Human Milk Feeding in the NICU

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Human Milk Feedings of High-Risk Infants - State of the Science, State of the Art . The Prolacta Bioscience mission is to make a meaningful difference in the lives of thousands of the most vulnerable infants through world class research and innovative products.

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  • And, this Schanler study also showed reductions on late onset sepsis and NEC when the feedings were predominately human milk vs. formula.
  • Human Milk Feeding in the NICU

    1. 1. Human Milk Feedings of High-Risk Infants State of the Science, State of the Art
    2. 2. Human Milk Feeding in the NICU <ul><li>Today there will be 1,367 babies born prematurely in the United States… </li></ul><ul><li>and human milk feedings offer benefit for all of these morbidity issues. </li></ul>
    3. 3. Human Milk Feeding of High-Risk Infants <ul><li>“ Lack of breast milk may be the commonest immunodeficiency of infancy.” </li></ul>Tarnow-Mordi W et al Adjunctive immunologic interventions in neonatal sepsis. In Clinics in Perinatology 37(2) (2010) Hanson LA. Session 1: Feeding and infant development breastfeeding and immune function. Proc Nutr Soc 2007; 66(3): 384-96. <ul><li>&quot;Adjunctive Immunologic Interventions in Neonatal Sepsis “ </li></ul><ul><li>Listed with major clinical strategies , immunologic & pharmacologic therapies </li></ul>
    4. 4. <ul><li>Human Milk Contains Over 100,000 Components </li></ul>Human Milk Feeding of High-Risk Infants Anti-Microbial Factors Secretory IgA, IgM, IgG Lactoferrin Lysozyme Complement C3 Bifidus factor Antiviral mucins, GAGs Oligosaccharides Cytokines & Anti-Inflammatory Tumor Necrosis Factor Interleukins Interferon Prostaglandins Platlete –Activating Factor A-1 anti-trypsin A-1 anti-chymotrypsin Transporters Lactoferrin Folate binder Cobalamin binder IgF binder Thyroxine binder Corticosteroid bind er Hormones Insulin Prolactin Thyroid hormones Corticosteroids Oxytocin Calcitonin Parathyroid hormone Erythroppoietin Growth Factors Epidermal (EGF) Nerve (NGF) Insulin-like (IGF) Transforming (TGF) Polyamines Digestive Enzymes Amylase Bile acid stimulating esteras Bile acid-stimulating lipase Lipoprotein lipase Ribonuclease Others Lycopene Leptin Lutein DNA & RNA Casomprphins ¶-sleep peptides Stem cells
    5. 5. <ul><li>Immunobiology of Human Milk </li></ul><ul><ul><li>Major components of human milk are not primarily for nutrition, but for host defense </li></ul></ul><ul><ul><li>HM has protective effects against </li></ul></ul><ul><ul><ul><li>NEC, late onset sepsis, UTI, obesity, certain cancers, anti-inflammatory/autoimmune disorders </li></ul></ul></ul><ul><ul><ul><li>It is beneficial against allergies & in improving vaccine responses </li></ul></ul></ul><ul><ul><li>“ Milk as Medicine ” </li></ul></ul>Human Milk Feeding of High-Risk Infants Hanson, LA Immunobiology of human milk ( 2004).
    6. 6. <ul><li>Antibody SIgA </li></ul><ul><ul><li>Predominate antibody in HM/colostrum </li></ul></ul><ul><ul><ul><li>80-90% in human milk and colostrum </li></ul></ul></ul><ul><ul><ul><li>Primarily secreted across the mucosal tract </li></ul></ul></ul><ul><ul><ul><li>Large amounts produced in specialized lymphoid areas (Peyers Patches) </li></ul></ul></ul><ul><ul><ul><li>Mass equivalent to the immunoglobulin producing tissue of the spleen </li></ul></ul></ul><ul><ul><ul><li>Stimulate T & B lymphocyte production </li></ul></ul></ul><ul><ul><ul><li>Produce antibodies to microbes and antigens in the mother's intestines </li></ul></ul></ul>Human Milk Feeding of High-Risk Infants Kirsten GF (2009) PNT Sep/Oct 2009 Vol. 13 No. 5 ; 27-29
    7. 7. <ul><li>Antibody SIgA </li></ul><ul><ul><li>Predominate antibody in HM/colostrum </li></ul></ul><ul><ul><ul><li>Role in immunity </li></ul></ul></ul><ul><ul><ul><ul><li>Favors formation of a biofilm on epithelial surface that promotes normal microbial colonization of the gut </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Causes bacteria and allergic substances to stick to the mucus membranes; prevents lung eosinophilia </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Turns on the alternative complement pathways </li></ul></ul></ul></ul><ul><ul><ul><ul><li>More stable than serum antibodies; resistant to proteolytic enzymes </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Protects without inducing energy- consuming inflammation </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Level of SIgA is ↑ in milk from mothers of premature infants </li></ul></ul></ul></ul>Human Milk Feeding of High-Risk Infants Kirsten GF (2009) PNT Sep/Oct 2009 Vol. 13 No. 5 ; 27-29
    8. 8. <ul><li>Lactoferrin </li></ul><ul><ul><li>Globular, multifunctional lipoprotein </li></ul></ul><ul><ul><ul><li>Bactericidal for many Gram -/+ bacteria </li></ul></ul></ul><ul><ul><ul><li>Also anti-viral & anti-fungal properties </li></ul></ul></ul><ul><ul><ul><li>Efficiently anti-inflammatory </li></ul></ul></ul><ul><ul><ul><li>Resistant to degradation in the gut </li></ul></ul></ul><ul><ul><ul><li>Promotes the growth of Bifidobacteria </li></ul></ul></ul><ul><ul><ul><li>Synergistic with lyzozyme </li></ul></ul></ul><ul><ul><ul><li>Higher volume in colostrum </li></ul></ul></ul><ul><ul><ul><ul><li>(~ 5-7 g/liter/ verses 1-3 g/liter in mature milk) </li></ul></ul></ul></ul>Human Milk Feeding of High-Risk Infants Hanson, LA Immunobiology of human milk ( 2004).
