Human Milk Oligosaccharides (HMOs) and Supplementation of Human Milk in Infant Nutrition: Aiming to Thrive-Hot Topics in Infant Nutrition

Transcription

1 Transcript Details This is a transcript of a continuing medical education (CME) activity accessible on the ReachMD network. Additional media formats for the activity and full activity details (including sponsor and supporter, disclosures, and instructions for claiming credit) are available by visiting: Released: 06/20/2016 Valid until: 06/20/2017 Time needed to complete: 15 Minutes ReachMD info@reachmd.com (866) Human Milk Oligosaccharides (HMOs) and Supplementation of Human Milk in Infant Nutrition: Aiming to Thrive-Hot Topics in Infant Nutrition Announcer Program Open Welcome to CME on ReachMD. This segment, "Aiming to Thrive: Hot Topics in Infant Nutrition Human Milk Oligosaccharides (HMOs) and Supplementation of Human Milk", is sponsored by Prova Education and supported by an educational grant from Abbott Nutrition. Your experts joining us today are Lars Bode, PhD, President, International Society for Research in Human Milk and Lactation (ISRHML) Associate Professor of Pediatrics Division of Neonatology and Division of Gastroenterology and Nutrition at the University of California, San Diego in La Jolla, CA; 2018 ReachMD Page 1 of 7

2 Sharon Groh-Wargo PhD, RD, Professor Pediatrics and Nutrition at Case Western Reserve University MetroHealth Medical Center in Cleveland, OH; and Terry S. Johnson, APN, NNP-BC, CLEC MN Neonatal Nurse Practitioner and Founder of Lode Star Enterprises, Inc. in Downers Grove, IL. Hello, my name is Lars Bode. I am the current President of the International Society for Research in Human Milk and Lactation, and I am also an Associate Professor in Pediatrics at the University of California-San Diego. My lab is dedicated to investigating biosynthesis and functions of human milk oligosaccharides. And I'm also the Director of the UC San Diego MoMI CoRE, the New Mother Milk Infant Center of Research Excellence. Hello, I'm Sharon Groh-Wargo. I am a registered dietitian and clinical neonatal nutritionist at Case Western Reserve University School of Medicine and at Metro Health Medical Center. I am Professor of Pediatrics and Nutrition and have spent my entire career as a registered dietitian and as a neonatal nutritionist in the neonatal intensive care unit. I'm happy to be here with Terry and Lars today. And my name is Terry Johnson. I'm a neonatal nurse practitioner with 35 years experience in the NICU. I'm a certified lactation educator. I am an Associate in the Society of Professionals for Patient Safety and I serve as the Director of Professional Education and Development for Prolacta Bioscience. So, we're talking about human milk oligosaccharides today, and just to give you a brief introduction, human milk oligosaccharides are the third most abundant component in human milk after lactose, the milk sugar, and lipids, milk fats, and they are so unique that they are not present currently in infant formula. And infant formula now contains other oligosaccharides that are not present in human milk. So, Sharon, what are your thoughts? Do you think that the oligosaccharides in infant formula, since they are structurally different, do you think that they have different ways of impacting infant growth and health? Well, as you say, at this point there are infant formulas, commercial infant formulas, available on the market that have oligosaccharides added to them, but they are nonhuman milk oligosaccharides. The most common ones are the galacto-oligosaccharide, GOS, or the fructo-oligosaccharide, FOS. They actually have a different chemical structure than human milk oligosaccharides, but they do influence the microbiota and the composition, for example, of the stools in formula-fed infants, and they do provide 2018 ReachMD Page 2 of 7

