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Oct 24 CAPHC Lunch Symposium - Sponsored by Prolacta - Dr. Jae Kim

This document discusses best practices for improving neonatal outcomes through exclusive human milk feeding. It summarizes the nutritional and non-nutritional components of human milk that are beneficial for preterm infant development. Exclusive human milk feeding is associated with reduced rates of necrotizing enterocolitis, sepsis, retinopathy of prematurity, and bronchopulmonary dysplasia in preterm infants. Following standardized feeding protocols and providing human milk is a cost-effective strategy that can improve neonatal outcomes and reduce healthcare costs.

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Best Practices: Improving Neonatal Outcomes through Exclusive Human Milk Jae Kim, MD, PhD Department of Pediatrics Division of Neonatal-Perinatal Medicine Division of Pediatric Gastroenterology, Hepatology and Nutrition CAPH Conference, Halifax, Oct 2016
Conflict of Interest Disclosures • Medical Advisory Board • Medela • Speakers Bureau • Prolacta Biosciences • Nestle Nutrition • Nutricia • Abbott Nutrition • Mead Johnson Nutrition • Medela • Shares • Pedia Solutions • I do not intend to discuss an unapproved/investigative use of a commercial product/device in my presentation
Human milk is a tissue! Human Milk Blood CELLS ENZYMES HORMONES TRANSPORTERS CYTOKINES IMMUNE MODULATORS GROWTH FACTORS NUTRIENTS
Nutritional Components of Human Milk MACRONUTRIENTS Lipids Triglycerides (167 identified) Phospholipids Sphingolipids Sterols Fatty acids Proteins Caseins Whey Amino acids Mucins Carbohydrates Lactose Glucose Galactose Oligosaccharides Vitamins vitamin A niacin thiamin vitamin B6 panthothenic acid biotin folate vitamin B12 vitamin C vitamin D vitamin E vitamin K Minerals calcium phosphorus iron zinc copper manganese magnesium sodium potassium chloride sulphur MICRONUTRIENTS
Non-Nutritional Components of Human Milk Hundreds of different compounds Transporters lactoferrin (Fe) xanthine oxidase glutathione peroxidase alkaline phosphatase folate binder cobalamin binder IgF binder thyroxine binder corticosteroid binder Growth factors epidermal (EGF) nerve (NGF) insulin insulin-like (IGF) transforming (TGF) taurine polyamines gastrin gastric inhibitory peptide (GIP) Gastric regulatory peptide (GRP) neurotensin peptide histidine methionine (PHM) Peptide YY (PYY) Hormones feedback inhibitor of lactation (FIL) insulin prolactin thyroid hormones (T2, T3, Reverse T3) corticosteroids, ACTH oxytocin calcitonin parathyroid hormone erythropoietin progesterone estrogen Anti-inflammatory tumour necrosis factor interleukins interferon-g prostaglandins a1-antichymotrypsin a1-antitrypsin platelet-activating factor: acetyl hydrolase Antimicrobial secretory IgA, IgM, IgG lactoferrin lysozyme complement C3 leukocytes bifidus factor lipids and fatty acids antiviral mucins, GAGs oligosaccharides Digestive enzymes amylase bile acid-stimulating esterase bile acid-stimulating lipases lipoprotein lipase Proteases
Ingredients of Infant Formula MACRONUTRIENTS • water • nonfat milk • lactose • high oleic safflower oil, soy oil, coconut oil, C. cohnii oil (DHA), M. alpina oil (ARA) • whey protein concentrate MINERALS • potassium citrate, calcium carbonate, potassium chloride, magnesium chloride, sodium chloride, ferrous sulfate, choline chloride TRACE ELEMENTS • zinc sulfate, cupric sulfate, manganese sulfate, sodium selenate VITAMINS • d-alpha-tocopheryl acetate, ascorbic acid, niacinamide, riboflavin, calcium pantothenate, vitamin A palmitate, thiamine chloride hydrochloride, phylloquinone, pyridoxine hydrochloride, beta-carotene, folic acid, cyanocobalamin, vitamin D3, biotin EMULSIFIERS • mono- and diglycerides, soy lecithin, carrageenan, choline bitartrate, taurine, m- inositol, L-carnitine BIOLOGICS 1. nucleotides 2. prebiotics (term formula only) 3. probiotics (term formula only)
Benefits of mother’s milk to preterm infants • Cognitive development • Reduction in necrotizing enterocolitis (NEC) • Reduction in sepsis • Favorable alteration of microbiome • Reduction in retinopathy of prematurity (ROP) • PLUS all the health benefits known for mother’ milk in term infants: reduction in infant mortality, SIDS, autism, ADHD, allergy, asthma, infection, celiac disease, cognitive outcomes, etc.
2016 March of Dimes Prematurity Report Card
Impact of Neonatology to Healthcare Burden • Between 7% (CAN) to 12% (US) of live births are preterm (less than 37 weeks gestation) • NICU patients (preterm and sick newborns) represent a disproportionate share of hospital costs • Lifelong impact to healthcare burden and costs enormous • In the US, NICU is a top generator of financial revenue to hospitals
Morbidities of the preterm infant • Growth • Impaired growth • Altered body composition • Failure to thrive • Brain • Intracranial hemorrhage • Loss of white and gray matter, reduced size • Cardiovascular • Effects of patent ductus arteriosus • Long-term risk of cardiovascular disease and metabolic syndrome • Lung • Chronic lung disease • Asthma • GI • Necrotizing enterocolitis • Gastroesophageal reflux • Feeding intolerance/difficulties • Hematologic • Anemia • Neutropenia • Thrombocytosis • Renal • Impaired kidney development • Immune system • Skin
Goal of Feeding Preterm Infants Provide nutrients to approximate the rate of growth and composition of weight gain for a normal fetus of the same post-conceptional age and to maintain normal concentrations of blood and tissue nutrients. American Academy of Pediatrics Committee on Nutrition, In Pediatric Nutrition Handbook, 2013.
