Juring gizi : AminoAcid Formula in Preterm

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AMINO ACID–BASED FORMULA AS A RESCUE STRATEGY IN FEEDING VERY-LOW-BIRTH-WEIGHT INFANTS WITH

INTRAUTERINE GROWTH RESTRICTION

Presenter:Argadia Yuniriyadi

Francesco Raimondi, Anna Maria Spera, Maria Sellitto, Francesca Landolfo, and Letizia Capasso

Nutrition Journal Reading

SupervisorEndang D.L., dr. Consultant Pediatrician, MPH

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INTRODUCTION

: Birth Weight : 1000 - 1500 gr

VERY-LOW-BIRTH-WEIGHT INFANTS(VLBW)

Failure to attain optimal intrauterine growth

INTRAUTERINE GROWTH RESTRICTION

(IUGR)

IUGR

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INTRODUCTION

VLBW&

IUGR

GIT ImmatureNutritional

Need

ENTERAL NUTRITION

PARENTERAL NUTRITION

HUMAN MILIK

SPF(Standard Preterm Formula)

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INTRODUCTION

VLBW&

IUGR

GIT ImmatureNutritional

Need

ENTERAL NUTRITION

PARENTERAL NUTRITION

HUMAN MILIK

SPF(Standard Preterm Formula)

Good Outcome

Feeding Intolerance

NEC

Rescue with AAF ??

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INTRODUCTION

Protein Partial Hydrolyzed Protein

Full Hydrolyzed Protein

• Full Hydrolyzed Protein• Indication for Cow Milk Protein Allergy

Amino Acid Based Formula

GIT rescue in VLBW+IUGR with

Feeding Intolerance

Easy metabolism & absorbs

in GIT

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METHOD

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SUBJECT

Prospective StudyCase control pilot studyClinical Trial

IUGR VLBW neonates

Neonatal intensive care unit (NICU) of the University ‘‘Federico II’’ of Naples

January 2006 and June 2009,

Maternal milk was not available

Exclusion criteria :major congenital malformations and anomaliessevere sepsis, andtransfer to another hospital

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Study Flowchart

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Definition

• Gastric residual volume, • ≥ 5 mL/kg or • higher than the scheduled

feed; • >70% of milk feeds were not

tolerated in the previous 24 hours;

• Biliary or bloody gastric residuals;

• Abnormal abdominal examination• Abdominal distension,

persistent visible bowel loops, absent bowel sounds;

• Abnormal abdominal x-ray

Feeding Intolerance

The assessment was done by a

blinded Neonatologist

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OUTCOME

Primary

Time (days) to reach full enteral

feedings

Secondary

Time (days) of parenteral nutrition (central venous catheter and peripheral venous catheter),

Time (days) on central venous catheter (umbilical vein and percutaneous catheter),

Formula tolerability (residual) : AAF-SPF; Before and after AAF

Serum parameter at day 3 of full enteral feeding+ Discharge output

Growth at 12 month of life (age corrected)

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RESULT

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SUBJECT CHARACTERISTIC

Case Control

No. Patients 22 42

Birth weight (mean ± SD)

1060 ± 283 1116 ± 241

GA (mean ± SD) 31.5 ± 2.7 32.3 ± 2.1

No. ELBW infants 10/22 (45%) 11/42 (26%)

Use of antenatal steroid

86.3% 90.4%

SNAP-II Score* 25.1 ± 22.2 12.5 ± 17.6

ELBW = extremely-low-birth-weight; GA = gestational age; SD = standard deviation*p<0.005 at Maan-Whitney U test

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SUBJECT CHARACTERISTIC

Case Control

No. Patients 22 42

Birth weight (mean ± SD)

1060 ± 283 1116 ± 241

GA (mean ± SD) 31.5 ± 2.7 32.3 ± 2.1

No. ELBW infants 10/22 (45%) 11/42 (26%)

