groh wargo osteopenia
TRANSCRIPT
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Osteopenia: Risk Factors,
Prevention Strategies andManagement Options
Sharon Groh-Wargo PhD, RD, LD
Associate Professor Nutrition and Pediatrics
Senior Nutritionist
Case Western Reserve University School ofMedicine
MetroHealth Medical Center, Cleveland, OhioMay 24, 2013
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Objectives
Screen patients for medical and nutritionalrisk factors that contribute to thedevelopment of osteopenia
Implement prevention strategies to minimizethe incidence and severity of osteopenia
Follow best practice nutritionalmanagement options to optimize outcomes
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Objective One
Screen patients for medical andnutritional risk factors that contribute tothe development of osteopenia
Definitions Incidence
Screening
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Important terminology
Osteopenia: decrease in the amount of organic
bone matrix (osteoid) Osteomalacia: lack of mineralization of the organic
bone matrix
Rickets: when loss of mineralization involves thegrowth plate
Osteoporosis: decrease in bone mineral density
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Incidence : Osteopenia
Up to 30% of infants under 1500 g
[Koo WW et al (Canada) 1989]
Occurs in up to 55% of babies with BW < 1000 g[Mcintosh et al (UK) 1985]
Prevalence is 40% in premature infants who arebreastfed, in contrast to 16% of those fed with aformula designed for preterm infants andsupplemented with calcium and phosphorus[Mcintosh et al (UK) 1985]
Fractures are reported in ~10% at 36 to 40 weeksCGA [Vachharajani AJ 2009]
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Infants: S Viswanathan et al; MetroHealth Medical Center,Cleveland, OH
Retrospective chart review of ELBW infants admitted to theNICU between Jan 2005 and Dec 2010 (n=230)
Cases: radiological evidence (n=71/230; 30.9% at DOL 58.2 28):
24/71 (33.8%) developed spontaneous fractures (DOL 100 61)
18/71 (25.4%) radiological rickets
Controls: no radiological evidence (n-159/230 or 69.1%)
Compared to controls, cases
Were smaller at birth and more preterm
Received more mechanical ventilation, parenteral nutrition,
antibiotics, steroids and diuretics Had more chronic lung disease, cholestasis & higher AlkPhos levels
Received lower average weekly intakes of kcal, pro, Ca, P and Vit D
Had higher mortality and longer lengths of hospital stay
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Causes of Osteopenia
Low nutrient stores of calcium and phosphorus as a
result of prematurity Increased nutrient losses of minerals as a result of renal
immaturity or drug therapy
Inadequate provision of calcium and phosphorus Limits of solubility in TPN solutions
Delayed feeding
Use of unfortified human milk or non-preterm formulas
Vitamin D deficiency
Lack of mechanical stimulation
Aluminum contamination of parenteral nutrition
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Risk Factors
Extreme prematurity
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Screening and Assessment(Vachharajani AJ 2009; Groh-Wargo, Thompson, Cox, 2000)
Markers of bone formation
Alkaline phosphatase: 500 U/L
Serum phosphorus: 5.0 mg%
Serum 25 (OH) vitamin D: 20 ng/ml
Markers of bone resorption Urinary calcium:
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Recommended screeningschedule for VLBW (AAP 2013)
Starting at ~4-5 weeks of age and then blood
levels weekly/biweekly; radiographs Q5-6 wks Alkaline Phosphatase levels >800 IU/L, serum
phosphorus ~4 mg/dl, or clinical evidence of
fractures should lead to radiographicevaluation for rickets
Assess Vitamin D when cholestasis is present
and target for levels >20 ng/ml Treatment should focus on maximizing calcium
and phosphorus intake
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Objective Two
Implement prevention strategies tominimize the incidence and severity ofosteopenia
Key nutrients Recommended intakes
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Key nutrients important to bone
health
Protein and energy Calcium
Phosphorus (primary nutritional problem)
Vitamin D
Miscellaneous: Vitamin K, Fluoride, etc
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Sources of RecommendedIntakes for Newborns
Uauy R (Ed). Global Neonatal Consensus Symposium:
Feeding the Preterm Infant. Journal of Pediatrics:162(3);Supplement 1. March, 2013.
