Melinda Elliott, MD FAAP Senior Director, Clinical Education and Professional Development, Prolacta Bioscience Neonatologist, Pediatrix Medical Group

Transcription

1 Melinda Elliott, MD FAAP Senior Director, Clinical Education and Professional Development, Prolacta Bioscience Neonatologist, Pediatrix Medical Group of Maryland

2 Disclosures I have had no disclosures August 1, 2016 when I became a Prolacta Employee. I had no support from Prolacta, financial or otherwise, at the time of my study.

3 Breast Milk is for Babies, Cows Milk is for Cows

4 Breastfeeding and The Use of Human Milk/ Donor Human Milk for the High- Risk Infant* All preterm infants should receive human milk. Priority should be given to providing donor human milk to infants <1500 g birthweight. Human milk should be fortified, with protein, minerals, and vitamins to ensure optimal nutrient intake for infants weighing <1500 g at birth. Pasteurized donor human milk, appropriately fortified, should be used if mother s own milk is unavailable or its use is contraindicated. Methods and training protocols for manual and mechanical milk expression must be available to mothers. Neonatal intensive care units should possess evidence-based protocols for collection, storage, and labeling of human milk. Neonatal intensive care units should prevent the misadministration of human milk ( 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. AAP Policy Statement. Pediatrics. 2012;129(3):e827-e841.Pediatrics.2017;139(1):e

5 Major components of human milk are not primarily for nutrition, but for host defense Hanson, LA Immunobiology of human milk (2004).

6 What is So Special About Human Anti-Microbial Factors Secretory IgA, IgM, IgG Lactoferrin Lysozyme Complement C3 Bifidus Factor Antiviral Mucins, GAGs Oligosaccharides Milk?? Human Milk Contains Over 100,000 Components Transporters Lactoferrin Folate Binder Cobalamin Binder IGF Binder Thyroxine Binder Corticosteroid Binder Cytokines & Anti-Inflammatory Tumor Necrosis Factor Interleukins Interferon Prostaglandins Platelet Activating Factor Alpha-1 anti-trypsin Alpha-1 anti-chymotrypsin Hormones Insulin Prolactin Thyroid Hormones Corticosteroids Oxytocin Calcitonin Parathyroid Hormone Erythropoetin Digestive Enzymes Amylase Bile acid stimulating Esterase Bile acid stimulating Lipase Lipoprotein Lipase Ribonuclease Growth Factors Epidermal Nerve Insulin-like Transforming Polyamines Others Lycopene Leptin Lutein DNA & RNA Casomorphins Sleep peptides Stem Cells

7 Lack of breast milk may be the commonest immunodeficiency of infancy. Hanson LA. Session 1: Feeding and infant development breastfeeding and immune function. Proc Nutr Soc 2007; 66(3):

8 American Academy of Pediatrics Breastfeeding and the use of human milk Section on Breastfeeding Pediatrics originally published online February 27, 2012; DOI: /peds I N F A N C Y Condition Dose-Response Benefits of Breastfeeding % Lower Risk Breastfeeding Comments ORc 95% CI NEC 77 NICU Stay Preterm infants; exclusive HM SIDS 36 Any > 1 mo RSV Bronchiolitis 74 >4 mo Otitis media 23 Any Otitis media 50 3 or 6 mo Exclusive BF ALL, acute lymphocytic leukemia; AML, acute myelogenous leukemia; BF, breastfeeding; HM, human milk; Respiratory syncytial virus. a Pooled data. b % lower risk refers to lower risk while BF compared with feeding commercial infant formula or referent group specified. c OR expressed as increase risk for commercial formula feeding. d Referent group is exclusive BF 6 months.

9 Later Benefits of Breast Milk C H I L D H O O D Condition % Lower Risk Dose-Response Benefits of Breastfeeding Breastfeeding Comments ORc 95% CI Recurrent OM 77 Exclusive BF 6 mo d Compared with BF to <6 mo d URTI 63 >6 mo Exclusive BF LRTI 72 4 mo Exclusive BF LRTI 75 Exclusive BF 6 mo Compared with BF 4 - <6 mo ALL, acute lymphocytic leukemia; AML, acute myelogenous leukemia; BF, breastfeeding; HM, human milk; Respiratory syncytial virus. a Pooled data. b % lower risk refers to lower risk while BF compared with feeding commercial infant formula or referent group specified. c OR expressed as increase risk for commercial formula feeding. d Referent group is exclusive BF 6 months. American Academy of Pediatrics Breastfeeding and the use of human milk Section on Breastfeeding Pediatrics originally published online February 27, 2012; DOI: /peds

