Osteopenia: Risk Factors, Prevention Strategies and Management Options

Sharon Groh-Wargo PhD, RD, LD Associate Professor Nutrition and Pediatrics Senior Nutritionist Case Western Reserve University School of Medicine MetroHealth Medical Center, Cleveland, Ohio May 24, 2013 Objectives

 Screen patients for medical and nutritional risk factors that contribute to the development of  Implement prevention strategies to minimize the incidence and severity of osteopenia  Follow “best practice” nutritional management options to optimize outcomes Objective One

 Screen patients for medical and nutritional risk factors that contribute to the development of osteopenia – Definitions – Incidence – Screening Important terminology

 Osteopenia: decrease in the amount of organic matrix (osteoid)  Osteomalacia: lack of mineralization of the organic bone matrix  : when loss of mineralization involves the growth plate  : decrease in bone mineral density <2.5 SD below the norm (not defined for infants)  Metabolic : preferred term for condition in prematurity 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 are breastfed, in contrast to 16% of those fed with a formula designed for preterm infants and supplemented with and [Mcintosh et al (UK) 1985]  Fractures are reported in ~10% at 36 to 40 weeks CGA [Vachharajani AJ 2009] Osteopenia of Prematurity in ELBW Infants: S Viswanathan et al; MetroHealth Medical Center, Cleveland, OH

 Retrospective chart review of ELBW infants admitted to the NICU 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 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  D deficiency  Lack of mechanical stimulation  Aluminum contamination of parenteral nutrition Risk Factors

 Extreme prematurity <27 weeks GA  Extreme low birth weight <1000g  Parenteral nutrition >4-5 weeks  Severe respiratory disease treated with diuretics and fluid restriction  Long-term steroid use  History of necrotizing enterocolitis  Failure to tolerate fortified human milk or preterm formula Screening and Assessment (Vachharajani AJ 2009; Groh-Wargo, Thompson, Cox, 2000)

 Markers of bone formation – : ≤ 500 U/L – Serum phosphorus: ≥ 5.0 mg% – Serum 25 (OH) : ≥ 20 ng/ml  Markers of – Urinary calcium: <1.2 mmol/L (4.8mg/dl) – Tubular resorption phosphorus: <85-90%  Imaging and absorptiometry – Serial radiographs, DEXA, Quantitative ultrasonography (SOS) Recommended screening schedule 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 radiographic evaluation 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 Objective Two

 Implement prevention strategies to minimize the incidence and severity of osteopenia – Key nutrients – Recommended intakes Key nutrients important to

 Protein and energy  Calcium  Phosphorus (primary nutritional problem)  Vitamin D  Miscellaneous: Vitamin K, Fluoride, etc Sources of Recommended Intakes 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 of the Preterm Infant, 2 nd Edition. Digital Publishing, Cincinnati, Ohio. 2005  ESPGHAN (Agostoni C et al, JPGN. 2010;50:85-91)  American Academy of Pediatrics. (Kleinman RE (ed). Nutrition needs of the preterm infant. In, Pediatric Nutrition Handbook, 6 th Ed. Elk Grove 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] Building a Strong Structure

Lourdes Pereda, MD. USF, FL 2002 Macrominerals: Physiological Role

 Calcium: Over 95% in and teeth; remainder in blood, ECF, muscle – mediates vascular contraction/dilation, muscle contraction, nerve transmission and glandular secretion  Phosphorus – structural – over 85% in bone; functional – most of the remainder is throughout soft tissue mostly in phospholipids of RBCs and plasma lipoproteins; small amount (~1%) as inorganic phosphate which is a primary source from which cells in all tissues derive high-energy phosphate (ATP) Reasonable Nutrient Intakes:

Parenteral (Tsang, Uauy, Koletzko and Zlotkin, 2005)