Use of antenatal steroid

86.3% 90.4%

SNAP-II Score* 25.1 ± 22.2 12.5 ± 17.6

ELBW = extremely-low-birth-weight; GA = gestational age; SD = standard deviation*p<0.005 at Maan-Whitney U test

SNAP (Score for Neonatal Acute Physiology) II Higher in case group “infant with worse SNAP-II score may developed to feeding intolerance”

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Primary Outcome

Case Control

No. Patients 22 42

Day on parenteral nutrition (CVC + PVC)

22.5 ± 13.6*

10.8 ± 6.8*

Day on parenteral nutrition (CVC + PVC) with AAF

12.3 ± 8.3

Day on central venous catheter 19.2 ± 13.9*

8.02 ± 5.2*

Day on central venous catheter with AAF

8 ± 7.6

Day to full enteral feeding 23.6 ± 15.6*

14 ± 6.8*

Day to full enteral feeding with AAF 15.4 ± 12.3

AAF = Amino acid formula; CVC = central venous catheter; PVC = peripheral venous catheter*p<0.05 at t test

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CONTROL NP 1 + NP 2 (SPF)

Full enteral feeding

CASE NP 1(SPF)

(feeding

intolerance)

NP 2 (AAF)

+ parenteral nutrition

Day to full enteral feeding Control (14 ± 6.8) vs Case (23.6 ± 15.6)

Day to full enteral feeding with AAFCase (15.4 ± 12.3)

Day on parenteral nutritionControl (10.8 ± 6.8) vs Case (22.5 ± 13.6)

Day on parenteral nutrition with AAFCase (12.3 ± 8.3)

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Secondary Outcome

Case Control

No. Patient 22 42

No. (%) gastric residual volume > 5ml/kg at 48 h over total no. feedings

3/264 (1.1) 17/504 (3.3)

Mean gastric residual at 72 h, ml

0.6 ± 1.2 0.9 ± 1.5

P>0.05

Formula tolerance in case on AAF versus control on SPF

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Secondary Outcome

Case before AAF introduction

Case after AAF introduction

No. Patient 22 22

No. (%) gastric residual volume > 5ml/kg at 48 h over total no. feedings*

14/248 (5.6) 3/264 (1.1)

Mean gastric residual at 72 h, ml

2.7 ± 4.68 0.6 ± 1.2

AAF = amino acid formula*p<0.05 at Χ2 test**p<0.05 at Maan-Whitney U test

Formula tolerance in case before and after AAF

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Secondary Outcome

pH Urea Creatinine

Albumin

Total Protein

**

Ca P ALP

Case (mean ± SD)

7.38 ± 0.06

10.3 ± 3.8

0.3 ± 0.09

3.06 ± 0.2

4.3 ± 0.3

9.4 ± 1.1

5.5 ± 0.8

330 ± 141

Control (mean ± SD)

7.4 ± 0.02

16.8 ± 18.3

0.4 ± 0.3

3.2 ± 0.4

4.7 ± 0.3

9.4 ± 0.6

5.6 ± 1.5

291 ± 71

AAF = amino acid formula; ALP = alkaline phospatase; SD = standard deviation*Serum parameters were obtained within 3 days after achieving full enteral nutrition. At that time both case and control were fed SPF**p<0.05

Main serum parameter in case on AAF and control on SPF*

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Secondary Outcome

Outcome at discharge

Death BPD IVH>2 PVL ROP>2 NEC

Case (%)

1/22 (4.5)

2/22 (9) 3/22 (13.6)

1/22 (4.5)

1/22 (4.5)

0/22

Control (%)

2/42 (4.7)

1/42 (2.3)

0/42 0/42 1/42 (2.3)

0/42

Growth at 12 month of life (percentile for corrected age)

