Donor Human Milk Barbara L Carr MD FAAP

Donor Human Milk Barbara L. Carr, MD, FAAP Medical Director Heart of America Mothers’ Milk Bank Medical Director Saint Luke’s Hospital of Kansas City NICU

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Human Milk Banking Association of North America ¢ Established in 1985 ¢ Mission To set standards for and facilitate the establishment and operation of milk banks in North America Be a forum for information sharing Educate the medical community Encourage research Act as a liaison between member banks and government agencies

HMBANA ¢ Consists of 14 operational banks 4 developing banks 1 mentoring bank ¢ Dispensed: 2000 2005 2010 2011 ~410, 000 oz ~745, 000 oz ~1. 7 million oz ~2. 2 million oz

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Donor Human Milk-who donates? ¢ Donated milk from women with excess milk Often later in lactation Recognize the importance of human milk ¢ May be preterm or term milk Sometimes part of bereavement

Donor Screening Process ¢ Initial contact with milk bank may be by phone or email ¢ Screeners discuss basic information with potential donors and determine preliminary eligibility Smoker? Medications? Drug ¢ Health Use? screen and physician letters are sent ¢ Commit to donating at least 100 -150 oz*.

Donor Screening Process ¢ Donor Screens and physician approvals are triple checked ¢ Blood work obtained at the time milk is sent in HIV ¢ Milk (0, 1, 2), HTLV I/II, Syphilis, Hepatitis B/C quarantined until eligibility confirmed.

Milk processing ¢ Initial bacterial culture is obtained ¢ Milk is then pooled ¢ Holder method of pasteurization ¢ Repeat bacterial culture obtained and milk is again held until results available. ¢ Milk frozen until dispensed. ¢ Some milk may be deemed suitable only for research

Who receives it ¢ Dispensed by prescription ¢ Infants, usually premature, in Neonatal Intensive Care Units ¢ Limited outpatient use ¢ Some compassionate use pending availability

Nutritional content ¢ Protein 1. 16% ± 0. 25% (range 0. 7% to 2. 1%) Typical mature milk 1. 0 -1. 2% ¢ Fat* 3. 22% ± 1% (range 0. 71% to 7. 06%) Typical mature milk 3. 9 -4. 2% ¢ Carbohydrate 7. 8% ± 0. 88% (range 4. 86% to 12. 67%) Typical mature milk 7. 2 -7. 3% ¢ Average calories per oz = 19. 2 ± 3. 1 kcal/oz 25% of samples were <17 kcal/oz J Am Diet Assoc. 2009; 109: 137 -140

Nutritional Content ¢ Preterm infants need ~120 kcal/kg/d intake and 3. 54 g protein per day ¢ Notably tested term milk, not 24 h samples ¢ Likely reflects realistic picture of nutrient content ¢ Preterm milk not tested J Am Diet Assoc. 2009; 109: 137 -140

DHM-Nutrition ¢ Growth is decreased in premature infants when using unmodified term DHM. ¢ Studies have confirmed this-all but one have compared unfortified term DHM. ¢ Need studies to evaluate fortified DHM (incl preterm) vs. maternal milk or formula as the primary outcome (typical NICU practice). ¢ Can target pool DHM for higher protein, fat, low dairy etc.

Human milk –Not just Nutrition! ¢ For the preterm infant, human milk is considered by many to be lacking nutritionally (not just DHM). (? ) Enter ¢ Need preterm formula to remember the importance of gut related immunity and the developmental/complementary role that human milk plays.

Benefits of Human Milk ¢ Anti-infective s. Ig. A Glycoproteins (oligosaccharides) Lactoferrin lysozyme ¢ Anti-inflammatory Cytokines Platelet activating factor acetylhydrolase Transforming growth factor Beta

Immunologic content

Immune System Benefits of Human Milk ¢ Barrier/Receptor Site Binding s. Ig. A-binds s. Ig. A receptors lining mucosa and competing for adherence sites/invasion by pathogens¢ Highly targeted to the maternal environment ¢ Preemies have the most significant uptake Glycoproteins (mucin, lactadherin, and oligosaccharides) provide alternate receptor site binding Lactoferrin competes for iron binding sites and damages membranes of pathogens The Evidence for Use of Human Milk in Very Low Birthweight Preterm Infants Neoreviews 2007; 8: e 459 -e 466 The Mucosal Immune System and Its Integration with the Mammary Glands. JPeds; 156(2)Suppl 1; s 8 -s 16

Immune system benefits of Human Milk ¢ Oligosaccharides –the premier prebiotic encourage g. I colonization of commensal bacteria (bifidobacteria)-act to tighten mucosal barriers and compete for adherence sites ¢ Bacterial Cell wall lysis Lysozyme and byproducts of lipid digestion assist in cell wall lysis The Evidence for Use of Human Milk in Very Low Birthweight Preterm Infants Neoreviews 2007; 8: e 459 -e 466 Newburg, DS et al Annu Rev Nutri 2005; 25: 3758

