Improving Neonatal Outcomes with Human Milk Roger G

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Improving Neonatal Outcomes with Human Milk Roger G. Faix, MD Division of Neonatology University

Improving Neonatal Outcomes with Human Milk Roger G. Faix, MD Division of Neonatology University of Utah Primary Children’s Intermountain Medical Center

0 DISCLOSURE The content of this presentation does not relate to any product in

0 DISCLOSURE The content of this presentation does not relate to any product in which I have a financial interest or potential conflict of interest.

Learning Objectives 1 - Learn why breast milk is the recommended form of enteral

Learning Objectives 1 - Learn why breast milk is the recommended form of enteral nutrition for all infants. 2 - Learn how commercial formulas differ from human breast milk. 3 -Appreciate longitudinal and other changes in content of human breast milk. Got Milk? Got Breast Milk?

Breastfeeding and Use of Human Milk Policy Statement. Pediatrics 2012; 129: e 827 -841

Breastfeeding and Use of Human Milk Policy Statement. Pediatrics 2012; 129: e 827 -841 �Breastfeeding and use of human milk confer unique nutritional and non-nutritional benefits to infant and mother and, in turn, optimize infant, child, and adult health as well as child growth and development. �Recently published evidence-based studies have confirmed and quantitated risks of not breastfeeding. Infant feeding should not be considered as a lifestyle choice but rather as a basic health issue.

Improving Outcomes with Human Milk Lifestyle Choices �Have a family �Have a career �Have

Improving Outcomes with Human Milk Lifestyle Choices �Have a family �Have a career �Have a snowmobile Basic Health Issues �Deliver in a hospital �Immunize your baby �Use a car seat �Infant feeding (breast milk)

Improving Outcomes with Human Milk in the Nursery and NICU Provider Choices �Switch ventilators

Improving Outcomes with Human Milk in the Nursery and NICU Provider Choices �Switch ventilators �Order a β-natriuretic peptide assay �Be nice to residents Basic Health Issues �Treat respiratory failure �Treat sepsis �Be nice to staff �Infant feeding (breast milk)

Meinzen-Derr J, et al. Role of human milk in extremely low birth weight infants’

Meinzen-Derr J, et al. Role of human milk in extremely low birth weight infants’ risk of necrotizing enterocolitis or death. J Perinatology 2009; 29: 57 -62 o NEC (7. 7%) or death > 14 d, 173/1272(13. 6%) Each 100 ml/kg increase in HM intake during the first 14 d was associated with decreased risk of NEC or death. (HR 0. 87 (95% CI 0. 77, 0. 97)

Ronnestadt A, et al. Late-onset sepsis in a Norwegian national cohort of extremely premature

Ronnestadt A, et al. Late-onset sepsis in a Norwegian national cohort of extremely premature infants receiving very early human milk feedings. Pediatrics 2005; 115: e 269 o 80/405 LOS (23%) Feedings started at 1 -2 m. L q 2 -3 h within a few hours of delivery and advanced 0. 51 m. L q 6 -8 h Survival free from LOS according to week when full feedings established RR of LOS if full feedings not established within a certain age (days) 92% MM 6% donor

Infectious Diseases Influenced by Infant Diet Infants - Children Pediatrics 2012; 129: e 827

Infectious Diseases Influenced by Infant Diet Infants - Children Pediatrics 2012; 129: e 827 -841

Diseases and Conditions influenced by Infant Diet Pediatrics 2012; 129: e 827 -841

Diseases and Conditions influenced by Infant Diet Pediatrics 2012; 129: e 827 -841

Basic Nutrients Proteins Fats Carbohydrates Vitamins Minerals Water All are present in milk of

Basic Nutrients Proteins Fats Carbohydrates Vitamins Minerals Water All are present in milk of all species, but types and proportions vary by species, making each specific and apparently uniquely suited Breast milk is more than good nutrition

Milk Protein Species Specific Content Protein Human Milk Cow’s Milk Quantity Low 3 -4

Milk Protein Species Specific Content Protein Human Milk Cow’s Milk Quantity Low 3 -4 X Higher Type Whey predominant Casein predominant Digestibility Curds soft, easy to digest Curds rubbery, harder to digest Brain and Eye development Taurine present Taurine absent Bioactive proteins Present Calves are mostly muscle and bone. They double their weight in <50 days. Humans are designed to grow more slowly, with emphasis on brain growth and social development.

