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EARLY AGGRESSIVE TOTAL PARENTERAL NUTRITION TO PREMATURE

INFANTS IN NEONATAL INTENSIVE CARE UNIT

Article in Journal of Pediatric Sciences · July 2015

DOI: 10.17334/jps.14027

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 Journal of Pediatric Sciences

Early aggressive total parenteral nutrition to premature

infants in neonatal intensive care unit (NICU)

Kae Shih Law, Lee Gaik Chan

Journal of Pediatric Sciences 2015;7:e242

How to cite this article:

Law KS, Chan LG. Early aggressive total parenteral nutrition to premature infants in
neonatal intensive care unit (NICU). Journal of Pediatric Sciences. 2015;7:e242.
 2

ORIGINAL ARTICLE

Early aggressive total parenteral nutrition to premature

infants in neonatal intensive care unit (NICU)
Kae Shih Law*, Lee Gaik Chan**
Department of Pharmacy*, Department of Paediatrics**, Sarawak General Hospital, Malaysia.

Abstract:
Introduction: Iatrogenic intrauterine growth restriction in NICU has been a prevailing problem in these days when smaller
babies are being salvaged. Early aggressive TPN is defined when total of 4g/kg/day of amino acid is administrated via
standardized TPN to neonates over first week of life. Our main objective of the study is to evaluate the efficacy, safety and
tolerability of early aggressive standardized TPN to infants. We also explore the impact of early and high dose of amino acid
with hypophosphatemia in extreme low birth weight (ELBW) infants, growth velocity in infants with TPN therapy and TPN
cost when the hang time is extended from 24 hours to 48 hours.
Methods: This is a prospective study on premature infants in NICU, Sarawak General Hospital for 6 months. Demographics
and anthropometric data of eligible infants were collected. Biochemical test, growth velocity and cost of TPN therapy were
analysed.
Results: There are 69 eligible infants recruited. Serum electrolytes of all infants were found to be within normal range
throughout TPN therapy except serum phosphate concentration. We found that incidence of hypophosphatemia is high with
high amino acid supply in ELBW infants. There is a negative correlation (-0.26) between serum urea concentration and birth
weight. Targeted growth velocity is achieved with standardized TPN and ELBW premature infants were found to have highest
weight growth velocity. By extending TPN hang time to 48 hours, TPN related cost is associated with minimizing and resulted
in yearly savings of RM 62556.60, exclusive of labour cost and nursing cost.
Conclusion: Early aggressive PN therapy is safe and it achieved goal of postnatal growth velocity and body composition in
premature infants. This study also demonstrated that the current practice of extending hang time is financially beneficial to
hospital.

Keywords: Preterm infants, low birth weight infants, aggressive PN therapy, electrolytes, serum phosphate concentration,
urea, growth velocity, hang time, TPN related cost
Accepted: 29.12.2014

Corresponding author: Kae Shih Law, Sarawak General hospital, Jalan Universiti, 93586, Kuching, Sarawak, Malaysia,
[email protected].

Introduction (PN) is defined when total of 4g/kg/day of amino

acid is administrated via standardized PN to neonates
First week of life is a molding period in neonates,
over first week of life. Aggressive nutrition and
especially premature babies. Iatrogenic intrauterine
optimal energy intake has a positive impact on
growth restriction (IUGR) in neonatal intensive care
growth [1, 2], pulmonary morbidity, reduces risk of
unit (NICU) has been a prevailing problem in these
necrotizing enterocolitis and decreases hospital stay
days when smaller and smaller babies are being
[3]. PN should therefore be started as soon as possible
salvaged. Early aggressive total parenteral nutrition
to achieve glucose level and enhance positive protein

Journal of Pediatric Sciences 2015; 7; e242

 3

accretion. Increased protein intake at first week of followed by 1.8 g/kg/day thereafter. However, if
life is also associated with improved preterm infants were only given glucose, they will
neurodevelopmental outcome.[4] However, lose more than 1% of total protein stores each day. In
nutritional regimens to achieve these goal have not a premature infant, optimal growth is achieved by a
been fully understood, thus the varying parental protein intake of 3.5 g/kg/day (0.56 g/kg/day of
nutrition formularies. Intrauterine protein accretion nitrogen). Studies have shown that protein intake as
rate occur at 2 g/kg/day until 32 weeks of life and high as 4 g/kg/day are safe.[3]