Matching In Utero Growth Zeigler et al., Growth. 1976 Dec;40(4):329-41. WEIGHT CLASS GROWTH G/KG/DAY ~ 3 lbs per day for 70 kg adult
The Developing Gut 1st Trimester 2nd Trimester 3rd Trimester Adapted from Commare and Tappenden, 2007 Nut Clin Pract Cytodifferentiation Absorption Motility Digestion Morphogenesis Swallowing 0wk 14 22 28 40 Viability Line STRUCTUREFUNCTION
Preterm Risk Factors for Bowel Injury • Ischemia • Immature gut and systemic immune system • Dysmotility • Underdeveloped physical mucosal barrier (tight junctions, mucin) • Poor acid production • Abnormal bacterial colonization
Necrotizing Enterocolitis • NEC is the most common life- threatening gastrointestinal emergency in the newborn period • NEC is marked by intense inflammation and acute intestinal necrosis • Most common sites include terminal ileum, cecum and ascending colon
The Perfect Storm for NEC PREMATURITY ISCHEMIA PATHOGENIC BACTERIA ENTERAL FEEDING TRANSMURAL BOWEL INFLAMMATION BOWEL NECROSIS BREAKDOWN OF MUCOSAL BARRIER/DEFENSE
NEC Pathogenesis Hunter et al. 2008 Pediatr Res 63;2:117
Pneumatosis Intestinalis
Coagulative Necrosis
NEC Morbidity • Growth failure due to bowel injury • Intestinal obstruction and subsequent surgery • Longer hospital stay • Risk of dying • Risk for more pain and suffering • Short bowel syndrome and/or intestinal failure • Can lead to need for long-term PN use and later bowel transplantation • Neurodevelopmental impairment!
Necrotizing Enterocolitis
Strategies to prevent NEC • Prevent preterm birth • Standardized feeding protocol • Exclusive human milk feeding • Antibiotic stewardship • Reduce anti-acid meds • Probiotics • Blood transfusions • Patent ductus arteriosus • Congenital heart disease • Prebiotics • Minimize osmolality
NEC is the result of a biochemical reaction WARMTH MOISTURE BACTERIA SUBSTRATE (MILK OR FORMULA)
Standardized Feeding Protocol Having a feeding protocol is associated with reduced NEC rates Patole, Arch Dis Child Fetal Neonatal Ed. 2005;90(2):F147-151. Key Elements of a Great Feeding Protocol • Established consensus from medical faculty • Visible, nurse-driven advancement • Linear advancement • Trophic feeding for extremely preterm infants • Incorporate timing of fortification and vitamins
10% of very preterm babies developed NEC 30-50% NEED SURGERY 25-50% DIE! Human milk can reduce NEC (medical and surgical) by at least 50% Most very preterm infants are fed formula!!
Fractional Human Milk Feeding Reduces Chances of NEC Fraction of Human Milk Feeding Meinzen-Derr et al. NICHD Network, J Perinatol 2008:1-6
Lactation support • Ideally mothers should initiate pumping or breastfeeding within 2h after vaginal delivery and 4h after cesarean section • Peak lactation volumes may be influenced by very early pumping/expressing milk within the first hour of life Parker et al. Breastfeed Med. 2015 Mar;10(2):84-91. <1h and ≤6h >6h
Human Milk Human Milk Bovine (intact or hydrolyzed) HMF Human HMF Current Standard Emerging Standard Preterm Formula Past Progress in Human Milk Fortification
Exclusive Human Milk vs Preterm Formula: RCT in Extremely Preterm HM PF p Birth weight (g) 996 ± 152 983 ± 207 NS Gestational age (wks) 27.7 ± 1.5 27.5 ± 2.4 NS Study duration (d) 50 ± 20 50 ± 23 NS Preterm <1250 g Planned for Infant Formula Preterm Formula (PF) n=23 Exclusive Human Milk (HM) and Fortiifier n=29 Cristafalo et al. J Pediatr. 2013 Dec;163(6):1592-1595.e1.
Results • First randomized double-blind trial in infants of exclusive diets of HM vs PF • The significantly shorter duration of TPN and lower HM PF p n 29 23 Duration of TPN (d) 27 36 0.04 NEC 1 (3.6%) 5 (21.7%) 0.08 Surgical NEC 0 4 0.04 Cumulative morbidity 0.7 ± 0.5 1.2 ± 1.0 0.03 Length increment (cm/d) 0.12 ± 0.03 0.16 ± 0.04 0.006 Cristafalo et al. J Pediatr. 2013 Dec;163(6):1592-1595.e1.
Exclusive human milk reduces overall NEC and surgical NEC Sullivan et al (2010) J Pediatr. 2010;156:562-7 Protocol violations: received bovine product
Impact of choosing bovine products No NEC Medical NEC Surgical NEC Mortality 10.6% 20.9% 23.2% Double the risk of death! Sullivan et al (2010) J Pediatr. 2010;156:562-7 Ganapathy et al. 2011 Breastfeeding Medicine
NEC continues to add to long-term costs within the first three years of life • Texas Medicaid healthcare utilization database • Jan 2012 to Dec 2013 • 253 survivors of NEC (73 surgical NEC) • 2909 matched controls • Medical NEC incurred higher costs than controls between 6 and 12 months • Surgical NEC incurred higher costs than controls up to 36 months • Costs tapered down from ~ 18K to 8K per survivor Ganapathy et al. BMC Pediatr. 2013 Aug 20;13:127.
An exclusive human milk (EHM) diet reduces TPN need Ghandehari et al. BMC Res Notes. 2012 Apr 25;5:188. 11-14% Reduction in TPN use Greater when looking at TPN after initial use Increased likelihood if HMF started earlier EHM
Balance of effects in developing NEC
Decreased cost and improved feeding tolerance in VLBW infants fed an exclusive human milk diet • Retrospective study including preterm infants ⩽28 weeks and/or VLBW (⩽1500 g) • Single center (The Herman & Walter Samuelson Children’s Hospital at Sinai, Baltimore, MD, USA) • March 2009 until March 2014 • (2012-2014) • group H (exclusive human milk or EHM) • (2009-2012) • group B (bovine-based fortifier and maternal milk) • group M (mixed combination of maternal milk, bovine-based fortifier and formula) • group F (formula fed infants) • N = 293 infants between 23 to 34 weeks gestation and birth weights between 490 and 1700 g Assad et al. J Perinatol. 2016 Mar;36(3):216-20.
Less feeding intolerance (P<0.0001) Lower number of days to full feeds by 9-10 days (P<0.001) Lower incidence of NEC (P<0.011) Shorter length of stay by 4 to 22 days for EHM group Similar average weight gain per among the four groups (18.5 to 20.6 g per day) Assad et al. J Perinatol. 2016 Mar;36(3):216-20.
Lower total hospitalization costs by up to $106,968 per infant (P<0.004) in those fed an EHM diet Assad et al. J Perinatol. 2016 Mar;36(3):216-20.
Beyond Necrotizing Enterocolitis Prevention: Improving Outcomes with an Exclusive Human Milk-Based Diet • Retrospective cohort study • 4 centers, N =1,587 infants (Texas, Illinois, Florida, and California) • Lower NEC (16.7% versus 6.9%, p < 0.00001) • Reduced mortality (17.2% versus 13.6%, p = 0.04) • Reduced late-onset sepsis (30.3% versus 19.0%, p < 0.00001) • Reduced ROP (9% versus 5.2%, p = 0.003) • Reduced BPD (56.3% versus 47.7%, p = 0.0015) Hair et al. Breastfeed Med. 2016 Mar;11:70-4.