Weight, g ± SD Height, cm ± SD HC, percentile ± SD

Case 8936 ± 728 75.2 ± 2 45.2 ± 1.1

Control 8914 ± 957 72.5 ± 2.4 45.1 ± 1

BPD = bronchopulmonary dysplasia; IVH = intraventricular hemorrhage; NEC = necrotizing enterocolitis; PVL = perventricular leukomalacia; ROP = retinopathy of prematurityp > 0.05

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DISCUSSION

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GASTROINTESTINAL IMMATURITY IN VLBW+IUGR INFANT

Josef Neu (2007), Gastrointestinal development and meeting the nutritional needs of premature infants

Digestive & absorptive organ immaturity• GIT surface area << than term

infant• Intrinsic immaturity of the enteric

nervous system Delayed intestine motility and emptying

Immune system immaturity

• Delayed motility bacterial overgrowth

• Immature GIT immune function & barrier

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SNAP-II SCORE IN VLBW & IUGR

↑ risk for feeding intolerance

VLBW+IUGR Infant with ↑ SNAP II Score

“SCORE FOR NEONATAL ACUTE PHYSIOLOGY” II :

• mean blood pressure • lowest temperature• PO2/FIO2 ratio• serum pH

• multiple seizures• urine output

A Physiologic Severity Index for Neonatal

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NUTRITION FOR VLBW

WHO (2011) Guideline on optimal feeding of low birth-weight infants

Day Old

NUTRITIONAL SUPPORT

PARETERAL

NUTRITION

ENTERAL NUTRITION

1st

TPN

-

2nd

Preterm infant’s mother human milk

orDonor Human Milk

or Standard Preterm Formula

Daily increment 10-150 ml/kg/day

3th…

Purpose :• Support the

caloric and nutritional need

• GIT stimulation

MonitoringDaily monitoring for intolerance

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FEEDING INTOLERANCE MANAGEMENT IN PRETERM INFANT• Drug (Prokinetic Agent)– Domperidone (Gounaris et all, 2002)

– Cisapride (Enriquez et al, 1999)

– Erythromycin (Ng et al, 2007)

• Diet–Hydrolyzed Formula??

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HYDROLYZED PROTREIN FORMULA

HYDROLYZED

PROTREIN FORMULA

PARTIAL HYDROLYZED

FULL HYDROLIZEDEXTENSIVE HYDROLIZEDELEMENTAL FORMULA

AMINO-ACID BASED FORMULA

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HYDROLYZED FORMULA FOR FEEDING INTOLERANCE IN VLBW INFANT

HPF improved the feeding tolerance and enabled a more rapid establishment of full enteral feeding in VLBW infants compared with SPF (Mihatsch, et al, 2002)

HPF induce higher motilin in GIT (Tormo et al, 1998)

Accelerate gastrointestinal transit via a reduced B-casomorphin activity (Daniel, 1990)

AAF Indication : Inflammatory bowel disease (ie, cow’s milk protein intolerance, Crohn disease)

Raithel et all (2007); Johson et al (2006); Claud et al (2009)Assumed Decrease the inflammation response

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AAF WAS SAFE FOR RESCUE

No significant difference in routine laboratory work at the time full enteral feeding was

reached and cases were switched back to SPF

Both short and long-term growth were not impaired

AAF was safe

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STUDY CONCLUSION

VLBW IUGR newborns with severe feeding intolerance, a

short course on AAF was a safe and effective means of nutritional

rescue

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CRITICAL APPRAISAL

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STUDY RESUME

TITLE Amino Acid–based Formula as a Rescue Strategy in Feeding Very-Low-Birth-Weight Infants With Intrauterine Growth Restriction

Author Francesco Raimondi, Anna Maria Spera, Maria Sellitto, Francesca Landolfo, and Letizia Capasso

Design A Prospective, case-control pilot study

Subject VLBW+IUGR infant

Dependend variable

Feeding Intolerance

Independend variable

Amino acid based formula

Conclusion VLBW IUGR newborns with severe feeding intolerance, a short course on AAF was a safe and effective means of nutritional rescue

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PICO

PROBLEMVery low birth weight & Intrauterine growth restriction infant with feeding intolerance

INTERVENTION

Amino-acid based formula

CONTROLSubject without feeding intolerance

OUTCOMETime to reach full enteral feeding

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VALIDATION

Question Answ

Evidence

Was the assignment of patients to treatments randomized? Was the randomization list concealed?