Tsang RC, Uauy R, Koletzko B, Zlotkin SH, eds. Nutrition ofthe Preterm Infant, 2nd Edition. Digital Publishing, Cincinnati, Ohio. 2005
ESPGHAN (Agostoni C et al, JPGN. 2010;50:85-91)
American Academy of Pediatrics. (Kleinman RE (ed). Nutritionneeds of the preterm infant. In, Pediatric Nutrition Handbook, 6th Ed. ElkGrove Village, IL: AAP, 2009. p 79-112)
Dietary Reference Intakes (term infants) (IOM)http://iom.edu/Home/Global/News%20Announcements/DRI
[accessed 3/7/11]
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Building a Strong Structure
Lourdes Pereda, MD. USF, FL 2002
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Macrominerals: Physiological
Role
Calcium: Over 95% in bones and teeth; remainder
in blood, ECF, muscle mediates vascularcontraction/dilation, muscle contraction, nervetransmission and glandular secretion
Phosphorus structural over 85% in bone;functional most of the remainder is throughoutsoft tissue mostly in phospholipids of RBCs andplasma lipoproteins; small amount (~1%) as
inorganic phosphate which is a primary sourcefrom which cells in all tissues derive high-energyphosphate (ATP)
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Reasonable Nutrient Intakes:
Parenteral (Tsang, Uauy, Koletzko and Zlotkin, 2005)
ELBW
Energy (kcal/kg/d)
Day 0: 40-50
Transition: 75-85
Growing: 105-115
Protein (g/kg/d)
Day 0: 2
Transition: 3.5
Growing: 3.5-4.0
VLBW
Energy (kcal/kg/d)
Day 0: 40-50
Transition: 60-70
Growing: 90-100
Protein (g/kg/d)
Day 0: 2
Transition: 3.5
Growing: 3.2-3.8
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Macrominerals: Parenteral Intake
Recommendations (Tsang et al, 2005)
Day 0 Transition Growing
Ca (mg/kg)(mEqX40/2=mg)
20-60 60 60-80
P (mg/kg)(mmoleX31=mg)
0 45-60 45-60
Mg (mg/kg)(mEqX24/2=mg)
0 4.3-7.2 4.3-7.2
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Macromineral IV Sources
Calcium: Calcium gluconate (9% elemental
calcium). For example: 300 mg calciumgluconate = 27 mg elemental calcium; Ca:P1.3:1 to 1.7:1
Phosphorus: Sodium and potassiumphosphate. NaPhos significantly lower thanKPhos in aluminum (5977 vs. 16598 g/l(Sedman et al, 1985)
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Macromineral IV Balance (mg)
Ca P Mg
Concentration ( /liter) 600 465 72
Delivery (per kg/day at110 ml/kg/day)
66 51 7.9
Expected Retention
(% intake)
92 85 68
Calculated Retention
(per kg/day)
61 43 5.4
InUtero Accretion (/kg) 90-120 60-75 2.5-3.4
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Enteral Protein and Energy
Requirements of Preterm Infants
Ziegler E. J Pediatr Gastroenterol Nutr2007;45:S170-4.
Body weight, g
Protein,
g/kg/d
Energy,
kcal/kg/d P/E, g/100 kcal
500-700 4.0 105 3.8
700-900 4.0 108 3.7
900-1200 4.0 119 3.4
1200-1500 3.9 127 3.1
1500-1800 3.6 128 2.8
1800-2200 3.4 131 2.6
P/E = Ratio of protein to energy, expressed as grams of protein per 100 kcal.