Table 1: Compositions of standardized PN formulations

Standard High sodium 7.5% Dextrose
Components Starter PN Term PN
Preterm PN Preterm PN Preterm PN
Conc/Litre
Amino acid, g 33 30 30 30 23
Glucose, g 100 100 100 75 120
Na, mmol 20 33 60 33 25
K, mmol 0 22 22 22 20
Cl, mmol 0 22 22 22 20
Ca, mmol 6 6 6 6 6
Mg, mmol 2.5 2.5 2.5 2.5 2.5
P, mmol 7.4 7.4 7.4 7.4 7.4
Acetate, mmol 5.2 18.2 45.2 18.2 10.2
Osmolarity,
849.08 895.98 949.98 758.87 933.19
mosm/L
At 60mL/kg/day At 135ml/kg/day
Amino acids, g 2 4 4 4 3
Glucose, g 6 13.5 13.5 10 16.2
Na, mmol 1.2 4.5 8.1 4.5 3.4
K, mmol 0 3 3 3 2.7
Cl, mmol 0 3 3 3 2.7
Ca, mmol 0.36 0.8 0.8 0.8 0.8
Mg, mmol 0.15 0.3 0.3 0.3 0.3
P, mmol 0.44 1.5 1.5 1.5 1.5
Acetate, mmol 0.3 2.5 6.1 2.5 1.4
*Na: Sodium, K Potassium, Cl: Chloride, Ca: Calcium, Mg: Magnesium, P: Phosphorus

Generally, PN is gradually advanced within 1 to 2 regimen provides amino acids of 2 g/kg/day at 60

weeks of life due to fear of intolerance attributed by ml/kg/day at 24 hours of life. It contains minimum
immature metabolic pathways and ill state of amount of sodium and no potassium.
premature newborns. There were concerns of uremia
Standard preterm PN regimen provides 13.5 g/kg/day
and metabolic acidosis if amino acid load were
of glucose and 4 g/kg/day of amino acid when it runs
increased too aggressive in these infants.
at maximum of 135 mL/kg/day. Electrolytes and
The objective of our study is to promote growth essential trace elements are formulated as per
without causing metabolic derangement in extremely recommendation of European Society of Paediatric
preterm and extremely low birth weight infants via Gastroenterology, Hepatology and Nutrition
PN. There are 5 different PN regimens to fulfill (ESPHAN) and American Academy of Paediatrics
nutritional requirement of infants. Started PN (AAP). [5, 6]

Journal of Pediatric Sciences 2015; 7; e242

 4

Term PN regimen is designed for term infants with PN regimens are designed at 135 ml/kg/day and lipid
amino acid of 3 g/kg/day. 7.5% of dextrose PN emulsion at 3 g/kg/day (15 ml/kg/day) meets the
regimen and high sodium PN regimen are designed to parenteral nutrient and energy requirement, both
cater for hyperglycemia and hyponatremia in infants protein and non protein energy, of the infant.
respectively.
Table 2: Parenteral and enteral feeding regimen in our unit’s policy
Mean
Protein Mean Protein
Parenteral
Lipid intake intake from Lipid intake enteral intake from
intake
(mL/kg/day) PN (g/kg/day) intake enteral
(mL/kg/day)
(g/kg/day) (mL/day) feeding
(g/kg/day)
Day 1 60 5 2 1 - -
Day 2 90 10 2.7 2 - -
Day 3 120 15 3.6 3 - -
Day 4 135 15 4 3 - -
Day 7 105 15 3.1 3 30 0.4
Day 10 63 15 1.9 3 72 0.8
* When lipid is given at 3 g/kg/day, the volume of 15 mL/kg/day will be included in total fluid intake per day.