3 some benefits to the baby, including some studies that suggest a reduced incidence of atopic dermatitis in young infancy and some reduced subsequent allergy and infections during the first 2 years of life. So, even though they are not the human milk oligosaccharides, they do have some functions similar to human milk oligosaccharides. The long-term benefits of these products require further investigation, but obviously, the human milk oligosaccharides provide the most benefit. So, Sharon, what are the recent innovations in infant formula that are closing the gap between human milk and formula? Well, Terry, I think that we can start by saying that infant formula will never equal or match human milk. I think that is probably an impossible task given the complexity of human milk, but there are a couple of innovations recently that have closed the gap just a bit. We've been talking about the nonhuman milk oligosaccharides that have been added to infant formula that function as prebiotics, and so that's an innovation. The other two things are nucleotides, which are constituents that prepare the immune system and meet requirements for protein synthesis and cell growth, so adding nucleotides to infant formula is an innovation that's been very exciting. And the last sort of classification of innovations have been a couple of antioxidant constituents, including the addition of DHA (docosahexaenoic acid) a primary Omega 3 fatty acid, which is a very important antioxidant to protect against free radical formation, as well as the natural form of vitamin E, which is a primary biological antioxidant. The form that's in human milk is quite bioavailable, and that form of vitamin E from human milk has been added to infant formula. And then, lastly, lutein, which is a really important carotenoid which protects eyes and brain, and that has been added in. Interesting, both DHA and lutein can be enhanced by mother's diet, so we can encourage mothers to eat those things for their own health, and they have been added to infant formula to protect those babies who are formula-fed. So those are some recent innovations that have come along to close that gap just a bit. Sharon, I find it fascinating when you spoke about the antioxidants because of the rich availability in them colostrum. The highest known amount of antioxidants that we have been able to measure have been found in human colostrum at a time when babies undergo the most tremendous amounts of oxidative stress as they transition from intrauterine oxygenation saturations to extrauterine oxygenation saturations, and also with our preterm babies who require ventilation, surfactin for respiratory disease, who have a lot of oxidative stress going on. So, Lars, is it possible to supplement infant formula with critical HMOs to improve infant growth and 2018 ReachMD Page 3 of 7

4 health? The answer is, yes, it is possible. The question is: How feasible is it at this point to add some of these oligosaccharides? Ideally, we would like to add a whole mix of different oligosaccharides, but we'll probably have to start one by one as they become available. And I think this is a very exciting time that there is new technology, new innovation coming out that allows us to produce some of these human milk oligosaccharides in bio fermenters, so microbes now help us produce some of these oligosaccharides, and they can then be cleared and added to infant formula. So, we have one or two different oligosaccharides become available that are now FDA approved, also approved in Europe, and will be ending up in some of the products very soon. Lars, do we have evidence that supplementing infant formula with HMOs like those found in human milk improves infant's growth and health? We do have some evidence, and most of the evidence though comes from preclinical studies, so studies in tissue culture or in animals or from human cohort studies. There's currently not a lot of intervention studies available. And we have some work in others as well looking at infant body composition. We're talking about human milk oligosaccharides shaping the microbiome in the infant intestine, and the microbiome is potentially important, or essential maybe even, in metabolic phenotype of the infant. So, what kind of energy can we get out of nutrition is highly determined by what microbes live in our gut and what metabolites can they generate out of the nutrients that come with the food and make it available, or not available, to the infant or to the adult. So, human milk oligosaccharides shaping the microbiome which then shapes the metabolome and shapes the metabolic phenotype of an infant might just as well impact infant growth, impact infant's risk for obesity, and the oligosaccharides seem to play a very strong role in that. We've shown in data that there is strong correlation between human milk oligosaccharide composition in mom's milk and infant growth parameters measured by DEXA, so that gives you very good accurate measurements of infant lean mass, infant fat mass, weight and other parameters. There's also coming out of other groups where they have seen that oligosaccharides correlate with malnutrition in infants in Malawi, so we've seen both sides of the metabolic spectrum that there is an impact or at least correlations of oligosaccharides and infant metabolic phenotype, either obesity or malnutrition. Lars, it's so interesting that you bring up the topic of the oligosaccharides and body composition and 2018 ReachMD Page 4 of 7