Continuum of Health Benefits from Human Milk Newborn SeniorChild NEC Neurodevelopment ROP Visual performance BPD Asthma, Lung Disease, Neurodevelopment Adult Sepsis Neurodevelopment
Containing Health Care Costs • What motivates reduction in health care costs? • Public model of cost-bundled that limit spending per patient (Medicaid) • Fee for service • Payer that pay out for sicker patients staying longer in hospital • Performance or outcomes based incentives • Value based models • Perspective matters • Cost to the patient and family • Cost to the hospital • Cost to the healthcare system • Cost to society
Economic Costs of NEC • One case of medical NEC is almost $75,000 USD • One case of surgical NEC is almost $200,000 USD • NEC costs the health care system $5 billion USD annually (assume 10% incidence of NEC and 30% mortality) • NEC constitutes 19% of the total costs for initial care for all newborns in the US Bisquera J et al. Pediatrics 2002;109:423-428 Ganapathy et al. Breastfeed Med. 2012 Feb;7(1):29-37
Balancing the cost of an exclusive human diet Feeding of 160 mL/kg/day Powder HMF: 1 packet per 25 mL of milk =$0.06/mL = 100X costs Ganapathy et al. Breastfeed Med. 2012 Feb;7(1):29-37
Cost equation • Costs CAN 12,500 per patient • Protocol to 34 weeks according • Net savings of CAN 10,208 per patient given EHM diet • If human milk was a drug, would we act differently? Ganapathy et al. Breastfeed Med. 2012 Feb;7(1):29-37
History of Donor Milk • 1909: the first milk bank was established in Vienna, Austria • 1910: milk bank in Boston • North American history in milk banking is 100 years old • 1974: Canada’s first milk bank in Vancouver • By early 1980’s 23 banks in Canada and 30 in US • 1981: HIV identified as a pathogen; North America reduced to 8 banks • 1985: Human Milk Banking Association of North America (HMBANA) established • 2000: Vancouver Milk Bank almost closes http://en.wikipedia.org/wiki/File:HIV-budding-Color.jpg Images from Toronto SickKids Archives HIV
Modern Human Milk Banking • HMBANA • International Human Milk Banking Association • Organizations in other countries • UKAMB & other European countries • South America – Brazil & Venezuela • South Africa • Other countries – India, Japan, China • National Milk Bank (est. 2005) • Prolacta Bioscience (est. 2005) • Medolac (est. 2013)
Donor Milk Banking in North America hmbana.org Existing Milk Banks Cities Served by Milk Banks
Donor human milk PROS • Human specific • Bridges gap when mother’s milk supply insufficient to meet infant’s requirements CONS • Lower quality milk compared to fresh milk • No cellular components or probiotics • Less protein due to maturity of milk • No lipase activity that may alter digestion • Reduced bioactive components due to processing • Reduced salts and vitamins
Screening (Questionnaire and Blood) Expression of milk Freezing, storage, and transport Thawing and Bacterial culture Batching Pasteurization Culture of batch Freezing Processing of Donor Human Milk Thawed for use
Mothers’ Own Milk Bank of Austin, Texas HMBANA NONPROFIT MILK BANKING
COMMERCIAL MILK BANKING
Major Concerns For Use of Donor Human Milk • Nutrition • Loss of bioactivity (immunologic protection) • Infectious risk • Tampering • Cost • Supply • Legal
Level of Quality of Human Milk • Breastfeeding • Fresh human milk • Refrigerated human milk • Really frozen human milk (-80ºC) • Frozen human milk (-20ºC) • Donor human milk TRIAGE • Colostrum > Fresh mature > Refrigerated > Frozen
Recommendations for Donor Human Milk Banking AAP Committee on Nutrition Statement (in press) CPS Committee of Nutrition (Kim and Unger) 2012 • Donor human milk is an acceptable alternative to mother’s own milk for preterm infants when it is not available • HMBANA or commercial donor banks are suitable sources • AAP • The use of donor human milk in appropriate high-risk infants should not be limited by an individual’s ability to pay. • Policies are needed to provide high-risk infants access to donor human milk on the basis of documented medical necessity, not financial status. • Avoid unpasteurized milk sharing off Internet • CPS • Recognized functions of the human milk bank should include the promotion of breastfeeding and ongoing human milk research. • Pasteurized human donor breast milk should only be prescribed following written informed consent from a parent or guardian.
Canadian Milk Banking
California Milk Banking MMB of San Diego 2017 • All of California is currently served by one milk bank • UC San Diego is developing a milk bank in San Diego for Southern California
Benefits of Donor Human Milk to Preterm Infants • DOMINO Study (Canada) • Recently completed • Saw reduction in NEC • Long-term followup data pending • NICHD (Donor milk trial) • Ongoing recruitment • Slowing recruitment due to loss of equipoise • Optimom study (Canada) • Donor milk derived fortifier study • Closed but not reported
Oral Colostrum Care Oropharyngeal administration involves placing small amounts of a liquid directly onto the oral mucosa with expectation that the liquid, or any of its components, is absorbed by the mucous membranes. Rodriguez, N.A., et al., Oropharyngeal administration of colostrum to extremely low birth weight infants: theoretical perspectives. J Perinatol, 2009. 29(1): p. 1-7. Colostrum Breast Milk Total Protein (g/100mL) 3.7 1.3 IL-6 (pg/mL) 978.8 86.92 Fat (g/100mL) 2.9 4.2 Lactose (g/100mL) 57 7.4 IgM (mg/g protein) 30 4 IgA (mg/g protein) 175 20 IgG (mg/g protein) 3 2
Colostrum • Produced when the tight junctions in the mammary epithelium are open • Paracellular transport of immunologically derived protective components from mother’s circulation into milk • Contain various immunomodulatory agents • Secretory immunoglobulin A [sIgA] • Growth factors • Lactoferrin • Anti-inflammatory cytokines • More highly concentrated in mother’s of preterm infants
Evidence that oral colostrum care benefits preterm babies • Seigel 2013 • Retrospective cohort study of 369 inborn ELBW infants, 5 day treatment • Mortality, surgical NEC, SIP rates unchanged • Higher weight at 36 weeks (1666g vs. 1380g p<0.001) • Lee 2015 • Double blind, placebo-controlled trial of 45 infants <28 weeks gestation in South Korea • Increased urine levels of immunoglobulin A and lactoferrin • Significant decrease in clinical sepsis • Sohn 2016 • Impact of buccal administration of human colostrum on the oral microbiota of 12 VLBW infants • OCC altered the colonization of the oral cavity with effects lasting after the intervention ELBW = birth weight less than 1000 grams; VLBW = birth weight less than 1500 grams
