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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

OSTEOPENIA OF PREMATURITY

ICN – JUNE / 2004

Vilma I. Dobbs, MD

calcium ca
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
ca regulation of serum concentration
Ca- Regulation of serum concentration
  • PTH
  • Calcitonine (CT)
  • Vitamin D
ca regulation of serum concentration4
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
ca regulation of serum concentration5
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
ca regulation of serum concentration6
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
ca gi transport
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
ca gi transport8
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 ↑
ca gi transport9
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.
ca gi transport10
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

osteopenia of prematurity oop
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.
slide12
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.
slide13
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.
slide14
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

oop risk factors
OOP – RISK FACTORS
  • < 34 Wks
  • < 1500 gr
  • Delayed establishment of full enteral feedings
    • Complicated neonatal course
    • Prolonged parenteral nutrition
oop risk factors16
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
oop clinical findings
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
oop diagnosis
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
oop general nutrition labs
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
contin oop general nutrition labs
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
oop diagnosis21
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)
preventive nutrition
PREVENTIVE NUTRITION
  • Theoretically => Feeds w ↑↑ Ca & P

(Equivalent to utero accretion rates)

  • Parenteral nutrition
  • Partial Parenteral / Enteral nutrition
  • Enteral nutrition
preventive nutrition23
PREVENTIVE NUTRITION
  • PARENTERAL NUTRITION
  • 1ST few days or wks
  • Amount of Ca & P given is limited 2ry to precipitation
preventive nutrition24
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
preventive nutrition25
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
preventive nutrition26
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
preventive nutrition27
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
preventive nutrition28
PREVENTIVE NUTRITION
  • Conversion to gr.
  • Ca mEq to gr = x 20
  • P mM to gr = x 30
vitamin d
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