    9. 9. <ul><li>Lysozyme </li></ul><ul><ul><li>A nonspecific antimicrobial factor against bacterial cell wall components </li></ul></ul><ul><ul><ul><li>Non-specific innate opsonin </li></ul></ul></ul><ul><ul><ul><li>Facilitates phagocytosis </li></ul></ul></ul><ul><ul><ul><li>Role in the development of intestinal flora </li></ul></ul></ul><ul><ul><li>Levels increase during lactation </li></ul></ul><ul><ul><ul><li>Human lysozyme is antigenically & serologically different from bovine enzyme </li></ul></ul></ul><ul><ul><ul><li>Content in human milk 3000X > bovine milk </li></ul></ul></ul><ul><ul><ul><li>Activity is 100 times that of bovine </li></ul></ul></ul>Human Milk Feeding of High-Risk Infants Hanson, LA Immunobiology of human milk ( 2004).
    10. 10. <ul><li>α - Lactalbumin </li></ul><ul><ul><li>Aggregate of α lactalbumin molecule that induces apoptosis of malignant cells </li></ul></ul><ul><ul><li>H uman α -lactalbumin m ade le thal to t umor cells </li></ul></ul><ul><ul><ul><li>HAMLET effect of killing malignant cells </li></ul></ul></ul><ul><ul><ul><li>Anti-tumor activity against > 40 different carcinomas </li></ul></ul></ul><ul><ul><ul><li>? ↓ incidence of </li></ul></ul></ul><ul><ul><ul><ul><li>Childhood leukemia in breast fed infants </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Breast cancer in women who breastfeed </li></ul></ul></ul></ul>Human Milk Feeding of High-Risk Infants
    11. 11. <ul><li>Immune system cells </li></ul><ul><ul><li>Leukocytes, neutrophils, macrophages </li></ul></ul><ul><ul><ul><li>Part of cellular, innate, non-specific immunity </li></ul></ul></ul><ul><ul><li>T & B Lymphocytes </li></ul></ul><ul><ul><ul><li>Acquired, specific immune responses </li></ul></ul></ul><ul><ul><ul><li>Maternal HLA, role in transplantation </li></ul></ul></ul><ul><ul><li>Interferons </li></ul></ul><ul><ul><ul><li>Strong antiviral activity; ↑ amounts in colostrum </li></ul></ul></ul><ul><ul><li>Fibronectins </li></ul></ul><ul><ul><ul><li>Present in large quantities in colostrum </li></ul></ul></ul><ul><ul><ul><li>Minimize inflammation </li></ul></ul></ul><ul><ul><ul><li>Aid in repairing tissue damaged by inflammation </li></ul></ul></ul>Human Milk Feeding of High-Risk Infants Hanson, LA Immunobiology of human milk ( 2004).