5 obesity, because for a long time we've been trying to unravel how human milk and breastfeeding appear, in most studies, appear to protect against obesity in a pediatric and a childhood population, but the data are a little conflicting and confusing, and some of it certainly has to do with -- I always like to say -- the package, which is babies self-regulate when they're breastfeeding, and some of that selfregulation disappears if they're fed human milk in a bottle where we've taken away their self-regulation, but there's this definite trend toward a protective effect. And I think the possible role that human milk oligosaccharides, specifically in the microbiome, just generally carry part of the answer of how human milk protects against overweight and obesity in childhood and possibly in later adulthood. Yes, I absolutely would emphasize that. That's what we think as well, that yes, you see in some studies a bigger correlation than in others between breastfeeding and obesity protection. Sometimes it's very strong. Sometimes it's not so strong. And we believe it's that individual variation of human milk components. I mean, breastfeeding is not just breastfeeding. Milk components are very different between different breast milks, between different mothers, so by really looking at the different factors in human milk and how they relate to outcome will give us a clearer picture of how human milk really contributes to these different outcomes, including obesity. Lars, how about the impact of human milk oligosaccharides on necrotizing enterocolitis? Well, necrotizing enterocolitis still remains a major problem in the NICU, and you are really the expert on that. So, necrotizing enterocolitis is an acute inflammatory disease, disorder, in preterm infants mostly. Five to 10% of all very low birth weight infants develop necrotizing enterocolitis, and about a quarter of them die from the disorder, so there is still a very, very strong need to look for biomarkers to identify those infants at risk, but also then come up with therapeutics. And we were guided by data, epidemiological data, that showed that the breastfed infant has about a 6- to 10-fold lower incidence of necrotizing enterocolitis, and we were wondering is it maybe the human milk oligosaccharides that are in human milk but not in infant formula that contribute to this lower incidence of NEC? So, we had some data published from a preclinical model that showed that human milk oligosaccharides really are protective in animal model of necrotizing enterocolitis, and we identified one specific compound, one specific oligosaccharide called disialyllacto-n-tetraose, or short, DSLNT, that is responsible for the effect at least in the animal model. Now, rats are not humans. The model is not very good. It's just a scientific model. That's where we start, usually, in the lab. But we've shown over the last few years that in two independent cohort studies in human infants, we found that those infants that received human milk with lower concentrations of DSLNT, this protective compound, that those infants were at higher 2018 ReachMD Page 5 of 7

6 risk to develop necrotizing enterocolitis. So, taken together the preclinical data and the cohort data gives us very strong confidence moving forward to really show in an interventional study that this specific human milk oligosaccharide might indeed protect from necrotizing enterocolitis. It's interesting, we are seeing more and more of those studies coming out looking at exclusive human milk diets where the baby has no exposure to a cow-based formula reducing the incidence of NEC by as high as 77% by Schanler and Sullivan's study, and also, Dr. Abrams and his group in Texas recently published in Breastfeeding Medicine looking at almost what appears to be a dose response relationship between the amount of human milk a baby receives and decreased risk for necrotizing enterocolitis, surgical NEC, and for sepsis. And so it's fascinating to look at how just this availability of these human milk oligosaccharides and other immune properties in human milk can protect not just lifelong but in the acute stages in the NICU in these babies with this very devastating disease. The issue of dose is so important, Terry, because we see that in a variety of outcomes, that there's this dose effect. And I guess what I wanted to say about that to mothers and providers, that the message is a little bit of human milk is good. More is better, but any amount is good, and that gets to this issue of the dose effect. Lars, is there anything else related to HMOs and supplementation of human milk that we should be discussing today? It will be very, very interesting to see in the next few months and years how individual oligosaccharides become available, how they can be tested now in clinical studies and in the field to really see what their impact is. So far we have been limited to studying this in the lab either tissue culture or in animal models, but now we really have this milestone reached, and we have oligosaccharides available to use in human infants and see what the effects are and how they benefit. Sharon, do you have anything you'd like to add related to HMOs and supplementation of human milk that we should be discussing today? Well, the only final comment I'd like to make is that I get a lot of questions from mothers about their own diets and if they're not perfect that they're not going to make good milk, and I guess what I'd like to say is on the topic of human milk oligosaccharides, but also, just on the topic of quality of human milk, 2018 ReachMD Page 6 of 7

7 mothers' diets do not have to be perfect for them to make perfect milk, so I think we need to remind mothers that their milk is just perfect for their baby. And what we've been talking today is about the contribution that human milk oligosaccharides make, but I think we have to remind mothers that they don't have to have a perfect diet to make perfect milk for their baby. And, Sharon, I think you said something that's so important. It is so important that we realize the work these mothers do in providing their human milk for their babies and that we need to be supporting them. When they think of the concept of milk as medicine, it is still fundamentally something that the mother supplies for that baby that is so beneficial lifelong to the health and wellness of that baby and to support our moms in their efforts. On behalf of my colleagues Dr. Lars Bode and Sharon Groh-Wargo, I'm Terry Johnson, neonatal nurse practitioner. Thank you so much for joining us today. Announcer Close This segment of 'CME on ReachMD' is sponsored by Prova Education and supported by an educational grant from Abbott Nutrition. To receive your FREE CME credit or to download this segment, go to reachmd.com/cme. Thank you for listening ReachMD Page 7 of 7