HOT TOPICS in NEONATOLOGY Washington DC Dec 2014 David H Adamkin Professor of Pediatrics Director of Division of Neonatology University of Louisville ID: 594266
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Customized Fortification of Human Milk for the VLBW Infant
HOT TOPICS inNEONATOLOGY Washington, D.C. Dec 2014David H Adamkin Professor of Pediatrics, Director of Division of Neonatology, University of Louisville Slide2
DisclosuresConsultant and Investor in Medolac Laboratories I will not discuss any off-label use and/or investigational use in my presentationSlide3
AAP Recommendations on Breastfeeding Management of Preterm Infants
( Ped 2012) The potent benefits of human milk are such that all preterm infants should receive human milkMother’s Own Milk, fresh or frozen, should be the primary diet, and it should be fortified “appropriately” for the infant born < 1500g.
If mother’s milk is unavailable despite significant
lactation support, pasteurized donor milk should be usedSlide4
VLBW
Does Human Milk Meet The Nutritional RequirementsSlide5
Human Milk Alone Does Not Meet the Nutritional Needs of VLBW Infants
Human milk requires fortification to provide nutritional needs of preterm infants
VLBW = very low birth weight.
1.
Premji SS, et al. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD003959; 2. Carlson SJ, Ziegler EE. J Perinatol. 1998;18:252-258;
3. Zeigler EE, et al. In: Suskind RM,
Lewinter-Suskind L,
eds.
Textbook of Pediatric Nutrition
. 1981:29-39.
(g/kg/d)
Preterm human milk
Term human milk
Recommended (for VLBW)Slide6
Protein, Calcium, and Sodium Requirements for VLBW Infants and Human Milk
Protein
g/kg
Calciummg/kgPhosphorusmg/kgSodium mEq/kg
Estimated Requirements
3 - 4
185 - 210
123-140
3 - 4
Banked
HM*
1.8
52
26
1
PTHM**
2.25
52
26
2-3
Fomon SJ 1977
Groh-Wargo S 2000
Ziegler E 2007
*0.9g/dl @ 200ml/k/d
**1.5g/dl @ 150ml/k/dSlide7
Human Milk NutrientsThe high variability in nutrient content in human milk makes meeting nutrient recommendations inherently inaccurate.Milk composition varies with volume of milk expressed, the type of milk obtained (foremilk or
hindmilk), and the stage of lactation. For example, two to three fold differences in protein, fat and hence energy have been demonstrated regardless of stage of lactation.The creamatocrit accuracy has been challenged and the creamatocrit
does not measure carbohydrate or protein.Slide8
Fortification StrategiesStandard, Fixed Dosage EnhancementAdjustable Fortification Based on BUN
Targeted Customized, IndividualizedDaily or triggered by defined needSlide9
Human Milk Protein and Fortification
Recommended Intake 3.5 – 4.4 g/kg/d
Schanler, 1980
FORTIFICATIONIndustry StandardDonor MilkSlide10
Assumed and Actual Protein, Fat and Energy Content of the Fortified Human Milk and Assumed and Actual Protein, Energy Intakes of the Infants STD ADJ (BUN<9,>14)
Assumed values Actual values Assumed values Actual values IntakesProtein intake (g/kg/d) First week 3.4±0.1
2.9±0.4 3.7±0.1 2.9±0.3
Second week 3.5±0.1 2.9±0.3 4.0±0.4 3.2±0.4 Third week 3.5±0.1 2.8±0.2 4.2±0.3 3.4±0.5Energy intake (kcal/kg/d) First week 126.1±5.2 125.9±7.9 132.2±1.8 127.2±12.1 Second week 128.4±2.4 126.6±11.8 135.2±4.2 125.6±11.6 Third week 127.6±2.4 120.5±8.3 135.9±2.7 128.0±8.3Protein Δ STD 0.5 to 0.7g/k/d Wt gain 14 vs 18g/k/d, HC 0.7vs 1.0 cm/wk p=0.001 Protein Δ ADJ 0.8g/k/d
Arslanos, Ziegler et al J of Peri 2009
1 gramSlide11
Mid Infrared Spectrophotometry (MIRSA)Point-of-careAccurate
Measures Protein, Fat, Energy and CarbohydratesUses relatively small volume of milkAffordable $$
FastSmall footprint
Commercially available - validated for goat, donkey, and bovine milkLacto-engineeringSlide12
Breast Milk Analyzer Results99 discrete PT samples from 24 women were analyzed (mean ± SD; range)
Fat (g/
dL
)Protein (g/dL)Lactose (g/dL)Energy (kcal/oz)
3.3 ± 1.2
1.6 ± 0.3
8.0 ± 0.5
20.1 ± 4.1
0.9, 7.43
Range
0.9, 2.5
6.2, 10.1
11.2, 32.3
Range
Radmacher, Adamkin et al J Invest Med 2010Slide13
Stage of lactation
0-2 weeks2-4 weeks≥4 weeksDHM* (term)pProtein (g/dL)1.7 ± 0.31.5 ± 0.21.3 ± 0.41.0 ± 0.1<0.02 (
DHM vs. all stages)Fat (g/dL)
3.0 ± 0.9
3.6 ± 1.1
3.8 ± 0.9
2.5 ± 0.3
≤0.015
(
DHM
vs 0-2
wks
and ≥4
wks
)
Lactose
(g/dL)
6.5 ± 0.5
6.6 ± 0.3
6.5 ± 0.2
6.1 ± 0.4
<0.005
(
DHM