A Partial List of Protein Functions New Peptide Derivatives Continue to be Discovered There

A Partial List of Protein Functions New Peptide Derivatives Continue to be Discovered There are 268 proteins in human milk from which even more bioactive peptides are released. Though some proteins are common to both species, they occur in significantly different quantities. Hetinga K et al. The Host Defense Proteome of Human and Bovine Milk. PLo. S One. 2011; 6(4): e 19433

“The expression of genes can be altered by changing the molecular environment that cells

“The expression of genes can be altered by changing the molecular environment that cells inhabit. . . no single act alters the environment of the cells of the body more than the ingestion of food. ” Sanderson, IR. Dietary Regulation of Gene Expression. Gastroenterology and Nutrition, Saunders, 2008, p 28

Gut Transformation after Birth Walker A, J Pediatrics 2010; 156: S 3 -7 o

Gut Transformation after Birth Walker A, J Pediatrics 2010; 156: S 3 -7 o → FETUS at birth Sterile GI tract Immature epithelium Delayed enterocyte proliferation Sparse lymphoid cells Breast fed NEONATE Bacterial colonization (2 -3 hr) Proliferating epithelium All subclasses of enterocytes Abundance of lymphoid tissues

Greater Enterocyte Proliferation with Colostrum than with Mature Breast Milk o Proliferation of enterocytes

Greater Enterocyte Proliferation with Colostrum than with Mature Breast Milk o Proliferation of enterocytes as measured by the incorporation of 3 H-thymidine after exposure to early (3 d) or late (57 d) breast milk. Tapper et al. J Pediatric surgery 1979; 14: 803 -8

“If peptides derived from gastrointestinal digestion of dietary proteins play a specific role as

“If peptides derived from gastrointestinal digestion of dietary proteins play a specific role as metabolic or physiological regulators, it seems logical that the biological activity exerted in the newborn by infant formulas or breast milk could be different. ” Hernandez-Ledesma B, et al. Interntl Dairy Journal 2007; 17: 42 -49

Colostrum is Part of Transition Constituent Colostrum 1 -5 d Mature BM > 30

Colostrum is Part of Transition Constituent Colostrum 1 -5 d Mature BM > 30 d Lysozyme (g) 218 161 Lactoferrin (g) 330 167 Ig. A (g) 364 142 1) Colostrum (Birth-4 d) is high in protein, fat-soluble vitamins, minerals, and immunoglobulins. It is different because normal transition requires it. 2) Transitional milk (2 d-2 wks) includes high levels of fat, lactose, water-soluble vitamins, and contains more calories than colostrum

Composition of Cow Milk formulas Based on nutrient content of human milk at 1

Composition of Cow Milk formulas Based on nutrient content of human milk at 1 -3 mo o Protein: nonfat bovine milk and whey concentrate o Fat: blend of vegetable oils o Carbohydrate: corn syrup solids and lactose o Vitamin and mineral mix o Additional ingredients are manufacturer-based: iron (1959), taurine (1984), DHA (2000), leutein (2012) Content is regulated by the FDA and is based on the AAP Committee on Nutrition recommendations

Milk Protein o Protein Human Milk Cow’s Milk Formula Quantity Low 3 -4 X

Milk Protein o Protein Human Milk Cow’s Milk Formula Quantity Low 3 -4 X Higher Type Whey predominant Casein predominant Digestibility Curds soft, easy More intolerance Bioactive proteins Species-specific differences associated with better outcomes Different in many ways Human milk protein is not ‘merely for nutrition. ’ It displays medicinal qualities that initiate and modulate development resulting in profound effects on infant survival and health

Milk Fat Species Specific Content Differences Fat Human Milk Cow’s Milk Formula Content during

Milk Fat Species Specific Content Differences Fat Human Milk Cow’s Milk Formula Content during feeding Low → High Constant Content if feed frequently High Constant Digestibility Lipoprotein Bile Salt-stimulated lipase No Lipases Essential FA 6 -10 times Higher Lower ARA, DHA (brain/eye) Present Recent additives Breastfeeding is associated with improved child cognitive development. MA Quigley et al. J Pediatrics 2012; 160: 25 -32