    12. 12. Human Milk Feeding in the NICU 0 5 10 15 20 25 30 35 40 45 50 [Fortified Mother ’s Milk >50 mL/kg/day] 0 5 10 15 20 25 30 35 40 45 50 Mother ’s Milk Preterm Formula % Infants Late onset sepsis Necrotizing enterocolitis LOS/NEC p < 0.01 Schanler, PEDIATRICS 1999;103:1150 Effect of predominant mother ’s milk feeding on late onset sepsis (LOS) and NEC in premature infants
    13. 13. Human Milk Feeding in the NICU <ul><li>Today there will be 1,367 babies born prematurely in the United States… </li></ul><ul><li>and human milk feedings offer benefit for all of these morbidity issues. </li></ul>
    14. 14. Human Milk Feeding in the NICU <ul><li>Aerobic Organisms </li></ul><ul><ul><li>Have an oxygen based metabolism </li></ul></ul><ul><ul><li>Cells require uninterrupted delivery of molecular O2 and a substrate </li></ul></ul><ul><ul><li>In a process known as cellular respiration or oxidative phosphorylation, oxygen oxidizes substrates (glucose, fats & protein) into ATP </li></ul></ul><ul><ul><li>Energy is produced </li></ul></ul><ul><ul><li>CO2 & water are the metabolic by-products </li></ul></ul>
    15. 15. Human Milk Feeding in the NICU <ul><li>Oxidative Stress </li></ul><ul><ul><li>However, due to the abrupt change to a hyperoxic extrauterine environment </li></ul></ul><ul><ul><li>pO 2 levels are suddenly five times higher than intrauterine values </li></ul></ul><ul><ul><li>Elevated levels of vitamin E oxidation product in infants cord blood is > than found in maternal serum </li></ul></ul><ul><ul><li>Normal, full term, healthy infants without resuscitation show metabolic evidence of oxidative stress </li></ul></ul>Jain et al J Am Coll Nutr 199615:44-48 “ From conception through delivery… mammalian development occurs under a physiologic hypoxia ”
    16. 16. Human Milk Feeding in the NIC U <ul><li>Oxidative Stress </li></ul><ul><ul><li>Radical Oxygen Species (ROS) </li></ul></ul><ul><ul><ul><li>Produced via oxidative activity </li></ul></ul></ul><ul><ul><ul><li>Highly reactive atoms or molecules </li></ul></ul></ul><ul><ul><ul><li>Unstable, unpaired electrons </li></ul></ul></ul><ul><ul><ul><li>Combines with other non-radicals </li></ul></ul></ul><ul><ul><ul><li>Initiates & perpetuates cellular chain reactions, induce cellular injury, and promote inflammation </li></ul></ul></ul>
    17. 17. Human Milk Feeding in the NICU <ul><ul><li>ROS ’s </li></ul></ul><ul><ul><ul><li>Play a role in normal growth and development </li></ul></ul></ul><ul><ul><ul><li>Fertilization, developing embryos </li></ul></ul></ul><ul><ul><ul><li>Aerobic metabolism, fetal growth </li></ul></ul></ul><ul><ul><ul><li>Granulocyte function </li></ul></ul></ul><ul><li>ROS's </li></ul><ul><ul><li>Activate complex array of physiologic processes </li></ul></ul><ul><ul><ul><li>Amplified inflammatory response </li></ul></ul></ul><ul><ul><ul><li>Outpouring of cytokines, chemokines </li></ul></ul></ul><ul><ul><ul><li>Increased reactivity of endothelium </li></ul></ul></ul><ul><ul><ul><li>Promotion of a pro-coagulation state </li></ul></ul></ul><ul><ul><ul><li>Altered nitric oxide synthesis </li></ul></ul></ul><ul><ul><ul><li>Stimulates necrotic & apoptotic cell death mechanisms </li></ul></ul></ul>
    18. 18. Human Milk Feeding in the NICU <ul><li>Oxidative Processes in the Preterm Infant </li></ul><ul><ul><ul><li>Exposure to supraphysiologic oxygen </li></ul></ul></ul><ul><ul><ul><ul><li>Resuscitation, RDS, mechanical ventilation </li></ul></ul></ul></ul><ul><ul><ul><li>Exposure to inflammation & infection </li></ul></ul></ul><ul><ul><ul><ul><li>FIRS, inflammatory mediators, free radicals </li></ul></ul></ul></ul><ul><ul><ul><li>Ischemia and reperfusion </li></ul></ul></ul><ul><ul><ul><ul><li>Hypotension, hypoperfusion </li></ul></ul></ul></ul><ul><ul><ul><li>Parenteral solutions exposed to light </li></ul></ul></ul><ul><ul><ul><li>Increased free circulating transition metals </li></ul></ul></ul><ul><ul><li>All have been implicated in the origin of certain neonatal diseases </li></ul></ul>Saugstad, OD (2001) Seminars in Perinatology , 8;39-49
    19. 19. Human Milk Feeding in the NICU <ul><li>Oxygen Radical Disease of Neonatology </li></ul>Trindade & Rugolo . NeoReviews 2007;8;e522-e632 Cell/Tissue/Organ Injury Retinopathy of Prematurity Chronic Lung Disease/BPD Periventricular Leukomalacia Intraventricular Hemorrhage Necrotizing Enterocolitis Patent Ductus Arteriosus Cerebral Palsy