Fluid intake of 60 ml/kg/day was started on day 1 of METHODS

life and increase by 30 ml/kg/day every 24 hours to a
Study design
maximum fluid intake of 150 ml/kg/day. The volume
contributed by SMOF Lipid emulsion 20% is We performed a prospective study in NICU, in
included when it reaches 3 g/kg/day. Amino acid Sarawak General Hospital (SGH), from April 2013 to
content in expressed breast milk (EBM) is 1.1 September 2013. Consent was taken from parents for
g/100mL. Enteral feeding was initiated at day 1 of insertion of umbilical venous catheter (UVC) for
life but due to inconsistent EBM supply and minimal administration of PN.
volume from enteral feeding, it was not included in Subjects
total fluid requirement per day until averagely day 7
All newborns who admitted to NICU, SGH, with a
of life. SMOF Lipid emulsion 20% was initiated at 1
gestation age of ≤ 32 weeks and/ or ≤ 1500g, or
g/kg/day at day 1 of life and titrate it according to
preterm infants with gestation age of > 32 weeks or >
serum triglycerides level.
1500g, or term infants, who is anticipated that enteral
OBJECTIVES feeding of at least 120 ml/kg/day is unable to be
1) To evaluate the efficacy, safety and established by day 5 and day 7 of life respectively,
tolerability of early aggressive of with PN, are eligible for participation in the study.
standardized TPN to neonates in NICU Exclusion criteria were the duration of PN therapy is
2) To relate the impact of early and high dose of less than 5 days.
amino acid in PN with hypophosphatemia in All newborns received PN when keep nothing by
extreme low birth weight infants mouth. Enteral nutrition, expressed breast milk
3) To study the velocity of growth in neonates (EBM), was slowly introduced to stable newborns
after PN therapy according to unit’s feeding protocol guideline,
4) Cost evaluation of PN therapy concurrent with PN therapy. PN are taken off once
they achieved near full feeding of at least 120
ml/kg/day of enteral feeding.

Journal of Pediatric Sciences 2015; 7; e242

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Protocol taken twice per week. Daily weighing was done but
only weekly weights were collected.
Eligible infants were commenced with PN within 24
hours of life, unless specified. UVC is inserted after In the event of any signs of line sepsis, UVC will be
consent by parents. Once UVC is inserted, PN will be removed and PN halted. Blood cultures were then
connected straight by the medical personnel who had taken both from UVC or PICC and peripherally to
inserted the UVC, to ensure the sterility. Peripheral confirm site of sepsis.
indwelling central catheter (PICC) will be inserted if
The Statistical Package for Social Sciences (SPSS,
UVC dislodged or not suitable for use. During the
Version 16) software was used for statistical analysis.
first 24 hours of life, all infants were commenced
Correlation between two categorical variables was
with starter PN regimen which does not contain any
assessed by correlation coefficient.
potassium in the bag. After 24 hours of life, either
standard term regimen or standard preterm regimen RESULT
was given according to their gestation age. All PN This is a prospective study which involving of 69
regimens had been formulated according to the eligible infants. Demographic characteristic are
recommendations of AAP and ESPGHAN and were displayed in Table 3.
prepared by qualified pharmacy team in aseptic
compound. In our sample population, 97% were premature and
among the premature infants, 38% were extremely
Each PN bag lasts for 48 hours and glucose low birth weight infants, 46% were very low birth
concentration of the standard PN can be varies, either weight infants and 13% were low birth weight infants.
7.5% or 10%. However, generally 10% glucose PN 5.8% of infants who started PN after 24 hours were
was given, unless specified. not able to tolerate feeding as targeted.
All recruited infants are subjected to blood taking on Starter PN bag is introduced to newborn infants at
the first 3 days after initiation of PN then every day 1 of PN therapy. Starter PN, with total fluid
alternate day, which corresponds to PN ordering day. volume of 60 mL/kg/day is administrated to infants,
Blood investigations that were monitored include full which composes of 2 g/kg/day of amino acid;
blood count, renal profile, liver profile, biochemical electrolytes are initiated at the minimum requirement
test, blood gas and sugar profile. Occipitofrontal head of a newborn baby and potassium only initiated to
circumference (OFC) and body length of infants were infants at day 2 of life onwards, in view of their not
well established renal function.
Table 3: Demographics characteristic of recruited infants
Mean ±
Mean ± SD
Mean ± SD Mean ± SD Mean ± SD SD
N birth
gestation OFC at length at duration
(F:M) weight
age (weeks) birth (cm) birth (cm) of TPN
(grams)
days
26
ELBW (< 1000g) 26 ± 2 791 ± 130 22.6 ± 2.1 31.7 ± 3.5 13 ± 2
(15:11)
32
VLBW (1000g –1500g) 30 ± 2 1253 ± 150 26.5 ± 2.18 36.6 ± 2.75 10 ± 3
(15:17)
9
LBW (>1500g - ≤ 2500g) 33 ± 3 1822 ± 304 28.7 ± 1.1 42 ± 2.1 9±1
(5:4)
2
Term (≥ 2500g) 39 ±1 3118 ± 187 32 ± 0 49.8 ± 1.1 12 ± 3
(0:2)
69
TOTAL 29 ± 3 1210 ± 500 25.5 ± 3.2 35.9 ± 5.1 11 ± 3
(35:34)
*SD: Standard deviation