No Both case and control group were chosen by the author

Was follow-up of patients sufficiently long and complete?

Yes The study was done until the full enteral feeding are achieved

Were all patients analyzed in the groups to which they were randomized?

Yes All subjects were analyzed

Were patients and clinicians kept "blind" to treatment?

Yes The neonatologist were blinded from the study purpose

Were the groups treated equally, apart from the experimental treatment?

Yes All group were treated equally

Were the groups similar at the start of the trial?

Yes Except for the SNAP II Score, both group were similar

http://ktclearinghouse.ca/cebm/teaching/worksheets/therapy

Are the results of this single preventive or therapeutic trial valid?

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VALIDATION

Question Answ

Evidence

Was the assignment of patients to treatments randomized? Was the randomization list concealed?

No Both case and control group were chosen by the author

Was follow-up of patients sufficiently long and complete?

Yes The study was done until the full enteral feeding are achieved

Were all patients analyzed in the groups to which they were randomized?

Yes All subjects were analyzed

Were patients and clinicians kept "blind" to treatment?

Yes The neonatologist were blinded from the study purpose

Were the groups treated equally, apart from the experimental treatment?

Yes All group were treated equally

Were the groups similar at the start of the trial?

Yes Except for the SNAP II Score, both group were similar


Are the results of this single preventive or therapeutic trial valid?

VALID

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IMPORTANCY

• Ratio scale can’t measured the NNT

Are the valid results of this randomized trial important?

TABEL. PRIMARY OUTCOMECase Control

No. Patients 22 42

Day on parenteral nutrition (CVC + PVC) 22.5 ± 13.6*

10.8 ± 6.8*


12.3 ± 8.3


8.02 ± 5.2*

Day on central venous catheter with AAF 8 ± 7.6


14 ± 6.8*


*p<0.05 at t test


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IMPORTANCY

• Ratio scale can’t measured the NNT

Are the valid results of this randomized trial important?

TABEL. PRIMARY OUTCOMECase Control

No. Patients 22 42

Day on parenteral nutrition (CVC + PVC) 22.5 ± 13.6*

10.8 ± 6.8*


12.3 ± 8.3


8.02 ± 5.2*

Day on central venous catheter with AAF 8 ± 7.6


14 ± 6.8*


*p<0.05 at t test

IMPORTANT


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APLICABLE

Do these results apply to your patient?

Is your patient so different from those in the study that its results cannot apply?

No

Is the treatment feasible in your setting? Yes

What are your patient's potential benefits and harms from the therapy?

Unmeasurable

Are your patient's values and preferences satisfied by the regimen and its consequences?

Do your patient and you have a clear assessment of their values and preferences?

Yes

Are they met by this regimen and its consequences? Yes

Can you apply this valid, important evidence about therapy in caring for your patient?


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APPLICABILITY

Do these results apply to your patient?

Is your patient so different from those in the study that its results cannot apply?

No

Is the treatment feasible in your setting? Yes

What are your patient's potential benefits and harms from the therapy?

Unmeasurable

Are your patient's values and preferences satisfied by the regimen and its consequences?

Do your patient and you have a clear assessment of their values and preferences?

Yes

Are they met by this regimen and its consequences? Yes

Can you apply this valid, important evidence about therapy in caring for your patient?