Preterm Lipid Study Pediatrics 2001; 108: 359 – 371 “Whether or not formulas designed

Preterm Lipid Study Pediatrics 2001; 108: 359 – 371 “Whether or not formulas designed for the premature infant should be supplemented with long-chain PUFA, including arachidonic acid and docosahexaenoic acid has become one of the most controversial issues in infant nutrition today. . . ” “. . . Several lines of logic suggest that premature infants fed formulas without AA and DHA may be at increased risk of slower development related to suboptimal blood and tissue levels of these fatty acids compared with the term infant. ”

Milk Carbohydrate Breast Milk is not just Lactose �Oligosaccharides - nonnutritive, the third most

Milk Carbohydrate Breast Milk is not just Lactose �Oligosaccharides - nonnutritive, the third most common solute in human milk after lactose and fat. Cow’s-milk formulas contain very little. �Prebiotic agents that encourage the growth of beneficial (probiotic) organisms �Anti-infective in the intestinal, respiratory and urinary tracts. >130 identified pathogen-specific, binding (decoy) inhibitors �Functional components of brain gangliosides essential to nerve cell transmission, memory formation and cell-to-cell communication. Miller JB. Invited Commentary: Human milk oligosaccharides: 130 reasons to breast-feed. British Journal of Nutrition 1999; 82: 333– 335 Ballard O and Morrow A. Human Milk Composition. PCNA 2013; 60(1)49 -74

Milk Vitamins and Minerals Species Specific Content Differences �All vitamins and minerals in human

Milk Vitamins and Minerals Species Specific Content Differences �All vitamins and minerals in human milk have a higher bioavailability than in cow milk formula � 50 -75% of Fe in BM is absorbed compared to 4% in formula �To compensate, more is added to formula: Fe (mg/L) HM (T) HM (PT) +HMF 1 0. 3 -0. 9 1. 21 4. 58 HM (PT) + HMF 2 PF 1 - 24 PF 2 - 24 15. 6 14. 61 14. 6 Excess, unabsorbed minerals (especially iron) alter gut flora and facilitate growth of potentially harmful bacteria

Vitamin and Mineral Supplementation Pediatrics 2012; 129: e 827 -e 841 �Vitamin K 0.

Vitamin and Mineral Supplementation Pediatrics 2012; 129: e 827 -e 841 �Vitamin K 0. 5 to 1. 0 mg IM after the first feeding at breast and before 6 hours �Vitamin D 400 U/day PO at hospital discharge �No Fluoride during the first 6 months and thereafter only if [fluoride] < 0. 3 ppm �Iron orally before 6 months if low iron stores Premature infants need multivitamins and iron until ingesting a mixed diet and growth is normalized

Optimal Source of Nutrients Breast milk content is essential for optimal development �Basic nutrient

Optimal Source of Nutrients Breast milk content is essential for optimal development �Basic nutrient and bioactive component content and proportions are species specific. Many differences exist. �Breast milk content can be (and is) altered by individual needs and circumstances. Formula content is fixed. �Formula is not milk. Many components are missing. Content is further altered by pasteurization. What formula lacks or has in it can make a difference

Term vs Preterm Milk Content Nutrient/L Term Preterm Vitamins Term Preterm Cal/oz 19. 5

Term vs Preterm Milk Content Nutrient/L Term Preterm Vitamins Term Preterm Cal/oz 19. 5 -21 20. 1 Vit A, IU 2252 3899 Protein, g 9 14. 09 Vit D, IU 20 20 Fat, g 39. 05 38. 93 Vit E, IU 4. 1 10. 7 Carb, g 79 66. 4 Vit K, mcg 2 -3 2 Calcium, mg 200 -250 248 Iron, mg 0. 3 -0. 9 1. 21 Sodium, mg 120 -250 248 Zinc, mg 1 -3 3. 42 m. Osm/L 257 255 Composition of human milk varies with maternal diet, lactation stage, within feedings, diurnally, and among mothers. Pediatric Nutrition Handbook 2009

Morton J, et al. Combining hand techniques with electric pumping increases the caloric content

Morton J, et al. Combining hand techniques with electric pumping increases the caloric content of milk in mothers of preterm infants J Perinatol 2012; 32: 791 -796 o Frequency of hand expression in first 3 d Group I < 2 times/day Group II 2 -5 times/day Group III > 5 times/day Increased frequency of hand expression in first 3 d increases milk production.