10 Later Benefits of Breast Milk C H I L D H O O D Dose-Response Benefits of Breastfeeding Condition % Lower Risk Breastfeeding Comments ORc 95% CI Asthma 40 3 mo Atopic family history Asthma 26 3 mo No atopic family history Atopic dermatitis 27 >3 mos Exclusive BF; (-) family history Atopic dermatitis 42 >3 mo Exclusive BF; (+) family history ALL, acute lymphocytic leukemia; AML, acute myelogenous leukemia; BF, breastfeeding; HM, human milk; Respiratory syncytial virus. a Pooled data. b % lower risk refers to lower risk while BF compared with feeding commercial infant formula or referent group specified. c OR expressed as increase risk for commercial formula feeding. d Referent group is exclusive BF 6 months. American Academy of Pediatrics Breastfeeding and the use of human milk Section on Breastfeeding Pediatrics originally published online February 27, 2012; DOI: /peds

11 American Academy of Pediatrics Breastfeeding and the use of human milk Section on Breastfeeding Pediatrics originally published online February 27, 2012; DOI: /peds Later Benefits of Breast Milk C H I L D - A D U L T H O O D Dose-Response Benefits of Breastfeeding Condition % Lower Risk Breastfeeding Comments ORc 95% CI Gastroenteritis 64 Any Inflammatory Bowel Disease 31 Any Obesity 24 Any Celiac Disease 52 > 2 mo Gluten exposure when breastfeeding ALL, acute lymphocytic leukemia; AML, acute myelogenous leukemia; BF, breastfeeding; HM, human milk; Respiratory syncytial virus. a Pooled data. b % lower risk refers to lower risk while BF compared with feeding commercial infant formula or referent group specified. c OR expressed as increase risk for commercial formula feeding. d Referent group is exclusive BF 6 months

12 American Academy of Pediatrics Breastfeeding and the use of human milk Section on Breastfeeding Pediatrics originally published online February 27, 2012; DOI: /peds Later Benefits of Breast Milk C H I L D - A D U L T H O O D Dose-Response Benefits of Breastfeeding Condition % Lower Risk Breastfeeding Comments ORc 95% CI Type 1 diabetes 30 >3 mo Exclusive BF Type 2 diabetes 40 Any Leukemia (ALL) 20 >6 mo Leukemia (AML) 15 >6 mo ALL, acute lymphocytic leukemia; AML, acute myelogenous leukemia; BF, breastfeeding; HM, human milk; Respiratory syncytial virus. a Pooled data. b % lower risk refers to lower risk while BF compared with feeding commercial infant formula or referent group specified. c OR expressed as increase risk for commercial formula feeding. d Referent group is exclusive BF 6 months.

13 Why is Human Milk Critical for Premature Newborns? Infants with GA 28 weeks or BW 1500 grams have very immature GI tracts Neonatal GI tract must be colonized with normal bacteria after birth Evidence of abnormal bowel colonization prior to development of NEC (Mai PLOS One 2011) BW = birthweight; GA = gestational age; NEC = necrotizing enterocolitis.

14 Mucosal Immunologic System (MIS) The lining of the GI tract provides the largest interface with the external environment and is critical to host defense. Epithelial Cells Mucous Secretions Pulmonary Gastrointestinal Epithelial Cells Mucous Secretions Epithelial Cells Mucous Secretions Genitourinary Jakaitis, Brett M. et al. (2014) Human Breast Milk and the Gastrointestinal Innate Immune System. Clinics in Perinatology, Volume 41, Issue 2,

15 Mucosal Immunologic System (MIS) At no time in life is this function more important than shortly after birth. Epithelial Cells Mucous Secretions Pulmonary Gastrointestinal Epithelial Cells Mucous Secretions Epithelial Cells Mucous Secretions Genitourinary Jakaitis, Brett M. et al. (2014) Human Breast Milk and the Gastrointestinal Innate Immune System. Clinics in Perinatology, Volume 41, Issue 2,

