QI: Exclusive Human Milk Diet for Preterm Infants

QI: Exclusive Human Milk Diet for Preterm Infants Amy B. Hair, MD Assistant s Professor of Program Director of Neonatal Nutrition Program Director of NICU Intestinal Rehab Team Section of Neonatology Department of Texas Children s Hospital abhair@texaschildrens.org

Disclosures I receive research support from: Prolacta Bioscience for the Human Milk Cream Length of Stay and Bronchopulmonary dysplasia Multicenter Study (Study PI) I receive speaker honoraria from Prolacta Bioscience Page 2

Overview Human milk use in preterm infants Necrotizing enterocolitis and Human Milk Fortification of Human Milk Exclusive human milk-based diet Postnatal Growth Failure Implementation Page 3

AAP Statement 2012 Breastfeeding and the Use of Human Milk All preterm infants should receive human milk. Human milk should be fortified, with protein, minerals, and vitamins to ensure optimal nutrient intake for infants weighing <1500 grams at birth Pasteurized donor human milk (DHM), appropriately fortified, should be used if mother s own milk is unavailable or its use is contraindicated Significant short and long-term beneficial effects of feeding preterm infants human milk American Academy of Section on Breastfeeding. Breastfeeding and the use of human milk.. 2012; 129(3): e827-e841. Page 4

AAP Statement 2012 Breastfeeding and the Use of Human Milk Significant short and long-term beneficial effects of feeding preterm infants human milk Lower rates of sepsis and necrotizing enterocolitis Reduction in incidence of NEC include not only lower mortality rates but also lower long-term growth failure and neurodevelopmental disabilities Improved feeding tolerance Fewer hospital readmissions for illness in the year after NICU discharge Improved neurodevelopment American Academy of Section on Breastfeeding. Breastfeeding and the use of human milk.. 2012; 129(3): e827-e841. Page 5

Benefits of Human Milk respiratory tract infections and otitis media sudden infant death syndrome and mortality GI infections risk of celiac disease and IBD asthma, atopic dermatitis and eczema incidence of NEC Associated with a decrease in obesity and diabetes Beneficial influence on neurodevelopmental outcomes Possible reduction in severity of retinopathy of prematurity American Academy of Section on Breastfeeding. Breastfeeding and the use of human milk.. 2012; 129(3): e827-e841. Page 6

Necrotizing Enterocolitis NEC is a devastating illness that affects 5.4 to 7.4% of VLBW infants/year (Vermont Oxford Network) Despite years of ongoing research, the exact pathophysiology of necrotizing enterocolitis is still not known Multifactorial Mucosal injury leading to an exaggerated immune response, which then results in bacterial translocation, systemic infection, and inflammation Page 7

Necrotizing Enterocolitis Problems of the Neonate. (2007). http://web.squ.edu.om/med-lib/med/net/e- TALC9/html/clients/who/hcfc_images/necrotising%20enterocolitis%201.jpg Page 8

Human Milk and NEC Study No. Infants Characteristics Results Lucas et al, 1990 926 infants Schanler et al, 1999 62 (FHM) 46 formula Multicenter study FHM vs. formula Sisk et al, 2007 222 infants FHM vs. formula in 1 st 14 days Henderson et al, 2007 10 neonatal centers -53 infants Look at practices associated with NEC - 6-10 times more NEC in formula fed vs. HM -No difference in type of HM - NEC in FHM 1 (1.6%) vs. formula 6 (13%) - late onset sepsiss -Associated with a 6 fold decrease in NEC with an intake of just 50% HM -Human milk was associated with lower risk of NEC FHM=Fortified human milk Page 9

Survival Curves for NEC or death* by amount of human milk (ml/kg/d) 1.00 Survival Estimate *For NEC or Death after 14 days, adjusted for birth weight, race, PDA treatment, ventilation, and site. 0.95 0.90 0.85 080 0.80 100 ml 50 ml 20 ml 10 ml 0 ml 0 10 20 30 40 50 60 70 80 90 100 110 120 Postnatal age (d) Meinzen-Derr, et al NICHD Neonatal Network, J Perinatology 2009 Page 10

Pasteurized Donor Human Milk Human Milk Banking Association o of North America Medolac / Mothers Milk Cooperative Prolacta Bioscience Hospital Based Milk Banks Page 11