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based on age (and need for
catch-up)(Rigo and Senterre, J Peds 2006)
26-30weeks 30-36weeks 36-40weeks
Protein g/kg 3.8-4.2(4.4)
3.4-3.6(3.6-4)
2.8-3.2(3-3.4)
Energykcal/kg
126-140(134)
121-128(120-130)
116-123(115-121)
PE Ratio g:100kcal
3 (3.3) 2.8 (3) 2.4-2.6(2.6-2.8)
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recommendations for specialpopulations of infants(Uauy R 2013)
Ca mg/kgper day
P mg/kgper day
Vitamin DIU/day
Micropreterm 29 wks 120-180 60-90 800-1000
Late preterm 34-36 wks 120-140 60-90 400
Preterm, SGA 120-160 60-90 400
Post-discharge VLBW(34-38 weeks; assuming no
accumulated nutritional deficits)
70-140 35-90 400
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Macromineral Balance: Enteral
Calcium (mg) at 120 kcal/kg (AAP 2013)
Human
Milk
Fortified Human Milk or
Preterm FormulaCa Content (mg/dl) 25 145
Intake (mg/kg per day) 38 220
Absorption (% intake) 60 50-60
Total absorption (mg/kgper day)
25 120-130
Approximate retention(mg/kg per day)
15-20 100-120
Third Trimester In-Utero Accretion (mg/kg per day): 90-120
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Bone Mineral Content in PretermInfants (Atkinson 2005)
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7-dehydrocholesterol in skin
Pre-vitamin D3
Vitamin D3
Vitamin D
25 (OH) D
major circulating metabolite
1,25 di(OH) DCalcitriol (biologically active metabolite)
INTESTINECalcium, phosphorous absorption
BONECalcium resorption
DIETChylomicrons
Solar UVB Radiation
(290-315 nanometers)
Liver (25 hydoxylase)
Kidney ( 1 hydroxylase)
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AAP Recommendations 2008
WHO: All Breastfed infants and any formula fed
infant taking < 1 quart or liter per day WHEN: Within the first few days of life
WHAT: 400 IU vitamin D per day supplement
HOW: Infant ADC drop 1 ml per day WHY: Increasing incidence of vitamin D
deficiency in the maternal population has
resulted in deficiency in newborns Wagner C, Greer FR, Section Breastfeeding and CON.
Pediatrics 2008 122:1142-1152.
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Forms of Vitamin D
Cholecalciferol: Vitamin D3 Infant formulas and human milk
Baby Ddrops (1 drop provides 400, 1000 or 2000 IU)
Vi-sol and Just D drops (1 ml = 400 IU)
AquADEKs and SourceCF drops (1 ml = 400 IU)
Ergocalciferol (UV irradiation of ergosterol fromyeast): Vitamin D2
Calciferol and Drisdol (1 ml = 8000 IU)
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Vitamin K and Bone
Function
Vitamin K dependent proteins:osteocalcin (or bone Gla protein) aswell as matrix Gla protein of the
skeleton
Gla proteins are required for calciummediated interactions
Storage: limited compared to other fatsoluble vitamins
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Vitamin K and Bone
Sources
Newborn IM injection 0.5-1 mg
Pediatric parenteral multi-vitamins provide ~ 60-130mcg per day (1.5-3.25 ml per day)
Concentration low in HM
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Fluoride
Affinity for calcified tissues; ingestion during
pre-eruptive development of the teeth has acariostatic effect; post-eruptive effect mainlythrough reduced acid production of plaque
bacteria; unique ability to stimulate boneformation; no specific recommendations forpreterm infants
Emerging evidence for parenteral fluoride(Nielsen FH Gastroenterology 2009)
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Other micronutrients important to
bone health
Vitamin C, Copper, and Zinc
Cofactors for the synthesis or cross-linking ofmatrix proteins
Interference with cross-linking results in
structurally weak bone
Deficiency during growth periods results in themost profound impact
Ross AC et al, Modern Nutrition in Health and Disease, 11th Ed.Pg 1221
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Objective Three
Follow best practice nutritional
management options to optimizeoutcomes Parenteral nutrition
Calcium:Phosphorus solubility
Phosphorus shortages
Aluminum contamination
Human milk: fortification
Formula feeding: choice of formula Supplementation: Ca and P; Vitamin D
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Calcium Phosphate Solubility Curves
Fitzgerald KA, MacKay MW. Calcium and phosphate solubility in neonatal
parenteral nutrient solutions containing TrophAmine.Am J Hosp Pharm 1986
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Factors that Increase Solubility of
Calcium and Phosphorus
Very acidic pH
Higher [concentration] of dextrose &protein
Cysteine in TPN Cooler temperature
Ca and P concentration and ratio
Addition of P before Ca Fat emulsion by IV piggyback
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Parenteral Nutrition Solution
Shortages: General Strategies
Prioritize: ELBW, neonates, pediatric patients Individualize: reconsider automatic protocols
Centralize: minimize waste by compounding in a
central location Ration: for example, 75% of dose
Substitute: enteral feeding, fortification ASAP
Observe: be alert for deficiency; monitor
Holcombe B et al. 2011 JPEN 35(4):434-436; Holcombe B et al. 2012 JPEN 36:44S-47S.