Formula content Neofax 2011, 24 th Edition Nutrient/L Term Milk Preterm PF-1 20 Cal/oz

Formula content Neofax 2011, 24 th Edition Nutrient/L Term Milk Preterm PF-1 20 Cal/oz 19. 5 -21 20 Protein, g 9 14. 09 20 Fat, g 39. 05 38. 93 36. 7 Carb, g 79 66. 4 69. 7 Calcium, mg 200 -250 248 1217 Iron, mg 0. 3 -0. 9 1. 21 12. 2 Sodium, mg 120 -250 248 291 Zinc, mg 1 -3 3. 42 10. 1 Because of poorer bioavailability, more is often needed

Vohr B, et al. Beneficial effects of breast milk in the neonatal intensive care

Vohr B, et al. Beneficial effects of breast milk in the neonatal intensive care unit on the developmental outcome of extremely low birth weight infants at 18 months of age. Pediatrics 2006; 118(1) no BM < 20 th 20 -40 40 -60 60 -80 > 80 th p BM (ml/kg) qd 0 1 7 24 64 111 - BM @ discharge 0 22 45 67 95 124 Mean MDI 76 74 77 78 80 87 . 004 Mean PDI 81 81 83 84 84 89 . 003 BRS percentile 46 45 52 50 52 59 . 028 Rehosp < 1 y 30 25 32 26 23 13 . 046 No diff BW, GA, sex, IVH gr 3 -4, PVL, NEC, sepsis, BPD, LOS, CP, blindness, hearing loss, weight and OFC @ 18 mo. Adj for mom age, edu, race, income For every 10 ml/kg/d increase in BM, there was an increase in MDI (0. 53 points), PDI (0. 63 points), BRS (0. 82 %ile), and a decreased likelihood of re-hospitalization (6%)

Vohr B, et al. Persistent beneficial effects of breast milk ingested in the neonatal

Vohr B, et al. Persistent beneficial effects of breast milk ingested in the neonatal intensive care unit on outcomes of extremely low birth weight infants at 30 months of age. Pediatrics 2007; 120(4) o The principal effects of BM in children at 30 months CA are on cognition and behavior.

Cost to Use Breast milk (no cost) PF 1 ($1. 18/oz) Expressed ($15/mo pump)

Cost to Use Breast milk (no cost) PF 1 ($1. 18/oz) Expressed ($15/mo pump) Elemental 1 ($1. 77/oz) Donor ($3. 50/oz + freight) Elemental 2 ($2. 48/oz) Commercial ($30. 00/oz) HMF/packet ($1. 08 -1. 50)

Cost to Not Use Breast Milk �If 90% of US families followed guidelines to

Cost to Not Use Breast Milk �If 90% of US families followed guidelines to BF exclusively for 6 mo, the US would annually save $13 billion from reduced medical and other costs. Bartick, M. Pediatrics 2010; 125: e 1048 -e 1056 (2007 dollars) CDC Start Any BF 6 mo Any BF 12 mo Exclusive 3 mo Exclusive 6 mo US 74% 43% 21% 32% 12% Utah 90% 60% 26% 43% 17% Healthy People 2010 75% 50% 25% 40% 17% 2012 AAP Policy 90% �Health care costs for newborns are three times lower for babies whose mothers participate in the company’s employee maternity and lactation program. www. surgeongeneral. gov/topics/breastfeeding/

Ganapathy V, et al. Breastfeeding Med 2012; 7(1): 29 -36 COSTS for extremely premature

Ganapathy V, et al. Breastfeeding Med 2012; 7(1): 29 -36 COSTS for extremely premature infants Supplements/infant BOVINE HUMAN 195 10, 321 Baseline Hospitalization (EP, no NEC) 207, 378 Medical NEC ($74, 004/EP infant) 11, 798 Surgical NEC ($198, 000/EP infant) 12, 583 1, 798 $ 231, 954 $ 223, 787 TOTAL Net Savings per EP Infant Admitted $ 8, 167* ( *p<0. 0001, 95% confidence interval, $4, 405–$11, 930) “The analyses presented in this article may assist healthcare providers and institutions to justify an increased use of human milk and human milk products to promote better health outcomes in EP infants. ”