APPLICABLE

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CONCLUSION

VALID

IMPORTANT

APPLICABLE

Level of Evidence : 3B

Grade of Recommendation : B

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THANK YOU

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Feeding Intolerance TreatmentNo

Author

Years Title Conclusion

1 Enriquez, et al

1996 Randomised controlled trial of cisapride in feed intolerance in preterm infants

Cisapride in preterm infants is not recommended

2 Gounaris, et al

2010 Gastric emptying of preterm neonates receiving domperidone.

Domperidone significantly reduces gastric emptying in preterm neonates, and this may account for its effect in cases of disturbances related to gut motility

3 Ng, et al

2007 High-dose oral erythromycin decreased the incidence of parenteral nutrition-associated cholestasis in preterm infants

High-dose oral erythromycin can be considered as a rescue measure for VLBW infants who fail to establish adequate enteral nutrition

http://www.ncbi.nlm.nih.gov/pubmed?term=Gounaris%20A%5BAuthor%5D&cauthor=true&cauthor_uid=19648772

http://www.ncbi.nlm.nih.gov/pubmed?term=Gounaris%20A%5BAuthor%5D&cauthor=true&cauthor_uid=19648772

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STANDARD PRETERM FORMULA SECTION CONTAIN Min Max Note

WATER AND POTENTIAL RENALSOLUTE LOAD

POTENTIAL RENALSOLUTE LOAD

22 mOsm/100 kcal

32 mOsm/100 kcal for a formula containing 81 kcal/100 mL

ENERGY AND THE PROTEIN-ENERGYRELATIONSHIP

The Expert Panel estimated that energy intakes for preterm-LBW infants would be in the range of 110–135 kcal/(kg d). Unless otherwise noted, an energy intake of 120 kcal/(kg d) was assumed when making a recommendation for minimum and maximum levels of nutrients in this report.ENERGY DENSITY

67 kcal/100 mL. 94 kcal/100 mL. Assumption that the caloric densityof the administered formula would be 81 kcal/100 mL, at anaverage intake of 110–135 kcal/(kg _ d).

P:E ratio 2.5–3.6 g/100 kcal PROTEINS, AMINO ACIDS, AND OTHERNITROGENOUS SUBSTANCES

Protein concentration

2.5 g/100 kcal,

3.6 g/100 kcal,

HISTIDINE 53 mg/100 kcal 76 mg/100 kcal ISOLEUCINE 129 mg/100

kcal186 mg/100 kcal

LEUCINE 252 mg/100 kcal

362 mg/100 kcal

LYSINE 182 mg/100 kcal

263 mg/100 kcal

METHIONINE+CYSTEINE

85 mg/100 kcal 123 mg/100 kcal

PHENYLALANINE+TYROSINE

196 mg/100 kcal

282 mg/100 kcal

THREONINE 113 mg/100 kcal

163 mg/100 kcal

TRYPTOPHAN 38 mg/100 kcal 55 mg/100 kcal VALINE 132 mg/100

kcal191 mg/100 kcal

ARGININE 72 mg/100 kcal 104 mg/100 kcal

Catherine J. Klein (2002), Nutrient Requirements For Preterm Infant Formulas

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CARBOHYDRATES TOTAL CARBOHYDRATE

9.6 g/100 kcal. 12.5 g/100 kcal.

LACTOSE 4 g of Lactose / 100 kcal or 40% of the carbohydrate intake

12.5 g/100 kcal.

GALACTOSE The Expert Panel found no evidence to justify a recommendation for galactose in preterm infant formula.

OLIGOSACCHARIDES

The Expert Panel found no evidence to justify a recommendation for oligosaccharides in preterm infant formula

NONLACTOSE DIETARY CARBOHYDRATES: GLUCOSE POLYMERS AND MALTOSE

The Expert Panel found no evidence to justify a specific recommendation for glucose polymers or maltose persen in preterm infant formula. However, the use of these carbohydrates (or potentially other more readily digestible carbohydrates) as a partial alternative to lactose may have beneficial effects.

MYO-INOSITOL 4mg/100 kcal 44mg/100 kcal.