    20. 20. Human Milk Feeding in the NICU <ul><li>Antioxidant activity in fresh human milk </li></ul><ul><ul><li>Hanna, et al Arch Dis Child Fetal Neonatal Ed 2004;89:F518-F520 </li></ul></ul><ul><ul><ul><li>8 samples of human milk </li></ul></ul></ul><ul><ul><ul><ul><li>From others who delivered at term (38.8 weeks) </li></ul></ul></ul></ul><ul><ul><ul><li>8 samples of human milk </li></ul></ul></ul><ul><ul><ul><ul><li>From mothers who delivered preterm (27.4 weeks) </li></ul></ul></ul></ul><ul><ul><ul><li>Milk collected within 24 hours of birth </li></ul></ul></ul><ul><ul><ul><ul><li>Fresh samples immediately tested </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Remainder stored, later analyzed at 48 hours and 7 days </li></ul></ul></ul></ul><ul><ul><ul><ul><li>5 formula samples also tested </li></ul></ul></ul></ul>
    21. 21. Human Milk Feeding in the NICU <ul><li>Antioxidant activity in fresh human milk </li></ul><ul><ul><li>Hanna, et al Arch Dis Child Fetal Neonatal Ed 2004;89:F518-F520 </li></ul></ul><ul><ul><li>Results </li></ul></ul><ul><ul><ul><li>No difference in antioxidant activity in milk from mothers who delivered prematurely </li></ul></ul></ul><ul><ul><ul><li>Antioxidant activity at both refrigeration & freezing temperatures were reduced </li></ul></ul></ul><ul><ul><ul><ul><li>Freezer > refrigerator; 7 days > 48 hours </li></ul></ul></ul></ul><ul><ul><ul><li>Significantly lower antioxidant activity in formula than fresh human milk </li></ul></ul></ul><ul><ul><ul><li>Antioxidant capacity of the formulas was similar </li></ul></ul></ul>
    22. 22. Human Milk Feeding in the NICU <ul><li>Antioxidants and Infant Nutrition </li></ul><ul><ul><li>Neutralize oxidative stress </li></ul></ul><ul><ul><ul><li>Transitional production of ROS ’s </li></ul></ul></ul><ul><ul><ul><li>Inflammation-induced ROS ’s </li></ul></ul></ul><ul><ul><ul><li>“ Traps” neutrophil-generated ROS’s </li></ul></ul></ul><ul><ul><li>Antioxidants in colostrum </li></ul></ul><ul><ul><ul><li>Vitamin A (3x mature milk) </li></ul></ul></ul><ul><ul><ul><li>Vitamin E (2-3x mature milk) </li></ul></ul></ul><ul><ul><ul><li>Carotenoids (10x mature milk) </li></ul></ul></ul><ul><ul><ul><ul><li>Β -carotene </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Lycopene </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Lutein </li></ul></ul></ul></ul>
    23. 23. Human Milk Feeding in the NICU <ul><li>Antioxidants and Human Milk </li></ul>Zarban et al J Clin Biochem Nutr . 2009 September; 45(2): 150–154. Published online 2009 August 28. doi: 10.3164/jcn.08-233 Values are presented as Mean ± SD and * indicate significant difference in comparison with colostrums ( p <0.05) Colostrum Mature Milk Time from Delivery 2 ± 1 days (n = 150) 7 ± 3 days (n = 97) 30 ± 3 days (n = 102) 90 ± 7 days (n = 100) 180 ± 10 days (n = 91) Total Antioxidant Capacity ( μ mol/L) 1061.6 ± 500.6 915.3 ± 511.4* 816.3 ± 379.4* 862.7 ± 457.7* 724.7 ± 302.4* DPPH Radical Scavenging Activity (% in μ mol/L) 50.4 ± 19.7 40.8 ± 20.0* 41.9 ± 19.4* 44.6 ± 18.5* 38.2 ± 17.3*
    24. 24. <ul><li>Carotenoids </li></ul><ul><ul><li>Naturally occurring organic pigments (biochromes) </li></ul></ul><ul><ul><li>Synthesized by </li></ul></ul><ul><ul><ul><li>Bacteria, fungi, algae, & green plants </li></ul></ul></ul><ul><ul><ul><li>Over 600 identified carotenoids in nature </li></ul></ul></ul><ul><ul><ul><li>50 carotenoids in diet </li></ul></ul></ul><ul><ul><ul><li>~20 carotenoids in serum </li></ul></ul></ul><ul><ul><ul><li>Only lutein and zeaxanthine are in the eye </li></ul></ul></ul><ul><ul><ul><li>Present at 1000x more than serum </li></ul></ul></ul>Human Milk Feeding in the NICU
    25. 25. <ul><li>Carotenoids </li></ul><ul><ul><li>Carotenes – pure hydrocarbons </li></ul></ul><ul><ul><li>β -carotene </li></ul></ul><ul><ul><ul><li>Main carotenoid in human milk </li></ul></ul></ul><ul><ul><ul><li>Precursor of vitamin A </li></ul></ul></ul><ul><ul><ul><li>Role in antioxidant status of the skin </li></ul></ul></ul><ul><ul><ul><li>Skin as barrier </li></ul></ul></ul><ul><ul><ul><li>Similar tissue as brain and CNS structures </li></ul></ul></ul><ul><ul><ul><li>Changes in skin after birth </li></ul></ul></ul><ul><ul><li>Lycopene </li></ul></ul><ul><ul><ul><li>Present in HM and acts as an antioxidant </li></ul></ul></ul><ul><ul><ul><li>Absorbed in the intestine by passive diffusion </li></ul></ul></ul><ul><ul><ul><li>Highest concentrations seen in colostrum </li></ul></ul></ul>Human Milk Feeding in the NICU