Human milk derivatives: value of a cream supplement • HM-derived cream supplement if energy density of HM <20 kcal/oz using a near infrared HM analyzer • Treated until 36 weeks PMA • HM-derived cream should be considered an adjunctive supplement to an exclusive HM-based diet to improve growth rates in premature infants Human Milk Human HMF Exclusively Human Human milk cream Velocity Cream supplemented (n=39) No cream (n=39) p Weight (g/kg/d) 14.0 +/- 2.5 12.4 +/- 3.0 0.03 Length (cm/wk) 1.03 +/- 0.33 0.83 +/- 0.41 0.02
Terminology Microbiota The collection of microbes in a particular environment Microbiome The catalog of microbes and their genes in a particular environment Metagenomics The collection of genes and genomes from microbiota
Terminology PROBIOTICS POSTBIOTICSPREBIOTICS SYNBIOTICS Human Milk is the Original Synbiotic
The human gastrointestinal microbiota • First inoculation during birth with passage through birth canal • Influenced by prebiotics and probiotics • Adult microflora by 2 years of age • Over 500 bacterial species • 1010 organisms (at least ten fold higher than human cells) • Symbiosis between man and bacteria • 5-10 lbs of bacteria, about 60% of fecal mass • The “forgotten organ”
We need microbes! N Engl J Med. 2002 Sep 19;347(12):911-20. FALL OF INFECTION RISE OF AUTOIMMUNITY AND IMMUNE DYSFUNCTION
Dysbiosis • sick ecosystem • low diversity of species • Imbalance • lack of functional redundancy • susceptibility to disease
Type of birth Vaginal birth C-section • Sterile environment • Frequent use of antibiotics • Preterm infants born ~70% by C/S • Exposure to nosocomial microbes • Long-term risk of food allergy • Papathoma et al. 2016 • Long-term risk of immune dysfunction • Asthma, laryngitis, gastroenteritis, ulcerative colitis, rheumatoid arthritis, celiac disease • Kristensen et al. J Allergy Clin Immunol. 2016 Feb;137(2):587-90. • Delivery through birth canal • Direct contact to and ingestion of vaginal flora • Vaginal flora a mix of maternal vaginal and colonic flora
Risk of the preterm infant • Often not delivered from birth canal • Frequent use of broad spectrum antibiotics • Delay in enteral feedings • Sterilization of infant formulas • Nosocomial bacterial colonization
Impaired Colonization of the Preterm Gut • Delay in establishment of gut flora • Reduction in the number of bacteria • Reduction in the diversity of bacteria
Dietary differences and predominant organisms Bifidobacteria Lactobacilli E. coli Bacteroides Clostridia Harmsen et al., J Pediatr Gastroenterol Nutr. 2000;30(1):61-67. Gronlund et al. Clin Exp Allergy. 2007 Dec;37(12):1764-72. Breastfed Formula fed
Mai et al 2011 PLoS One. 2011; 6(6): e20647. MICROBIOTA BEFORE NEC OCCURS
Maternal infant microbiome There are no sterile environments. Not uterus, not fetus. Vinturache et al 2016 Sem Fetal Med 1-6
Human Milk Microbiome • Human milk has its own microbiota • Phyla include Firmicutes, Proteobacteria and Actinobacteria • Each mother’s microbiota is unique • Donor human milk is pasteurized and therefore microbe-free Hunt et al. PLoS One. 2011;6(6):e21313.
BIFIDOBACTERIA LACTOBACILLI • B. infantis • B. breve • B. adolescentis • B. longum • B. bifidus • B. catenulatum • B. animalis • B. suis • B. globosum • L. reuterii • L. fermentum • L. rhamnosus • L. salivarius • L. gasseri • L. caseii • L. planarum infant adult Bold found in human milk
Human Milk Oligosaccharides (HMO) • Third largest component in human milk! • Small chain sugars (>150 variations) • Resist digestion • Substrate for beneficial intestinal microflora • Support favorable bacteria population in infant colon (“BIFIDOGENIC”) • Beneficial microflora stimulate the developing immune system Bode, J Nutr 2006;136:2127-30. Boehm J Nutr 2007;137(3 Suppl 2):847S-9S.
Bacteria Fungal Viral HIVIntestinal development Intestinal immune function NEC Multitude of effects of HMO Intestinal epithelial health HMO
Diffusion of Innovation Rogers EM, 1962 Law of Diffusion of Innovation
Trend in feeding in last decade Human milk based fortifiers Preterm formula Mother’s milk Donor milk Hydrolyzed bovine Oral colostrum care S Curve
Mother pumps Milk in bottle Milk in storage container Milk in home freezer Milk in cooler for transport Milk in NICU freezer Milk thawed Milk measured Milk fortified Milk drawn into syringes Milk in tubing Milk in baby (finally!) MILK “TRAFFIC” CHAIN
Changing the clinical practice towards a dominant mother’s milk culture in hospitals is very challenging but cost effective in promoting a healthier long term outlook for premature infants
The future… Exclusively Human Human Milk Human HMF Donor milk derived additives • Maternal lactation support • Donor human milk banking • Lacto-engineering science • Addition of cream • Addition of protein • Human milk derivative bioactive additives • Refinement of processing of human milk for preservation of function • Increased cost benefit analysis for other long-term morbidities Priorities 1. Maternal lactation 2. Donor human milk 3. Human milk fortifiers 4. Human milk derivatives
The SPIN Program Ten Steps 1. Have a NICU nutrition/human milk policy 2. Educate all mother/baby staff in SPIN 10-steps 3. Educate NICU families about optimal premature infant nutrition 4. Prevent extra-uterine growth restriction 5. Standardize enteral feeding procedures 6. Target 100% human milk nutrition 7. Maximize mothers’ milk production 8. Optimize milk quality and safety 9. Encourage skin-to-skin care and breastfeeding 10. Plan a nutritional discharge from NICU NUTRITION LACTATION
THE SPIN TEAM • Medical director • Lactation director • NICU F/U Neo • NICU CNS • Lactation • OT • NICU Dietician • Research RN • NICU Staff RN
spinprogram.ucsd.edu
Take home points • Human milk is the single most powerful intervention to optimize the best health outcomes in all babies • In the absence of maternal milk, donor human milk is a superior substitute to formula • Donor milk derivatives now support the provision of an exclusively human milk diet • Initiating and maintaining a balanced gut microbiota begins with maternal milk • Moving towards an exclusively human milk diet will show increasing cost savings and long-term healthcare benefits to preterm infants
It takes a village to care for our babies!
Parent Advocacy against NEC www.necsociety.org
Oct 24 CAPHC Lunch Symposium - Sponsored by Prolacta - Dr. Jae Kim

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Oct 24 CAPHC Lunch Symposium - Sponsored by Prolacta - Dr. Jae Kim

  • 1.
