 Yn ystod, yng Nghymru, mae'r profesi Jayne Harding yn ystod yn fawr yn fawr. Profesi Harding wedi'u gwneud hynny yn ymweld o'r Llywodraeth Llywodraeth, ac yn ymweld i'r gweithio yng Nghymru, yw'r CEO yw'r ysgolio ar y Llywodraeth. Jayne yn ymweld i'r record fenomenol yw ysgrifesio yn ymdano i'r llyfr. Byddwch yn ddweud yn ymwybod i'r awdurdodau yn ymweld, yn ymweld i'r llyfr o'r Llywodraeth a'r Ysgolio, Off tumwyr gyda'r oeddo na Llywodraeth Newid. Mae'r Meddl Edward Williams o ffordd ddwy'r roi y Lansett a'r Yng Nghymru yng Nghymru yng Nghymru. Jane will talk to us about how her research into a simple therapy for low blood sugar levels in newborn babies is changing clinical practice around the world. Thank you Jane. Thank you Frank and good evening. My task this evening is to take you from research to reality and that's quite a tall order because that process is usually a long one and I think we should not shy away from the fact that much of the research that we do will produce changes in reality if you like in clinical practice but it might take a long time to do so and this is only the 15th anniversary of the Liggins Institute. Nevertheless what I'm hoping to do for the next few minutes is to tell you three short stories of examples of research that has had an effect on our clinical practice over that time period and a little longer in some cases. So I started by thinking what research were we doing when the institute was founded and at that time I was working and a number of my colleagues some of whom are in the room were working on what regulates growth of the baby before birth and we were working in sheep and in sheep it is really quite easy to show that what regulates growth of the baby before birth is nutrition and this is a fetal lamb in the mother's womb growing along from day to day each spot is a measurement by day and here we start a period of maternal relative under nutrition and the baby simply stops growing and we refeed the mother and the baby starts growing again. It is very obvious in sheep that this is an important regulator of fetal growth but of course they're sheep and they don't quite all do the same thing and it's very frustrating if you're a researcher because mostly lambs were growing along and slowing down and starting up again but some of them just kept growing when we undernourished the mother and it took me longer than I would like to admit to work out that the difference is actually back here before the under nutrition and you can see that fetuses that were growing rapidly slowed down and fetuses that were already growing slowly had made some kind of adaptation and were able to keep going and we thought that's very interesting what is it that's determined that these fetuses are already growing slowly so we postulated that this was about events that had happened very early in pregnancy and we designed this experiment where sheep were either well fed or undernourished from before this is 60 days before until 30 days after mating so in my head this was something like a mother who's not eating well who's relatively undernourished before pregnancy and in the first month of pregnancy until she knows she's pregnant now she starts eating well for the rest of pregnancy and what we found in those animals was that in fact everything was changed about their babies their fetuses from that period of under nutrition that finished one month into a five month pregnancy so you can see that these lambs grew slowly not much different but they definitely were growing slowly right out to turn even though mother had been well nourished for the last four months we had altered the way that insulin was secreted in response to a stimulus in the fetus before birth and it takes a few years to find out but in fact that insulin secretion was impaired in the adults when they grew up so that period of under nutrition around the time of conception changed the way insulin was secreted in their adult offspring this was a permanent change and to our surprise the ones that had been undernourished delivered early so sheep all delivered about the same time here but this is the ones who'd been undernourished right at the beginning of pregnancy and they delivered early you'll notice the author of this paper is somebody familiar tonight we were very surprised about that because of course all of the focus on the causes of preterm birth is about what's happening in pregnancy and this study suggested that what was going on about preterm birth had actually started before pregnancy and that the key was right at the beginning of pregnancy of course when we published that nobody believed us and everybody said it was a sheep you know but in fact there've been a number of subsequent studies showing very similar findings in humans here is a relationship for example between maternal size at the beginning of pregnancy these are thin women down here and they're risk of having a preterm baby and here is a variety of odds ratios so risk if you like of women whose babies are already small right at the beginning of the pregnancy were really small at the time of the first scan they are twice as likely to have an early delivery or to have a small baby as those that are growing well now you're all familiar with the idea of the first thousand days it's sort of all over the place you can find a thousand different pictures of it on the internet the first of those thousand days is the period before conception and the reason we've focused right from the beginning of before conception in part is due to those studies that we did that said actually the time around the time of conception is critical for the whole of the rest of the pregnancy and for the lifelong health of the offspring so that's one little story the second I have to tell you about antenatal steroids because we are talking about the ligans institute and antenatal steroids really are the legacy of mont's early work and I was very privileged to work with Peter Gluckman the founding director of the ligans institute and with the immense support of mont who taught me when I was a medical student and was a tremendous sport ever since and of course he did do his sheep studies at national women's and he did keep his sheep in cornwall park and he was doing in the late 60s some very important work on what is it that determines the timing of birth and he did some very elegant work showing that it was steroid cortisol levels in the fetus that regulated the timing of the onset of labour and he showed in the course of those experiments rather by accident that if he gave steroids not only did the you go into labour and get pretern delivery but the lam survived in all preterm lam's died because they got lung disease and this is the report in 1969 that there was partial aeration of the lungs suggesting that this might be accelerated maturation of the lungs and of course preterm babies died of lung disease they got this terrible respiratory disease this little baby is sucking in its chest because the lungs are so stiff and he went on with Ross Howey to do this iconic study reported in 1972 that giving steroids to mothers before preterm birth saved the lives of their babies it was dramatic changes huge changes at a time when many preterm babies died of lung disease that wasn't of course the end of the story 2006 21 studies later how many times do we have to check that it still works we still know that the risk of death in babies exposed to steroids for example versus those not exposed was reduced to 77% respiratory distress cerebral palsy developmental delay half is likely to be developmentally delayed if the baby got exposed to steroids