    26. 26. <ul><li>Carotenoids </li></ul><ul><ul><li>Xanthophylls – contain oxygen </li></ul></ul><ul><ul><li>Lutein and Zeaxanthin </li></ul></ul><ul><ul><ul><li>L utein concentration is over 1000-fold greater in the eye than in circulating blood </li></ul></ul></ul><ul><ul><ul><li>Lutein selectively accumulates in the macular region of the retina responsible for central vision </li></ul></ul></ul><ul><ul><ul><li>Role in protecting the eye from oxidative injury by absorbing blue and ultraviolet light </li></ul></ul></ul>Human Milk Feeding in the NICU <ul><ul><ul><ul><li>Krinsky NI, et al. Annu Rev Nutr . 2003;23:171–201. 2. Landrum JT, et al. Arch Biochem Biophys . 2001;385:28–40. </li></ul></ul></ul></ul>
    27. 27. <ul><li>Antioxidants and the Eye </li></ul><ul><ul><li>The retina & retinal vasculature are the last eye structures to develop in the human fetus/neonate </li></ul></ul><ul><li>Macula Lutea </li></ul><ul><ul><li>Oval-shaped, highly pigmented yellow spot on the center of the retina </li></ul></ul><ul><ul><li>Fovea, in the center, has highest concentration of cone cells which are responsible for high resolution vision </li></ul></ul><ul><ul><li>Lutein & zeaxanthin selectively accumulate in macular region of the eye with a concentration of over 1000-fold greater in than in circulating blood </li></ul></ul>Human Milk Feeding in the NICU
    28. 28. Human Milk Feeding in the NICU <ul><li>Today there will be 1,367 babies born prematurely in the United States… </li></ul><ul><li>and human milk feedings offer benefit for all of these morbidity issues. </li></ul>
    29. 29. <ul><li>Incidence </li></ul><ul><ul><li>6-7% of all VLBW infants </li></ul></ul><ul><ul><li>Inverse relationship of incidence & EGA </li></ul></ul><ul><ul><ul><li>~90% of all cases are in premature infants </li></ul></ul></ul><ul><ul><li>↑ Fatality rates for infants requiring surgery ~50% </li></ul></ul><ul><ul><ul><li>20-40% of all infants with NEC require surgery </li></ul></ul></ul><ul><ul><ul><li>1 in 7 NEC hospitalizations end in death </li></ul></ul></ul><ul><ul><li>NEC survivorship issues </li></ul></ul><ul><ul><li>Srinivasan, et al (2008) Clinics in Perinatology 35 </li></ul></ul>
    30. 30. <ul><li>Incidence </li></ul><ul><ul><li>6-7% of all VLBW infants </li></ul></ul><ul><ul><li>Inverse relationship of incidence & EGA </li></ul></ul><ul><ul><ul><li>~90% of all cases are in premature infants </li></ul></ul></ul><ul><ul><li>↑ Fatality rates for infants requiring surgery ~50% </li></ul></ul><ul><ul><ul><li>20-40% of all infants with NEC require surgery </li></ul></ul></ul><ul><ul><ul><li>1 in 7 NEC hospitalizations end in death </li></ul></ul></ul><ul><ul><li>NEC survivorship issues </li></ul></ul><ul><ul><ul><li>Outcomes </li></ul></ul></ul><ul><ul><ul><li>Financial impact </li></ul></ul></ul>Human Milk Feeding of High-Risk Infants <ul><ul><li>Srinivasan, et al (2008) Clinics in Perinatology 35 </li></ul></ul>
    31. 31. <ul><li>Necrotizing Enterocolitis (NEC) Guidelines </li></ul><ul><ul><li>Cincinnati Children ’s Hospital 2007 </li></ul></ul><ul><ul><li>http://www.cincinnatichildrens.org/svc/alpha/h/health-policy/ev-based/nec_vlbw.htm </li></ul></ul><ul><ul><ul><li>Intended for use in preterm infants less than 1500 grams birth weight </li></ul></ul></ul><ul><ul><ul><li>Team consisted of staff RN ’s, NNP, neonatal nutritionist, pharmacist ,pediatric surgeons, neonatologists, pediatric gastroenterologists, EBM specialists, group of parents </li></ul></ul></ul><ul><ul><ul><li>608 articles found & screened; 445 reviewed </li></ul></ul></ul>Human Milk Feeding of High-Risk Infants
    32. 32. <ul><li>Necrotizing Enterocolitis (NEC) Guidelines </li></ul><ul><ul><li>Cincinnati Children ’s Hospital 2007 </li></ul></ul><ul><ul><li>http://www.cincinnatichildrens.org/svc/alpha/h/health-policy/ev-based/nec_vlbw.htm </li></ul></ul><ul><ul><li>There are many articles about NEC, but not many prospective, randomized double-blind, controlled trials (PRDBCT) </li></ul></ul><ul><ul><li>Meta-analyses have been done related to topics concerning NEC </li></ul></ul><ul><ul><ul><li>Some results obscured by wide-range of articles in the meta-analysis </li></ul></ul></ul><ul><ul><ul><li>Some statistical significance, but results not clear to clinicians trying to extrapolate findings into care practices </li></ul></ul></ul><ul><ul><ul><li>608 articles found & screened; 445 reviewed </li></ul></ul></ul>Human Milk Feeding of High-Risk Infants
