For$fying Human Milk May 2014

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1 For$fying Human Milk May Feeding Premature Infants: Why, When, & What To Add To Human Milk 1 RONALD S. COHEN, MD MEDICAL DIRECTOR - PICN LUCILE S. PACKARD CHILDREN S HOSPITAL CLINICAL PROFESSOR OF PEDIATRICS STANFORD UNIVERSITY SCHOOL OF MEDICINE MEDICAL DIRECTOR MOTHERS MILK BANK OF SAN JOSÉ Goals of Talk 1. Identify common nutritional concerns for premature babies a. While they are in the NICU, and b. After they ve gone home from the NICU. 2. Can we tell when these needs are not being met? a. Can human milk be used to meet these needs, and b. Can adding to human milk help meet these needs? 3. Review evidenced-based discharge feeding practice for prematurely born infants. 2 Unique Abbreviations What is Banked Donor Milk? 3 4 BDM = Banked Donor Milk MAT = Maternal Milk PTF = Pre-Term Formula PDF = Post-Discharge Formula HMBANA = Human Milk Banking Association of North America HMF = Human Milk Fortifier H2MF = Human-milk derived HMF NEC = Necrotizing Entero-Colitis LPF = Liquid Protein Fortifier Mother s health screened By their own MD/OB Same health questionnaire used by Blood Bank Serologic testing except for CMV Medication use tightly restricted No tobacco or non-prescription drug use allowed Milk thawed & cultured prior to processing Milk Holder Pasteurized & re-cultured Milk pooled prior to re-freezing & distribution Does Holder Pasteurization Work? Holder pasteurization was, however, an effective means by which to remove any detectable bacteria from samples of donor human milk bottles (Table) had been thawed for 7 to 122 hours (mean 46.7 ± 28.4). None of the samples had any bacterial growth, including 18 bottles thawed and refrigerated appropriately for more than 24 hours. 2 No infections linked to HMBANA BDM in >30 years Landers S, Updegrove K. Breastfeed Med 2010; 5: Cohen RS, et al. Breastfeed Med 2012; 7: BDM & CMV Heat treatment destroys CMV 1 : Holder 62.5 C; Flash 72 C. Freeze/thaw may not eliminate CMV: Freezing for 1 year, then freeze/thaw x 3 did NOT eliminate infectious virus 1 ; 5 of 36 CMV positive mothers transmitted CMV to 6 babies despite freezing 2 ; 2 of 23 CMV positive mothers transmitted CMV to 2 babies despite freezing & Cesaerean delivery Hamprecht K, et al. Pediatr Res 2004; 56: Jim W-T, et al. Pediatr Infect Dis J 2004; 23: Lee HC, et al. Pediatr Infect Dis J 2007; 26:

For$fying Human Milk May HMBANA & HIV 7 Donor human milk banks that belong to the Human Milk Banking Association of North America (http:// www.hmbana.

milk. Holder pasteurization (ie, heating at 62.

2 For$fying Human Milk May HMBANA & HIV 7 Donor human milk banks that belong to the Human Milk Banking Association of North America ( voluntarily follow guidelines of the Centers for Disease Control and Prevention (CDC), which include screening of donors for infectious transmissible agents as well as heat treatment of the milk. Holder pasteurization (ie, heating at 62.5 C for >30 minutes) is the only method that completely eradicates HIV in all human milk components and is the current standard 8 World Association of Perinatal Medicine: Consensus Arslanoglu S, Ziegler EE, Moro GE, at al. J Perinat Med 2010; 38: When mother s milk is not available, fortified donor human milk is the recommended alternative for this group of infants. Committee on Pediatric Aids. Pediatrics 2013; 131: DOI: /peds Breastfeeding and the Use of Human Milk Policy Statement AAP Section on Breastfeeding Pediatrics 2012; 129:e827 e841 doi: /peds Pasteurized donor human milk, appropriately fortified, should be used if mother s own milk is unavailable or its use is contraindicated. Extra- Uterine Growth Restriction Ehrenkranz RA, et al. Pediatrics 1999; 104: Extra Uterine Growth Restriction Caloric deficits. Protein deficits. Calcium-Phosphorus deficits. NICU Growth vs Outcome Short-term Ehrenkranz RA, et al. Pediatrics 2006;117: Short-term outcome 2

For$fying Human Milk May 13 Impact of increased early protein intake 14 NICU Growth vs Outcome Long-term Ehrenkranz RA, et al. Pediatrics 2006;117;1253-61. 1 g/kg daily Protein added = increase 8.

