22 to 24 weekers that have been embryologically arrested. Okay, I'm going to stop there, Actually. Sorry, I've run over any questions. I'm gonna pick up prematurity stabilisation next week. Actually, I know it's a bit it's a terrible, but it's absolutely fascinating. And we'll pick up lungs a bit in that as well, and I can also talk about pulmonary hypertension of the newborn and fetal circulation next week. Thank you very much, Doctor. Um, I don't see any questions in the chat. We don't want to ask something. Yeah, um, I was just going to ask you, uh, I know it all sounds very good when we talk about patient's, um the baby's, I suppose, are in the hospital, and we have all the, uh, facilities to treat them. What if because I'm predominantly going to be practicing neural India, So I'm trying to work out how these babies, you know, in their preterm or but there is a small chance of, uh, them thriving. Um, is there, uh, is there a way to administer as a fact in and all these steroids and everything? How does it work? Okay, that's stupid thing to ask. I don't know, but absolutely not because resources around the world are very significant, right? So India uses a lot of bubble cpap, which is very simple, actually, and it's it's It's great. Um, so actually, with less invasive surfactant because you don't have to put the baby on the ventilator, and you don't need an e t tube and endotracheal tube because in India you will have feeding tubes. You will have no so gastric tubes, and you will have CPAP because you tend to use. You tend to give pressure. Actually, believe it or not, some units will even inflate a bag, UM, a fluid bag, a normal saline bank, for example. And they will have it flowing down at an inflation pressure. I appreciate that's not measured, and they will have oxygen being delivered as well. So they are delivering their oxygen by inflating a pressure cuff on their oxygen delivery so they'll have a system set up by giving less invasive surfactant. If you have it, it is expensive, but you don't need so much equipment. So it's theoretically cheaper and easier to administer because you don't need a ventilator. Um, you need oxygen and you need your CPAP if you have it. But I am aware that you pressurize your oxygen delivery by inflating a BP cough and using banks of fluid as well to drive things through. I'm putting a BP cuff around your bag of oxygen to give it some pressure so that it's getting delivered under a little bit of pressure. Okay, So you won't. I suspect you're not resuscitate in 22 to 24 weekers. I think you may find that you're starting at 24 to 26. Okay, I understand. Thank you. Postnatal steroids are steroids are cheap. Prednisolone in particular is very cheap, but hydrocortisone is cheap. Um, we tend to start intravenously, but then we will go oral, so you can give it orally so you can give it down your nasogastric tube. What you can do is make sure that you've got good nutrition, but yeah, you. If you're in a area where you don't have the means, then it's much more difficult. Thank you. And it varies across India. Actually, it's a very ruhr, a place that, uh, nearly 50 60 miles to even have a small hospital. So, uh, I think that's difficult. I think it's difficult. It'll be the older babies. I think what you can do is try not to give them too much oxygen and titrate the oxygen that they need and actually make sure that they're well nourished. Give them nutrition. Because nutrition is hugely important. Okay, But the beauty of less invasive surfactant, and particularly if we can get nebulized going. This study is going on about not even putting it down into the lungs, putting it into the oropharynx and hoping that the baby can self breathe it, Um, and take some into the lungs. So you just put it in the mouth and that you hope that they can. And the back of the oropharynx. So there are studies going on and that obviously be much more feasible. Okay. But we're not anesthetizing babies to do this. Where aren't you doing it without anesthetic? We're giving them to cruise as as you've got your Oh, you've got a thumbs up. Right? But what I will talk about next week actually is premature care. And that will be very relevant of what you can do, because you have to keep the baby warm and you have to keep a baby nourished. Um, there's no questions in the chance that nobody has any more questions. Um, thank you, as always, Doctor, for an amazing lecture. Um, and if everyone could please do the feedback form again, that would be great. Um, next lecture is in an hour. So we have a break. Um, I will put the zoom link in the chat, but again, please do book on eventbrite. Um, it's better for us to know the numbers beforehand. Um and that's it. So I'll give everyone a chance to do the feedback form, and then I'll post as a difficult, but yeah, thank you very much. Okay. Bye. Thank you. Bye. Thank you.