- Discuss the link between gut microbiome and lung in respiratory disease
- Understand the role of human milk-based nutrition in programming health in very preterm infants
- Evaluate the lung protective effects of an exclusive human milk-based nutrition in very preterm infants
Rangasamy Ramanathan, MD
Professor of Pediatrics
Chief, Division of Neonatology at Keck School of USC
Director, NPM Fellowship Program and NICU
LAC+USC Medical Center & PH Good Samaritan Hospital
Good morning. I would like to welcome all of you to our first time PNG conference. I know many of you are listening from different parts of the globe. Thank you for attending this event today. It's very difficult to follow Dr. Evelyn Lucas who gave a great talk before me, but I will try my best. I'm going to focus on the gut-lung axis. human milk may be the missing link between the gut and lung.
So I have some disclosures. I have no conflicts of interest to disclose regarding my talk today; however, I do receive grant support from Prolacta Bioscience for my annual Life After Fellowship Workshop that I run that the annual American Academy of Pediatrics district nine California has in the in adult school topics meetings every year. And for this and while PNG contracts, if I receive any honorarium might donate to charity, for charities that help mothers, newborns, and infants globally.
My objectives are: I'm going to show what is the link between the gut microbiome and the lung microbiome in respiratory disease on health. And what is the role of human milk–based nutrition in programming health in very preterm infants in lung protective effects of exclusive human milk. When I say exclusive human milk based on the accretion it means mother's own milk, or donor milk from Prolacta, Bioscience or any donor milk bank, plus human milk-based fortifier from Prolacta Bioscience, as they're the only ones that provide human milk-based fortifier. So when I say to see human milk, that's what it means mom's own milk, or donor milk with human milk-based fortifier rather than cow’s milk based fortifier.
Let's look at BPD so multifactorial disease, it needs a multipronged approach. We have about 13,000 cases of BPD bronchopulmonary split every year in the United States. From a pathophysiological point of view, I think of BPD as an inflammatory lung disease, or ILD. Let's look at factors contributing to the pathobiology or BPD the new BPD maternal factors like placental insufficiency, lack of antenatal corticosteroids, maternal infection, like codium unitas or maternal smoking will increase the risk for BPD. What about neonatal factors or fetal factors, genetic susceptibility? male sex, the raw data of controversial that some study that showed that African American babies have a higher risk for BPD than Caucasian, but some studies have shown the Caucasian babies are at a higher risk. Fetal risk only we need to look into it not that the race is probably the environmental factors. Genetic factors play a major role than race or ethnicity. Altered microbiome, which is going to be a focus of my talk today. And postnatal sepsis, all of them will increase the risk for bronchopulmonary dysplasia, we are all familiar with the role of mechanical ventilation, barotrauma polytrauma, at electric former contribute to the lung injury, of course, oxygen toxicity, free radical mediator disorders leading to DNA damage, lipid peroxidation, and protein oxidation. So what can we do to prevent it, there is a link between the mother and baby which is human milk, that may be able to decrease the risk for BPD?
This is a nice review article written by Dr. Andrew who's another speaker today. If you have any questions about cat dysbiosis, you should ask him. So when there is malnutrition, or use of antibiotics in the NICU, but using acid blocking drugs or h2 receptor blockers, because it's dysbiosis and increases as a result of that you increase gut permeability, translocation of pathogenic bacteria, and leading to necrotizing enterocolitis. And through altered gut microbiome you upregulate toll like receptor for TLR signaling, which is a very potent activator for inflammation. So this inflammation leads to NEC. But unfortunately, the cytokines produced are the factors that are active, the gut, doesn't stay in the gut, keeps translocated gets into the portal vein into the system in circulation and carry direct impact on the lung or through the bone marrow. So that leads to bronchopulmonary dysplasia and or BPD-associated pulmonary hypertension. There is also a link in association between necrotizing enterocolitis and parliamentary means you gnosis. You don't don't connect these things. The reason is we forget that lung actually develops from the forecast as outpouching right. So, because babies necrotizing enterocolitis have an association with an iris or foundry vein stenosis because nitric acid production is decreased, as well as endothelium nitric oxide synthase or Enos expression is decreased. Vascular endothelial growth factors decrease and vegetable is very essential, extremely important for touring vasculogenesis. That may be one of the reasons why there is an association between NEC and pulmonary vein stenosis.