Anti-inflammatory effects ¢ Binding of toll like receptors CD 14 Decreased IL-8 production via lack of activation of NF-kappa-B ¢ Epidermal growth factors, prostaglandins, antiinflammatory cytokines (IL-10) ¢ Platelet activating factor acetylhydrolase (PAF-AH) Minimal concentrations in gut until 6 weeks Is present in human milk The Evidence for Use of Human Milk in Very Low Birthweight Preterm Infants Neoreviews 2007; 8: e 459 -e 466

Anti-Inflammatory effects ¢ High concentrations of LCPUFA ¢ Antioxidants (vitamin E, inositol, beta carotene) ¢ Additional research particularly focusing on oligosaccharides is ongoing.

Immunologic content

Use of DHM in premature infants ¢ Reach full enteral feedings sooner ¢ Decreased TPN days so late onset infection and other associated side effects are decreased. ¢ NEC reduction Schanler et al Seminars in Perinatology 1994 (18) Quigley et al Cochrane Review 2007

Donor human milk, prevention of necrotizing enterocolitis Mc. Guire & Anthony, Arch Dis Child 88: F 11 (2003)

Donor milk and NEC in premature infants DM (n=78) Sepsis (%) 29 NEC (%) 6 BPD (%) 15 Wt gain (g/kg/d) 17. 1 p PF (n=88) (n=70) 30 11 0. 048 0. 001 p MM 0. 022 28 20. 1 23 0. 044 6 13 Schanler et al. , Pediatrics 2005; 116: 400 -406 Note: All infants initially received their mother’s milk 18. 8

NEC reduction ¢ Increasing evidence of a dose dependent relationship (Schanler, Meinzen-Derr). ¢ NICHD study 1433 infants 1272 met inclusion criteria 13% reduction for each 100 ml/kg incremental increase in intake) Meinzen-Derr et al J Perinatol 2009; 29: 57 -62

Adjusted survival curves for NEC or death by proportion of HM to total intake over the first 14 d of life (Meinzen-Derr et al)

Neurodevelopmental Outcomes ¢ Lucas et al showed a sig higher IQ (8. 3 point advantage)in HM fed group; dose response with 9. 0 point advantage for those fed exclusive HM ¢ Furman et al –no effect on cognitive development and overall neurodevelopment

Neurodevelomental Outcomes ¢ NICHD Glutamine Trial-dose response relationship between amount of HM and neurodevelopmental outcomes at 18 mos ¢ For each 10 m. L/kg/day incr in HM feeding Psychomotor Development Index incr 0. 63 points Mental Development Index incr 0. 53 points ¢ No data for DHM

Potential negatives of DHM ¢ Decreased growth Shown in multiple studies to have slower growth rates versus mother’s own milk or formula No studies comparing current standard of use Fortification allows normal growth rates. ¢ Mother won’t pump? Most units see an increase in mother’s own milk production (initiation and duration) ¢ Infection No evidence of transmitted infection with pasteurized milk from milk banks.

Potential negatives of DHM ¢ Expense ≥$4. 50 per ounce Cost not typically covered by insurance Compare to NEC ($150, 000/2 weeks longer stay) ¢ Outcomes No long term outcome studies available-length of stay, neurodevelopment, bone mineralization/growth (existing data supports use of maternal milk)

Use of Donor Human Milk at Saint Luke’s Hospital ¢ Began as part of two quality improvement projectspart of Pediatrix Medical Group’s 100, 000 Babies Campaign. ¢ Increase the use of human milk and lower the incidence of NEC. ¢ Concept introduced by multidisciplinary team to the NICU

Use of Donor Human Milk at Saint Luke’s Hospital ¢ Support garnered from medical and nursing staff Dealt with concerns re: safety, nutrition, “yuck” factor, “need more science”. RN champions on all shifts ¢ Proposal supported by hospital administration ¢ Protocols developed for use in the NICU

Use of Donor Human Milk at Saint Luke’s Hospital ¢ Mothers receive a pamphlet during the prenatal consultation ¢ Additional fact sheet in the “Jungle Book” ¢ MD or NNP obtains consent after risk/benefit discussion ¢ Emphasis placed on the importance of mothers’ own milk and use of DHM as a bridge/supplement.