16 Colonization of the Microbiome First Stage: Birth to 1 Week of Age Role of mode of delivery is major determining factor Composition of infant s evolving microbiota initially defined by mother Role of ROM, labor, SVD exposes the infant to maternal GI flora Establishing colonization Cabrera-Rubio R, Collado MC, Laitminen K et al July 25, 2012, doi: / ajcn Am J Clin Nutr September 2012 vol. 96 no

17 Colonization of the Microbiome Second Stage: 1-4 Weeks of Age Role of infant s diet is a major determining factor Human milk has lower buffering capacity - acidic milieu potentiates growth of nonpathogenic bacteria Human milk (including colostrum) has specific antibodies and oligosaccharides to support growth of commensal bacteria in the infant s gut ( Pre-biotics ) Cabrera-Rubio R, Collado MC, Laitminen K et al July 25, 2012, doi: / ajcn Am J Clin Nutr September 2012 vol. 96 no

18 Human Milk Oligosaccharides (HMO) Composed of 5 monosaccharides HMO mount/composition vary between women over the course of pregnancy Wide range of interpersonal variation Not every woman synthesizes the same set of HMOs Composition mirrors maternal blood group characteristics Bode L (2012). Human milk oligosaccharides; every baby neds a sugar mama. Glycobiology 2299); doi: /glycob/cws074; Jantscher-Renn E & Bode L Human milk oligosaccharides and their potential benefits Minerva Pediatr 2012;64:83-99

19 Human Milk Oligosaccharides (HMO) Resist the low ph in stomach Are non-digestible Reach the small intestine/colon intact Appear in urine of preterm breastfed infants, but not in the urine of formula- fed infants This finding suggests they are absorbed and reach the systemic circulation and support immune system development Bode L (2012). Human milk oligosaccharides; every baby neds a sugar mama. Glycobiology 2299); doi: /glycob/cws074; Jantscher-Renn E & Bode L Human milk oligosaccharides and their potential benefits Minerva Pediatr 2012;64:83-99

20 Human Milk Oligosaccharides (HMO) Immune Function Anti-adhesive antimicrobials Serve as soluble decoy receptors Prevent attachment of pathogens on the mucosal/epithelial surfaces Regulates immune-inflammatory processes connecting the intestine, liver, muscle, and brain Bode L (2012). Human milk oligosaccharides; every baby neds a sugar mama. Glycobiology 2299); doi: /glycob/cws074; Jantscher-Renn E & Bode L Human milk oligosaccharides and their potential benefits Minerva Pediatr 2012;64:83-99

21 Human Milk Oligosaccharides (HMO) HMOs are present in colostrum, early, and mature milk HMO concentration in colostrum HMO concentration in preterm infant HMO concentrations in mature milk Large variety/number in donor milk Survive pasteurization intact Low content in bovine/cow milk Recent bio-fermentation of 2 oligosaccharides from bovine ~ 150 HMOs are present in Human Milk

22 What is an Exclusive Human Milk Diet (EHMD)? Diet consisting of 100% Human Milk Derived Products Mother s Own Milk (MOM) Preferred Donor Milk if MOM not available Only Human Milk Derived Fortifiers (Protein, Fats, Carbohydrates)

23 Published Advantages of Human Milk for Premature Newborns EHMD had lower rate of NEC than diet of MOM/Donor Milk and Bovine fortifier (Sullivan S. J Pediatr, 2010). EHMD had lower PN days and lower NEC than diet of premature formula (Cristafalo E. J Pediatr, 2013) Decreased incidence of NEC seen in those infants fed human milk (Bhatia J. Ann Nutr Metab, 2013) EHMD= Exclusive Human Milk Diet; PN= Parenteral Nutrition

24 Any Human Milk and ROP Any amount of HMI is significantly associated with protection (compared with no HMI) from the risk of developing All ROP (all stages of ROP pooled together) and Severe ROP ( stage 3 and ROP requiring intervention). An exclusively human milk-fed infant in the first month after birth may have better health outcomes compared with an infant who received low doses of human milk throughout the NICU stay. Bharwani SK, et.al. Systematic review and meta-analysis of human milk intake and retinopathy of prematurity: a significant update. Journal of Perinatology (2016) 36, ; doi: /jp

25 Exclusive Human Milk Diet and ROP Reduction in Severe ROP seen with Exclusive Human Milk Diet from 10.7% in Bovine fortifier group to 1.6% in EHMD group O Connor D. Comparison Of A Human Milk-Based To A Bovine-Based Human Milk Fortifier In Infants Born Less Than 1250 G: A Randomized Clinical Trial. Presented at PAS San Francisco, CA.