    33. 33. <ul><li>Necrotizing Enterocolitis (NEC) Guidelines </li></ul><ul><ul><li>Cincinnati Children ’s Hospital 2007 </li></ul></ul><ul><ul><li>http://www.cincinnatichildrens.org/svc/alpha/h/health-policy/ev-based/nec_vlbw.htm </li></ul></ul><ul><li>Insufficient Evidence To Support or Recommend </li></ul><ul><ul><li>Either early or delayed initiation of feedings </li></ul></ul><ul><ul><li>Specific rate of feeding volume advancement </li></ul></ul><ul><ul><li>Gastric or transpyloric feedings </li></ul></ul><ul><ul><li>Bolus or continuous feeding </li></ul></ul><ul><ul><li>Specific placement of a UAC </li></ul></ul><ul><ul><li>Use or avoidance of probiotics </li></ul></ul><ul><ul><li>Role of M.E.N. in preventing NEC </li></ul></ul><ul><ul><li>Use of gastric residuals as a predictor of NEC </li></ul></ul><ul><ul><li>No specific pathogen has been shown to have a consistent causal relationship with NEC </li></ul></ul>Human Milk Feeding of High-Risk Infants
    34. 34. <ul><li>Necrotizing Enterocolitis (NEC) Guidelines </li></ul><ul><ul><li>Cincinnati Children ’s Hospital 2007 </li></ul></ul><ul><ul><li>http://www.cincinnatichildrens.org/svc/alpha/h/health-policy/ev-based/nec_vlbw.htm </li></ul></ul><ul><li>Prevention </li></ul><ul><ul><li>Mothers of infants at risk of NEC encouraged to supply breast milk as the optimal nutrition and to decrease their infant ’s risk of NEC </li></ul></ul><ul><ul><li>Providing human milk to 20 preterm infants will prevent one case of NEC </li></ul></ul><ul><ul><li>When mother ’s milk unavailable, recommend donor milk as an alternative </li></ul></ul>Human Milk Feeding of High-Risk Infants
    35. 35. Human Milk Feeding of High-Risk Infants Meinzen-Derr 6 (2009) Sisk 5 (2007) <ul><li>1 Lucas,A.; Cole,T.J. Lancet 1990 (ii) 1519-1522 </li></ul><ul><li>2 Schanler,Richard J; Hurst,Nancy M.; Lau,Chantal Clinics in Perinatology 1999 (26) 379-398 </li></ul><ul><li>3 McGuire W & Anthony MY J Pediatr 2003 Jul;143(1): 137-8. </li></ul><ul><li>4 Schanler, RJ Am J Clin Nutr 2007 (85[SUPP]) 625s- </li></ul><ul><li>5 Sisk PM et al Journal of Perinatology (2007) 27, 428–433; doi:10.1038/sj.jp.7211758; published online 19 April 2007. </li></ul><ul><li>6 Meinzen-Derr J, et al. J Perinatol . 2009 Jan;29(1):57-62. Epub 2008 Aug 21 </li></ul><ul><li>7 Sullivan S, Schanler RJ, Kim JH, et al. J Peds e- published 2009: DOI 10.1016/jpeds 2009-10.040 </li></ul>The Arc of Human Milk Feeding and NEC Studies
    36. 36. n=207 Preterm Infants BW ≤ 1250 g Own Mothers Milk Bovine HMF @100 mL/kg/d Human HMF @ 40 mL/kg/d Human HMF @ 100 mL/kg/d Donor Milk When OMM is not available in sufficient quantity H100 n=69 H40 n=71 B100 n=69 Study Protocol Sullivan, S et al 10.1016/j.jpeds.2009.10.040 Preterm Formula When OMM is not available in sufficient quantity 1 NEC surgery will be eliminated for every 10 babies treated with 100% human diet. 1 case of NEC or death will be eliminated for every 7.7 babies treated with exclusive human milk diet. For infants <1250 g these data strongly support an entirely human milk-based diet, including HM fortifier, through 60 days of age. Human Milk Feeding of High-Risk Infants
    37. 37. <ul><li>A Pilot Study to Determine the Safety and Feasibility of Oropharyngeal Administration of Own Mother's Colostrum to Extremely Low-Birth-Weight Infants. </li></ul><ul><ul><li>Results: </li></ul></ul><ul><ul><ul><li>All infants began to suck on the ET tube during the administration of colostrum drops </li></ul></ul></ul><ul><ul><ul><li>Oxygen saturation measures remained stable or increased slightly during each treatment </li></ul></ul></ul><ul><ul><ul><li>No episodes of apnea, bradycardia, hypotension or other adverse effects associated with the administration </li></ul></ul></ul><ul><ul><li>Conclusion: </li></ul></ul><ul><ul><ul><li>Administration of mother's own colostrum is easy, inexpensive and well-tolerated </li></ul></ul></ul>Human Milk Feeding of High-Risk Infants Rodriquez NA, Meier PP, Groer, MW ,Zeller JM, Engstrom JL and Fogg L (2010). Advances in Neonatal Care, Vol 10, No. 4, pp.206-212.