Donor Human Milk Human Milk Banking Association of North America 20 Milk Banks Medolac- Mother s Milk Cooperative Mother s are paid Prolacta DHM Extensive screening process Donors have the option to be paid or donate $ to charity DNA fingerprinting, Drug Screens, tests for bacterial contamination Page 12

Donor Qualification Requirements POTENTIAL DONORS: Are screened via an online survey and are assigned a number Must obtain approval from physician and pediatrician Stored milk must be frozen and cold enough to donate DONOR EBM SCREENING PROCESS: A blood test are conducted for presence of HIV 1&2, HTLV I&II, HBV, HCV, and syphilis. Full microbiological panel is obtained including Aerobic count, B. cereus, Escherichia coli, Salmonella, Pseudomonas, coliforms, Staphylococcus aureus, yeast and mold. Bovine protein Will screen for drugs of abuse Page 13

Pasteurization Effect of Pasteurization Conditions on Human Milk Constituents: Parameter Untreated Human Milk Pasteurized Human Milk % Remaining Immunoglobulin A 315 230 73 (mg/ml) Secretory IgA 462 379 83 Lysozyme (IU/mL) 39,000 22,000 57 Lactoferrin (g/100 ml) Vitamin B6 (µg/100 ml) (g/100 ml) 0.24 0.033 14 8.8 7.8 89 Page 14

Meta-Analysis: Donor Milk vs. Formula Table 2- Studies of Donor Human Milk and NEC Donor Milk Formula Gross 1983 1/42 (2%) 3/29 (10%) Cooper 1984 1/24 (4%) 3/15 (20%) Lucas 1990 1/87 (1%) 4/80 (5%) Schanler 2005 5/78 (6%) 10/88 (11%) Overall 8/231 (3%) 20/212 (9%) Risk of NEC is reduced significantly with pasteurized donor milk 0.35 (0.15; 0.81) Morales Y and RJ Schanler. Human milk and clinical outcomes in VLBW infants: how compelling is the evidence of benefit? Semin Perinatol 2007; 31:83. Page 15

Donor Human Milk Formula fed infants had a higher incidence of NEC - 8 studies included (RCT with preterm or LBW infants) -5 trials (812 infants) showed a statistically significant increased incidence of NEC in formula group vs. donor human milk group -Risk ratio 2.5 (CI 1.2, 5.1) Quigley, et al. Cochrane Database of Systematic Reviews 2007. Page 16

Human Milk Fortification A response to the need to provide additional nutrients, especially minerals, for premature infants Protein Calcium Phosphorus Zinc Page 17

Human Milk Fortification Liquid HMF (LHMF)-Bovine Each packet/vial of LHMF is 5 ml 1 packet/vial of LHMF + 25mL EBM = 30 ml of 24 kcal/ounce Powder HMF-Bovine Each packet/sachet of HMF, when added to 100 ml EBM increases calories by 1 kcal/oz 4 packets/sachets of HMF per 100 ml EBM = 24 kcal/oz Donor human milk-derived fortifier 24 kcal/oz: 80 ml EBM+20 ml +4 (4:1) 26 kcal/oz: 70 ml EBM+30 ml +6 (7:3) 28 kcal/oz: 60 ml EBM+40 ml +8 (3:2) 30 kcal/oz: 50 ml EBM+50 ml +10 (1:1) Page 18

Human Milk Fortification: Pros & Cons Bovine human milk fortifier- Liquid Sterile, DHA Displaces more human milk than powder Bovine human milk fortifier- Powder Displaces less human milk than liquid Not sterile, lower protein Donor human milk-based fortifier Early fortification, provides an exclusive human milk protein diet Need to supplement vitamins and iron, $ Page 19

Nutrients per kg/day AAP 1 2014 ESPGHAN 2 2010 *<1000g EBM + 4 Similac Powder HMF per 100 ml EBM + 4 MJ Liquid id HMF per 100 ml EBM + 4 Similac Liquid id HMF per 100 ml EBM + Prolacta+6 per 100 ml Volume (ml) -- -- 150 150 150 150 Energy (kcal) 105-130 110-135 120 120 120 135 Protein 35-4 3.5 (g) 3.5-4 *4-4.5 2.9 3.9 3.6 3.6 Calcium (mg) 100-220 120-140140 202 174 179 183 Phosphoru s (mg) 60-140 60-90 120 96 102 96 Iron (mg) 2-4 2-3 0.6 2.3 0.6 0.3 1 Kleinman RE (ed.) American Academy of. Committee on Nutrition. Pediatric Nutrition Handbook 6th edition. Academy of, Elk Grove Village, Illinois. 2009 2 Agostoni C, et al; ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr. 2010;50(1):85-91. Page 20