In a group of infants with birthweight less than 1250 g who were receiving exclusive parenteral nutrition over the first days of life, no correlation was found between amino-acid intake and serum BUN

3 For$fying Human Milk May 13 Impact of increased early protein intake 14 NICU Growth vs Outcome Long-term Ehrenkranz RA, et al. Pediatrics 2006;117; g/kg daily Protein added = increase 8.2-point MDI! Stephens BE, at al. Pediatrics 2009;123: BUN to Monitor IV Protein Intake? Ridout E, et al. J Perinatol 2005; 25: In a group of infants with birthweight less than 1250 g who were receiving exclusive parenteral nutrition over the first days of life, no correlation was found between amino-acid intake and serum BUN concentration. Given the data supporting the importance of early amino-acid administration in premature infants, limiting amino acid intake based on serum BUN concentrations is not warranted. 16 Oral Protein Intake & Weight Gain 4.6 vs 3.8 g/kg daily protein intake. Caloric intake not different. Volume ~ 160 ml/kg daily. High protein resulted in better gain. Average 23.1 ± 7 vs 16.7 ± 6 g/kg daily. Effect greater in males than females. Nitrogen absorption ~ 80%. 16 Cooke R, et al. Pediatr Res 2006; 59: HMF vs HMF + Protein ~1 g/dl Oral Protein Intake & BUN - 17 BUN mg/dl Cooke R, et al. Pediatr Res 2006; 59: Biasini A, et al. J Matern Fetal Neonatal Med 2012; 25(Suppl 4):S

For$fying Human Milk May 19 Oral Protein Intake & Base Excess Sequential analysis of human milk 20 The

J Am Diet Assoc 2009; 109:137-40. About 1.1 g/dl Prolacta claims 0.9 g/dl in their milk Bauer J, Gerss J.

4 For$fying Human Milk May 19 Oral Protein Intake & Base Excess Sequential analysis of human milk 20 The DARLING Study Cooke R, et al. Pediatr Res 2006; 59: Approximately 1.2 g/dl Protein Nommsen LA, et al. Am J Clin Nutr 1991; 53: Analysis of Preterm vs Term Milk Analysis of Donor Milk 22 Wojcik KY, et al. J Am Diet Assoc 2009; 109: About 1.1 g/dl Prolacta claims 0.9 g/dl in their milk Bauer J, Gerss J. Clin Nutr 2011; 30: Variability of Human Milk: Fortification 23 Comparison of Protein Analysis 24 De Halleux V, Rigo J. Am J Clin Nutr 2013;98(suppl):529S 35S. De Halleux V, Rigo J. Am J Clin Nutr 2013;98(suppl):529S 35S. 4

For$fying Human Milk May Milk from NICU Mothers 25 MMB San José Donor Milk - Then 26 Protein Lactose Calories 1.24 g/dl 7.23 g/dl 20.5 kcal/oz ± 16% ± 6.7% ± 10% Rivera A. Personal Communication.

5 For$fying Human Milk May Milk from NICU Mothers 25 MMB San José Donor Milk - Then 26 Protein Lactose Calories 1.24 g/dl 7.23 g/dl 20.5 kcal/oz ± 16% ± 6.7% ± 10% Rivera A. Personal Communication. Stellwagen L, et al. Breastfeed Med 2013; 8: MMB San José BDM Analysis Now Can Milk Provide Enough Protein? Protein Fat Lactose Calories 0.87 g/dl 3.34 g/dl 7.42 g/dl kcal/oz +/ / / / New Algorithm!! N = 73; January 2012 Rivera A. Personal Communication. Milk Protein Content (g/dl) Fluid Intake (ml/kg daily) Protein Intake (g/kg daily) Fortification Protein vs Osmolality? Measured vs Predicted Milk Content Arslanoglu S, et al. J Perinatol 2009; 29: Corvaglia L, et al. Early Hum Dev 2010; 86:

6 For$fying Human Milk May 31 Milk Composition and Breastfeeding Pattern Over a 24-Hour Period 32 Variation in Milk Fat Content During A Feed Khan S, et al. J Hum Lact 2013; 29:81-9. Khan S, et al. J Hum Lact 2013; 29:81-9. Adjusted Fortification? Growth with Fortified Human Milk Adjust fortification per BUN: Protein powder added above standard HMF; Decrease if > 14 mg/dl; Increase if < 9 mg/dl. No difference in serum Albumin or Creatinine: Clinically insignificant increase in BUN (~ 2 mg/dl). No NEC: No formula feedings; Diet ~ 60% Maternal & 40% BDM. Arslanoglu S, et al. J Perinatol 2006; 26: Arslanoglu S, et al. J Perinatol 2006; 26: Calories & Protein levels not as expected. Most units cannot analyze milk in timely way. Calories varied from pumping to pumping. Analysis dependent upon good mixing. Analysis varies from lab to lab. Thus, vary fortification based upon growth and metabolic status! Analyze Human Milk? 35 Treat the baby, not the bottle! Arslanoglu S, et al. J Perinatol 2009; 29: Optimum Early Nutrition in NICU? 1. Parenteral Protein a. Initiate right away, and b. Advance to 3 4 g/kg daily. 2. Initiate Enteral Nutrition immediately 3. Push for idealized weight gain early a. 15 g daily, or b. 10% body weight weekly. 4. Maximize Milk intake ml/kg daily. 5. Fortify with non-allergenic protein early a. Increase if weight gain falters, or b. Unable to maintain normal serum Albumin. 36 6

7 For$fying Human Milk May Recommendations for Adequate Nutrition (1) early, aggressive parenteral nutrition; (2) early enteral nutrition; (3) feeding of human milk with appropriate fortification, especially in VLBW infants; and 37 (4) feeding of premature infant formula when human milk feeding is not possible. NICU Standard Feeding Orders Parental Assent: Parents informed of benefits & risks of BDM & formula. Document assent before using BDM, H2MF or formula. Similar assent needed for blood transfusion (CA law). Feeding Orders: Colostrum up to 0.5 ml q 6 h buccal when available. 38 Maternal milk xx ml q 3 h. When not available may use banked donor milk. Bhatia J, et al. J Pediatr 2013; 162:S31-6. Early Feeding Protocol Early Feeding Protocol McCallie KR, et al. J Perinatol 2011; 31:S61-7. McCallie KR, et al. J Perinatol 2011; 31:S61-7. Transition off H2MF at ~34 wk PMA: Maternal Milk Supply Adequate 41 Transition off H2MF at ~34 wk PMA: Maternal Milk Supply Inadequate 42 Low risk VLBW Medium risk VLBW High risk VLBW Low risk VLBW Medium risk VLBW High risk VLBW Routine feeders & growers; or Wt gain adequate; or Labs WNL SGA; or Wt gain inadequate; or Labs mildly ABNL Fluid restricted; or EUGR (Wt < 10 th %); or Wt gain poor; or Labs very ABNL Routine feeders & growers; Wt gain adequate; Labs WNL SGA; Wt gain inadequate; Labs mildly ABNL Fluid restricted; EUGR (Wt < 10 th %); Wt gain poor; Labs very ABNL Unfortified MAT up to ml/kg/d MAT plus LPF 1 g/kg/d (4 ml/100 ml) ml/kg/d MAT:PTF 30 2:1 ~23 kcal/oz 1:1 ~25 kcal/oz 1:2 ~27 kcal/oz MAT:PTF 30 2:1 (~23 kcal/oz) or PDF 22 kcal/oz up to ml/kg/d MAT:PTF 30 1:1 (~25 kcal/oz) or PDF 24 kcal/oz up to ml/kg/d MAT:PTF 30 1:1 ~25 kcal/oz 1:2 ~27 kcal/oz or PTF 24 kcal/oz up to ml/kg/d LABS: albumin, BUN, alkaline phosphatase, calcium, phosphorus LABS: albumin, BUN, alkaline phosphatase, calcium, phosphorus 7

For$fying Human Milk May Early PO Protein & Sepsis?? 43 Moltu SJ, et al. Clin Nutr 2013; 32:207-12. Fortified formulas after discharge? 44 1.