Journal of Pediatric Sciences 2015; 7; e242

 6

Mild hypokalemia was noticed at day 2 of therapy; concentrations and serum triglyceride concentrations
however, it resolved when standard preterm PN bag were in increasing trend on the first 3 and 5 day of
was initiated. Hypophosphatemia was noticed as well PN therapy but stabilized after that. Serum bilirubin
even though it is adequately supplemented with the and serum alkaline phosphatase are the indicators for
dose recommended by AAP and ESPGHAN.[5, 6] cholestasis and PN is the common cause of that.
Other serum electrolytes were maintained within Figure displayed in Table 5 showed increasing trend
normal range throughout the PN therapy. of both indicators throughout PN days but were still
In our sample population, all the indicators for safety maintained in normal range of pediatrics group.
measure were fall within normal range. Serum BUN

Table 4: Serum electrolytes concentration to reflect the efficacy of TPN therapy (Outcome: Efficacy measure)
Normal
Electrolytes
range Day 1 Day 2 Day 3 Day 5 Day 7 Day 10
(mmol/L)
(mmol/L)
Sodium 132-147 137 ± 4.9 140 ± 4.4 142 ± 4.7 139 ± 4.0 138 ± 4.5 135 ± 4.5
Potassium 3.6-6 3.9 ± 0.7 3.5 ± 0.6 3.6 ± 0.6 4.1 ± 0.7 4.4 ± 0.8 4.4 ± 0.7
Calcium 2.1-2.7 2.1 ± 0.2 1.9 ± 0.3 2.1 ± 0.3 2.3 ± 0.4 2.3 ± 0.2 2.3 ± 0.2
Phosphate 1-2.58 2.1 ± 0.5 1.8 ± 0.5 1.5 ± 0.4 1.3 ± 0.4 1.3 ± 0.5 1.4 ± 0.4
Magnesium 0.8-0.95 0.9 ± 0.2 1.0 ± 0.4 1.1 ± 0.3 1.1 ± 0.4 1.1 ± 0.3 1.0 ± 0.1

Table 5:Indicators to reflect the tolerability to PN therapy (Outcome: Safety measure)

Indicators
Day 1 Day 2 Day 3 Day 5 Day 7 Day 10
(mmol/L)
Triglyceride 0.53 ± 0.43 1.04 ± 0.63 1.34 ± 0.69 1.53 ± 0.68 1.50 ± 0.56 1.43 ± 0.60
Urea 4.0 ± 2.4 6.8 ± 2.7 7.5 ± 3.0 6.8 ± 2.9 6.5 ± 3.1 5.5 ± 2.9
Serum bilirubin 59.8 ± 34.3 91.8 ± 28.1 102 ± 365 122.2 ± 48.3 130 ± 50.6 127.3 ± 30.5
Alkaline
188 ± 73.9 179.2 ± 68.1 183.1 ± 63.4 213.3 ± 62.1 266.6 ± 133.4 379.1 ± 193.2
Phosphatase

Correlation coefficient of -0.26 showed a negative acid utilization for both energy and lean mass
correlation between serum urea concentration and production.[10]
birth weight (grams) with different gestation age Another unusual phenomenon is arising when various
groups, which displayed in Figure 1. In our sample clinical trials are supporting aggressive amino acid to
population, same amount of amino acid were premature infants. During our study period, we
supplied to all preterm infants. Extremely premature noticed that with higher amount of amino acid
infants with extremely low birth weight had highest supply, the lower is the serum phosphate level, in all
mean urea concentration if compared to moderate to infants recruited. Correlation coefficient of -0.92
late preterm infants. As reported, extremely low birth showed a perfect negative correlation between
weight infants have highest growth rate.[7] amounts of amino acid administrated and serum
Therefore, rising BUN values are not just a reflection phosphate concentration.
of extremely low birth weight infant’s intolerance to
amino acid infusion but it reflects appropriate amino