So let's look at gut dysbiosis. And the developing lung in a preterm Baby, I just mentioned about the a lot of four in the gut lambda axis when there is you activate the TLR. Four, it acts through interleukin one beta, il one beta, and then NF Kappa b nuclear factor Kappa b. So this is the hypothesis role for gut dysbiosis and TLR signaling in the development lab. So all TLR four, IL one beta nuclear factor Kappa b are all pro inflammatory molecules. So when there is gut dysbiosis, you're actually starting an inflammatory song, resulting in bronchopulmonary dysplasia, a new hypertension.
So let's look at gut microbiome and lung health. Again, short, this is the gut microbiome. This is the catalyst and columnar sites here and this is the lungs this circulation. So factoring fatty acids, which are a byproduct of feeding butyrate, acetate, lactate to butyrate pressmen metabolite, or human milk oligosaccharides, or HMOs. Under normal conditions, enhances intestinal barrier function and down regulates inflammation. You remember epds and inflammatory lung disease, right? You can down regulate this inflammation, for example, short chain fatty acids, and they're metabolized. Butyrate is produced and we rate is a very good energy source for the melanocytes, and resident immune cells. So it can get into the bloodstream and aquia bone marrow or the regular cells in the lung or some of the other innate lymphocytes cells. The innate lymphoid cells can also move from the gut into the lung and have an effect on respiratory immunity. Other products byproducts of bacterial digestion, for example, that does some inner tyrosyl can cross the blood through the blood brain barrier impact on type one interference. Again, this will help to decrease the risk from interference. So breastfed babies breathe better. They have less risk for TH-two activation and asthma reactive airway disease.
Okay, is there a link between necrotizing enterocolitis, bronchopulmonary dysplasia and BPD-associated hypertension? The simple answer is yes, here is a study from Netherlands published in 2018, where the where the looked-at proportional baby's developing pulmonary hypertension, no BPD babies have very little dress, mild BPD, moderate BPD and severe BPD severe low degree of BPD. The higher the risk for BPD associated pulmonary hypertension, again due to vascular, abnormal vasculogenesis when the babies have done this BPD development
is another paper from a New Haven published in 2017. Looking at Is there a link between NEC, BPD, and BPD permanent hypertension? The answer: Yes, so they looked at presence of NEC was an independent risk factor. In babies less than 32 weeks were far without BPD. The odds ratio was 5.5. Confidence Interval 1.9 to 15.4. And the speculator, as I mentioned before, decreased nitric oxide due to decrease in US activity, endothelial nitric oxide synthase activity in NEC. NEC was the only factor when the other factor that looked at is the ibH or mortality only factor associated with pulmonary hypertension in infants without BPD. There are some baby that level of public opinion with mild or no BPD. So they found that in this database, they found an issue was the independent risk factor.
Same thing happens in adults. It's not only just in the newborn period, there is the cut lung crossbar happens all the time and this crosstalk is bidirectional. If there is an airway dysbiosis, it can affect lung gut function. And gut dysbiosis can affect lung function. For example, a patient with influenza, they get GI symptoms, right? It's likely related to this crosstalk. So inhale, you have predominance of Bacteroidetes and less of proteobacteria, that when you burn them in the gap, same thing is in the lump predominance of decorators less proteobacteria, that in this state, like in NEC, you can see back guided is low, our proteobacteria species are increased. Firmicutes also increased and the same thing happens like a mirror image in the lump less speculators market increasing proteobacteria and parameters in the lung. So what happens in the gap gets reflected in the lungs and vice versa? In lung disease status, or curato proteobacteria Firmicutes as I just mentioned.
What about nutrition, either antenatal fetal malnutrition, IUGR, or x-ray to new growth rate in UGR? Again, Dr Mark Underwood and Dr Satyan, UC Davis, publish this. So maternal factors we talked about age, malnutrition, disease state, for example, hypertension, pH, smoking, fatal factors, we talked about genetic causes postnatal infection. In critical growth restriction leads to impaired alveolar growth, especially babies that are born in the canalicular stage of lung development, decrease the elasticity and increase stiff Nautilus vessels. So they tend to have pulmonary hypertension, globular heart that also had cardiac changes in them. If you can, to some extent, you can minimize these adverse effects in the first zero to seven to 10 days, the first two weeks, if we can provide normally adequate nutrition with good intake of protein and energy, provide protein energy malnutrition, you can minimize the risk of BPD and neurodevelopment impairment. We all know that our babies that develop BPD are at a much higher risk for abnormal neurodevelopment. Now, so if can protect the lungs, you're also protecting the baby's brain. So it's extremely important for us as neonatologist, to try to decrease the risk of development of BPD in these babies.