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Case Report: Hypercalcemia associated
with phosphate deficiency in the neonate(Miller RR, Menke JA, Mentser MI. J Peds 1984)
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Phosphorus deficiency:
Signs and Symptoms Respiratory muscle function
Impaired diaphragmatic contractility Respiratory failure
Failure to wean from mechanical ventilation
Cardiovascular system
Decreased myocardial contractility Increased inotropic requirement
Arrythmias
Central nervous system Paralysis, weakness, paresthesias, seizures
Increased mortality
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IV Phosphate Critical Shortage:
Clinical Strategies
Encourage Enteral Feeding Begin feeds as soon as possible
Fortify human milk to 22/kcal at 50 ml/kg/day of feed
Judicious use of TPN
Provision of daily IV fat emulsion to all PN patients (IV fat emulsionscontain 15 mmol/L of phosphate)
IV Fluids and enteral feeds instead of TPN 34 wks
For babies >1 kg , stop TPN at 80 ml/kg/day
Modify TPN for larger infants (>1500g BW) no phosphorous Monitor phosphorous levels critical replacement if serum level
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Aluminum Contaminant in parenteral solutions
Associated with impaired neurological developmentand decreased bone calcium uptake
Preterm infants may be a risk of Al toxicity due to
renal immaturity, neurological/bone development FDA rules mandating labeling of content became
effective in 2004
Recommended IV exposure is no more than 5mcg/kg per day
Goal is to label products and limit exposure
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Regarding IV Aluminum
Exposure
Reported aluminum concentration is maximumpossible at product expiration
Measured aluminum content is significantlyless than calculated aluminum content
Measured aluminum of 40 neonatal TPNsolutions were ~50% of calculated value (PooleRL et al JPGN 2010)
Actual intake still exceeded recommended safelimit of
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O
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WHO should receive human milk
fortification?
34 weeks gestation 1800 g birth weight Parenteral nutrition > 2 weeks > 1800 g birth weight with suboptimal
growth and/or feeding volume restrictionand/or significant medical/surgicalcomplications
[Schanler RJ and Abrams SA, 1995; Schanler RJ et al, 1999;Atkinson SA, 2000; Abrams SA 2013]
WHAT h i f
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WHAT are the options for
fortification?
Commercial human milk fortifier (1:25) (powder
and concentrated liquid) (Kuschel CA, Harding JE.Cochrane Database Syst Rev. 2004;(1):CD000343)
Commercial nutrient dense preterm formula (1:1
etc) (liquid) (Moyer-Mileur L et al JPGN 1992; Lewis J et al JInvest Med 2010)
Concentrated donor human milk enriched with
minerals (frozen liquid) [Prolacta Biosciencehttp://prolacta.com accessed 8/23/11] (~$40/oz) (Sullivan S etal. J Pediatr 2010)
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WHERE should human milk
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WHERE should human milk
fortifier be added to human milk?
The addition of human milk fortifier to
expressed human milk at the bedside is notadvised (Ohio Department of Health, TheAmerican Dietetic Association, ASPEN)
A NICU Milk lab as a separate location isideal to insure
Cleanliness and safety of expressed human milk
Accuracy and adequacy of mixing
WHEN h ld h ilk
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WHEN should human milk
fortification start and stop? Start
As early as 25 ml/day of human milk (Univ Iowa)
As late as attainment of full enteral feedings (150 ml/kgper day)
Most usual start time is attainment of 80-100 ml/kg per
day enteral feedings Stop
As early as a few days prior to NICU discharge (mostusual)
As late as 52 weeks post-conceptional age or weight of3.5 kg, whichever comes first
WHY do e gi e h man milk
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WHY do we give human milk
fortification?