8 For$fying Human Milk May Early PO Protein & Sepsis?? 43 Moltu SJ, et al. Clin Nutr 2013; 32: Fortified formulas after discharge? on balance the evidence supports the use of fortified formulas in formula-fed preterm infants after hospital discharge. 2. We are unaware of any evidence that any of the commonly proposed nutritional interventions in human milk fed infants after hospital discharge are either safe or efficacious. 3. it seems prudent to avoid untested interventions in this population and to concentrate our efforts on the encouragement of breast-feeding after hospital discharge. Griffin IJ, Cooke RJ. J Pediatr Gastroenterol Nutr 2007; 45:S Fortified Formula Post-Discharge 45 Fortified Formula & Weight 46 Roggero P, et al. Pediatrics 2012;130:e1215 e1221 Roggero P, et al. Pediatrics 2012;130:e1215 e1221 Fortified Formula & Head Growth Fortified Formula & Fat-free Mass Roggero P, et al. Pediatrics 2012;130:e1215 e1221 Roggero P, et al. Pediatrics 2012;130:e1215 e1221 8

For$fying Human Milk May Fortify maternal milk after discharge? 49 1. No nutrition interventions have been proved in human milk-fed infants. 2.

9 For$fying Human Milk May Fortify maternal milk after discharge? No nutrition interventions have been proved in human milk-fed infants. 2. Replacement of half to one third of the energy intake of human milk fed infants with a PDF or a preterm formula leads to modest increases in nutrient intakes, and these replacements, although untested, could be offered to such infants who are under the 10 th centile for weight at hospital discharge. 3. The use of weaning foods enriched by energy, protein, iron, and zinc should be encouraged. Impact of Formula Fortified Human Milk 50 Griffin IJ, Cooke RJ. J Pediatr Gastroenterol Nutr 2007; 45:S Griffin IJ, Cooke RJ. J Pediatr Gastroenterol Nutr 2007; 45:S Fortification After Discharge for Growth? Fortification After Discharge for Bones? Aimone A, et al. JPGN 2009; 49: Aimone A, et al. JPGN 2009; 49: Fortification After Discharge vs Lactation? 53 Fortification After Discharge for Development? 54 Aimone A, et al. JPGN 2009; 49: No statistically significant differences were found between groups in the mental, motor, or behavior rating scale scores of the Bayley II at 18-month CA. Aimone A, et al. JPGN 2009; 49:

10 For$fying Human Milk May Nutrient Enrichment of Mother s Milk and Growth of Very Preterm Infants After Hospital Discharge. 55 Nutrient Enrichment of Mother s Milk and Growth of Very Preterm Infants After Hospital Discharge. 56 WHAT THIS STUDY ADDS: Fortification of mother s milk while breastfeeding her very preterm infant after hospital discharge is possible without influencing breastfeeding duration. The amount of fortification given in this study did not improve growth at 1 year of age compared with unfortified mother s milk. Zachariassen G, et al. Pediatrics 2011; 127:e995-e1003. Zachariassen G, et al. Pediatrics 2011; 127:e995-e1003. Fortified Milk RE: Weight 57 Fortified Milk RE: Head Size 58 Young L, et al. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD DOI: / CD pub4. Young L, et al. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD DOI: / CD pub4. Fortified Milk Post-Discharge? 59 The limited available data do not provide convincing evidence that feeding preterm infants with multinutrient fortified breast milk compared with unfortified breast milk following hospital discharge affects important outcomes including growth rates during infancy. There are no data on long-term growth. Since fortifying breast milk for infants fed directly from the breast is logistically difficult and has the potential to interfere with breast feeding, it is important to determine if mothers would support further trials of this intervention. Early Post-discharge Weight Gain Bad? 60 Conclusions: In infants born very preterm, weight gain before 32 wk of gestation is positively associated with adult body size but not with body composition and fat distribution. More early postnatal and, to a lesser extent, late infancy weight gain are associated with higher BMI SD scores and percentage body fat and more abdominal fat at age 19 y. Young L, et al. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD DOI: / CD pub4. Euser AM, et al. Am J Clin Nutr 2005;81:

For$fying Human Milk May Catch-up Growth Good, Bad, When? Rapid Weight Gain in Infancy Bad?

protective against later development of cardiovascular disease.

reference range. Increments in height and weight during childhood contribute to the development of insulin resistance and high blood pressure in young adulthood. Thureen PJ.

11 For$fying Human Milk May Catch-up Growth Good, Bad, When? Rapid Weight Gain in Infancy Bad? In humans, rapid rates of growth in childhood reportedly increase the risk for cardiovascular disease, hypertension, obesity, and type 2 diabetes later in life, but slower growth appears to be protective against later development of cardiovascular disease. the trajectory of growth of subjects that later develop glucose intolerance, hypertension, and coronary heart disease is often characterized by the crossing of SDS lines, normally still within the reference range. Increments in height and weight during childhood contribute to the development of insulin resistance and high blood pressure in young adulthood. Thureen PJ. J Pediatr Gastroenterol Nutr 2007; 45:S Rotteveel J, et al. Pediatrics 2008;122; Crossing Growth Percentiles in Infancy and Risk of Obesity in Childhood. Taveras EM, et al. Arch Pediatr Adolesc Med 2011;165: Upward crossing of major weightfor-length percentiles in infancy, especially in the first 6 months of life, is associated with high rates of obesity at ages 5 and 10 years. Early Infant Weight Gain, Insulin Resistance, & Cardiovascular Risk Factors in Adolescence 64 Early infant weight gain from birth to three months was positively associated with the fasting insulin concentration, HOMA-IR, basal lipid levels and systolic blood pressure at 17 years in the SGA group. This study suggests that accelerated growth during the first three months of life may confer an increased risk of later metabolic disturbances particularly of glucose metabolism in individuals born SGA. Fabricius-Bjerre F, et al. PLoS ONE 2011; 6(6): e doi: /journal.pone Fetal and Infant Growth and Asthma Symptoms in Preschool Children. The Generation R Study. 65 Conclusions Weight gain acceleration in early infancy was associated with increased risks of asthma symptoms in preschool children, independent of fetal growth. Early infancy might be a critical period for the development of asthma. Rapid growth in Infancy? Increased risk of adult hypertension? Increased risk of adult obesity? Increased risk of diabetes? New preliminary data increased risk of asthma? 66 Maybe we shouldn t push growth so hard? Sonnenschein-van der Voort AM, et al. Am J Respir Crit Care Med 2012;185: doi: /rccm oc 11

For$fying Human Milk May Reasons for Earlier Than Desired Cessation of Breastfeeding 67 RESULTS: Approximately 60% of mothers who stopped breastfeeding did so earlier than desired.

