Groh Wargo Osteopenia

8/13/2019 Groh Wargo Osteopenia

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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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Groh Wargo Osteopenia

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