    38. 38. <ul><li>Definitions of Breastfeeding </li></ul><ul><ul><li>Full </li></ul></ul><ul><ul><ul><li>Exclusive </li></ul></ul></ul><ul><ul><ul><li>Almost exclusive </li></ul></ul></ul><ul><ul><li>Partial </li></ul></ul><ul><ul><ul><li>Low </li></ul></ul></ul><ul><ul><ul><li>Medium </li></ul></ul></ul><ul><ul><ul><li>High </li></ul></ul></ul><ul><ul><li>Token </li></ul></ul><ul><ul><ul><li>Not for nutritive purposes </li></ul></ul></ul>Human Milk Feeding of High-Risk Infants Do not capture the critical components of human milk feeding patterns for NICU infants . ” Labbok M, Krasovec K. Toward consistency in breastfeeding definitions. Stud Fam Plann 1990;21(4); 226-30.
    39. 39. <ul><li>Immunonutrition </li></ul><ul><ul><li>The modulation of the immune and inflammatory responses in critically ill patients with the use of enteral feedings enriched with immune-enhancing ingredients. </li></ul></ul>Human Milk Feeding of High-Risk Infants Neu J & Bernstein, H Update on host defense and immunonutrients Clinics in Perinatology 29(1); 2002.
    40. 40. <ul><li>“ Critical Exposure Periods” </li></ul><ul><ul><li>For the use of Human Milk </li></ul></ul><ul><ul><ul><li>Colostrum as the transition from amniotic fluid </li></ul></ul></ul><ul><ul><ul><li>Transition from colostrum to mature milk feedings </li></ul></ul></ul><ul><ul><ul><li>Human milk feedings throughout NICU stay </li></ul></ul></ul><ul><ul><ul><li>Human milk feedings after NICU & discharge </li></ul></ul></ul>Human Milk Feeding of High-Risk Infants Labbok M, Krasovec K. Toward consistency in breastfeeding definitions. Stud Fam Plann 1990;21(4); 226-30. Meier PP, Engstrom JL, Patel AL, Jegier BJ & Bruns, NE. Improving the Use of Human Milk During and After the NICU Stay. Clin Perinatol 37 (2010) 217–245 doi:10.1016/j.clp.2010.01.013.
    41. 41. <ul><li>Colostrum </li></ul><ul><ul><li>Secretion from </li></ul></ul><ul><ul><ul><li>Paracellular pathways in mammary epithelium open to facilitate transfer </li></ul></ul></ul><ul><ul><ul><ul><li>Profile of growth factors similar to amniotic fluid </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Antibodies, IgA </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Anti-inflammatory factors </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Growth factors </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Anti-infective components </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Anti-inflammatory cytokines </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Oligosaccharides </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Soluble CD14 </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Antioxidants </li></ul></ul></ul></ul></ul><ul><ul><ul><li>Absorption of factors via oropharyngeal associated lymphoid tissues (OFALT) and then pass through the open paracellular pathways in infant's GI tract </li></ul></ul></ul>Human Milk Feeding of High-Risk Infants Rodriquez NA, Meier PP, Groer, MW ,Zeller JM, Engstrom JL and Fogg L (2010). Advances in Neonatal Care, Vol 10, No. 4, pp.206-212.
    42. 42. <ul><li>Colostrum Feedings </li></ul><ul><ul><li>? Compensate for ↓ in utero swallowing </li></ul></ul><ul><ul><li>In last trimester infant would swallow ~750 mL of amniotic fluid daily </li></ul></ul><ul><ul><li>Role of growth factors in doubling weight of intestinal mucosa </li></ul></ul><ul><ul><ul><li>Facilitates endocytosis of protein </li></ul></ul></ul><ul><ul><ul><li>Induces digestive enzyme production </li></ul></ul></ul>Human Milk Feeding of High-Risk Infants Rodriquez NA, Meier PP, Groer, MW ,Zeller JM, Engstrom JL and Fogg L (2010). Advances in Neonatal Care, Vol 10, No. 4, pp.206-212.
    43. 43. <ul><li>Colostrum Composition </li></ul><ul><ul><li>Higher concentrations of </li></ul></ul><ul><ul><ul><li>Secretory IgA </li></ul></ul></ul><ul><ul><ul><li>Growth factors </li></ul></ul></ul><ul><ul><ul><li>Lactoferrin </li></ul></ul></ul><ul><ul><ul><li>Anti-inflammatory cytokines </li></ul></ul></ul><ul><ul><ul><li>Oligosaccharides </li></ul></ul></ul><ul><ul><ul><li>Soluble CD14 </li></ul></ul></ul><ul><ul><ul><li>Antioxidants </li></ul></ul></ul><ul><li>Colostrum Composition </li></ul><ul><ul><li>With premature birth </li></ul></ul><ul><ul><ul><li>Inverse relationship between duration of pregnancy and the concentration of factors </li></ul></ul></ul><ul><ul><ul><li>Least mature infants - most protective colostrum </li></ul></ul></ul><ul><ul><ul><li>Secretion of colostrum may be prolonged by several hours/days following extreme premature birth </li></ul></ul></ul>Human Milk Feeding of High-Risk Infants Rodriquez NA, Meier PP, Groer, MW ,Zeller JM, Engstrom JL and Fogg L (2010). Advances in Neonatal Care, Vol 10, No. 4, pp.206-212.