Inadequate concentration of Protein Minerals, for example
Calcium Phosphorus
Zinc
Sodium
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HMF Meta-Analysis: BMC
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HMF Meta-Analysis: NEC
Intake of Ca, P and Vitamin D
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from Selected Feedings at 160ml/kg/dCa mg/kg
per day
P mg/kg
per day
Vitamin D
IU/dayUnfortified HM 20 kcal/oz 30-40 20-25 2-3
Fortified HM 24 kcal/oz 180-220 100-125 280-380
Preterm Formula
(24 kcal/oz)
210-235 100-130 290-470
Post-discharge formula
(22 kcal/oz)
125-150 70-80 125-130
Recommendations:VLBW (Post-D/C)
150-220(70-140)
75-140(35-90)
200-400(400)
Human Milk (HM) After
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Human Milk (HM) After
Discharge: Evidence Feeding HM is associated with improved
neurocognitive outcomes but decreased growth(OConnor DL 2003, Lucas A 2001)
Feeding fortified HM improves nutrient intake, bonemineralization, visual acuity and length and headgrowth compared to feeding HM without fortification
(OConnor DL 2008, Aimone A 2009, OConnor DL2012) Feeding fortified HM may not improve overall growth
compared to feeding preterm formula (Zachariassen G2011)
Fortification of HM following discharge does notinterfere with breastfeeding success (OConnor DL2008; Zachariassen G 2011)
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Anthropometric measurements of human milk-fed infantssent home (study day 1) fed human milk alone (- -) or withapproximately half of the human milkfed mixed with a
multi-nutrient fortifier () for 12 weeks. Asterisks denote asignificant difference between feeding groups at a specifictime point. (Aimone A et al 2009)
Human Milk After Discharge: Evidence
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The Sprinkles Problem
kcal/kg/d
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kcal/kg/d
Nutrient
HumanMilk(HM)
HMenriched
withPTDF*
HMalternatedwith PTDF*
HM withHMF1:50
HM withHMF1:25
Volume, mL/kg 175 150 165 165 150
Protein, g/kg 1.6 1.9 2.6 2.5 2.9
Ca, mg/kg 49 64 92 124 197
P, mg/kg 26 35 52 69 110
Zn, mcg/kg 210 412 848 852 1470
Vit D, IU/d 4 36 95 216 411*PTDF: preterm discharge formula; Term HM; Estimated needs at D/C: Protein (2.8-3.4 g/kg);Ca (100-220 mg/kg); P (60-140 mg/kg); Zn (1000-3000 mcg/kg); Vitamin D (>400 IU/d)
Who should be fortified at
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Who should be fortified at
discharge?
VLBW infants still
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Formula Choice
Preterm Formula (PF) and/or PretermDischarge Formula (PTDF) for Feeding
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Discharge Formula (PTDF) for FeedingPT Infants after Discharge:Advantages
Improved nutritional intake of key nutrients Increased weight, length and head
circumference growth
Improved bone mineral content (BMC)
Enhanced lean body mass accretion
Normalization of biochemical indices of
nutritional status
Selected Nutrient Levels (per 100
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Selected Nutrient Levels (per 100kcal) for Three Formulas
PretermFormula (PF)
Preterm DischargeFormula (PTDF)
Standard TermFormula
(TF)
Kcal/oz 24 22 20
Pro (gm) 3 (3.3) 2.8 2.1
A (IU) 1250 460 350
B6 (g) 250 100 60
Ca (mg) 180 105 78
Zn (mg) 1.5 1.2 0.75
Intake of Ca, P and Vitamin D
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from Selected Feedings at 160ml/kg/dCa mg/kgper day
P mg/kgper day
Vitamin DIU/day
Unfortified HM 20 kcal/oz 30-40 20-25 2-3
Fortified HM 24 kcal/oz 180-220 100-125 280-380
Preterm Formula
(24 kcal/oz)
210-235 100-130 290-470
Post-discharge formula
(22 kcal/oz)
125-150 70-80 125-130
Recommendations:VLBW (Post-D/C)
150-220(70-140)
75-140(35-90)
200-400(400)
PF and PTDF After Discharge:
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PF and PTDF After Discharge:Evidence
Feeding PF for 8 weeks following discharge
results in improved BMC compared to feedingPTDF or TF (Chan G 1993; Picaud J-C 2008) Feeding PTDF for 3-6 months following
discharge results in improved weight and
length growth, better BMC, and increased leanbody mass accretion but no difference in fatmass or central adiposity compared to feedingTF or unfortified HM (Brunton JA 1998; Cooke
RJ 2010; Amesz EM 2010)
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Summary: Osteopenia Prematurity is a primary cause of osteopenia occurring
in 30-50% of VLBW infants Key nutrients include protein, calcium, phosphorus and
vitamin D
Parenteral nutrition provides inadequate amounts of
calcium and phosphorus Human milk is the ideal feeding for nearly all newborns
but requires fortification to meet the nutritional needs ofVLBW infants
Supplementation with 400 IU/day of vitamin D is routine
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Thank you
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a you