Let’s go over the maternal gut. So that maternal gut breast access, programming health for life. There are complex interactions between maternal gut, mom's breast, and milk, as well as infant gut and the relevance to infant growth, development and health. What the mom takes mom, maternal dietary has a major impact on what gets across the breastmilk into the baby's gut. And there are a number of biotech bioactive components in precursors in the breastmilk, which helps to upregulate that immune function and commensal bacteria. And then when it gets into the milk, and baby starts to ingest maternal mom's own milk, it helps gut development, immune tolerance, immunomodulation, cap barrier function and difference. So early programming, the earlier the babies get exposed to moms on milk, the better. It is not only just in the calculator, systemic effects, growth and development, health, lifelong and transgenerational effects, not just in one generation.
Programming health for life again, there is complementarity between maternal gut breasts and infant gut. The top panel is the mothers get what the mom takes, what mom's gut microbiota and what gets synthesized in the mammalian gland and gets into the breastmilk, including immune cells, secretory, IgA, IgT, lipase, lipids, HMOs, human milk oligosaccharides, and then how much the baby takes so they are extra cell cycles which contain lipids, proteins, mRNA micro RNAs, based on their size, these extra cellular vesicles are classified as exosomes and microvesicles. They promote growth of the current epithelial cells protect against oxidative stress. Remember, we know what the oxidative stress mediated disorders and babies are: BPD, IBH, NEC, and ROP. So, they play a broad immunoregulatory function. Again, the extra cellular vesicles present in preterm versus term breastmilk can also be different. For example, preterm milk has the highest amount of HMOs, human milk oligosaccharides, and human milk oligosaccharides is the third largest solid component investment after lipids and lipase. What you get is HMOs. Stem cells are there, postnatal micro Kaymer ism has been reported in number of Unum immunomodulators and growth factors as we just discussed transforming growth factor beta IG of one insulin like growth factor one vitamin A, as we all know, they promote lung remodeling, and alveo biogenesis and lung growth.
Let's look at the animal microbiome and BPD in preterm infants. There was systematic review published by Pemmi Mohan et al. Six studies, the early airway microbiome was dominated by Staphylococcus and Ureaplasma spp. Two studies reported difference in alpha and beta diversity indices in preterm birth with BPD compared to those that did not have BPD. Increased microbial community turnover, changes in the relative abundance of Proteobacteria and Firmicutes, and decreased Lactobacilli reported with BPD progression. However, there was no data available in the systematic review regarding feeding of human milk are correlations for the development of gut microbiota. They concluded microbial dysbiosis may be a source of BPD progression and severity. And for the study of microbiome optimization in preterm infants’ factors for BPD swatted. Again, they didn't have much data about human milk reading in the systematic review.
Let's look at mom's mother's own milk versus donor human milk. We know there's different because for the pasteurization, either you know pasteur, time and the duration all of them affect the properties of the donor human milk, they are different depending on what type of pasteurization or technique use retard versus fat pasteurization versus holder pasteurization. So in this study,
they looked at microbiome, phylum level, at the family level, in 69 babies less than 32 weeks, less than 1500 grams study from Spain. So they showed that even for me, who is not a gut expert, you can see that this is mother's own milk here, donor human milk and formula fed baby a significant difference. So they concluded that donor human milk favors an intestinal microbiome more similar, not exactly the same, but more similar to mom's own milk than formula, despite the difference between mother's own milk and donor human milk. Same thing happens that the family level bipolar bacteria species is predominant both in mother's own milk but babies are donor human babies compared to formula fed babies they have a totally different species in their gut.
Again, I can show hundreds of studies that looking at airborne microbiota dysbiosis in BPD. So if you have gut microbiota dysplasia, you also get lung micro biota, dysplasia dysbiosis is this crosstalk is bidirectional, as I mentioned before, so again, the final common pathway for lung injuries, inflammation, that's mediated when there is dysbiosis, either in the airway or in the gut, it doesn't matter where it happens. It can impact both systems. Again, we talked about all the factors. Unfortunately, preterm babies for example, they cannot make enough anti-inflammatory cytokine for example, IL-10 so very good anti-inflammatory side again, but they don't produce but they are capable of producing very high amounts of pro inflammatory cytokines. So they
There's an imbalance more towards pro inflammatory. So for example, prebiotics may play a role in decreasing this inflammation and increasing BPD.
So dysbiosis activates lung immune responses through gut-lung axis again, you know, gut-associated lymphoid tissue
that's where most of the immune cells in our body. So when there is gut dysbiosis, we talked about all these multiple pathways are activated. And either they get through the bone marrow or blood circulation with a lung and cause airway dysbiosis and lung injury.