12 For$fying Human Milk May Reasons for Earlier Than Desired Cessation of Breastfeeding 67 RESULTS: Approximately 60% of mothers who stopped breastfeeding did so earlier than desired. Early termination was positively associated with mothers concerns regarding: (1) difficulties with lactation; (2) infant nutrition and weight; (3) illness or need to take medicine; and (4) the effort associated with pumping milk. Odom EC, et al. Pediatrics 2013;131:e726 e732 Diet Regimens for NICU Grads Milk + PDF powder added (22 kcal/oz) Milk + PTF 24 2 Bottles/d Milk + PDF 24 2 Bottles/d Milk + PDF 22 2 Bottles/d Energy (Kcal/kg) 68 Ca (mg/kg) Phos (mg/kg) Protein (g/kg) Assuming an intake of 180 ml/kg daily Per Olivia Mayer, RD - LPCH VLBW Nutritional Support Post-Discharge: Maternal Milk Supply Adequate 69 VLBW Nutritional Support Post-Discharge: Maternal Milk Supply Inadequate 70 Low Risk Medium Risk High Risk Routine feeders & growers; or Wt gain adequate; or Labs WNL Breast Feed ad lib SGA; or Wt gain inadequate; or Labs mildly ABNL Breast Feed ad lib & PDF 22 2 feeds/d (or Protein 1 g/kg/d?) Fluid restricted; or EUGR (Wt < 10 th %); or Wt gain poor; or Labs very ABNL Breast Feed ad lib & PDF feeds/d (or Protein 1 g/kg/d?) Low Risk Medium Risk High Risk Routine feeders & growers; Wt gain adequate; Labs WNL Breast Milk & PDF ml/kg/d SGA; Wt gain inadequate; Labs mildly ABNL Breast Milk & PDF ml/kg/d Fluid restricted; EUGR (Wt < 10 th %); Wt gain poor; Labs very ABNL Breast Milk & Hydrolyzed Formula ml/kg/d LABS: albumin, BUN, alkaline phosphatase, calcium, phosphorus LABS: albumin, BUN, alkaline phosphatase, calcium, phosphorus Extra-Uterine Growth Restriction Extra-Uterine Growth Restriction New Goal Bad Old Ehrenkranz RA, et al. Ehrenkranz RA, et al. Pediatrics 1999; 104: Pediatrics 1999; 104:

For$fying Human Milk May It can be done!

This may reduce the risk of adverse metabolic consequences later in life.

13 For$fying Human Milk May It can be done! 73 Timing of Nutritional Interventions 74 In VLBW preterm infants the most optimal nutritional intervention, which optimizes growth and brain development, is immediate postnatal high-protein nutrition. This can be obtained by innovative TPN and individualized fortified human breast milk to limit extrauterine growth restriction and to prevent the need for exaggerated post-term catch-up growth. This may reduce the risk of adverse metabolic consequences later in life. For extrauterine growth restriction in some VLBW infants, postdischarge nutrition given by a formula that is normal in energy but high in protein may result in a normal body composition and consequently may lower the risk of the development of metabolic syndrome later in life. Real growth chart from real 27-wk premie at LPCH, June Lafeber HN, et al. Am J Clin Nutr 2013;98(suppl):556S 60S. Can We Prevent Bad Bones? 75 Fetal Calcium & Phosphorus Accrual 76 Last trimester Ca mg/kg daily Phos mg/kg daily Maternal supplements minimal impact Post-natal supplements do not provide enough Calcium absorption ~ 60 70% Phosphorus absorption ~ Harryhausen R. Jason and the Argonauts Sharp M. Early Hum Dev 2007; 83: Current Recommended Oral Intakes 77 Neonatal Calcium & Phosphorus Intake 78 AAP ESPGAN Ca (mg/100 Kcal) Phos (mg/100 Kcal) Ca:Phos Ratio ~ 1.5: :1 Demarini S. Acta Pædiatrica 2005; 94(Suppl 449): Land C, Schoenau E. Best Pract Res Clin Endocrinol Metab 2008; 22:

14 For$fying Human Milk May Mineral Bioavailability: HMF vs Formula Mineral Bioavailability: HMF vs Formula Data: Rigo J, Santerre J. J Pediatr 2006; 149:S80-S88. Figure: Cohen RS, McCallie KR. Rigo J, Santerre J. J Pediatr 2006;149:S80-S88. (doi: /j.jpeds ) JPEN 2012; 36 (S1): S20-S24. Alkaline Phosphatase Levels? 81 Bone mineralisation in premature infants cannot be predicted from serum alkaline phosphatase or serum phosphate. 82 Wide fluctuations Derived from Liver, Gut, and Bone Increased by Bone healing, too AlkPhos > low Phos may be significant AlkPhos > 5x normal may be significant AlkPhos > 1200 decreased length? DeMarini S. Acta Paediatr 2005; 94(Suppl 449): Lucas A, et al. Arch Dis Child 1989; 64: Faerk J, et al. Arch Dis Child Fetal Neonatal Ed 2002;87:F AAP Committee on Nutrition & Alkaline Phosphatase Usefulness of Alkaline Phosphatase? 83 Typically, the APA will peak at 400 to 800 IU/L and then decrease in VLBW infants who do not develop rickets. clinical experience indicates that if the infant has APA values in this range and has achieved full feeds of human milk with a mineral-containing fortifier or formula designed for preterm infants, there is minimal, if any, risk of developing rickets, and measurement of APA can usually be stopped. Abrams SA, et al. Pediatrics 2013; 131:e1676 e The in vivo effects of ALP remain under investigation and reflect the current evidence that it is not a useful indicator of disease when taken as a stand-alone marker. Independent measures of ALP are of little use in predicting and determining risk, or treatment thresholds, for MBD in preterm infants. ALP is not useful in monitoring on-going treatment for metabolic bone disease. High ALP levels in preterm infants are strongly associated with phosphorus deficiency and later growth, but do not predict outcome. ALP isoenzyme analysis is rarely helpful in determining causes of raised ALP. Tinnion RJ, Embleton ND. Arch Dis Child Educ Pract Ed 2012; 97:

15 For$fying Human Milk May Diet and Bone Mineral Content at Term in Premature Infants 85 Diet and Bone Mineral Content at Term in Premature Infants 86 No significant differences! Faerk J, et al. Pediatr Res 2000; 47: Faerk J, et al. Pediatr Res 2000; 47: Diet and Bone Mineral Content at Term in Premature Infants. Calcium retention mg/kg daily enterally for Premature infant, Up to 140 mg/kg daily 3 rd trimester in utero. 87 mineral supplementation in premature infants during admission does not significantly improve bone mineralization outcome at term if infants are fed 200 ml per kg per day. supplementation with phosphate is recommended only for prevention of hypophosphatemia. Focus More on Phosphate? 88 Although most attention is focused on calcium intake, the very high urinary calcium concentrations found in preterm infants fed unfortified human milk suggests that phosphorus deficiency is at least as important, if not more important, than calcium deficiency in the etiology of this disease. The exact serum phosphorus concentration for which evidence demonstrates a need to supplement phosphorus without calcium is not known, but a serum concentration below 4.0 mg/dl, especially if present for more than 1 to 2 weeks, suggests consideration of adding phosphorus directly. Faerk J, et al. Pediatr Res 2000; 47: Abrams SA, et al. Pediatrics 2013; 131:e1676 e1683. Early Diet & Long-term Bone Milk vs PTF: Bone Follow-up Results: Infant dietary randomization group did not influence peak bone mass or turnover. The proportion of human milk in the diet was significantly positively associated with WBBA and BMC. Subjects receiving >90% human milk had significantly higher WBBA (by 3.5%, p=0.01) and BMC (by 4.8%, p=0.03) than those receiving <10%. Compared to population data, subjects had significantly lower height SDS ( 0.41 (SD 1.05)), higher BMI SDS (0.31 (1.33)) and lower LSBMD SDS ( 0.29 (1.16)); height and bone mass deficits were greatest in those born SGA with birthweight<1250 g (height SDS 0.81 (0.95), LSBMD SDS 0.61 (1.3)). Fewtrell MS, et al. Bone 2009; 45: mineral intakes in all groups were markedly below current recommendations Radial bone mass was significantly higher in subjects who had been randomized to BBM plus MBM than in those who were fed PTF plus MBM, with increasing BMC as the proportion of MBM in the diet increased comparison of subjects fed BBM or PTF as their sole diet BA and BMC were consistently higher in the BBM group (though underpowered to achieve significance) Fewtrell MS, et al. Bone 2009; 45:

For$fying Human Milk May Early Diet & Long-term Bone 91 the intake of human milk during the early postnatal period was positively associated with later whole body bone size and bone mass.

milk, may represent another long-term benefit for human milk, adding to the benefits for later cardiovascular health already documented in this population.