Exclusive Human Milk-Based Diet The use of an exclusive human milk-based diet in infants 1250 grams birth weight is associated with a lower rate of necrotizing enterocolitis (NEC) 1,2 and decreased parenteral nutrition days 2. An exclusive human milk diet is associated with lower mortality and morbidity compared to a cow milk based protein diet 3. 1 Sullivan et al: An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products. J Pediatr 156(4): 562-567, 2010. 2 Cristafalo et al: Randomized Trial of Exclusive Human Milk versus Preterm Formula Diets in Extremely Premature Infants. J Pediatr 163 (6): 1592-1595, 2013. 3 Abrams et al: Greater mortality and morbidity in extremely preterm infants fed a diet containing cow milk protein products. Breastfeeding Medicine 9 (6): 281-5, Page 2014. 21

An Exclusive Human Milk-Based Diet and NEC¹ 18.0% 16.0% 14.0% 12 0% 10.0% 8.0% 6.0% 4.0% 2.0% 0.0% NEC NEC 12.0% Surgery HM100 HM40 BOV All HM (n=67) (n=71) (n=69) (n=138) Medical NEC by 60% Surgical NEC by 90% ¹Sullivan et al: An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products. J Pediatr 156(4): 562-567, 2010. Page 22

NEC Surgery Bovine HM 40 HM 100 Combined Surgical NEC 8 / 69 1 / 71 1 / 67 2 / 138 Rate 11.6% 1.4% 1.5% 1.4% p-value 0.017 0.03 0.0027 Ab baby b receiving i bovine products has 8ti times higher h odds of requiring surgery for NEC. 1 Sullivan et al: An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products. J Pediatr 156(4): 562-567, 2010. Page 23

Exclusive Human Milk-Based Diet Sullivan et al 1 showed that there is no difference in growth between infants fed an exclusively human milk-based diet and infants fed human milk plus bovine milk-based products. However, concerns remain related to risks of slow growth in these infants. 1 Sullivan et al: An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products. J Pediatr 156(4): 562-567, 2010. 2 Cristafalo et al. A Randomized Trial of Exclusive Human Milk Versus Preterm Formula Diets in Extremely Premature Infants. J Pediatr 163 (6): 1592-1595, 2013. Page 24

Growth and Donor Human Milk Small descriptive studies suggest that the nutrient content t of DHM is lower in fat, calories, protein, sodium, and calcium as compared to formula Premature infants have increased nutritional requirements All infants with a birth weight 1250g are at risk for poor growth and metabolic abnormalities One meta-analysisanalysis showed that DHM is associated with slower growth in the early postnatal period Boyd et al. Donor breast milk versus infant formula for preterm infants: systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 92: F169-F175, 2007. Page 25

Postnatal Growth Restriction/Failure NICHD Neonatal Research Network reported outcomes of VLBW infants cared dfor at t14 participating i centers 4,438438 infants 501-1500 1500 gram BW 22% of infants were < 10 th percentile at birth 97% of the VLBW population had growth failure at 36 weeks corrected age Infants weighing 501-1000 grams BW 17% of infants were < 10 th percentile at birth 99% had growth failure at 36 weeks corrected age Lemons, JA, Bauer CR, Oh W, et al: Very low birth weight outcomes of the National Institute of Child Health and Human Development Neonatal Research Network, January 1995 through December 1996. 107 (1): e1, 2001. Page 26

Postnatal Growth Failure Clark et al: Database review of growth data 24,371 premature infants 23-34 weeks gestation 28% of infants had postnatal growth failure The incidence of growth failure increased with decreasing gestational age and birth weight Clark RH, Wagner CL, et al. Nutrition in the neonatal intensive care unit: how do we reduce the incidence of extrauterine growth restriction? J Perinatol, 23(4): 337-44, 2003. Page 27

