Juring gizi : AminoAcid Formula in Preterm

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
Supervisor
Endang D.L., dr. Consultant Pediatrician, MPH
1

INTRODUCTION
: Birth Weight : 1000 - 1500 gr
VERY-LOW-BIRTH-WEIGHT INFANTS
(VLBW)
Failure to attain optimal intrauterine growth
INTRAUTERINE GROWTH RESTRICTION
(IUGR)
IUGR
2

INTRODUCTION
VLBW
&
IUGR
GIT Immature Nutritional Need
ENTERAL
NUTRITION
PARENTERAL
NUTRITION
HUMAN MILIK
SPF
(Standard Preterm
Formula)
3

INTRODUCTION
VLBW
&
IUGR
GIT Immature Nutritional Need
ENTERAL
NUTRITION
PARENTERAL
NUTRITION
HUMAN MILIK
SPF
(Standard Preterm
Formula) Good Outcome
Feeding Intolerance
NEC
Rescue with
AAF ??
4

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
5

SUBJECT
Prospective Study
Case control pilot study
Clinical 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 anomalies
severe sepsis, and
transfer to another hospital
7

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
9

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)
10

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
12

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”
13

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
14

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 AAF
Case (15.4 ± 12.3)
Day on parenteral nutrition
Control (10.8 ± 6.8) vs Case (22.5 ± 13.6)
Day on parenteral
nutrition with AAF
Case (12.3 ± 8.3)
15

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
16

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
17

Secondary Outcome
pH Urea Creatini
ne
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*
18

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 prematurity
p > 0.05
19

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
21

SNAP-II SCORE IN VLBW & IUGR
↑ risk for feeding intoleranceVLBW+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
22

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
or
Donor Human Milk
or
Standard Preterm Formula
Daily increment 10-150 ml/kg/day
3th…
Purpose :
• Support the caloric
and nutritional
need
• GIT stimulation
Monitoring
Daily monitoring for
intolerance
23

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??
24

HYDROLYZED PROTREIN FORMULA
HYDROLYZED
PROTREIN
FORMULA
PARTIAL HYDROLYZED
FULL HYDROLIZED
EXTENSIVE HYDROLIZED
ELEMENTAL FORMULA
AMINO-ACID BASED FORMULA
25

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
26

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
27

STUDY CONCLUSION
VLBW IUGR newborns with severe
feeding intolerance, a short course on
AAF was a safe and effective means of
nutritional rescue
28

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
30

PICO
PROBLEM
Very low birth weight & Intrauterine
growth restriction infant with feeding
intolerance
INTERVENTION Amino-acid based formula
CONTROL Subject without feeding intolerance
OUTCOME Time to reach full enteral feeding
31

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?
32

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?
VALID
33

IMPORTANCY
• Ratio scale  can’t measured the NNT
Are the valid results of this randomized trial important?
TABEL. PRIMARY OUTCOME
Case Control
No. Patients 22 42
Day on parenteral nutrition (CVC + PVC) with AAF 12.3 ± 8.3
*p<0.05 at t test
http://ktclearinghouse.ca/cebm/teaching/worksheets/therapy 34

IMPORTANCY
• Ratio scale  can’t measured the NNT
Are the valid results of this randomized trial important?
TABEL. PRIMARY OUTCOME
Case Control
No. Patients 22 42
Day on parenteral nutrition (CVC + PVC) with AAF 12.3 ± 8.3
*p<0.05 at t test
IMPORTANT

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?
Unmeasu
rable
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?

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?
Unmeasu
rable
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
37

CONCLUSION
VALID
IMPORTANT
APPLICABLE
Level of Evidence : 3B
Grade of Recommendation : B
38

Feeding Intolerance Treatment
N
o
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
40

STANDARD PRETERM FORMULA
SECTION CONTAIN Min Max Note
WATER AND
POTENTIAL RENAL
SOLUTE LOAD
POTENTIAL RENAL
SOLUTE LOAD
22 mOsm/100 kcal 32 mOsm/100 kcal for
a formula containing
81 kcal/100 mL
ENERGY AND THE
PROTEIN-ENERGY
RELATIONSHIP
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 density
of the administered formula would be 81 kcal/100
mL, at an
average intake of 110–135 kcal/(kg _ d).
P:E ratio 2.5–3.6 g/100 kcal
PROTEINS, AMINO
ACIDS, AND OTHER
NITROGENOUS
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 kcal 186 mg/100 kcal
LEUCINE 252 mg/100 kcal 362 mg/100 kcal
LYSINE 182 mg/100 kcal 263 mg/100 kcal
METHIONINE+CYS
TEINE
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 kcal 191 mg/100 kcal
ARGININE 72 mg/100 kcal 104 mg/100 kcal
41Catherine J. Klein (2002), Nutrient Requirements For Preterm Infant Formulas

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.
OLIGOSACCHARI
DES
The Expert Panel found no evidence to justify a recommendation for
oligosaccharides in preterm infant formula
NONLACTOSE
DIETARY
CARBOHYDRATE
S: 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.

FAT TOTAL FAT 4.4 g/100 kcal 5.7 g/100 kcal.
ESSENTIAL FATTY ACIDS
Linoleic 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 6-16
γ-Linolenic acid The Expert Panel concluded that there is no demonstrated benefit of adding GLA to preterm
infant formulas.
Arachidonic,
docosahexaenoic and
eicosapentaenoic longchain
polyunsaturated fatty acids
No Minimum AA : 0.6% of total fatty acids
DHA : 0.35% of total fatty
acids
EPA : 30% of the
concentration of DHA.
The Expert Panel also
recommended that the final ratio
of AA to DHA in any
supplemented preterm formula
be 1.5-2.0.
OTHER FATTY ACIDS AND RELATED SUBSTANCES
Myristic 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.

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.

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 BIOTIN
VITAMIN 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
Catherine J. Klein (2002), Nutrient Requirements For Preterm Infant Formulas 45

Juring gizi : AminoAcid Formula in Preterm

Recommended

Recommended

More Related Content

What's hot

What's hot (16)

Viewers also liked

Viewers also liked (18)

Similar to Juring gizi : AminoAcid Formula in Preterm

Similar to Juring gizi : AminoAcid Formula in Preterm (20)

Recently uploaded

Recently uploaded (20)

Juring gizi : AminoAcid Formula in Preterm