    Best Practices: Improving NeonatalOutcomes through Exclusive Human Milk Jae Kim, MD, PhD Department of Pediatrics Division of Neonatal-Perinatal Medicine Division of Pediatric Gastroenterology, Hepatology and Nutrition CAPH Conference, Halifax, Oct 2016
  • 2.
    Conflict of InterestDisclosures • Medical Advisory Board • Medela • Speakers Bureau • Prolacta Biosciences • Nestle Nutrition • Nutricia • Abbott Nutrition • Mead Johnson Nutrition • Medela • Shares • Pedia Solutions • I do not intend to discuss an unapproved/investigative use of a commercial product/device in my presentation
  • 3.
    Human milk isa tissue! Human Milk Blood CELLS ENZYMES HORMONES TRANSPORTERS CYTOKINES IMMUNE MODULATORS GROWTH FACTORS NUTRIENTS
  • 4.
    Nutritional Components ofHuman Milk MACRONUTRIENTS Lipids Triglycerides (167 identified) Phospholipids Sphingolipids Sterols Fatty acids Proteins Caseins Whey Amino acids Mucins Carbohydrates Lactose Glucose Galactose Oligosaccharides Vitamins vitamin A niacin thiamin vitamin B6 panthothenic acid biotin folate vitamin B12 vitamin C vitamin D vitamin E vitamin K Minerals calcium phosphorus iron zinc copper manganese magnesium sodium potassium chloride sulphur MICRONUTRIENTS
  • 5.
    Non-Nutritional Components ofHuman Milk Hundreds of different compounds Transporters lactoferrin (Fe) xanthine oxidase glutathione peroxidase alkaline phosphatase folate binder cobalamin binder IgF binder thyroxine binder corticosteroid binder Growth factors epidermal (EGF) nerve (NGF) insulin insulin-like (IGF) transforming (TGF) taurine polyamines gastrin gastric inhibitory peptide (GIP) Gastric regulatory peptide (GRP) neurotensin peptide histidine methionine (PHM) Peptide YY (PYY) Hormones feedback inhibitor of lactation (FIL) insulin prolactin thyroid hormones (T2, T3, Reverse T3) corticosteroids, ACTH oxytocin calcitonin parathyroid hormone erythropoietin progesterone estrogen Anti-inflammatory tumour necrosis factor interleukins interferon-g prostaglandins a1-antichymotrypsin a1-antitrypsin platelet-activating factor: acetyl hydrolase Antimicrobial secretory IgA, IgM, IgG lactoferrin lysozyme complement C3 leukocytes bifidus factor lipids and fatty acids antiviral mucins, GAGs oligosaccharides Digestive enzymes amylase bile acid-stimulating esterase bile acid-stimulating lipases lipoprotein lipase Proteases
  • 6.
    Ingredients of InfantFormula MACRONUTRIENTS • water • nonfat milk • lactose • high oleic safflower oil, soy oil, coconut oil, C. cohnii oil (DHA), M. alpina oil (ARA) • whey protein concentrate MINERALS • potassium citrate, calcium carbonate, potassium chloride, magnesium chloride, sodium chloride, ferrous sulfate, choline chloride TRACE ELEMENTS • zinc sulfate, cupric sulfate, manganese sulfate, sodium selenate VITAMINS • d-alpha-tocopheryl acetate, ascorbic acid, niacinamide, riboflavin, calcium pantothenate, vitamin A palmitate, thiamine chloride hydrochloride, phylloquinone, pyridoxine hydrochloride, beta-carotene, folic acid, cyanocobalamin, vitamin D3, biotin EMULSIFIERS • mono- and diglycerides, soy lecithin, carrageenan, choline bitartrate, taurine, m- inositol, L-carnitine BIOLOGICS 1. nucleotides 2. prebiotics (term formula only) 3. probiotics (term formula only)
  • 7.
    Benefits of mother’smilk to preterm infants • Cognitive development • Reduction in necrotizing enterocolitis (NEC) • Reduction in sepsis • Favorable alteration of microbiome • Reduction in retinopathy of prematurity (ROP) • PLUS all the health benefits known for mother’ milk in term infants: reduction in infant mortality, SIDS, autism, ADHD, allergy, asthma, infection, celiac disease, cognitive outcomes, etc.
  • 8.
    2016 March ofDimes Prematurity Report Card
  • 9.
    Impact of Neonatologyto Healthcare Burden • Between 7% (CAN) to 12% (US) of live births are preterm (less than 37 weeks gestation) • NICU patients (preterm and sick newborns) represent a disproportionate share of hospital costs • Lifelong impact to healthcare burden and costs enormous • In the US, NICU is a top generator of financial revenue to hospitals
  • 10.
    Morbidities of thepreterm infant • Growth • Impaired growth • Altered body composition • Failure to thrive • Brain • Intracranial hemorrhage • Loss of white and gray matter, reduced size • Cardiovascular • Effects of patent ductus arteriosus • Long-term risk of cardiovascular disease and metabolic syndrome • Lung • Chronic lung disease • Asthma • GI • Necrotizing enterocolitis • Gastroesophageal reflux • Feeding intolerance/difficulties • Hematologic • Anemia • Neutropenia • Thrombocytosis • Renal • Impaired kidney development • Immune system • Skin
  • 11.
    Goal of FeedingPreterm Infants Provide nutrients to approximate the rate of growth and composition of weight gain for a normal fetus of the same post-conceptional age and to maintain normal concentrations of blood and tissue nutrients. American Academy of Pediatrics Committee on Nutrition, In Pediatric Nutrition Handbook, 2013.
  • 12.
    Matching In UteroGrowth Zeigler et al., Growth. 1976 Dec;40(4):329-41. WEIGHT CLASS GROWTH G/KG/DAY ~ 3 lbs per day for 70 kg adult
  • 13.
    The Developing Gut 1stTrimester 2nd Trimester 3rd Trimester Adapted from Commare and Tappenden, 2007 Nut Clin Pract Cytodifferentiation Absorption Motility Digestion Morphogenesis Swallowing 0wk 14 22 28 40 Viability Line STRUCTUREFUNCTION
  • 14.
    Preterm Risk Factorsfor Bowel Injury • Ischemia • Immature gut and systemic immune system • Dysmotility • Underdeveloped physical mucosal barrier (tight junctions, mucin) • Poor acid production • Abnormal bacterial colonization
  • 15.
    Necrotizing Enterocolitis • NECis the most common life- threatening gastrointestinal emergency in the newborn period • NEC is marked by intense inflammation and acute intestinal necrosis • Most common sites include terminal ileum, cecum and ascending colon
  • 16.
    The Perfect Stormfor NEC PREMATURITY ISCHEMIA PATHOGENIC BACTERIA ENTERAL FEEDING TRANSMURAL BOWEL INFLAMMATION BOWEL NECROSIS BREAKDOWN OF MUCOSAL BARRIER/DEFENSE
  • 17.