26 Sepsis Lower odds of sepsis and associated NICU costs with higher amounts of human milk (Patel A.L. J Perinatol 2013)

27 Greater Mortality and Morbidity in Extremely Preterm Infants Fed a Diet Containing Cow Milk Protein Products EHMD had lower Mortality, NEC, Surgical NEC, Sepsis For each 10% increase in the intake of other than an EHMD, the risk of NEC increases by 11.8%, and the risk of surgical NEC increases by 21%...For each 10% increase in the intake of other than an EHMD, there was a 17.9% increase in risk of sepsis. (Abrams S. Breastfeeding Medicine, 2014) Abrams SA, et. Al. Breastfeeding Medicine 2014:9;0:1-5

28 More Human Milk = More Chance of Remaining NEC Free Combined Clinical Trial Data Analysis Probability of Remaining NEC Free vs. % Cow Milk-Based Diet P (remaining NEC Free) Percent (%) Total Diet from Cow Milk-Based Abrams S, et al. Breastfeed Med. 2014;9: doi: /bfm

29 More Human Milk = More Chance of Remaining Sepsis Free Combined Clinical Trial Data Analysis Probability of Remaining Sepsis Free vs. % Cow Milk-Based Diet Abrams S, et al. Breastfeed Med. 2014;9: doi: /bfm

30 Beyond NEC Beyond Necrotizing Enterocolitis Prevention: Improving Outcomes with an Exclusive Human Milk- Based Diet 1587 Infants <1250 g 4 Centers in 4 states Retrospective cohort study EHMD had Significantly Lower: NEC Mortality Late Onset Sepsis ROP BPD Hair AB, et. al. Breastfeeding Medicine 2016;11(2):1-5.

31 Beyond NEC Hair AB, et. al. Breastfeeding Medicine 2016;11(2):1-5.

32 Decreased Cost and Improved Feeding Tolerance in VLBW Infants Fed an Exclusive Human Milk Diet (Assad M, et.al. J Perinatol 2016) Exclusive Human Milk Diet (EHMD) leads to decreased feeding intolerance, shorter time to full feeds, shorter length of stays, less ROP, less BPD, and lower costs for extremely premature and VLBW infants.

33 Additional Days To Full Feeds P= Bovine Mixed Formula Human (control) 0

34 Additional Hospital Cost (283 Infants) $120, $100, $80, P=0.004 $106,968 P= $60, $40, $20, $0.00 $27,387 $29,178 P=0.175 P= Bovine Mixed Formula Human (control) Human group includes cost of donor milk and fortifier products

35 Additional Physician Charges (293 Infants) Cost in dollars $30,000 $25,000 $20,000 $15,000 $10,000 $5,000 Bovine + Mixed, $25,765 P=0.001 Formula, $14,490 P=0.103 Human (control) $0 Human group includes cost of donor milk and fortifier products

36 Feeding Intolerance: Number of Times Feeds Held for >24 Hrs Fisher s exact test P= % 17% 17% 29% 7% 27% 94% 35% 66% 66% 37% H B M F Groups

37 Feeding Intolerance Alone Has a Price Increased Time to Full Feeds by 4-5 Days (p<0.002*) Increased Length of Stay by 1-4 Days Estimated additional cost for stopping feeds $ per infant, excluding NEC babies from analysis (p<0.05)* Includes cost of: Restarting or Increasing TPN/More TPN Days Longer Length of Stay Clinical investigation (Xrays, Blood cultures, Labs, etc.) *Adjusted for Gestational Age Assad, et.al. Data presented at INAC July 2017

38 What About Growth? Good Growth is what we strive to attain Only adequate weight gain without associated good growth in length and head circumference may lead to babies with increased body fat mass and poorer developmental outcomes!