Use of Donor Human Milk at Saint Luke’s Hospital ¢ For infants <1500 g DHM until 2 kg ¢ For infants 1500 -2000 g DHM for two weeks ¢ For infants >2000 g (and mother plans to breastfeed) DHM for one week ¢ For infants as medically indicated (ex NEC recovery, gastroschisis, etc)

Use of Donor Human Milk at Saint Luke’s Hospital ¢ Preterm donor milk for infants <1250 g (due to limited supply). ¢ High calorie term donor milk for infants >1250 g. ¢ term donor milk for infants >2 kg ¢ Donor colostrum (when available) for initial feedings for infants <1250 g

Use of Donor Human Milk at Saint Luke’s Hospital ¢ First feeding to be given as mother’s own milk, followed by donor milk as needed to supplement maternal supply. ¢ Do not dilute the initial maternal milk feeding with either donor milk or formula to achieve a specific volume

Use of Donor Human Milk at Saint Luke’s Hospital ¢ Infants are transitioned off of DHM when they have met the predefined criteria or are approaching discharge and taking ~50% oral feedings. ¢ “Hypoallergenic” formula may be used after DHM protocol in lieu of standard formula for mothers with insufficient but increasing supply.

Barriers to using DHM ¢ Availability – Lack of donors Competition-commercial use, informal sharing (internet sales) ¢ Medical community ¢ Formula ¢ Perception of community

Competition for Milk In 2011, the 11 dispensing non profit milk banks distributed ~2. 2 million ounces of milk to hospitals. ¢ The need continues to increase. ¢ To meet the needs of all VLBW infants in the US, we would need as estimated 9 million ounces annually. ¢ 39

The Cost of Milk Pasteurized donor milk costs ~$4. 50/ounce from HMBANA banks ¢ Milk that is higher in protein or kcals may cost up to $6 -7 per ounce ¢ Milk sold online from $1 -4 per ounce ¢ Prolacta Bioscience products: ¢ Up to $187 per ounce for H 2 MF $30 per ounce for “Neo 20” $45 per ounce for “Premie Lact” 40

Ounces of Milk Produced 41

HMBANA’s stance

FDA v On December 6, 2010, the U. S. Food and Drug Administration's Office of Pediatric Therapeutics convened a meeting of national experts, including directors of two HMBANA milk banks, to discuss the safety, ethics, and regulatory implications of donor human milk. v risks related to consumption of banked human milk and how that varies depending on the source and processing v the voluntary or regulatory controls currently in place v Explore ideas related to additional scientific research that might be needed to further advance our knowledge concerning the risks 44

FDA PAC Hearing on Donor Milk fda. gov The FDA Pediatric Advisory Committee endorsed donor human milk banking and deemed informal sharing of human milk to be unsafe ¢ See meeting agenda, briefing material and minutes on the FDA website ¢ 45

HMBANA’s stance v “It does not condone, and in fact, questions the practice of buying and selling of human milk as a commodity. Introducing the profit motive could put the infant of the lactating mother at risk if she feels pressure to provide a certain volume of milk to a bank or a recipient rather than feeding her own infant. A medical institution, which is given incentives to provide a specific volume of milk, may pressure mothers of patients to become donors regardless of their own infants’ needs. The recipient is also potentially at risk if this perceived pressure motivates a donor to adulterate her milk to increase volume. ” 46 v HMBANA position paper on

Heart of America Mothers’ Milk Bank at Saint Luke’s Hospital ¢ Group began meeting in summer 2009. ¢ Barbara Carr, Christine Pai, Stephanie Howard, Lissa Cross, Mary Grace Lanese; Katie Mac. Farland. ¢ Now includes Kristin Easter, Angie Moreno, Bonnie Nelson, Judy Junk, Patrick Altenhofer, Sharon Wood, Robin Evans ¢ Recognized a need within our community and an as yet untapped resource.

Why have a milk bank in Kansas City or anywhere else? ? ¢ Human milk provides the best nutritional, immunologic and developmental start for babies. ¢ It allows women in our area easier ability to donate their milk. ¢ It allows NICUs in our area easier access to this resource. ¢ Parents are aware of and beginning to expect DHM as an option ¢ Women will seek it elsewhere—let’s make it safe.

Heart of America Mothers’ Milk Bank at Saint Luke’s Hospital Our Mission ¢ To provide donor human milk to premature and ill infants by accepting, pasteurizing and dispensing human milk by physician prescription. ¢ To educate the medical and general communities about the indication for, benefits of, and use of donor human milk. ¢ To increase the initiation and duration of breastfeeding in the Kansas City regional area.

Heart of America Mothers’ Milk Bank at Saint Luke’s Hospital ¢ Member of the Human Milk Banking Association of North America (HMBANA) ¢ Initially functioned as a depot for Denver Mothers’ Milk Bank ¢ Began dispensing milk in Sept 2012 ¢ Goal to bring donor depots on board over the next several months ¢ Supply our region followed by the rest of the country where needed

Heart of America Mothers’ Milk Bank at Saint Luke’s Hospital ¢ Contact info “warm On line” 816. 932. 4888 the web at: www. saint-lukes. org Email us at kcmilkbank@saint-lukes. org

Thank you barbara_carr@pediatrix. com

Thank you barbara_carr@pediatrix. com

Thank you barbara_carr@pediatrix. com