Okay, another nice cartoon from Dr Underwood and Dr Sathyan's study looking at the relationship between gut dysbiosis and BPD in the fetal life, or postnatal life. So decreased protein and amino acid intake very early around, or decreased intake of gamma three polyunsaturated fatty acids for increased intake of omega three polyunsaturated fatty acids are interested in dysbiosis because of antibiotics and other things we do creates a pro inflammatory microbial state decrease in anti-inflammatory microbiomes. And microbial products that are released as a result will get in systemic circulation leading onto these two categories, pulmonary hypertension and BPD.
When you think about gut, always think about lung. You think about lung we always have to think about brain.
So what can we do to prevent BPD? Here, randomized control trials are a systematic review of 47 randomized control trials involving nearly 12,000 babies and 21 drugs in the last 40 years. Out of that, 13 randomized control trials came to a conclusion that only five drugs have been shown to be effective in decreasing BPD - caffeine, vitamin A Dexamethasone, Inositol, and Clarithromycin, a total of 4800 infants. 32 randomized control trials with 16 drugs in nearly 7000 infants do not reduce BPD
We spend enormous amount of time and research on these drugs that didn't seem to have any effect on BPD.
So what about human milk? Using human milk which is a multifunctional drug, in my opinion as a drug to prevent BPD can use human milk to prevent BPD cheap, readily available from mom. Let's see what the data shows. So this is exclusive human milk versus bovine milk based nutrition and BPD and other morbidity retrospective cohort study of less than 1250 grams, nearly 1600 babies published by Amy Hair et al from Houston, Texas. So here is the bovine milk-based diet. Birth rate was slightly bigger in the human exclusive human milk-based diet group 823 grams was 844 or 20 grams, but the gestational age is very similar. Look at the incidence of necrotizing enterocolitis which we all are familiar with all human milk diet decreases BPD and NEC right 7% versus 17%. Okay, the incidence of BPD 48% versus 56% significant decrease in BPD. ROP was significantly decreased, patent ductus arteriosus., late on-set sepsis, days on ventilator are all significantly lower. Mortality was also lower, 3% lower in the group of babies that are given exclusive human milk-based fortifier.
There's another study published from German neonatal network looking at exclusive human milk-based diet versus bovine milk-based diet in BPD. It is a multicenter prospective cohort study, 1400 babies, 239 were bovine milk–based diet and 223 were exclusively human milk-based diet. Bigger babies about one kilo, they were 29 weeks gestation, similar birth weight and gestational age. Necrotizing enterocolitis was again lower 0.9% versus 6% BPD was also lower 11% versus 21, nearly half 50% reduction in BPD, even in babies that are close to one kilo. ROP was not different because you don't expect that ROP serious ROP in these more mature babies, PDA was not different.
Based on oxygen, so significantly lower seven days versus 13 days in bovine based
They did a logistic regression on inflammatory complications in BPD preterm infants Babies that were fed exclusive formula or a mixed feeding combination of breast milk or human milk and formula, they still the odds ratio for BPD was significantly higher 2.59 to 1.61. Similarly, ROP odds ratio if you were exclusively formula fat is higher 1.8-fold increase odds ratio. Necrotizing enterocolitis is 12-fold increase, odds ratios 12.86., mixed feeding lower three point. Even some amount of
mom's milk or human milk is protective against BPD, ROP, and NEC in this network study.
There is also a dose dependent effect of exclusive human milk on BPD in very low birth weight infants. This was a study published from China last year, again a retrospective cohort study 964 babies all less than 1500 grams and less than or equal to 34-week gestation. So they looked at daily amount of human milk ingested by the babies per ml per kilo during the first four weeks. The babies did not get any breast milk, the risk for BPD was 40% if they got somewhere between one to 24 ml per kilo per day of human milk, they got 40%, 25 to 49 again about 34%. So that cut off in their study was if the babies are getting at least 50 ml or greater per kilo per day of human milk, then the risk for BPD was significantly lower 27% versus 35% and 40%. Moderate to severe BPD is also significant, nearly 50% less necrotizing enterocolitis was also lower, late onset sepsis was also lower, extra uterine growth restriction was also lower. So babies grew out in the lower risk for BPD and NEC, late onset sepsis. So we should try at least in the first three to four weeks, that babies are getting
50 or greater than 50 ml per kilo of human milk.
