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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 osteopenia 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 bone matrix (osteoid) Osteomalacia: lack of mineralization of the organic bone matrix Rickets: when loss of mineralization involves the growth plate Osteoporosis: decrease in bone mineral density <2.5 SD below the norm (not defined for infants) Metabolic bone disease: preferred term for condition in prematurity
Incidence : Osteopenia
Up to 30% of infants under 1500 g
[Koo WW et al (Canada) 1989]
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 calcium and phosphorus
[Mcintosh et al (UK) 1985]
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
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
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
Objective Two
Implement prevention strategies to minimize the incidence and severity of osteopenia
Key nutrients Recommended intakes
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, 6th Ed. Elk Grove Village, IL: AAP, 2009. p 79-112)
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
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 g/l
(Sedman et al, 1985)
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 weeks Protein g/kg Energy kcal/kg 3.8-4.2 (4.4) 126-140 (134)
Ca mg/kg P mg/kg Vitamin D per day per day IU/day 100-220 60-140 150-400a 150-220 120-140 120-160 150-220 100-130 135-338b 65-90 60-90 75-140 800-1000 400-1000 200-400
Micropreterm 29 wks Late preterm 34-36 wks Preterm, SGA Post-discharge VLBW
(34-38 weeks; assuming no accumulated nutritional deficits)
Total absorption (mg/kg 25 per day) Approximate retention 15-20 (mg/kg per day)
7-dehydrocholesterol in skin
Solar UVB Radiation (290-315 nanometers)
Pre-vitamin D3 Vitamin D3
DIET
Chylomicrons
Vitamin D
Liver (25 hydoxylase)
25 (OH) D
major circulating metabolite
Kidney ( 1 hydroxylase)
1,25 di(OH) D
Calcitriol (biologically active metabolite)
INTESTINE
Calcium, phosphorous absorption
BONE
Calcium resorption
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)
Requirements/Recommendations
Tsang 2005 VLBW/ELBW
Parenteral: 10 mcg/kg per day Enteral: 8-10 mcg/kg per 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)
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
Fitzgerald KA, MacKay MW. Calcium and phosphate solubility in neonatal parenteral nutrient solutions containing TrophAmine. Am J Hosp Pharm 1986
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
Cardiovascular system
Decreased myocardial contractility Increased inotropic requirement Arrythmias
Increased mortality
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
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)
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
100-125 280-380 100-130 290-470 70-80 75-140 (35-90) 125-130 200-400 (400)
Anthropometric measurements of human milk-fed infants sent home (study day 1) fed human milk alone (- -) or with approximately half of the human milkfed 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)
*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)
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
100-125 280-380 100-130 290-470 70-80 75-140 (35-90) 125-130 200-400 (400)
Brunton JA et al 1998
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
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
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. Metabolic bone disease 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.
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