    NEC Pathogenesis Hunter etal. 2008 Pediatr Res 63;2:117
  • 18.
  • 19.
  • 20.
    NEC Morbidity • Growthfailure due to bowel injury • Intestinal obstruction and subsequent surgery • Longer hospital stay • Risk of dying • Risk for more pain and suffering • Short bowel syndrome and/or intestinal failure • Can lead to need for long-term PN use and later bowel transplantation • Neurodevelopmental impairment!
  • 21.
  • 22.
    Strategies to preventNEC • Prevent preterm birth • Standardized feeding protocol • Exclusive human milk feeding • Antibiotic stewardship • Reduce anti-acid meds • Probiotics • Blood transfusions • Patent ductus arteriosus • Congenital heart disease • Prebiotics • Minimize osmolality
  • 23.
    NEC is theresult of a biochemical reaction WARMTH MOISTURE BACTERIA SUBSTRATE (MILK OR FORMULA)
  • 24.
    Standardized Feeding Protocol Havinga feeding protocol is associated with reduced NEC rates Patole, Arch Dis Child Fetal Neonatal Ed. 2005;90(2):F147-151. Key Elements of a Great Feeding Protocol • Established consensus from medical faculty • Visible, nurse-driven advancement • Linear advancement • Trophic feeding for extremely preterm infants • Incorporate timing of fortification and vitamins
  • 25.
    10% of verypreterm babies developed NEC 30-50% NEED SURGERY 25-50% DIE! Human milk can reduce NEC (medical and surgical) by at least 50% Most very preterm infants are fed formula!!
  • 26.
    Fractional Human MilkFeeding Reduces Chances of NEC Fraction of Human Milk Feeding Meinzen-Derr et al. NICHD Network, J Perinatol 2008:1-6
  • 27.
    Lactation support • Ideallymothers should initiate pumping or breastfeeding within 2h after vaginal delivery and 4h after cesarean section • Peak lactation volumes may be influenced by very early pumping/expressing milk within the first hour of life Parker et al. Breastfeed Med. 2015 Mar;10(2):84-91. <1h and ≤6h >6h
  • 28.
  • 29.
    Exclusive Human Milkvs Preterm Formula: RCT in Extremely Preterm HM PF p Birth weight (g) 996 ± 152 983 ± 207 NS Gestational age (wks) 27.7 ± 1.5 27.5 ± 2.4 NS Study duration (d) 50 ± 20 50 ± 23 NS Preterm <1250 g Planned for Infant Formula Preterm Formula (PF) n=23 Exclusive Human Milk (HM) and Fortiifier n=29 Cristafalo et al. J Pediatr. 2013 Dec;163(6):1592-1595.e1.
  • 30.
    Results • First randomizeddouble-blind trial in infants of exclusive diets of HM vs PF • The significantly shorter duration of TPN and lower HM PF p n 29 23 Duration of TPN (d) 27 36 0.04 NEC 1 (3.6%) 5 (21.7%) 0.08 Surgical NEC 0 4 0.04 Cumulative morbidity 0.7 ± 0.5 1.2 ± 1.0 0.03 Length increment (cm/d) 0.12 ± 0.03 0.16 ± 0.04 0.006 Cristafalo et al. J Pediatr. 2013 Dec;163(6):1592-1595.e1.
  • 31.
    Exclusive human milkreduces overall NEC and surgical NEC Sullivan et al (2010) J Pediatr. 2010;156:562-7 Protocol violations: received bovine product
  • 32.
    Impact of choosingbovine products No NEC Medical NEC Surgical NEC Mortality 10.6% 20.9% 23.2% Double the risk of death! Sullivan et al (2010) J Pediatr. 2010;156:562-7 Ganapathy et al. 2011 Breastfeeding Medicine
  • 33.
    NEC continues toadd to long-term costs within the first three years of life • Texas Medicaid healthcare utilization database • Jan 2012 to Dec 2013 • 253 survivors of NEC (73 surgical NEC) • 2909 matched controls • Medical NEC incurred higher costs than controls between 6 and 12 months • Surgical NEC incurred higher costs than controls up to 36 months • Costs tapered down from ~ 18K to 8K per survivor Ganapathy et al. BMC Pediatr. 2013 Aug 20;13:127.
  • 34.
    An exclusive humanmilk (EHM) diet reduces TPN need Ghandehari et al. BMC Res Notes. 2012 Apr 25;5:188. 11-14% Reduction in TPN use Greater when looking at TPN after initial use Increased likelihood if HMF started earlier EHM
  • 35.
    Balance of effectsin developing NEC
  • 36.
    Decreased cost andimproved feeding tolerance in VLBW infants fed an exclusive human milk diet • Retrospective study including preterm infants ⩽28 weeks and/or VLBW (⩽1500 g) • Single center (The Herman & Walter Samuelson Children’s Hospital at Sinai, Baltimore, MD, USA) • March 2009 until March 2014 • (2012-2014) • group H (exclusive human milk or EHM) • (2009-2012) • group B (bovine-based fortifier and maternal milk) • group M (mixed combination of maternal milk, bovine-based fortifier and formula) • group F (formula fed infants) • N = 293 infants between 23 to 34 weeks gestation and birth weights between 490 and 1700 g Assad et al. J Perinatol. 2016 Mar;36(3):216-20.
  • 37.
    Less feeding intolerance(P<0.0001) Lower number of days to full feeds by 9-10 days (P<0.001) Lower incidence of NEC (P<0.011) Shorter length of stay by 4 to 22 days for EHM group Similar average weight gain per among the four groups (18.5 to 20.6 g per day) Assad et al. J Perinatol. 2016 Mar;36(3):216-20.
  • 38.
    Lower total hospitalizationcosts by up to $106,968 per infant (P<0.004) in those fed an EHM diet Assad et al. J Perinatol. 2016 Mar;36(3):216-20.
  • 39.
    Beyond Necrotizing EnterocolitisPrevention: Improving Outcomes with an Exclusive Human Milk-Based Diet • Retrospective cohort study • 4 centers, N =1,587 infants (Texas, Illinois, Florida, and California) • Lower NEC (16.7% versus 6.9%, p < 0.00001) • Reduced mortality (17.2% versus 13.6%, p = 0.04) • Reduced late-onset sepsis (30.3% versus 19.0%, p < 0.00001) • Reduced ROP (9% versus 5.2%, p = 0.003) • Reduced BPD (56.3% versus 47.7%, p = 0.0015) Hair et al. Breastfeed Med. 2016 Mar;11:70-4.
  • 40.
    Continuum of HealthBenefits from Human Milk Newborn SeniorChild NEC Neurodevelopment ROP Visual performance BPD Asthma, Lung Disease, Neurodevelopment Adult Sepsis Neurodevelopment
  • 41.