What about you know, there are sometimes you don't have human mother's milk for whatever reason, donor human milk versus mother's own milk on BPD and other models. So they looked at donor human milk, or mother's own milk, and they looked at babies that got at least 50 ml or greater in the first four weeks. They found no difference in the outcomes of BPD, moderate to severe BPD, NEC, late onset sepsis, or extrauterine growth restriction, whether you give mom's old milk for donor human milk, as long as the daily intake of human milk is at least 50 ml per kilo or greater on BPD, NEC, LOS, IUGR. So what's best is mom's own milk, if you don't have that donor human milk is a very good alternative.
Whatever fortification, we always say that babies should be fortified, does it make any difference? Other than we always look at the growth shots we don't look at other complication. Right so here is a study from Houston et al from Portland, Oregon, published last year. Early fortification means, they started fortification with the human milk-based fortifier from Prolacta Bioscience. It's a multicenter retrospective cohort study 394 babies less than 1250-gram birth weight. So early fortification means less than 60 ml per kilo. Late fortifications when the babies are taken at least 60 ml per kilo per day. Gestational age or similar slightly bigger because this late fortification right 27.6 versus 27 birth rate was similar. BPD, if you start fortifying babies early with human milk-based fortifier exclusively human milk diet, they grow, BPD is less 28% versus 43%. I think that delivery, better maintenance of gut
bacteria and lung microbiome. Severe ROP no difference. Necrotizing enterocolitis was not increased from early fortification some people were concerned that babies may not tolerate if I start fortifying early but there was no difference in NEC rate, weight gain So exclusive human milk
Earlier fortification was associated with improved growth velocity for weight p value .007 that head circumference less negative changes in disease course, after adjusting for multiple linear regression analysis, again no adverse effects are seen with early fortification using human milk-based fortifier.
Cost, you will always think about cost right whenever we are doing an intervention. So here society by Assad and Elliot et al,
It was a retrospective study, single center 293 babies all of them are less than or equal to 28-week gestation. They looked at BPD rate, human milk versus bovine milk or mixed significantly decreasing the risk of BPD, just like in the previous studies, ROP is also lower human milk vs bovine milk and sepsis was also significantly lower. In addition, they also found a number of times feeds were held due to feeding intolerance was also less in babies that were given exclusive human milk based diet. Of course, the incidence of NEC was lower and total cost of hospitalization for physician charges were also lower. And days on hospitalization also lower so apparently exclusive human milk diet led to less feeding tolerance, less necrotizing enterocolitis, shorter length of stay, lower hospitals cost in physician charges. So I don't think we can argue that milk is expensive. For example, if you don't have mom's milk to go and use donor human milk, that cost can be easily offset by saving babies without BPD, without ROP, without necrotizing enterocolitis, or sepsis.
So there is a study from Manthe et al from University of Virginia is that can we implement exclusive human milk based nutrition and improve outcomes in their NICU. So obviously, they had a QA project and looked at it and this is they published their experience 26 gestation. This is cows milk based fortifier. This is exclusive human milk based fortifier diet. 26 weeks about 820 to 894 grams. BPD was again lower 48.5% 65% any ROP or severe ROP was not statistically significant. Necrotizing enterocolitis was not different. Late onset sepsis was less but not statistically significant. Again, growth velocity was not different 16.4 or 16.4. So you can implement exclusive human based nutrition based on what I showed you based on the benefits.
What about raw mom's own milk that's pasteurized maternal milk. In this systematic review and meta-analysis, mainly observational studies, they showed that fresh mother's own milk is better than pasteurized mother's own milk in decreasing BPD.
Also data in this systematic review and meta-analysis if mom's own milk is not available, that's the only human milk protects against BPD. The answer is yes. So mainly observational studies comparing donor human milk versus preterm formula and look at the BPD was significantly lower with a risk ratio of 0.78 p value 0.001.
So overall, I've taken through basic science, microbiome studies and clinical studies, mostly observational studies. I don't think to use breast milk, you really need a randomized control trial in my opinion. So it is anti-infective anti-inflammatory antioxidant properties. Of course microbiome promotes growth in trophic factors in the gut stem cells and optimal nutrition for a preterm baby.
These days, I don't think anybody can talk about any talk without looking at racial and socio-economic disparities in breastfeeding, or nutrition or care of preterm babies. So here I'm focusing on breastfeeding per tail at all from Chicago that looked at different regions in the country in the US, there are market regional variations by maternal race and ethnicity.