    44. 44. <ul><li>A Pilot Study to Determine the Safety and Feasibility of Oropharyngeal Administration of Own Mother's Colostrum to Extremely Low-Birth-Weight Infants. </li></ul><ul><ul><li>Purpose: </li></ul></ul><ul><ul><ul><li>To determine the safety of oropharyngeal administration of own mother's colostrum to ELBW infants in first days of life </li></ul></ul></ul><ul><ul><li>Subjects: </li></ul></ul><ul><ul><ul><li>5 ELBW infants </li></ul></ul></ul><ul><ul><ul><li>Mean BW and GA (657 g and 25.5 weeks respectively) </li></ul></ul></ul><ul><ul><li>Design: </li></ul></ul><ul><ul><ul><li>Quasi-experimental, 1 group, pretest-posttest design </li></ul></ul></ul>Human Milk Feeding of High-Risk Infants Rodriquez NA, Meier PP, Groer, MW ,Zeller JM, Engstrom JL and Fogg L (2010). Advances in Neonatal Care, Vol 10, No. 4, pp.206-212.
    45. 45. <ul><li>A Pilot Study to Determine the Safety and Feasibility of Oropharyngeal Administration of Own Mother's Colostrum to Extremely Low-Birth-Weight Infants. </li></ul><ul><ul><li>Methods: </li></ul></ul><ul><ul><ul><li>Subjects received 0.2 ml of own mother's colostrum administered oropharyngeally every 2 hours for 48 consecutive hours </li></ul></ul></ul><ul><ul><ul><li>Beginning at 48 hours of life </li></ul></ul></ul><ul><ul><ul><li>Concentrations of secretory immunoglobulin A and lactoferrin were measured in tracheal aspirates and urine of subjects at completion of the intervention and again 2 weeks later </li></ul></ul></ul>Human Milk Feeding of High-Risk Infants Rodriquez NA, Meier PP, Groer, MW ,Zeller JM, Engstrom JL and Fogg L (2010). Advances in Neonatal Care, Vol 10, No. 4, pp.206-212.
    46. 46. <ul><li>A Pilot Study to Determine the Safety and Feasibility of Oropharyngeal Administration of Own Mother's Colostrum to Extremely Low-Birth-Weight Infants. </li></ul><ul><ul><li>Results: </li></ul></ul><ul><ul><ul><li>All infants completed the entire protocol, each receiving 24 treatments </li></ul></ul></ul><ul><ul><ul><li>A total of 15 urine specimens were collected and 14 were sufficient in volume for analysis </li></ul></ul></ul><ul><ul><ul><li>A total of 15 tracheal aspirates were collected, but only 7 (47%) were sufficient in volume for analysis </li></ul></ul></ul><ul><ul><ul><li>There was a wide variation in concentrations of secretory immunoglobulin A and lactoferrin in both urine and tracheal aspirates </li></ul></ul></ul>Human Milk Feeding of High-Risk Infants Rodriquez NA, Meier PP, Groer, MW ,Zeller JM, Engstrom JL and Fogg L (2010). Advances in Neonatal Care, Vol 10, No. 4, pp.206-212.
    47. 47. <ul><li>American Academy of Pediatrics Policy </li></ul><ul><ul><li>Human milk </li></ul></ul><ul><ul><ul><li>Is species-specific </li></ul></ul></ul><ul><ul><ul><li>All substitute feeding preparations differ markedly from it, making human milk uniquely superior for infant feeding </li></ul></ul></ul><ul><ul><li>Exclusive breastfeeding </li></ul></ul><ul><ul><ul><li>The reference or normative model against which all alternative feeding methods must be measured with regard to growth, health, development, and all other short- and long-term outcomes </li></ul></ul></ul>Human Milk Feeding of High-Risk Infants
    48. 48. Human Milk Feeding in the NICU <ul><li>“ Critical Dosage” </li></ul><ul><ul><li>For the use of Human Milk </li></ul></ul><ul><ul><ul><li>Definition of “human milk fed” </li></ul></ul></ul><ul><ul><ul><li>Calculating percentage of human milk feeding vs. formula-based </li></ul></ul></ul><ul><ul><ul><li>Quality improvement strategies </li></ul></ul></ul><ul><ul><ul><li>Encouraging mother to provide her milk for her baby </li></ul></ul></ul><ul><ul><ul><li>Lactation support & use of lactation technologies </li></ul></ul></ul><ul><ul><ul><li>Prioritizing maintenance of maternal milk volume </li></ul></ul></ul>Labbok M, Krasovec K. Toward consistency in breastfeeding definitions. Stud Fam Plann 1990;21(4); 226-30 . Meier PP, Engstrom JL, Patel AL, Jegier BJ & Bruns, NE. Improving the Use of Human Milk During and After the NICU Stay. Clin Perinatol 37 (2010) 217–245 doi:10.1016/j.clp.2010.01.013.
    49. 49. Human Milk Feeding of High-Risk Infants <ul><ul><li>Infant Feedings: Guidelines for Preparation of Human Milk and Formula in Health Care Facilities , second edition . American Dietetic Association, 2011. </li></ul></ul>Pediatric Nutrition Practice Group Sandra T. Robbins, RD, CSP and Robin Meyersw, MPH, RD, Editors

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