Journal of Pediatric Sciences 2015; 7; e242

 7

Figure 1: Correlation between serum urea concentration and birth weight (grams) with different
gestation age groups
Correlation between serum urea concentration and birth weight
(grams) with different gestation age groups
12,0
Serum urea concentration (mmol/L)

10,0

8,0

Correlation coefficient -0.26

6,0

4,0

2,0 Extremely Very Moderate to late

premature preterm preterm
Term

0,0
0,00 0,50 1,00 1,50 2,00 2,50 3,00 3,50
Birth weight (grams)

Figure 2: Serum phosphate concentrations change in all infants stratified by amount amino acid intake
Trend of serum phosphate concentration (mmol/L) in all
infants against dose of amino acid administrated
2,5 4,5
Serum phosphate level (mmol/L)

4,0
Amino acid dose (g/kg/day)

2,0 3,5
3,0
1,5
2,5
2,0
1,0
1,5

0,5 1,0
Correlation coefficient: -0.92 0,5
0,0 0,0
D1 D2 D3 D5 D7 D10
Days

Phosphate Protein (g/kg/day)

Journal of Pediatric Sciences 2015; 7; e242

 8

In Figure 3, where all infants recruited are moderate to late preterm with low birth weight.In our
categorized under extremely preterm, with extremely PN regime, sodium acetate is added. Acetate content
low birth weight, very preterm with very low birth has been partially replacing the chloride in the PN
weight and moderate to late preterm with low birth bags to reduce hyperchloremic metabolic acidosis
weight, hypophosphatemia is found more prominent and improving serum bicarbonate. Metabolic acidosis
in extremely preterm infants with extremely low birth is improved when acetate intake increases alongside
weight during highest amino acid supply than with increasing total fluid intake.
Figure 3: Serum phosphate concentration change in different groups of infants stratified by amount
amino acid intake
Trend of serum phosphate concentration (mmol/L) in different groups
of infants agaisnt dose of amino acid administrated
3,0 Extremely preterm,
Extremely low birth
Serum phosphate concentration (mmol/L)

weight
2,5
Moderate to late
preterm, low birth
2,0
weight
Very preterm, very
1,5 low birth weight

1,0

0,5

0,0
2g/kg/day 2.7g/kg/day 3.6g/kg/day 4g/kg/day 3.5g/kg/day 2.7g/kg/day
Dose of amino acid administrated

Extremely preterm, Extremely low birth weight

Very preterm, very low birth weight
Moderate to late preterm, low birth weight

There are 12.9% of premature neonates did not regain Growth velocity = [1000 x ln (Wn/W1)] / (Dn - D1),
birth weight after 7 days of PN therapy. As displayed where W1 is initial weight and Wn is weight at second
in Table 8, ELBW premature neonates had highest time point, D is day of life. [8] As shown in Table 9,
weight growth velocity if compared to LBW standard PN per unit bag is slightly more expensive
premature neonates and term infants. However, they than previous custom PN; however the standard PN
did not have high OFC growth velocity. To calculate is given over 48 hours instead of previous 24 hours
weight gain velocity, exponential model (EM) is making a cost savings of almost half. With current
used. EM can accurately estimates postnatal growth practice, SMOF lipid emulsion 20% is added with
velocity in infants. The equation to calculate EM is soluble vitamins.

Journal of Pediatric Sciences 2015; 7; e242

 9

Table 6: Anthropometric characteristics before PN therapy (Outcome: Growth velocity)