Hi highest amount percentage of babies receiving early human milk at the time of discharge, or transfer from one hospital to the other, significantly higher in no matter
What region western United States northeast, Midwest, southern part of the United States Asian population had the highest incidence of breast milk. The lowest one is non-Hispanic black Americans, Native Americans and even Hispanic Americans. So we know in African American babies that perinatal mortality, morbidity including BPD is higher. So as a society, we need to decrease disparities and encourage these moms to bring produce or bring enough breast milk up to them or the advantage suppressant.
Is there a number of factors involved in it.
What are they- there are structural factors for example, insurance policies, the hospital campus system, paid maternity leave is not an issue not an option right now in this country, and breastfeeding, public messaging settings, you know, you have to provide free power.
Pick up if the mother is at home to deliver prematurely can we arrange for picking up the moms express milk in hospital lactation support home visits, to encourage the mothers to continue to pump and provide breast milk pumping after delivery immediately after delivery, bedside pumping space allocation when the baby's out of the NICU. No wide marketing the formula other milk substitutes individual mother and infant attributes of course.
So I've shown you so many advantages of breastmilk
but here is a baby you submitted. And I'll show you in a minute how did we get here.
This is how we got here. We told the mom that during consults, that we are providing kangaroo mother care to babies table we are going to encourage you to come pump your milk. colostrum is like gold. So even very little awkward. We want to carry that stuff KMC which means kangaroo mother care what we are doing is this, what I call kangaroo machine care. As soon as the baby gets admitted, we have some super specialists in our field.
neonatal pulmonologist, there is a neurocritical care expert among us he wants he or she wants nears pulmonologist expert expertise in us we want invasive or non-invasive isolate want to manipulate the knobs. Now even before giving surfactant, some people want to Dylan call person to decide about surfactant in the hemodynamics is very sexy, right? neonatal hemodynamics, they want to look at PDA they want to look at cardiac output they want to look at right heart function left heart function, we have a prewritten post that is saturation. You can see there's nothing here that monitors nutrition because these things are exciting. There are numbers and you do some intervention that numbers saying we are all happy with the malnutrition in inadequate nutrition or improper nutrition. We don't see that until they read develops NEC BPD ROP or extrauterine growth restriction and follow up normal neurodiverse outcome. So what we need is a monitor for something that says okay, colostrum, or breast milk, times one and whenever the nurse gives, she marks it and it shows up in a monitor times Baby got equals zero, maybe didn't get anything to give a visual input for all of us and say for us, we don't focus a lot. During rounds on nutrition we just say okay, how many calories the baby got per kilo per day how much fluids the baby got per kilo per day, we don't look at how much protein the baby got the baby get exclusively human milk than we don't know. So we have to focus on that make that as part of as exciting as these monitors. So we need a nutrition monitor. And an FNP, an FNP is not like a family nurse practitioner. What I want is a family neonatology practitioner. That's what my FNP meets whose will do family centered care, he treats the mother he or she loves to treat like a mother and baby as a single unit that somebody will provide the best care for babies.
So what are the principles of preterm nutrition to protect the lung because my topic is about BPD. But I also want to make sure that we protect the preterm infant as a whole not to work in silos. So first, human milk is a lifesaving drug. second principle, the best food special
for preterm babies, the principle is the main component of preterm infant nutrition should be human milk for human milk donated by mothers of preterm infants is truly a biological check as I mentioned before it has higher amounts of human milk oligosaccharides HMOs this higher amount of protein and fat deposits. Donor milk just a bridge to breastfeeding, so mother's own milk exemplifies what I call personalized medicines that's what we should aim for in our modern NICU shows where we have single rooms all these monitors are on the baby, we should have more access to the baby 24/7
So take home messages what are the benefits of exclusive human milk based nutrition we know clearly that it decreases BPD and BPD-associated primary hypertension. That's my focus and we know also it reduces necrotizing enterocolitis, ROP, extrauterine growth restriction, late-onset sepsis and it is a cost-effective intervention. It decreases later growth failures, decreases neurodevelopmental impairment and decreases metabolic syndromes as an adult.
For mothers it's also a benefit breastfeeding decreases breast and ovarian cancer. It serves lots of benefits both for the mom and the baby.
Thank you so much I would like to acknowledge Amy Gertz and Mark German from government from Prolacta Bioscience for outstanding support in getting this PNGconference organized and of course Dr Sathyan from UC Davis is these outstanding infographics that he allowed me to use. Thank you so much and I’ll be happy to answer any questions and hopefully you will enjoy the rest of the morning but the other speakers that are going to follow me thank you