39 It s All Interconnected! Good Growth Well tolerated Feeds CVL out early Off the Vent quickly Poor Growth Delayed Feeds No Feeding Protocol Maternal Infection Sepsis RDS BPD ICH NEC ROP

40 Nutrition Basics TPN (aka protein) should start on Day 1 Enteral feeds should start within hours of birth when medically feasible (vast differences in opinion/comfort level) Feeds should be advanced by ml/kg/day until goal feeding volumes are met (goal volume +/ ml/kg/day) Babies can be fed more rapidly with the EHMD

41 Working Up On Feeds Parenteral Nutrition Optimal TPN Enteral Nutrition Low volume enteral feeds (trophic/gut priming) Weaning TPN (Concentrate TPN protein to allow for attainment of protein goals) Increasing enteral feeding volume (20->26 cal/oz BM) Discontinuing TPN Suboptimal volume enteral feeds when CVL is pulled (TRANSIENT CALORIE DEFICIT)

42 Feeding Guidelines Early enteral feedings and a standardized approach to feeding have been shown to improve intestinal motility, stimulate hormonal response, improve feeding tolerance, promote earlier achievement of full feeds, and decrease problems related to prolonged TPN in the VLBW infant. Many clinicians do not adhere to the feeding protocol even if there is one. They base their decisions on previous experiences which will most likely lengthen the time to full volume feeds. Decisions are also based previous experiences with cow milk fortifiers.

43 Human Milk Feeding Supports Adequate Growth in Infants 1250 Grams Birth Weight Hair AB, et. al. BMC Research Notes ;2013(6):459 Lower Rate Extrauterine Growth Restriction (22%, excluding those SGA at birth) Mean Weight Gain of 25 g/kg/day SGA babies had same growth velocity as AGA babies, but remained SGA Exclusive human milk-based diet with early and rapid advancement of fortification was associated with weight gain exceeding targeted standards and with length and HC growth meeting targeted standards

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46 Sample Feeding Protocol Infants < 1250 grams or <29 weeks: Total Day 1 fluid volume will be ml/kg/day inclusive of feeds and Day 1 TPN Start feeds within hours at ml/kg/day, q 3 hrs. Use breast milk at 20 cal/oz (maternal or donor) Advance feeds and total fluids by ml/kg/day. Fortify with Human milk-based fortifier at+6 when feeds reach 60 ml/kg/day feeds Add Cream product at 100 ml/kg/day if growth not optimal or on donor milk (if cannot assure 20 cal/oz donor milk). When enteric feeds reach 120 ml/kg/day, TPN will no longer be used. After TPN, continue to advance enteric feeds by ml/kg/day to a goal of ml/kg/day Increase to +8 if growth not meeting goals after 3 days of full fortified feeds.

47 Weaning Start wean at 34 0/7 weeks Day 1: 6 feeds H2MF fortified, 2 feeds bovine fortifier or formula (Q 3 hr feeds) Day 2: 4 feeds H2MF, 4 feeds Bovine Day 3: 2 feeds H2MF, 6 feeds bovine Day 4: All Bovine fortifier with Mother s milk or premature infant formula if mother has no breast milk H2MF = Human milk-based Human Milk Fortifier

48 Excellent Growth with Similar Protocol at Samuelson Children s Hospital Average weight gain: 23 g/day Average Head Circumference Increase: 0.86 cm/wk Average Length Increase: 0.97 cm/wk Swerdfeger, Elliott. Presented at Region 4 Academic Pediatric Association Conf Charlottesville, VA

49 Optimizing Nutrition Length of Feeding Tubing? The longer the tubing, the more human milk fat that get stuck to it. If the calories are getting stuck in the tubing, the baby isn't getting them in his/her feeding. The syringe position (when the feeding is given via a pump)? Fat is a necessary nutrient. Fat rises to the top which means that the syringe tip facing up, will allow for maximal fat to be delivered to the patient. Are the feeds bolus or continuous? Continuous feeds allow for more fat sticking to the tubing and less fat getting to the baby. How often are feeding tubes changed? Frequent new tubes will give a greater new surface area for the fat to stick to which leads to loss of nutrition. All can contribute to poor weight gain!