16 For$fying Human Milk May Early Diet & Long-term Bone 91 the intake of human milk during the early postnatal period was positively associated with later whole body bone size and bone mass. This finding, which may most plausibly be interpreted as representing a non-nutritive effect of human milk on bone development related to one of the many growth factors or hormones present in human milk, may represent another long-term benefit for human milk, adding to the benefits for later cardiovascular health already documented in this population. Changes in milk components with milk expression and mineral supplementation Total Calcium (mm) 92 Ionized calcium (mm) Non-protein phosphate (mm) Bicarbonate (mm) Fresh Donor Milk 1 breast milk 7.5 contains 3.0 less ionized 1.8 calcium 6.0 than fresh 6.8 breast Preterm Donor milk because 5.7 it loses 0 CO 1.8 ~ during expression and Milk processing. 2 Preterm Donor Milk ~ Calcium Adding 2 supplemental calcium increases ionized calcium in donor Preterm breast Donor Milk milk ~ Phosphorus 2 ph Fewtrell MS, et al. Bone 2009; 45: Allen et al. AmJClinNutr 1991; 54: Fogleman AD, et al. JPGN 2012; 55: Calcium in vitro - Precipitate 93 Calcium in vitro - Soluble c a Insoluble Calcium (μg/ml) a b c b b c b Total Dialyzed Calcium (μg) c a b, c c c Milk Milk + Calcium Milk + Phosphorus Milk + Calcium & Phosphorus Milk + Similac Human Milk Forti>ier Fogleman AD, et al. JPGN 2012; 55: DOI: /MPG.0b013e318254ec07 Milk + Similac Neosure Milk + Enfamil EnfaCare Milk Milk + Calcium Milk + Phosphorus Milk + Calcium & Phosphorus Milk + Similac Human Milk Forti>ier Fogleman AD, et al. JPGN 2012; 55: DOI: /MPG.0b013e318254ec07 Milk + Similac Neosure Milk + Enfamil EnfaCare 95 Added Calcium vs Milk Protein Post-discharge Nutrition Around the World 96 Fogleman AD, et al. ICAN 2012; 4: DOI: / Klingenberg, C, et al. Arch Dis Child Fetal Neonatal Ed 2012; 97:F56 F61. doi: /f60 adc

For$fying Human Milk May 97 98 Diet vs BMC van de Lagemaat M, et al. J Nutr 2013; 143:1439-44.

17 For$fying Human Milk May Diet vs BMC van de Lagemaat M, et al. J Nutr 2013; 143: Role of Vit D van de Lagemaat M, et al. J Nutr 2013; 143: In conclusion, during the first 6 mo postterm, higher vitamin D intake and greater increase in serum 25(OH)D concentration in PDF-fed preterm infants were associated with increased bone accretion. Vit D Insufficiency in VLBW 99 Response to Vit D 400 IU/d 100 McCarthy RA, et al. Br J Nutr 2013; 110: McCarthy RA, et al. Br J Nutr 2013; 110: Discharge Diet Recommendations 101 Maximize intake of maternal milk Avoid powdered formulas if possible, Supplement with PDF 2-3 feeds/d if necessary. Give a Multi-vitamin. Formula fed infants use PDF Monitor growth parameters to avoid overgrowth. Supplemental Calcium Glubionate & NaKPhosphate Bad osteopenia, Chronic furosemide Rx. Stanford LPCH: Olivia Mayer, RD, Kari McCallie, MD, North Carolina: April D. Fogleman, PhD Jonathan Allen, PhD Mothers Milk Bank Pauline Sakamoto, RN Thanks To: 102 in memory of Mary Rose Tully. 17

Post Discharge Nutrition. Jatinder Bhatia, MD, FAAP

Post Discharge Nutrition. Jatinder Bhatia, MD, FAAP Post Discharge Nutrition Jatinder Bhatia, MD, FAAP Declaration of potential conflicts of interest Regarding this presentation the following relationships could be perceived as potential conflicts of interest: