title: Metabolic bone disease - Neonatal Intensive Care Drug Manual
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  Neonatal Intensive Care Drug Manual
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  bet | 475/654 | Sana | 03.01.2022 | Hajmi | 1,5 Mb. | | #14803 |
  Metabolic bone disease
  Goal: Aim for the upper end of the recommended range to prevent fractures and clinical symptoms of osteopenia: Ca and P of around 4-4.5 mmol/kg/day. Adjust the mineral intake with a goal of achieving a slight excess of urinary mineral excretion: Urinary calcium ≥1.2mmol/L and phosphate ≥0.4 mmol/L.14
  Step 1: Calculate the mineral intake from enteral feed:
  Example: 150 ml/kg/day of mature preterm EBM contains: Ca 1 mmol/kg/day and P 0.6 mmol/kg/day. 150 ml/kg/day preterm EBM+24kcal HMF contains: Ca 4.5 mmol/kg/day and P 2.7 mmol/kg/day.
  Preterm milk
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  Ca, mmol (mg)/100 mL
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  P, mmol (mg)/100 mL
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  1st week
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  0.7 (26)
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  0.4 (11)
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  2nd week
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  0.6 (25)
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  0.5 (15)
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  Week 3/4
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  0.6 (25)
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  0.5 (14)
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  Week 10/12
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  0.7 (29)
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  0.4 (12)
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  Term milk
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  1st week
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  0.7 (26)
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  0.4 (12)
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  2nd week
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  0.7 (28)
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  0.6 (17)
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  Week 3/4
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  0.7 (27)
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  0.5 (16)
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  Week 10/12
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  0.7 (26)
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  0.5 (16)
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  Elemental Ca, 1 mmol = 40 mg. Elemental Phosphorus, 1 mmol = 31 mg. Adapted from Gidrewicz and Fenton BMC Pediatrics 2014, 14:216.15
  Step 2: Calculate the gap in Ca and P intake/requirement: This will be the dose required.
  Step 3: Prescribe 50% of the required dose of Ca and P in 2-3 divided doses alternatively but not together. (example: Ca 8 AM, 2 PM, 8 PM and P 6 AM, 12 MD, 6 PM).
  Step 4: Once 50% dose is tolerated for 1 week, increase to 100% required dose.
  ORAL preparation during NICU stay: Sodium dihydrogen phosphate Phebra IV is the preferred preparation for oral administration due to its low osmolality.
  ORAL preparation at discharge or stable neonates: Phosphate-Sandoz tablets can be used.
  American Academy of Pediatrics Committee on nutrition 2013 Guidelines on management for Enterally Fed Preterm Infants With Radiologic Evidence of Rickets: 1. Maximize nutrient intake. 2. If no further increases in these can be made, add elemental calcium and phosphorus as tolerated. Usually beginning at 20 mg/kg per day of elemental calcium and 10–20 mg/kg per day elemental phosphorus and increasing, as tolerated, usually to a maximum of 70–80 mg/kg per day of elemental calcium and 40–50 mg/kg per day elemental phosphorus. May consider targeting 25-OH-D concentration of >20 ng/mL (50 nmol/L).8 However, breast milk content of phosphorus is variable and harder to estimate the intakes accurately. A more pragmatic approach suggested by our consensus group: start with P 0.5-1.0 mmol/kg/day in divided doses and increase as tolerated to a maximum of P 3 mmol/kg/day.
  Efficacy and safety
  An ideal oral form of phosphate for use in preterm infants does not exist. Administering the intravenous preparations orally can be considered, because they are lower in osmolarity than are commercially available phosphorus-containing liquids. For example, potassium dihydrogen phosphate provides 31 mg of elemental phosphorus per millimole. A dose of 10 to 20 mg/kg per day of elemental phosphorus is reasonable and will likely resolve hypophosphataemia in most preterm infants.8
  Oral phosphorus and feeds
  It is recommended to separate oral doses from calcium and antacids containing agents such as aluminium hydroxide, calcium or magnesium salts, as these may reduce the bioavailability of phosphate. Oral phosphate may combine with calcium in the milk, reducing its absorption. It is recommended to avoid giving phosphate with milk.
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  References
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  Tsang R, Uauy R, Koletzko B, Zlotkin SH. Calcium, magnesium, phosphate and vitamin D. In Nutrition of the preterm infant. Scientific basis and practical guidelines 2005:p 265.
  Dissaneewate S, Vachvanichsanong P. Severe hyperphosphatemia in a newborn with renal insufficiency because of an erroneous medical prescription. Journal of Renal Nutrition. 2009 Nov 30;19(6):500-2.
  Schanler RJ, Abrams SA, Garza C. Mineral balance studies in very low birth weight infants fed human milk. J Pediatr. 1988;113 (1 pt 2):230–238.
  AAP. Pediatric nutrition handbook. 6th ed. Kleinman RE, editor: AAP eBooks; 2009.
  Koletzko B, Goulet O, Hunt J, Krohn K, Shamir R. 1. Guidelines on Paediatric Parenteral Nutrition of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society for Clinical Nutrition and Metabolism (ESPEN), Supported by the European Society of Paediatric Research (ESPR). J Pediatr Gastroenterol Nutr. 2005;41 Suppl 2:S1-87.
  Bolisetty S, Osborn D, Sinn J, Lui K. Australasian Neonatal Parenteral Nutrition Consensus Group. Standardised neonatal parenteral nutrition formulations-an Australasian group consensus 2012. BMC Pediatr. 2014;14:48.
  Agostoni C, Buonocore G, Carnielli VP, et al; ESPGHAN Committee on Nutrition. Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition. J Pediatr Gastroenterol Nutr. 2010;50(1):85–91.
  Abrams SA, and the Committee on nutrition. Calcium and Vitamin D Requirements of Enterally Fed Preterm Infants. Pediatrics 2013;131:e1676–e1683.
  Tinnion RJ, Embleton ND. How to use... alkaline phosphatase in neonatology. Arch Dis Child Educ Pract 2012;97:157–63.
  Bozzetti V, Tagliabue P. Metabolic Bone Disease in preterm newborn: an update on nutritional issues. Italian J Ped 2009;35:20. Doi:10.1186/1824-7288-35-20.
  MIMS Product Info. Accessed on 11 April 2018.
  Mihatsch W, et al., ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: Calcium, phosphorus and magnesium, Clinical Nutrition (2018), https://doi.org/10.1016/j.clnu.2018.06.950.
  Schanler RJ, Atkinson SA. Human milk. In Nutrition of the preterm infant. Scientific basis and practical guidelines. Second edition 2005. Eds Tsang R, Uauy R, Koletzko B, Zlotkin SH.:p 336.
  Osborn DA. Metabolic bone disease. https://www.slhd.nsw.gov.au/rpa/neonatal%5Ccontent/pdf/guidelines/metabolicBD.pdf
  Gidrewicz DA, Fenton TR. A systematic review and meta-analysis of the nutrient content of preterm and term breast milk. BMC pediatrics. 2014 Dec;14(1):216.
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  Original version Date: 15/11/2016
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  Author: Neonatal Medicines Formulary Consensus Group
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  Current Version number: 2
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  Version Date: 2/3/2021
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  Risk Rating: Medium
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  Due for Review: 2/3/2024
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  Approval by: DTC
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  Approval Date: TBA
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