Ziegler EE. Meeting the Nutritional Needs of the Low-Birth. Weight Infant. Ann Nutr Metab

Ziegler EE. Meeting the Nutritional Needs of the Low-Birth. Weight Infant. Ann Nutr Metab 2011; 58(suppl 1): 8 -18 Growth failure is associated with impaired neurocognitive development Human milk must be fortified with nutrients in order to enable adequate growth Parameter 500 -700 700 -900 900 -1200 -1500 Fetal wt gain (g/kg/d) 21 20 19 18 Protein (g/kg/d) 4. 0 3. 9 Energy (kcal/kg/d) 105 118 119 127

When growth of preterm infants lags behind expected growth (that is, growth like the

When growth of preterm infants lags behind expected growth (that is, growth like the fetus), it is almost always protein that is limiting growth Carlson SJ, Ziegler EE. Nutrient intakes and growth of very low birth weight infants. J Perinatol 1998; 18: 252– 258. Olsen IE, et al. Intersite differences in weight growth velocity of extremely premature infants. Pediatrics 2002; 110: 1125– 1132. Embleton NE, Pang N, Cooke RJ. Postnatal malnutrition and growth retardation: an inevitable consequence of current recommendations in preterm infants? Pediatrics 2003; 107: 270 – 273.

Arslanoglu S, Moro GE, and Ziegler EE. Adjustable fortification of human milk fed to

Arslanoglu S, Moro GE, and Ziegler EE. Adjustable fortification of human milk fed to preterm infants: does it make a difference? J Perinatology 2006; 26: 614 -621 o End Point 2000 g 16 14 8 bovine whey protein concentrate

Arslanoglu S, Moro GE, and Ziegler EE. Adjustable fortification of human milk fed to

Arslanoglu S, Moro GE, and Ziegler EE. Adjustable fortification of human milk fed to preterm infants: does it make a difference? J Perinatology 2006; 26: 614 -621 o 3. 4 2. 8 Optimal Intakes: Intrauterine protein intake of fetuses weighing the same as the mean body weights of study infants for each week.

Arslanoglu S, Moro GE, and Ziegler EE. Preterm infants fed fortified human milk receive

Arslanoglu S, Moro GE, and Ziegler EE. Preterm infants fed fortified human milk receive less protein than they need. J Perinatology 2009; 29: 489 -492 Variable Adjusted Assumed Actual Standard Assumed Actual Protein content (g/d. L) 2. 8 2. 3 1. 9 Fat content (g/d. L) 3. 9 3. 6 3. 9 3. 4 Kcal/d. L 90. 5 85. 2 85. 0 80. 5 Protein intake (g/kg/d) 4. 2 3. 4 3. 5 2. 8 kcal/kg/d 136 128 121 The inadequate levels of actual protein intakes observed in the present study offer an explanation of why preterm infants fail to grow adequately in spite of receiving adequate energy intakes.

Wojcik KY, et al. Macronutrient Analysis of a Nationwide Sample of Donor Breast Milk.

Wojcik KY, et al. Macronutrient Analysis of a Nationwide Sample of Donor Breast Milk. J Am Diet Assoc 2009; 109: 137 -140 415 samples from 273 donors nationwide Nutrient/L Mature Milk Donor Milk* kcal/oz 20 19. 2 (11 -32) Protein, g/d. L 1. 0 -1. 2 (0. 7 -2. 1) Fat, g/d. L variable 3. 2 (0. 7 -7. 1) Carb, g/d. L - 7. 8 (4. 9 -12. 7) *majority mature milk, but also a “sizable amount” of premature milk, 65% < 20 kcal/oz and 35% > 20 kcal/oz ** Ziegler EE. Ann Nutr Metab 2011; 58(suppl 1): 8 -18 Human milk protein, fat and energy content may be lower

Effect of breastfeeding vs formula feeding on childhood obesity j Arenz et al. ,

Effect of breastfeeding vs formula feeding on childhood obesity j Arenz et al. , Int J Obes Relat Metab Disord 2004; 28: 1247 -1256 The mechanisms for the association between breastfeeding and obesity are unclear

