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OSTEOPENIA OF PREMATURITY

OSTEOPENIA OF PREMATURITY ICN – JUNE / 2004 Vilma I. Dobbs, MD CALCIUM (Ca) The most abundant mineral in the body 99% in skeleton From this 1/3 is readily interchangeable with ECF Serum Ca exist in 3 separated fractions:

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OSTEOPENIA OF PREMATURITY

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  1. OSTEOPENIA OF PREMATURITY ICN – JUNE / 2004 Vilma I. Dobbs, MD

  2. CALCIUM (Ca) • The most abundant mineral in the body • 99% in skeleton • From this 1/3 is readily interchangeable with ECF • Serum Ca exist in 3 separated fractions: • Protein-bound: 40% , > albumin • Complexed with anions: 10% , citrate, P, HCO3, & sulfate • Free ionized: 50%, physiologically active

  3. Ca- Regulation of serum concentration • PTH • Calcitonine (CT) • Vitamin D

  4. Ca – Regulation of serum concentration • PTH • PTH ↑ => If serum Ionized Ca ↓ • In Bone: ↑ Ca resorption (release of Ca & P into Extracelullar fluid & circulation • In Kidney: ↑ Ca urinary excretion • In GI: Indirectly through Vit-D ↑ GI absorption of Ca • Net effect of PTH is ↑ Ca concentration

  5. Ca- Regulation of serum concentration • CALCITONINE • CT ↑ If => ↑ Ca in serum • In Bone: bone resorption • In Kidney: @↑↑ of calcitonine ↑ urinary excretion of Ca & P • Net effect of CT is ↓ Ca & P

  6. Ca- Regulation of serum concentration • VITAMIN - D • PO / GI absorbed • Skin / UV light • Liver => 1stOH => 25 OH – Vit-D • Kidney => 2nd OH => 1,25 OH –Vit-D • Active form • In GI: small intestine => active absorption of Ca • In Bone w PTH => Bone resorption • Net effect of Vit-D (1,25OH) is ↑ Ca

  7. Ca GI Transport • GI tract is the 1ry site involved in the long term regulation of Ca balance. • Ca absorption: • Passive : • all small intestine • Related to intraluminal Ca concentration • Apparently no regulatory process • Active : • 1ry in duodenum • Strongly influenced by Vit-D • 1,25 OH Vit-D ↑ absorption of Ca

  8. Ca GI Transport • ↑ Alk Ph. when exposed to 1,25 OH-Vit-D • In PT baby if ↑ Ca intake => ↑ GI absorp. of Ca • Human milk & formula supplemented with Vit-D => ↑↑ Ca absorption • Intestinal maturation is accelerated by preterm delivery ↑

  9. Ca GI Transport • CHO & Glucose polymers ↑Ca / GI absorption. (unclear mech.). Independent of Vit-D • Osmotic forces that ↑ GI absorption of water also ↑ passive absorption of Ca.

  10. Ca GI Transport • If dietary restriction of Ca or P => ↑ prod. of 1,25 OH-Vit-D => ↑ active GI Ca absorption. • Fat malabsorption • PT baby w ↓ bile salts (micelle-phase) =>↓ fat absorption => unabsorbed free fatty acids<=> interact with ionic Ca => Insoluble Soaps => Ø Ca absorption

  11. OSTEOPENIA OF PREMATURITY (OOP) • DEFINITION • Is a Metabolic Bone Disease of PT infants, in which decreased bone mineral content occurs mainly as a result of lack of adequate Ca & P intake in extra uterine life.

  12. OOP • The bone mineral content of a PT infant is significantly decreased relative to the expected level of mineralization for a fetus or infant of comparable size or gestational age. It is a common problem in babies of <1000gr who have low intakes of Ca & P.

  13. OOP • The accretion of Ca & P ↑ exponentially in the fetus during 3er trimester, ≈ 80% present at term. • To achieve similar rates of accretion for normal growth & bone mineralization, small PT require higher intakes of Ca & P x Kg than do Term infants.