    Containing Health CareCosts • What motivates reduction in health care costs? • Public model of cost-bundled that limit spending per patient (Medicaid) • Fee for service • Payer that pay out for sicker patients staying longer in hospital • Performance or outcomes based incentives • Value based models • Perspective matters • Cost to the patient and family • Cost to the hospital • Cost to the healthcare system • Cost to society
  • 42.
    Economic Costs ofNEC • One case of medical NEC is almost $75,000 USD • One case of surgical NEC is almost $200,000 USD • NEC costs the health care system $5 billion USD annually (assume 10% incidence of NEC and 30% mortality) • NEC constitutes 19% of the total costs for initial care for all newborns in the US Bisquera J et al. Pediatrics 2002;109:423-428 Ganapathy et al. Breastfeed Med. 2012 Feb;7(1):29-37
  • 43.
    Balancing the costof an exclusive human diet Feeding of 160 mL/kg/day Powder HMF: 1 packet per 25 mL of milk =$0.06/mL = 100X costs Ganapathy et al. Breastfeed Med. 2012 Feb;7(1):29-37
  • 44.
    Cost equation • CostsCAN 12,500 per patient • Protocol to 34 weeks according • Net savings of CAN 10,208 per patient given EHM diet • If human milk was a drug, would we act differently? Ganapathy et al. Breastfeed Med. 2012 Feb;7(1):29-37
  • 45.
    History of DonorMilk • 1909: the first milk bank was established in Vienna, Austria • 1910: milk bank in Boston • North American history in milk banking is 100 years old • 1974: Canada’s first milk bank in Vancouver • By early 1980’s 23 banks in Canada and 30 in US • 1981: HIV identified as a pathogen; North America reduced to 8 banks • 1985: Human Milk Banking Association of North America (HMBANA) established • 2000: Vancouver Milk Bank almost closes http://en.wikipedia.org/wiki/File:HIV-budding-Color.jpg Images from Toronto SickKids Archives HIV
  • 46.
    Modern Human MilkBanking • HMBANA • International Human Milk Banking Association • Organizations in other countries • UKAMB & other European countries • South America – Brazil & Venezuela • South Africa • Other countries – India, Japan, China • National Milk Bank (est. 2005) • Prolacta Bioscience (est. 2005) • Medolac (est. 2013)
  • 47.
    Donor Milk Bankingin North America hmbana.org Existing Milk Banks Cities Served by Milk Banks
  • 48.
    Donor human milk PROS •Human specific • Bridges gap when mother’s milk supply insufficient to meet infant’s requirements CONS • Lower quality milk compared to fresh milk • No cellular components or probiotics • Less protein due to maturity of milk • No lipase activity that may alter digestion • Reduced bioactive components due to processing • Reduced salts and vitamins
  • 49.
    Screening (Questionnaire and Blood) Expressionof milk Freezing, storage, and transport Thawing and Bacterial culture Batching Pasteurization Culture of batch Freezing Processing of Donor Human Milk Thawed for use
  • 50.
    Mothers’ Own MilkBank of Austin, Texas HMBANA NONPROFIT MILK BANKING
  • 51.
  • 52.
    Major Concerns ForUse of Donor Human Milk • Nutrition • Loss of bioactivity (immunologic protection) • Infectious risk • Tampering • Cost • Supply • Legal
  • 53.
    Level of Qualityof Human Milk • Breastfeeding • Fresh human milk • Refrigerated human milk • Really frozen human milk (-80ºC) • Frozen human milk (-20ºC) • Donor human milk TRIAGE • Colostrum > Fresh mature > Refrigerated > Frozen
  • 54.
    Recommendations for DonorHuman Milk Banking AAP Committee on Nutrition Statement (in press) CPS Committee of Nutrition (Kim and Unger) 2012 • Donor human milk is an acceptable alternative to mother’s own milk for preterm infants when it is not available • HMBANA or commercial donor banks are suitable sources • AAP • The use of donor human milk in appropriate high-risk infants should not be limited by an individual’s ability to pay. • Policies are needed to provide high-risk infants access to donor human milk on the basis of documented medical necessity, not financial status. • Avoid unpasteurized milk sharing off Internet • CPS • Recognized functions of the human milk bank should include the promotion of breastfeeding and ongoing human milk research. • Pasteurized human donor breast milk should only be prescribed following written informed consent from a parent or guardian.
  • 55.
  • 56.
    California Milk Banking MMBof San Diego 2017 • All of California is currently served by one milk bank • UC San Diego is developing a milk bank in San Diego for Southern California
  • 57.
    Benefits of DonorHuman Milk to Preterm Infants • DOMINO Study (Canada) • Recently completed • Saw reduction in NEC • Long-term followup data pending • NICHD (Donor milk trial) • Ongoing recruitment • Slowing recruitment due to loss of equipoise • Optimom study (Canada) • Donor milk derived fortifier study • Closed but not reported
  • 58.
    Oral Colostrum Care Oropharyngealadministration involves placing small amounts of a liquid directly onto the oral mucosa with expectation that the liquid, or any of its components, is absorbed by the mucous membranes. Rodriguez, N.A., et al., Oropharyngeal administration of colostrum to extremely low birth weight infants: theoretical perspectives. J Perinatol, 2009. 29(1): p. 1-7. Colostrum Breast Milk Total Protein (g/100mL) 3.7 1.3 IL-6 (pg/mL) 978.8 86.92 Fat (g/100mL) 2.9 4.2 Lactose (g/100mL) 57 7.4 IgM (mg/g protein) 30 4 IgA (mg/g protein) 175 20 IgG (mg/g protein) 3 2
  • 59.
    Colostrum • Produced whenthe tight junctions in the mammary epithelium are open • Paracellular transport of immunologically derived protective components from mother’s circulation into milk • Contain various immunomodulatory agents • Secretory immunoglobulin A [sIgA] • Growth factors • Lactoferrin • Anti-inflammatory cytokines • More highly concentrated in mother’s of preterm infants
  • 60.
    Evidence that oralcolostrum care benefits preterm babies • Seigel 2013 • Retrospective cohort study of 369 inborn ELBW infants, 5 day treatment • Mortality, surgical NEC, SIP rates unchanged • Higher weight at 36 weeks (1666g vs. 1380g p<0.001) • Lee 2015 • Double blind, placebo-controlled trial of 45 infants <28 weeks gestation in South Korea • Increased urine levels of immunoglobulin A and lactoferrin • Significant decrease in clinical sepsis • Sohn 2016 • Impact of buccal administration of human colostrum on the oral microbiota of 12 VLBW infants • OCC altered the colonization of the oral cavity with effects lasting after the intervention ELBW = birth weight less than 1000 grams; VLBW = birth weight less than 1500 grams
  • 61.