 ELBW  VLBW  Energy (kcal/kg/d)  Energy (kcal/kg/d) – Day 0: 40-50 – Day 0: 40-50 – Transition: 75-85 – Transition: 60-70 – Growing: 105-115 – Growing: 90-100  Protein (g/kg/d)  Protein (g/kg/d) – Day 0: 2 – Day 0: 2 – Transition: 3.5 – Transition: 3.5 – Growing: 3.5-4.0 – Growing: 3.2-3.8 Macrominerals: Parenteral Intake Recommendations (Tsang et al, 2005)

Day 0 Transition Growing

Ca (mg/kg) 20-60 60 60-80 (mEqX40/2=mg) P (mg/kg) 0 45-60 45-60 (mmoleX31=mg) Mg (mg/kg) 0 4.3-7.2 4.3-7.2 (mEqX24/2=mg) Macromineral IV Sources

 Calcium: Calcium gluconate (9% elemental calcium). For example: 300 mg calcium gluconate = 27 mg elemental calcium; Ca:P 1.3:1 to 1.7:1  Phosphorus: Sodium and potassium phosphate. NaPhos significantly lower than KPhos in aluminum (5977 vs. 16598 µg/l (Sedman et al, 1985) Macromineral IV Balance (mg)

Ca P Mg Concentration ( /liter) 600 465 72 Delivery (per kg/day at 66 51 7.9 110 ml/kg/day) Expected Retention 92 85 68 (% intake) Calculated Retention 61 43 5.4 (per kg/day) InUtero Accretion (/kg) 90-120 60-75 2.5-3.4 Enteral Protein and Energy Requirements of Preterm Infants

Protein, Energy, Body weight, g g/kg/d 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.

Ziegler E. J Pediatr Gastroenterol Nutr 2007;45:S170-4. Daily Protein and Energy needs based on age (and need for catch-up) (Rigo and Senterre, J Peds 2006)

26-30 30-36 36-40 weeks weeks weeks Protein g/kg 3.8-4.2 3.4-3.6 2.8-3.2 (4.4) (3.6-4) (3-3.4) Energy 126-140 121-128 116-123 kcal/kg (134) (120-130) (115-121) PE Ratio g:100 3 (3.3) 2.8 (3) 2.4-2.6 kcal (2.6-2.8) Enteral nutrition recommendations for VLBW infants Ca mg/kg P mg/kg Vitamin D per day per day IU/day Tsang RC 2005 100-220 60-140 150-400 a Klein CJ (LSRO) 2002 150-220 100-130 135-338 b Agostoni C (ESPGHAN) 120-140 65-90 800-1000 2010 Uauy R 2013 120-160 60-90 400-1000 AAP 2013 150-220 75-140 200-400 aAim for 400 IU/d; b90-125 IU/kg, above for a 1.5 kg Enteral nutrition recommendations for special populations of infants (Uauy R 2013) Ca mg/kg P mg/kg Vitamin D per day per day IU/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 70-140 35-90 400 (34-38 weeks; assuming no accumulated nutritional deficits) Macromineral Balance: Enteral Calcium (mg) at 120 kcal/kg (AAP 2013)

Human Fortified Human Milk or Milk Preterm Formula Ca Content (mg/dl) 25 145 Intake (mg/kg per day) 38 220 Absorption (% intake) 60 50-60 Total absorption (mg/kg 25 120-130 per day) Approximate retention 15-20 100-120 (mg/kg per day) Third Trimester In-Utero Accretion (mg/kg per day): 90-120 Bone Mineral Content in Preterm Infants (Atkinson 2005) 7-dehydrocholesterol in skin Solar UVB Radiation (290-315 nanometers)

Pre-vitamin D 3

Vitamin D 3

DIET Chylomicrons Vitamin D Liver (25 hydoxylase)

25 (OH) D major circulating metabolite

Kidney ( ααα 1 hydroxylase) 1,25 di(OH) D (biologically active metabolite)

INTESTINE BONE Calcium, phosphorous absorption Calcium resorption 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 in the maternal population has resulted in deficiency in newborns  Wagner C, Greer FR, Section Breastfeeding and CON. Pediatrics 2008 122:1142-1152. Forms of Vitamin D