  14. OOP • Fetus of 28 – 38 wks -will ↑ Wt. x 3 -will ↑Ca content x 4 => rate: 120-150 mg/kg/d -will ↑P content => rate: 75- 85 mg/kg/d • While Mother will: -↑ PTH -↑ 1,25 OH-Vit-D -↑ Ca absorption -↑ Ca mobilization

  15. OOP – RISK FACTORS • < 34 Wks • < 1500 gr • Delayed establishment of full enteral feedings • Complicated neonatal course • Prolonged parenteral nutrition

  16. OOP – RISK FACTORS • Enteral feedings / low mineral content/bioavail. • Unsupplemented human milk • Soy-based infant formulas • Standard term milk-based formulas • Chronic use of meds. That ↑ mineral excretion • Diuretics, steroids, NaHCO3 • Cholestatic jaundice

  17. OOP- CLINICAL FINDINGS • From mild demineralization to overt rickets & non-traumatic Fxs., or rachitic RD • Clinically silent • Dx usually @ 2 - 4 mo • Craniotabes, frontal bossing • Thickening of wrist & ankles, rachitic rosary • Impaired rate of linear growth • Enamel hypoplasia

  18. OOP - DIAGNOSIS ROUTINE TESTS • ↑ serum Alk. Ph. > 400 IU • ↓ serum P < 3.5 mg/dl • Normal Ca • Abnormal X-ray of wrist or knee • ↓ bone density • Cupping & irregularity of metaphyses & Fxs. • X-ray evidence is often present by the end of 1st mo

  19. OOP – GENERAL NUTRITION LABS 500 - 1500 grs • BMP Q day until stable on TPN • BMP Wed & Sat until > 1500 gr unless stable • Ca & P Q wed & Sat while in TPN until stable • T & D Bili Q Wed while in TPN • D/Bili is the 1st↑ in TPN cholestasis • If D/Bili ↑ => F/U LFT’s w GGT Q other Wk • F/U D/Bili (even TPN off) until <1.5-2 mg/dl

  20. Contin….OOP – GENERAL NUTRITION LABS • Alkaline phosphatase Q other wed., started the 2dn wk of life. • Marker ↑ before changes noted on x-ray • Abnormal if > 400 or 500 U/L • F/U until < 300 or 350 U/L on PT formula • Spun Hct & retic. Q wed • Triglyceride: after 1st 24 hrs on lipids, then daily after 1.5 gr/kg/d until stable on 3mg/kg/d

  21. OOP - DIAGNOSIS • SUPLEMENTARY TESTS • Normal or ↓ 25, oh-Vit-D • ↑ 1,25, OH –Vit-D • ↑ or Normal PTH • Bone density • Single photon absormetry (SPA) • Dual energy X-ray asorptiometry (DXA) • Bone mineral content (BMC) • Bone mineral density (BMD)

  22. PREVENTIVE NUTRITION • Theoretically => Feeds w ↑↑ Ca & P (Equivalent to utero accretion rates) • Parenteral nutrition • Partial Parenteral / Enteral nutrition • Enteral nutrition

  23. PREVENTIVE NUTRITION • PARENTERAL NUTRITION • 1ST few days or wks • Amount of Ca & P given is limited 2ry to precipitation

  24. PREVENTIVE NUTRITION FACTORS / ↑ SOLUBILITY • Ca : salt form => ↑ Ca gluconate • P : order of mixing => ↑ 1st P =>Ca • AA : & composition => ↑cysteine • Dextrose : ↑ concentration • Temp : ↑ temp. • pH : ↓ pH

  25. PREVENTIVE NUTRITION THE GOAL IS : • Ca : P ratio => 1.7 : 1 • Trophamine 0.8 gr / dL • Ca gluconate • K phosphate • Advancing to or continuing feedings of fortified human milk or preterm formula

  26. PREVENTIVE NUTRITION • A wide range of Ca:P ratios have been used in Parenteral Nutrition solutions. • Studies using ratios of 1.3 : 1 to 1.7:1 have reported high mineral retention and minimal problems with tolerance

  27. PREVENTIVE NUTRITION • PRACTICAL WAY TO MIX Ca & P IN TPN SOLUTIONS • Trophamine 3 gr with Cysteine 40 mg • Ca 4 – 5 mEq for every 100 ml of TPN • P 1.5 – 2.5 mM for every 100 ml of TPN

  28. PREVENTIVE NUTRITION • Conversion to gr. • Ca mEq to gr = x 20 • P mM to gr = x 30

  29. PREVENTIVE NUTRITION(the numbers are rounded)

  30. VITAMIN - D • Deficiency is very rare in PT in USA • It is implicated in OOP • The main cause of OOP is deficiency of Ca & P • Recommended intake : 125 – 333 IU/100 kcal/d • Human milk fortified & special Pt formulas will supply 200 – 400 IU/d

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