vs. all stages)Energy (kcal/oz)17.2 ± 2.418.6 ± 2.918.9 ± 2.614.6 ± 1.40.021 (DHM vs 0-2 wks and ≥4 wks)
DHM: donor human milk Radmacher,
Adamkin
JNPM 2014 Macronutrient Analysis (mean ± SD) HUMAN MILK Analyzer
*
Foremilk protein = hindmilk protein
Foremilk energy < hindmilk energyUnpublished observations with HMASlide14
51.2% fell either below 18 kcal/oz or above 22 kcal/oz / 31% of the samples below 18 kcal/oz
14% were below 16 kcal/oz
Variability of human milk calories
N=85
Radmacher, Adamkin JNPM 2014Slide15
Bovine Augmentation vs Exclusive Human Milk Fortification Powder Protein Liquid
Liquid ConcentrateHuman Milk
Human Milk
Bovine AntigenHumanHMFDonor Conc80:20 24 cal
50:50 30 calSlide16
PT HUMAN MILK FORTIFICATION @ 150 ( ) Cal+ assumes PTHM @ 1.6 g/100 mL
PTHMPTF30/PTHM(24)
HM2(24)Conc
Liq(24)(HP)LIQ (24)AcidK Cal99125120120120Prot (g)˖2.43.43.53.6(4.3)4.8Fat (g)6.07.67.26.77.2CHO (g)10.511.29.811.29.7Ca (mg)33152120180174
P (mg)21855510596Slide17
Donor human milk Donor human milk + PTF30*
Donor human milk +HMF CL^
Donor human milk + HMF HP CL^^Donor human milk + HMF-Acidified#Donor human milk +HM2 + 4@Kcal102.00121.80126.07126.97129.97123.6Protein (g)1.582.773.414.31
4.613.06
Fat (g)
5.85
7.54
6.47
6.13
8.32
7.38
CHO (g)
10.80
11.18
13.84
13.50
10.80
11.34
Calcium (mg)
41.85
134.67
245.46
214.86
208.86
217.98
Phosphorus (mg)21.45
73.71137.87119.87112.37113.16
Currently available human milk fortifiers and added nutrients to donor human milk and fed at 150 mL. Fortifiers are mixed according to manufacturers’ instructions to make 24 kcal/oz fortified human milk.
*Similac Special Care 30 kcal/oz (Abbott Nutrition, Columbus, OH)^Similac Human Milk Fortifier Concentrated Liquid (Abbott Nutrition, Columbus, OH)
^^Similac Human Milk Fortifier Hydrolyzed Protein Concentrated Liquid (Abbott Nutrition, Columbus, OH)#Enfamil Human Milk Fortifier Acidified Liquid (Mead Johnson Nutrition, Evansville, IN)+Prolact+4 (Prolacta Bioscience, Monrovia, CA)
Donor Milk 150ml/kSlide18
LACTOENGINEERINGSlide19
Four Milk Samples to be “Fortified” Radmacher, Adamkin JNPM 2014
Protein (g/dL)
Energy (kcal/oz
)Low protein Donor MilkLow energy1.013.6Expected proteinExpected energy1.518.6Expected proteinHigh energy1.424.2High proteinMarginal energy1.916.9Slide20
Preterm Human Milk Protein (g) at 150 mL
Achieved with Four Different Fortifiers
Powder-Conc Liq 24
24Slide21
Preterm Human Milk Protein (g) at 150 mL
Achieved with Alternate Fortification Strategies
Conc Liq (5Pkt)Slide22
Preterm Human Milk Energy (kcal) at 150 mL Achieved with Alternate Fortifier StrategiesSlide23
Target Fortification of Breastmilk with Fat, Protein and Carbohydrates for Preterm InfantsRochow
et al J of Peds 2013 McMaster Ontario Canada
Fixed dosage enhancement vs targeted. N=10 vs matched pair analyses (1:2) fed for at least 3
weeks prior to PMA of 36 weeks --- 860g; 26weeks12 hour milk batch – NIRSESPGHAN Recommendations for Nutrient intakes: Macronutrients added reach final contents Fat 4.4g/dl (6.6) Protein 3.0g/dl (4.5) Carbohydrates 8.8g/dl (13.2) ( ) At Feedings of 150ml/k/d Slide24
Intervention ProductsJ of Peds 2013
3.6g Fortifier per 100ml Breastmilk =
0.36g FAT / 1.0g PROTEIN / 1.8g CHO per 100 ml
Microlipid : safflower oil for enteral (0.5g fat/ml)Beneprotein: whey protein powder (0.86g protein/ml)Polycose : glucose polymer (0.94g CHO/ml) Step 1 – Analyze native breast milk Step 2 – Routine fortification Step 3 - Additional amounts of fat/protein/CHO to achieve targets (ESPGHAN)Slide25
RESULTS---Targeted vs Fixed Fortification
All 650 pooled breastmilk samples required at least 1 macronutrient adjustment to meet recommendations.
Ave 0.3g fat, 0.7g protein, 1.2g CHO, were addedWeight gain/ volume/energy
Targeted 19.9 ± 2.7g/k/d ~ 150ml/k/d; 131 ± 16kcal/k/dFixed 19.7 ± 3.3g/k/d ~ 155ml/k/dOsmolarity 436 ± 13mosmol/kg with TargetedSlide26
Take Home PointsHuman Milk is the preferred feeding for all infants including VLBW infants.Despite its many advantages, human milk does not meet all the nutritional needs of the rapidly growing VLBW infant (specifically protein, calcium and phosphorous). Protein is even lower in donor milk.Newer strategies for fortification of human milk allows nutritional needs to be met despite significant macronutrient variability.