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FAT TOTAL FAT 4.4 g/100 kcal 5.7 g/100 kcal. ESSENTIAL FATTY ACIDSLinoleic acid 8% of total fatty acids. 25% of total fatty acids. α-Linolenic acid 1.75 % of total fatty acids. 4% of total fatty acids. Ratio LA:ALA 6-16γ-Linolenic acid The Expert Panel concluded that there is no demonstrated benefit of adding GLA to preterm

infant formulas.Arachidonic, docosahexaenoic and eicosapentaenoic longchainpolyunsaturated fatty acids

No Minimum AA : 0.6% of total fatty acidsDHA : 0.35% of total fatty acidsEPA : 30% of the concentration of DHA.

The Expert Panel also recommended that the final ratio of AA to DHA in any supplemented preterm formulabe 1.5-2.0.

OTHER FATTY ACIDS AND RELATED SUBSTANCESMyristic acid and lauric acid No minimum

Myristic acid : 12% of total fatty acids. Lauric acid : 12% of total fatty acids.

Medium-chain triglycerides preterm infant formulas. 50% of total fat content.2.2–3.0 g/100 kcal, depending on the total fat concentration.

Trans-fatty acids The Expert Panel recommended that the content of trans-fatty acids in preterm infant formula be limited to the minimum amount feasible

CHOLESTEROL The Expert Panel did not recommend addition of cholesterol to formulas intended for preterm infants.


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MINERALS: CALCIUM AND PHOSPHORUS

CALCIUM 123 mg/100 kcal.

185 mg/100 kcal.

Calcium-to-phosphorus ratio

1.7:1. 2.0:1.

PHOSPHORUS 82 mg/100 kcal. 109 mg/100 kcal. Recommendations are for bioavailable (nonphytate) phosphorus.

MINERALS: SODIUM, CHLORIDE,AND POTASSIUM

SODIUM 39 mg/100 kcal. 63 mg/100 kcal. CHLORIDE 60 mg/100 kcal. 160 mg/100 kcal. POTASSIUM 60 mg/100 kcal. 160 mg/100 kcal.

MINERALS: TRACE ELEMENTS

IRON 1.7 mg/100 kcal.

3.0 mg/100 kcal.

ZINC 1.1 mg/100 kcal.

1.5 mg/100 kcal.

COPPER 100 µg/100 kcal 250 µg/100 kcal MAGNESIUM 6.8 mg/100

kcal.17 mg/100 kcal.


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VITAMINS: FAT-SOLUBLE VITAMINS

VITAMIN A 204 µg RE (700 IU)/100 kcal

380 µg RE (1254 IU)/100 kcal.

VITAMIN D 75 IU/100 kcal. 270 IU/100 kcal. VITAMIN E 2 mg α-TE/100 kcal 8 mg α-TE/100 kcal. The vitamin E-to-PUFA ratio (mg

of a-tocopherol/g of total PUFA) should exceed 1.5 mg/g.

VITAMIN K 4 µg/100 kcal. 25 µg/100 kcal. VITAMINS: WATER-SOLUBLE VITAMINS

VITAMIN C 8.3 mg/100 kcal. 37 mg/100 kcal. FOLIC ACID 30 µg/100 kcal 45 µg/100 kcal. VITAMIN B6 30 µg/100 kcal. 250 µg/100 kcal. RIBOFLAVIN 80 µg/100 kcal. 620 µg/100 kcal. THIAMIN, NIACIN, VITAMIN B12, PANTOTHENICACID, AND BIOTINVITAMIN B1, THIAMIN

30 µg/100 kcal 350 µg/100 kcal

VITAMIN B3, NIACIN 550 µg/100 kcal 5000 µg/100 kcal VITAMIN B12, COBALAMIN

0.008 µg/100 kcal 0.70 µg/100 kcal

PANTOTHENIC ACID 300 µg/100 kcal 1900 µg/100 kcal BIOTIN 1 µg/100 kcal 37 µg/100 kcal


Health & Medicine

Juring gizi : AminoAcid Formula in Preterm