Why is this important? Infants 501-1000 grams BW were divided into quartiles of in-hospital growth velocity rates 495 infants were evaluated at 18-22 months CGA As the rate of weight gain increased from 12.0 to 21.2 g/kg/day (quartile 1 to 4) and head circumference increased from 0.77 to 107cm/wk 1.07 the incidence decreased significantly for: Cerebral palsy, Bayley II MDI 70 and PDI 70, abnormal neurologic exam, neurodevelopmental impairment and need for re-hospitalization Ehrenkranz RA et al: Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely low birth weight infants. 117(4): 1253-1261, 2006. Page 28

Human Milk Feeding Supports Adequate Growth Exclusive Human Milk-Based Diet Early and rapid advancement of fortification 1 104 infants, consecutively followed, BW 1250 g, received diet until 34 weeks PMA Weight gain 24.8 ± 5.4 g/kg/day, length 0.99 ± 0.23 cm/week, HC 0.72 ± 0.14 cm/week Compared to human milk-fed cohorts (Sullivan et al 2 ) Infants had greater growth in weight and length 43% of infants had postnatal growth failure 1 Hair et al: Human Milk Feeding Supports Adequate Growth in Infants 1250 grams birth weight. BMC Res Notes 2013; 6: 459. 2 Sullivan et al: An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products. J Pediatr 156(4): 562-567, Page 29 2010.

Hair et al Study 1 Sullivan et al. J. 2010 2 Human Milk + HMF 60 (n=104) Human Milk + HMF 40 (n=71) Human Milk + HMF 100 (n=67) Bovine (n=69) p-value Days to full feeds* 18.2 ± 10.6 24.4 ± 12.7 26.5 ± 18.0 25.0 ± 13.5 <0.001 TPN days 13 (10,19) 20 (11,33) 20 (13,34) 22 (13,34) <0.001 Feeds initiated (DOL)* 33± 3.3 ± 29 2.9 56± 5.6 ± 66 6.6 43± 4.3 ± 39 3.9 47± 4.7 ± 48 4.8 056 0.56 Fortification of feeds (DOL)* 13.0 ± 8.3 14.1 ± 9.0 21.0 ± 14.9 18.4 ± 9.2 <0.001 * Mean ± SD, Median (25 th, 75 th percentile). DOL = day of life; TPN = total parenteral nutrition. 1 Hair et al: Human Milk Feeding Supports Adequate Growth in Infants 1250 grams birth weight. BMC Res Notes 2013; 6: 459. 2 Sullivan et al: An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products. J Pediatr 156(4): 562-567, 2010. Page 30

Costs- Exclusive HM Diet Costs of NEC and cost-effectiveness of exclusively human milk-based diet compared to bovine based diet in extremely premature infants NEC $74,004 and NEC requiring surgery $198,040 Costs over the hospitalization for a preterm infant 100% human milk diet infants had decreased length of stay= cost savings of $8,167 Ganapathy V, Hay JW, Kim JH. Costs of Necrotizing enterocolitis and cost-effectiveness of exclusively human milk based products in feeding extremely premature infants. Breastfeed Med. 7(1):29-37, 2012. Page 31

Implementation Increase maternal milk supply for premature infants Pumps at the bedside Education about benefits of mother s own milk Lactation Support Use of Pasteurized Donor Human Milk Milk Bank Availability Drop off site for donated human milk Potential variability in energy density of donor human milk depending on milk bank Page 32

Implementation Plan Evaluate your highest risk population p for NEC and feeding intolerance Gather data regarding NEC rates, TPN days, and feeding intolerance so you have a baseline Implement Donor Human Milk and DHM Fortifier Evaluate your results using balancing measures If cost is an issue consider collecting data including length of stay as a surrogate marker Page 33

Positive Outcomes to Follow Rates of Necrotizing Enterocolitis Central line days, Parenteral Nutrition Days CLABSI infection Growth- weight, length, head circumference Postnatal growth failure Feeding tolerance- number of times feeds are stopped and restarted t Costs $$, Decreased Length of Stay Number of infants not transferred to higher level of care Page 34

Balancing Measures Extra Costs Administrative Staffing Milk Bank Techs, Nurses, Preparing Milk Donor Milk and DHM Fortifier Storage (Freezer) Implementation Education of Staff Implement Consent / Assent of Parents Risk of Milk Errors Possible Delay of Enteral Feeding Awaiting Mother s own milk or Donor Human Milk Consent Page 35

Advocacy to Prevent NEC www.necsociety.org Page 36

Thank You! abhair@bcm.edu Page 37