 Paikia. Reisec into nutrition for pre-term babies began over 100 years ago. But back then there was a much more pressing challenge, and that was just to keep the babies alive. As you can see from that photo, the main issues were breathing and feeding. And in 1916 only 15% of pre-term babies survived. And over half died in the first three days after birth. In the next 50 years there was some progress. But in 1963 when Patrick Kennedy was born at around 34 weeks gestation, he died two days after birth of respiratory distress syndrome. This was because at that time in the US there was no treatment for babies like Patrick. But Patrick's death sparked new interest in pre-term birth and in neonatal nutrition. So today almost all babies like Patrick survive. In 2016 there were 15 million pre-term babies born each year. That's one in ten. There's increased survival at much lower gestational ages, 23 to 24 weeks is the earliest, and much lower birth weights. But pre-term birth has long-term effects on development and disease risk. So for example up to half of the smallest pre-term babies have some form of neurodevelopmental impairment. So this may range from something quite mild like needing to wear glasses to something more severe like cerebral palsy. They also have an increased risk of obesity, diabetes and heart disease. And because this affects up to 10% of the population, that means it's a significant public health concern. But these long-term effects can be influenced by early nutrition. Pre-term birth has been described as a nutritional emergency. That's because these babies have very low nutritional stores and because they're very challenging to feed especially in the first few days after birth because there are limits to the volume and concentration of the fluids that they can tolerate. This means that they have a very low energy and protein intake. And many pre-term babies grow poorly. And this affects their, increases their risk of having a small stature and having effects on body composition and long-term metabolic effects. But most importantly it can affect their brain growth at a time when their brain is growing faster than any other time in the life cycle. So that's from about 23 weeks' gestation to 27 weeks. And you can see that even in the last 5 weeks of pregnancy the brain increases in size by about 50%. A period of nutritional deprivation like this is often followed by rapid growth. But rapid growth also brings risks. So there may be a trade-off between development and metabolic risk. In this study in the 1980s of pre-term infants those who had faster length growth in the first 4 months after birth had a decreased risk of having a low IQ but they also had an increased risk of being overweight or obese and also at 18 years of age. And this may be particularly important for boys because pre-term boys don't do as well as pre-term girls. They have increased risk of death, they tend to be sicker and so they have longer stays in hospital and they also have an increased risk of neurodevelopmental impairment. Boys also seem more susceptible to the effects of suboptimal nutrition in the early days and when we give them nutritional supplementation they also seem to have metabolic outcomes that differ from girls. At other times of very rapid growth such as adolescence boys have higher nutrient intakes in particular protein than girls do. But for pre-term infants we consider their requirements to be exactly the same and we prescribe the same nutrition for boys and girls. This graph shows the cognitive scores of term-born boys and girls at six years of age and compares it with pre-term. So you can see that the term-born boys and girls both have very similar cognitive scores and that they are higher than the babies and six-year-olds that were born pre-term. But what we also see there is that the boys have lower scores than the girls. So it may be that we need to be thinking about boys and girls differently and perhaps even feeding them differently in order to achieve the same metabolic and neurodevelopmental outcomes for boys as we do for girls. So we know that nutrition in early life is a key determinant of growth and long-term health and that preventing these deficits seems better than having accelerated growth. So the crucial question is what is the energy and protein intake that's needed to achieve optimal growth and development? And we don't yet know the answer to that question. But here's what we're doing at the Liggins Institute to find out. We've identified that nutritional intake in the first week after birth is very important for later growth. So this graph shows the protein intake of a fetus in utero, a baby during pregnancy and that's followed by the actual intake of a group of 50 extremely low birth weight babies from Auckland City Hospital from an observational study that we did over there. This is the intake that the babies over the road are having right now, extremely low birth weight babies. What you see inside that red box could be described as a serious nutritional insult at the time of most rapid growth in the human life cycle and especially the most rapid brain growth. So perhaps in order to achieve the growth for preterm babies if they hadn't been born preterm we need to be looking at matching their intake that occurs during pregnancy. And this is the basis of two studies that are being done at the Liggins Institute. These studies are both funded by the Health Research Council. The first is the Diamond Study which is a study in looking at early nutrition and moderate to late preterm infants. Those born at 32 to 36 weeks. And the second one is the Provide Study. This is a study looking at whether early nutrition intake in particular early protein intake and extremely low birth weight babies those born with a birth weight of less than one kilo whether that protein can improve their neurodevelopment. Protein is made up of chains of amino acids. These extremely low birth weight babies that I've been talking about need to have intravenous nutrition via a drip in their first few days after birth for about the first two weeks actually because they're not too immature to tolerate enough breast milk to meet their requirements so we give them nutrition via a drip and this is given as a mixture of glucose and protein and fat. The protein in this intravenous nutrition is given as a amino acid solution. So the Provide Study is an international multi-centre double-blind randomized placebo controlled trial of an extra one gram of intravenous protein as a amino acid solution for the first five days after birth. This is like a little protein chaser of an extra 30 to 50% on top of the intravenous protein that they're already receiving. So half the babies get that extra protein and the other half don't. This extra protein is being given by the umbilical arterial catheter and that's the way of making sure that the babies have that extra protein because in previous studies it's been really difficult to get much of a difference between the two groups when giving some higher protein and others the normal amount of protein. So the primary outcome of this study is survival free from neurodevelopmental impairment at two years. Secondary outcomes are growth clinical outcomes and body composition. What's unique about this study is the sample size. This will be the biggest study that's ever been done looking at this issue in extremely low birth weight babies. This study began in April 2014 and all six level three neonatal units in New Zealand are involved. We've got two Australian sites starting one next week and one in a few weeks after that. And to date we have recruited actually 211 babies because there was another one this afternoon which is still 49%. We've also just started the two year follow up of the babies around New Zealand. The first babies that were recruited. As part of the study we've been able to get access to the newborn metabolic screening results for these babies. You may know this as the Gusry Test which is that we can look at the amino acid concentrations in the blood of the babies. We've got some preliminary results which I'll show you for 119 babies at six sites all around New Zealand and we have results available for the amino acids that are listed on the slide. On the day of birth there was no difference between the boys and the girls for these amino acids. But on day five these four amino acids were higher in girls than they were in boys which we think is very interesting. Our amino acids are the building blocks of protein but they're also very important because some regulate the key metabolic pathways that are necessary for repair, growth and immune function. Two little of one amino acid just one can impair growth but too much of one amino acid can be toxic to the developing brain. So it's very important to have the right balance. What we are interested in is are the boys and girls using the protein that we're giving them differently and are the high amino acids too high or are the low ones too low. So whether these differences are associated with short or long-term outcomes needs further investigation and we intend to do that as part of this study. So in summary pre-term birth is a nutritional emergency that may need to faltering growth and long-term health effects and there's a wide variation around the country in nutritional intakes and those effects between the sexes. The provides study will provide the first direct evidence of whether more protein is better for extremely low birthrate babies and perhaps whether it's better for boys or for girls or for both and it's a simple inexpensive intervention that if it's found to be beneficial could easily be implemented all around the world. There's still a lot that we don't know about pre-term babies but this research has the potential to answer at least one of the really important questions before another 100 years goes by and I'd like to acknowledge and thank all of the people listed on that slide. Thank you.