 : Vitamin D 3 – 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 from

yeast): Vitamin D 2 – Calciferol and Drisdol (1 ml = 8000 IU) Vitamin K and Bone

 Function – Vitamin K dependent proteins: osteocalcin (or bone Gla protein) as well as matrix Gla protein of the skeleton – Gla proteins are required for calcium mediated interactions  Storage: limited compared to other fat soluble Vitamin K and Bone

 Sources – Newborn IM injection 0.5-1 mg – Pediatric parenteral multi-vitamins provide ~ 60-130 mcg per day (1.5-3.25 ml per day) – Concentration low in HM <1mcg/dl  Requirements/Recommendations – Tsang 2005 VLBW/ELBW • Parenteral: 10 mcg/kg per day • Enteral: 8-10 mcg/kg per day – US DRI 0-12 months 2-2.5 mcg/day Fluoride

 Affinity for calcified tissues; ingestion during pre-eruptive development of the teeth has a cariostatic effect; post-eruptive effect mainly through reduced acid production of plaque bacteria; unique ability to stimulate bone formation; no specific recommendations for preterm infants  Emerging evidence for parenteral fluoride (Nielsen FH Gastroenterology 2009) Other micronutrients important to bone health

 Vitamin C, Copper, and Zinc  Cofactors for the synthesis or cross-linking of matrix proteins  Interference with cross-linking results in structurally weak bone  Deficiency during growth periods results in the most profound impact  Ross AC et al, Modern Nutrition in Health and Disease, 11 th Ed. Pg 1221 Objective Three

 Follow “best practice” nutritional management options to optimize outcomes – Parenteral nutrition • Calcium:Phosphorus solubility • Phosphorus shortages • Aluminum contamination – Human milk: fortification – Formula feeding: choice of formula – Supplementation: Ca and P; Vitamin D Calcium Phosphate Solubility Curves

Fitzgerald KA, MacKay MW. Calcium and phosphate solubility in neonatal parenteral nutrient solutions containing TrophAmine. Am J Hosp Pharm 1986 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 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. Case Report: Hypercalcemia associated with phosphate deficiency in the neonate (Miller RR, Menke JA, Mentser MI. J Peds 1984)

 Male infant; 28 wk GA and 680g BW  TPN started DOL5: D10%, AA, Mg, Ca, D  DOL 16: PDA, CHF, enlarged liver, abdominal distention, Serum Ca 21.6 mg.dl  DOL 20: Lethargic, edematous, murmur, abnormal electrocardiogram, continued hypercemia despite decreased calcium in PN, serum phosphorus <1 mg/dl Case Report: Hypercalcemia associated with phosphate deficiency in the neonate (Miller RR, Menke JA, Mentser MI. J Peds 1984) Phosphorus deficiency:  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 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 emulsions contain 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 <2.0 Aluminum

 Contaminant in parenteral solutions  Associated with impaired neurological development and 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 5 mcg/kg per day’  Goal is to label products and limit exposure Strategies to Minimize Aluminum Load

 Use sodium phosphate in place of potassium phosphate as source of phosphate  Use solutions packaged in plastic instead of glass as much as possible  Compare products and choose carefully  Use multivitamin infusion with lowest aluminum concentration  These steps minimize the aluminum load but do not decrease it to the recommended level Good News – Bad News Regarding IV Aluminum Exposure

 Reported aluminum concentration is maximum possible at product expiration  Measured aluminum content is significantly less than calculated aluminum content  Measured aluminum of 40 neonatal TPN solutions were ~50% of calculated value (Poole RL et al JPGN 2010)  Actual intake still exceeded recommended safe limit of <5 mcg/kg/d (~18 mcg/kg/d) Human Milk Fortification

 WHO  WHAT  WHERE  WHEN  WHY 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 restriction and/or significant medical/surgical complications

[Schanler RJ and Abrams SA, 1995; Schanler RJ et al, 1999; Atkinson SA, 2000; Abrams SA 2013] 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 J Invest Med 2010)  Concentrated donor human milk enriched with minerals (frozen liquid) [Prolacta Bioscience http://prolacta.com accessed 8/23/11] (~$40/oz) (Sullivan S et al. J Pediatr 2010) WHAT are the options for fortification? (continued)

 Individualized: – Based on milk analysis (Polberger S et al. JPGN 1999; deHalleux V et al. Arch Pediatr 2007) – Based on nutrient content (Pohlandt F Pediatr Res 1993)  Adjustable: based on BUN (Arslanoglu S et al. J Perinatol 2006) WHERE should human milk fortifier be added to human milk?

 The addition of human milk fortifier to expressed human milk at the bedside is not advised (Ohio Department of Health, The American Dietetic Association, ASPEN)  A NICU “Milk lab” as a separate location is ideal to insure – Cleanliness and safety of expressed human milk – Accuracy and adequacy of mixing 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/kg per 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 (most usual) – As late as 52 weeks post-conceptional age or weight of 3.5 kg, whichever comes first WHY do we give human milk fortification?

 Inadequate concentration of – Protein – Minerals, for example • Calcium • Phosphorus • Zinc • Sodium HMF Meta-Analysis: BMC HMF Meta-Analysis: NEC Intake of Ca, P and Vitamin D from Selected Feedings at 160 ml/kg/d Ca mg/kg P mg/kg Vitamin D per day per day IU/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 210-235 100-130 290-470 (24 kcal/oz) Post-discharge formula 125-150 70-80 125-130 (22 kcal/oz) Recommendations: 150-220 75-140 200-400 VLBW (Post-D/C) (70-140) (35-90) (400) Human Milk (HM) After Discharge: Evidence

 Feeding HM is associated with improved neurocognitive outcomes but decreased growth (O’Connor DL 2003, Lucas A 2001)  Feeding fortified HM improves nutrient intake, bone mineralization, visual acuity and length and head growth compared to feeding HM without fortification (O’Connor DL 2008, Aimone A 2009, O’Connor DL 2012)  Feeding fortified HM may not improve overall growth compared to feeding preterm formula (Zachariassen G 2011)  Fortification of HM following discharge does not interfere with breastfeeding success (O’Connor DL 2008; Zachariassen G 2011) Human Milk After Discharge: Evidence

Anthropometric measurements of human milk-fed infants sent home (study day 1) fed human milk alone (- -) or with approximately half of the human milk–fed mixed with a multi-nutrient fortifier (–) for 12 weeks. Asterisks denote a significant difference between feeding groups at a specific time point. (Aimone A et al 2009) The ‘Sprinkles’ Problem Intake for 2 kg infant @ 120 kcal/kg/d

HM Human HM HM with HM with enriched Milk alternated HMF HMF Nutrient with (HM) with PTDF* 1:50 1:25 PTDF*

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 discharge?

 VLBW infants still <2 kg at discharge  Evidence of nutritional deficiency and/or osteopenia – BUN <10 mg/dl – Phosphorus <6 mg/dl – Alkaline Phosphatase >600 U/L – X-ray evidence of bone demineralization  Growth at less than the intrauterine rate of 15 g/kg per day Formula Choice Preterm Formula (PF) and/or Preterm Discharge Formula (PTDF) for Feeding PT 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 kcal) for Three Formulas Preterm Preterm Discharge Standard Term Formula (PF) Formula (PTDF) Formula (TF) Kcal/oz 24 22 20 Pro (gm) 3 (3.3) 2.8 2.1 A (IU) 1250 460 350

B6 (µg) 250 100 60 Ca (mg) 180 105 78 Zn (mg) 1.5 1.2 0.75 Intake of Ca, P and Vitamin D from Selected Feedings at 160 ml/kg/d Ca mg/kg P mg/kg Vitamin D per day per day IU/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 210-235 100-130 290-470 (24 kcal/oz) Post-discharge formula 125-150 70-80 125-130 (22 kcal/oz) Recommendations: 150-220 75-140 200-400 VLBW (Post-D/C) (70-140) (35-90) (400) PF and PTDF After Discharge: Evidence  Feeding PF for 8 weeks following discharge results in improved BMC compared to feeding PTDF 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 lean body mass accretion but no difference in fat mass or central adiposity compared to feeding TF or unfortified HM (Brunton JA 1998; Cooke RJ 2010; Amesz EM 2010) PF and PTDF After Discharge: Evidence (cont)  Feeding PTDF for 9-12 months following discharge results in improved weight, length and head circumference growth and better BMC in LBW infants, especially those <1250g at birth, compared to feeding TF or unfortified HM (Bishop NJ 1993, Carver JD 2001; Lucas A 2001)  Feeding PF supplemented with LC-PUFAs until term and PTDF supplemented with LC-PUFAs until 12 months corrected age results in improved lean body mass accretion compared to feeding PF and PTDF without supplemental LC-PUFAs (Groh-Wargo S 2005) Brunton JA et al 1998 Calcium & Phosphorus Supplementation: VLBW on low mineral feedings  Calcium (elemental): – Initial: 20 mg/kg per day – Maximum: 70-80 mg/kg per day – Source: Ca glubionate (23 mg/ml; high osmolality) or Ca carbonate (100 mg/ml; less bioavailable)  Phosphorus (elemental): – Initial: 10-20 mg/kg per day – Maximum: 40-50 mg/kg per day – Source: IV potassium phosphate (31 mg P/mmol)  Combination salts: Ca tribasic P (0.39 mg Ca & 0.28 mg P/mg powder)  Goal to provide approximate intake of fortified human milk or preterm formula Steps to Minimize Osteopenia

 Maximize solubility in TPN solutions  Limit calcium-losing medications  Introduce priming enteral feedings ASAP  Use human milk fortification  Provide adequate vitamin D  Continue enriched nutrient following discharge as appropriate  Monitor phosphorus and alkaline phosphatase Summary of 2013 Recommendations for Management of Osteopenia from the AAP  Risk: <27 wks or <1000g at birth  Screening: Start at 4 weeks for all VLBW – X-ray if alkaline phosphatase (APA) >800 IU/L – If P consistently <4, follow and consider supplement  Feeding: FHM or PT formula if <1800 g BW  Discharge: PDF if VLBW; follow APA for HM fed  Vitamin D: 400-1000 IU/d  Management of Osteopenia Diagnosis – Maximize Ca and P intake – minimizing factors leading to bone mineral loss – gentle handling Cases: Osteopenia

 Case 1: 638g BW 24 wk GA (AGA) – Intolerance to preterm formula; family hx of allergy – TPN 50 days (average 25-30 for BW and GA) – Lasix therapy 98 days  Case 2: 543g BW 27 wk GA (SGA) – Expressed human milk with late human milk fortification – Decreasing milk supply  Case 3 771g BW 24 wk GA (AGA) – BPD/ steroid therapy/fluid restriction – Fractured left clavicle DOL 83 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 of VLBW infants  Supplementation with 400 IU/day of vitamin D is routine References

 Abrams SA and the Committee on Nutrition, AAP. Calcium and Vitamin D Requirements of Enterally Fed Preterm Infants. Pediatrics online. www.pediatrics.org/cgi/doi/10.1542/peds.2013-0420  Begany M. Identification of fracture risk and strategies for bone health in the neonatal intensive care unit. Top Clin Nutr. 2012. 27(3):231-247.  Vachharajani AJ et al. of prematurity. 2009. NeoReviews. 10(8):e402-410.  Uauy R (Ed). Global Neonatal Consensus Symposium: Feeding the Preterm Infant. Journal of Pediatrics. 162(3):Supplement 1, 2013. Thank you…