De Onis M, et al. Global prevalence and trends of overweight and obesity among

De Onis M, et al. Global prevalence and trends of overweight and obesity among preschool children. Am J Clin Nutr 2010; 92(5): 1257 -64 o 16. 00% 14. 00% 12. 00% 10. 00% Developed 8. 00% Global 6. 00% 4. 00% 2. 00% 0. 00% 1 2 3 4 5 6 7 1990 1995 2000 2005 2010 2015 2020 Children age 0 -5 years > 2 SD weight for height median

Standards for Normal Growth have Changed www. cdc. gov/growthcharts/ “All young children have the

Standards for Normal Growth have Changed www. cdc. gov/growthcharts/ “All young children have the potential to grow similarly, regardless of their ethnic group or place of birth, if they are in a healthy environment and receive adequate nutrition. ” 8000 Infants

Characteristics and Potential Functions of Human Milk Adiponectin �Protein hormone produced by adipose tissue

Characteristics and Potential Functions of Human Milk Adiponectin �Protein hormone produced by adipose tissue which enhances fatty acid metabolism and reduces inflammation �Low levels are associated with obesity, type 2 diabetes, dyslipidemia, and cardiovascular disease �Higher levels in human milk are associated with lower infant weight in the first 6 months of life in BF infants and may attenuate inflammatory processes Newburg DS et al. J Pediatr 2010; 156: S 41 -6

Adequate Growth Summary • Historically, preterm infants gain weight faster on formula than on

Adequate Growth Summary • Historically, preterm infants gain weight faster on formula than on human milk (breast or donor). • Because protein and energy content of human milk vary, more than standard fortification may be needed to achieve short-term growth standards. • However, faster early growth may be associated with higher rates of obesity. Growth norms (mostly formulafed infants) are too high. • Despite slower growth, breastfed infants have better neurodevelopmental outcomes.

Consider these Suggestions: What % of your NICU infants receive all BM to discharge?

Consider these Suggestions: What % of your NICU infants receive all BM to discharge? �Make lactation support a part of parent interactions �Educate all mothers on the value of human milk �Explain the need for breastfeeding mothers to pump and express milk early and often (8 -12 times daily) �Know they are doing it and doing it effectively �Strongly encourage exclusive human milk feedings (as you would treatment for presumed sepsis)

Fewer than 11% of US working parents receive paid leave when a child is

Fewer than 11% of US working parents receive paid leave when a child is born Providing up to 12 weeks unpaid leave only applies to companies with 50 or more employees

Human Milk Banking Association of North America www. hmbana. org o

Human Milk Banking Association of North America www. hmbana. org o

Milk Bank Donor Requirements �In good health. �Non-smoker. No use of any Nicotine products.

Milk Bank Donor Requirements �In good health. �Non-smoker. No use of any Nicotine products. �Negative blood test for viruses (Prenatal results are NOT used). �Using no medications during the time milk is collected for donation, except for: vitamins and minerals; food supplements, progestin-only birth control, or replacement hormones: thyroid, insulin �Limited use of caffeine; and a waiting period is required after alcohol use before donating milk �Willing to donate a minimum of 150 ounces total during the time they are a donor

How is Donor Milk Processed? http: //www. milkbankcolorado. org/ o Milk from 3 -5

How is Donor Milk Processed? http: //www. milkbankcolorado. org/ o Milk from 3 -5 donor mothers is thawed, transferred to glass flasks, and mixed.

How is Donor Milk Processed? http: //www. milkbankcolorado. org/ �Milk samples are cultured during

How is Donor Milk Processed? http: //www. milkbankcolorado. org/ �Milk samples are cultured during the pasteurization process then frozen at -4°F and stored �Culture-positive milk is discarded j • Milk is shipped frozen overnight to hospitals and individuals

Types of Donor Milk Available �Early Full Term: from first 7 -10 days post

Types of Donor Milk Available �Early Full Term: from first 7 -10 days post partum - 2 oz bottles (when available) �Preterm: for infants under 1500 grams and/or less than 36 weeks gestation - 2 oz bottles (when available) �Full Term: (20 cal or higher) for infants at or over 36 weeks gestation - 4 oz bottles (Also used routinely for premies when preterm not available ) �Non-fat: for chylothorax therapy (0. 0 - 0. 3% fat) - 2 oz bottles Each Batch is also Analyzed for Macronutrient Content