50 Optimizing Nutrition Bolus feeds best over slow pump flow rates or continuous feeds Increased Fat loss with tubing (Kangaroo pump worse that syringe pump) H2MF and/or Cream improve fat delivery even with continuous feeds Cream shown to shorten Length of Stay in g infants (not specifically studied yet in <750g group) Substantial Calcium and Phosphorus losses with continuous feeds, minimized in vitro with Human milk based fortification (no direct CaPhos salt loss as in bovine fortified milk) Estimated calorie loss ranged between 3 kcal/kg/day to 25 kcal/kg/day depending on fortifier and feeding method

51 Fortifier and Cream Improve Fat Delivery in Continuous Enteral Infant Feeding of Breast Milk Tabata, et.al. 2015

52 Future Directions Further refinement of the best Human Milk Diet for premature infants with different disease states Development of a special, high nutrient Human Milk Diet for term infants with Congenital Heart Disease (in clinical trials now) Development of a special Human Milk Product for young children undergoing Bone Marrow Transplant (in clinical trials now) Possible development of pre-biotic supplements (potential uses in infants exposed to antibiotics)

53 References Bisquera JA, Cooper TR, Berseth CL. Impact of necrotizing enterocolitis on length of stay and hospital charges in very low birth weight infants. Pediatrics. 2002; 109: Sullivan S, et. al. An Exclusive Human Milk-Based Diet IS Associated with a Lower Rate of Necrotizing Enterocolitis that a Diet of Human Milk and Bovine Milk-Based Products. J Pediatr. 2010;156: Rogers SP, et.al. Continuous Feedings of Fortified Human Milk Lead to Nutrient Losses of Fat, Calcium and Phosphorous. Nutrients. 2010: 2: Viadyanathan G, Hay JW, Kim JH. Cost of necrotizing enterocolitis and cost-effectiveness of exclusively human milk based products in feeding extremely premature infants. Breastfeed Med. 2011; 6: 1-9. Neu J, Walker AW. Necrotizing Enterocolitis. N Engl J Med. 2011; 364: Ganapathy V, et.al. Costs of Necrotizing Enterocolitis and Cost-Effectiveness of Exclusively Human Milk-Based Products in Feeding Extremely Premature Infants. Breastfeeding Med.2012;7:29-37.

54 References Breastfeeding and the Use of Human Milk. AAP Policy Statement. Pediatrics. 2012;129(3):e827-e841. Bhatia, J. Human milk and the premature infant. Ann Nutr Metab. 2013; 62 (suppl. 3): Cristofalo EA, et.al. Randomized Trial of Exclusive Human Milk versus Preterm Formula Diets in Extremely Premature Infants. J Pediatr. 2013;163: Hair AB, et. al. Human milk feeding supports adequate growth in infants 1250 grams birth weight. BMC Research Notes.2013;6:459 Ganapathy V, et.al. Long term healthcare costs of infants who survived neonatal necrotizing enterocolitis: a retrospective longitudinal study among infants enrolled in Texas Medicaid. BMC Pediatrics. 2013;13:127 Patel AL, et. Al. Impact of Early Human Milk on Sepsis and Health-Care Costs in Very Low Birth Weight Infants. J Pernatol. 2013;33: National Center for Health Statistics. March of Dimes Peristatistics, Accessed September 29, Abrams SA, et. Al. Greater Mortality and Morbidity in Extremely Preterm Infants Fed a Diet containing Cow Milk Protein Products. Breastfeeding Medicine. 2014;9:1-5 Huston RK, et. al. Decreasing Necrotizing Enterocolitis and Gastrointestinal Bleeding in the Neonatal Intensive Care Unit The Role of Donor Human Milk and Exclusive Human Milk Diets in Infants <1500 g Birth Weight. ICAN: Infant, Child, & Adolescent Nutrition.2014;6(2):86-93.

55 References Zhou J, et. Al. Human Milk Feeding as a Protective Factor for Retinopathy of Prematurity: A Meta-analysis. Pediatrics. 2015;136(6):e1576-e1586. Tabata M, et.al. Fortifier and Cream Improve Fat Delivery in Continuous Enteral Infant Feeding of Breast Milk. Nutrients. 2015; 7: Assad M, Elliott MJ, Abraham JH. Decreased Cost and Improved Feeding Tolerance in VLBW Infants Fed an Exclusive Human Milk Diet. J Perinatol. 2016;36: Hair AB, et.al. Premature Infants 750 1,250 g Birth Weight Supplemented with a Novel Human Milk-Derived Cream Are Discharged Sooner. Breastfeeding Medicine. 2016;11(3): Hair AB, et.al. Beyond Necrotizing Enterocolitis Prevention: Improving Outcomes with an Exclusive Human Milk-Based Diet. Breastfeed Med.2016:11(2):1-5.