and in fact 20 years after the original publication the NIH the big powerful North American organization was trying to remind people that actually this was a rare example of something that not only worked but it saved money why 20 years later were we still trying to persuade people this was a good idea well in part because we all know steroids are bad for you there were lots of reasons why this treatment wasn't widely taken up for so long but one of them was that people continued to worry about whether there would be any long-term adverse effects of exposing preterm babies to this very powerful drug before birth and we realized that we really had to answer that question so I got to stand around in the middle and smile at everybody but Montlegans and Ross Howie the original authors very kindly allowed us to use their original data and Stuart Dalzeal who was a PhD student did all the work as the way things work because when I came back to New Zealand to take up a job at Nashda women's I was allocated the office that had been Ross Howie's and in the cupboard were the original records of the original trial so we set about to find out if the survivors of that original trial had any effects in the long term from their exposure to glucocorticoids we had the handwritten records we knew the name of the mother and the date of birth and sex of the baby but nothing else in finding 30 year olds when you don't know their name is a bit of a challenge but we did because New Zealand's a small place but of course 30 year old New Zealanders aren't just in New Zealand they're all over the world but they very generously came to take part in our study and the short answer of a lot of work was that 30 years later exposure to antenatal steroids had no effect on any of these things and nor did it have any effect on any of these things and we were able to fairly confidently tell the world that actually this is a very safe as well as effective treatment and people might get on with using it that was a very important study to help assuage some concerns but of course Mont always had his eye on the next problem he was very good at paper darts too and he published right back after the first trial that the treatment seemed to work best in the first week after it was given so if you had a woman who appeared to be about to deliver pre-term and you gave steroids but she didn't deliver in that next week should you then give another dose and about the time this was becoming a hot topic because people started using steroids so of course more is better they started using lots of steroids there were studies coming out in sheep suggesting there was a dose response so the more doses you got the better the lungs were in the offspring but the smaller the lamb was because steroids inhibit growth so was this a good thing or a bad thing very important to do proper trials and find out and Professor Caroline Crowther led this study in which we collaborated on both sides of the Tasman where we looked at where the repeat steroids was better than a single course for preventing lung disease and the short answer is that they are the risk of respiratory disease reduced to 80% the risk of serious outcomes is reduced but birth weight is also reduced 78 grams is not very much does it matter what should we be recommending for practice well we thought we needed to wait just a little longer and see how these children were when they grew up so we looked at them when they were two and when they were two they looked just fine so we recommended that it was time people were using this treatment but as is often the case the medical provision wasn't quite convinced and people were still worried about whether they might be long-term effects so we looked at them again when they were seven how long do you want to wait and at seven again the study led by Professor Crowther just published nearly a thousand children no difference in any of these things so they got early benefit with no late effects and Dr Chris McKinley who's recently joined the Liggins as a senior lecturer but was a PhD student doing this study showed that when we studied the New Zealand children in great detail they not only functioned fine but all of their hormones and all of their body composition and so on was also fine so Caroline has gone on to lead the production in Australia and New Zealand of the binational clinical guidelines so here is the definitive published this is what we need to do folks in the hope that we can in fact bring reality to this very helpful drug and the third very brief story I will tell you because it's a shorter one is about neonatal hypoglycemia this is some of our current research low blood glucose levels in babies are common it is the commonest metabolic problem of newborn babies it's perhaps the only common preventable cause of brain damage if glucose levels are low enough or long enough that causes brain damage because glucose is the major fuel for the brain and of course babies have relatively big brains so what do we do because babies don't tell us when they have low blood sugar levels we test their blood sugar levels and we test the babies who we think are at risk which is big babies and small babies and infants of diabetics and sick babies and in fact nearly a third of all babies turn out to be at risk so we do lots of blood tests but we don't really know for each individual baby how low is too low for this baby and we don't really know have a really good treatment for them even if we find a low sugar so we end up admitting them to intensive care to have a drip to get their blood sugars up take them away from their parents and then have it breastfeeding so we thought there ought to be a better way of doing this and Deborah Harris who's another PhD student who's a nurse practitioner on Hamilton did this project where we did a randomized trial to determine whether a dextrose gel a sugar gel was more affected than placebo in reversing hypoglycemia in the first 48 hours after birth and the short answer is it's very effective so this is the rate of treatment failure not getting the sugar up with two doses of gel you can see it decreases markedly if they get dextrose gel being admitted to intensive care for treatment of their hypoglycemia markedly reduced and to my great delight a marked decrease in formula feeding at two weeks of age our concern was that giving these babies gel might inhibit breastfeeding what we think it actually did was reinforce breastfeeding by keeping babies out of intensive care keeping them with their mothers and reducing the stress of having to have drips and other concerns this is an unusual story this is a research going to reality very quickly that paper was published in 2013 it's now only 2016 here are four published reports of other parts of the world who've taken up the use of dextrose gel and they have all reported a fall in the rate of admission for hypoglycemia big changes keeping babies out of intensive care within a very short time of our doing that research so we're now gone on to do another big study which we're in the midst of at the moment saying well if dextrose gel helps treat low sugar levels could we use it to help prevent low sugar levels and could if it did that could we keep babies out of intensive care improve breastfeeding reduce costs we're in the midst of that study at the moment so i hope i've given you three short stories about research to reality in the ligans institute in its short history there will be lots more and there's a lot of important research still going on and of course i get to talk about it but everybody else gets to do the work thank you very much