    Human milk derivatives:value of a cream supplement • HM-derived cream supplement if energy density of HM <20 kcal/oz using a near infrared HM analyzer • Treated until 36 weeks PMA • HM-derived cream should be considered an adjunctive supplement to an exclusive HM-based diet to improve growth rates in premature infants Human Milk Human HMF Exclusively Human Human milk cream Velocity Cream supplemented (n=39) No cream (n=39) p Weight (g/kg/d) 14.0 +/- 2.5 12.4 +/- 3.0 0.03 Length (cm/wk) 1.03 +/- 0.33 0.83 +/- 0.41 0.02
  • 62.
    Terminology Microbiota The collection ofmicrobes in a particular environment Microbiome The catalog of microbes and their genes in a particular environment Metagenomics The collection of genes and genomes from microbiota
  • 63.
  • 64.
    The human gastrointestinalmicrobiota • First inoculation during birth with passage through birth canal • Influenced by prebiotics and probiotics • Adult microflora by 2 years of age • Over 500 bacterial species • 1010 organisms (at least ten fold higher than human cells) • Symbiosis between man and bacteria • 5-10 lbs of bacteria, about 60% of fecal mass • The “forgotten organ”
  • 65.
    We need microbes! NEngl J Med. 2002 Sep 19;347(12):911-20. FALL OF INFECTION RISE OF AUTOIMMUNITY AND IMMUNE DYSFUNCTION
  • 66.
    Dysbiosis • sick ecosystem •low diversity of species • Imbalance • lack of functional redundancy • susceptibility to disease
  • 67.
    Type of birth Vaginalbirth C-section • Sterile environment • Frequent use of antibiotics • Preterm infants born ~70% by C/S • Exposure to nosocomial microbes • Long-term risk of food allergy • Papathoma et al. 2016 • Long-term risk of immune dysfunction • Asthma, laryngitis, gastroenteritis, ulcerative colitis, rheumatoid arthritis, celiac disease • Kristensen et al. J Allergy Clin Immunol. 2016 Feb;137(2):587-90. • Delivery through birth canal • Direct contact to and ingestion of vaginal flora • Vaginal flora a mix of maternal vaginal and colonic flora
  • 68.
    Risk of thepreterm infant • Often not delivered from birth canal • Frequent use of broad spectrum antibiotics • Delay in enteral feedings • Sterilization of infant formulas • Nosocomial bacterial colonization
  • 69.
    Impaired Colonization ofthe Preterm Gut • Delay in establishment of gut flora • Reduction in the number of bacteria • Reduction in the diversity of bacteria
  • 70.
    Dietary differences andpredominant organisms Bifidobacteria Lactobacilli E. coli Bacteroides Clostridia Harmsen et al., J Pediatr Gastroenterol Nutr. 2000;30(1):61-67. Gronlund et al. Clin Exp Allergy. 2007 Dec;37(12):1764-72. Breastfed Formula fed
  • 71.
    Mai et al2011 PLoS One. 2011; 6(6): e20647. MICROBIOTA BEFORE NEC OCCURS
  • 72.
    Maternal infant microbiome Thereare no sterile environments. Not uterus, not fetus. Vinturache et al 2016 Sem Fetal Med 1-6
  • 73.
    Human Milk Microbiome •Human milk has its own microbiota • Phyla include Firmicutes, Proteobacteria and Actinobacteria • Each mother’s microbiota is unique • Donor human milk is pasteurized and therefore microbe-free Hunt et al. PLoS One. 2011;6(6):e21313.
  • 74.
    BIFIDOBACTERIA LACTOBACILLI • B.infantis • B. breve • B. adolescentis • B. longum • B. bifidus • B. catenulatum • B. animalis • B. suis • B. globosum • L. reuterii • L. fermentum • L. rhamnosus • L. salivarius • L. gasseri • L. caseii • L. planarum infant adult Bold found in human milk
  • 75.
    Human Milk Oligosaccharides(HMO) • Third largest component in human milk! • Small chain sugars (>150 variations) • Resist digestion • Substrate for beneficial intestinal microflora • Support favorable bacteria population in infant colon (“BIFIDOGENIC”) • Beneficial microflora stimulate the developing immune system Bode, J Nutr 2006;136:2127-30. Boehm J Nutr 2007;137(3 Suppl 2):847S-9S.
  • 76.
    Bacteria Fungal Viral HIVIntestinal development Intestinalimmune function NEC Multitude of effects of HMO Intestinal epithelial health HMO
  • 77.
    Diffusion of Innovation RogersEM, 1962 Law of Diffusion of Innovation
  • 78.
    Trend in feedingin last decade Human milk based fortifiers Preterm formula Mother’s milk Donor milk Hydrolyzed bovine Oral colostrum care S Curve
  • 79.
    Mother pumps Milk in bottle Milkin storage container Milk in home freezer Milk in cooler for transport Milk in NICU freezer Milk thawed Milk measured Milk fortified Milk drawn into syringes Milk in tubing Milk in baby (finally!) MILK “TRAFFIC” CHAIN
  • 80.
    Changing the clinicalpractice towards a dominant mother’s milk culture in hospitals is very challenging but cost effective in promoting a healthier long term outlook for premature infants
  • 81.
    The future… Exclusively Human Human Milk Human HMF Donormilk derived additives • Maternal lactation support • Donor human milk banking • Lacto-engineering science • Addition of cream • Addition of protein • Human milk derivative bioactive additives • Refinement of processing of human milk for preservation of function • Increased cost benefit analysis for other long-term morbidities Priorities 1. Maternal lactation 2. Donor human milk 3. Human milk fortifiers 4. Human milk derivatives
  • 82.
    The SPIN ProgramTen Steps 1. Have a NICU nutrition/human milk policy 2. Educate all mother/baby staff in SPIN 10-steps 3. Educate NICU families about optimal premature infant nutrition 4. Prevent extra-uterine growth restriction 5. Standardize enteral feeding procedures 6. Target 100% human milk nutrition 7. Maximize mothers’ milk production 8. Optimize milk quality and safety 9. Encourage skin-to-skin care and breastfeeding 10. Plan a nutritional discharge from NICU NUTRITION LACTATION
  • 83.
    THE SPIN TEAM •Medical director • Lactation director • NICU F/U Neo • NICU CNS • Lactation • OT • NICU Dietician • Research RN • NICU Staff RN
  • 84.
  • 85.
    Take home points •Human milk is the single most powerful intervention to optimize the best health outcomes in all babies • In the absence of maternal milk, donor human milk is a superior substitute to formula • Donor milk derivatives now support the provision of an exclusively human milk diet • Initiating and maintaining a balanced gut microbiota begins with maternal milk • Moving towards an exclusively human milk diet will show increasing cost savings and long-term healthcare benefits to preterm infants
  • 86.
    It takes avillage to care for our babies!
  • 87.
    Parent Advocacy againstNEC www.necsociety.org