Before PN
Mean ± SD Mean ± SD birth Mean ± SD OFC Mean ± SD body
duration (days) weight (grams) (cm) length (cm)
ELBW (< 1000g) 13 ± 2` 791 ± 130 22.6 ± 2.1 31.7 ± 3.5
VLBW (1000g – 1500g) 10 ± 3 1262 ± 165 25.1 ± 1.8 36.6 ± 2.75
LBW (>1500g - ≤ 2500g) 9±1 1822 ± 304 28.7 ± 1.1 42 ± 2.1
Term (≥ 2500g) 12 ± 3 3118 ± 187 32 ± 0 49.8 ± 1.1
TOTAL 11 ± 3 1210 ± 500 25.5 ± 3.2 35.9 ± 5.1
*SD: Standard deviation
Table 7: Anthropometric characteristics after PN therapy
After PN
Mean ± SD body weight Mean ± SD body length
Mean ± SD OFC (cm)
(grams) (cm)
ELBW (< 1000g) 1012 ± 142 24.2 ± 1.7 34.4 ± 2.4
VLBW (1000g – 1500g) 1440 ± 219 26.9 ± 1.6 38.4 ± 3.4
LBW (>1500g - ≤ 2500g) 2069 ± 454 29.6 ± 1.7 43.9 ± 2.2
Term (≥ 2500g) 3535 ± 21 33.8 ± 0.4 51 ± 1.4
TOTAL 1388 ± 552 26.2 ± 2.8 37.8 ± 4.7
*SD: Standard deviation
Table 8: Measured velocity of growth after PN therapy
Velocity of growth
Weight gained OFC gained Length gained
(g/kg/day) (cm/week) (cm/week)
ELBW (<1000g) 19 0.86 1.45
VLBW (1000g – 1500g) 13 1.26 1.26
LBW (>1500g - ≤ 2500g) 14 0.70 1.48
Term (≥ 2500g) 11 1.05 0.7
TOTAL 14.3 1 1.2
*ELBW: Extremely low birth weight, VLBW: Very low birth weight, LBW: Low birth weight,

Table 9: Cost of PN bag per unit (inclusive of infusion tubing, filter, lipid tubing and syringes) (Evaluation: Cost analysis)
200ml 350ml 500ml 900ml
Custom PN RM 75.28 RM 97.59 RM 120.50 Not available
Standard PN starter RM 83.64 Only 200mL available
Standard PN preterm RM 82.05 RM 109.41 RM 136.73 Not available
Standard PN term RM 75.41 RM 97.95 RM 120.49 RM 179.88
Standard PN high sodium RM 83.11 RM 111.24 RM 139.38 RM 210.10
Standard PN 7.5% dextrose RM 81.86 RM 109.08 RM 136.26 RM 207.80
Table 10: Cost of lipid emulsion
15mL 30mL 45mL 60mL
Not
SMOF® Lipid Previous practice RM 10.00 RM 19.40 RM 26.40
available
emulsion 20%
Current practice RM 13.20 RM 30.50 RM 41.20 RM 43.60
Table 11: Annual cost saving
Annual expenses
Previous practice RM 309517.20
Current practice RM 246960.60
Annual cost saving RM 62556.60

Journal of Pediatric Sciences 2015; 7; e242

 10

Figure 4: Correlation between serum chloride concentrations (mmol/L) against metabolic acidosis

Correlation between serum chloride concentration (mmol/L) against

metabolic acidosis
30 112

25 110

Serum chloride concentration (mmol/L)

20 108

15 106
HCO3

10 104

5 102

0 100
D1 D2 D3 D5 D7 D10
-5 98

-10 96
Days

HCO3 BE Chloride

DISCUSSION growth in premature infants. In addition, studies have

shown that blood urea concentration up to 14 mmol/L
Recent data has been supporting the importance of
in premature infants who receiving PN is
early aggressive amino acid administration via PN to
acceptable.[2] Serum BUN is high when there is high
newborns. The major concerns about early and
amino acid oxidation. A study by Ridout et.al (2005)
aggressive delivery of amino acid especially to
showed that there was no correlation between high
ELBW infants are the development of azotemia,
amino acid intake and urea in preterm infants,
hyperammonemia and metabolic acidosis.
especially extremely low birth weight infants, but due
Various studies also showed that there was no to their high rate of protein breakdown.[9] Studies of
correlation between serum blood urea nitrogen fetal amino acid oxidation also suggest that higher
(BUN) and amino acid intake. Restricting amino acid BUN reflects appropriate amino acid utilization for
load solely based on serum BUN is not warrant both energy and lean mass production.[9, 10, 11]
because BUN also represents the complex interaction
Hypertriglyceridemia is defined as triglyceride level
of hydration, renal function, energy quality and
above 2.8 mmol/L. With balanced lipid emulsion
quantity and degree of illness. Rising BUN values
commenced at dose 1 g/kg/day at day 1 of PN
are, therefore, not just a reflection of the ELBW
therapy and increased in steps of 1 g/kg/day on day 2,
infant’s intolerance to amino acid infusion. In
maximum dose of 3 g/kg/day from day 3 onwards
addition, PN therapy started within 24 hours of life
and infusion rate of 0.125 g/kg/hr is relatively safe.
shown to have better weight gains in all infants.
With this infusion rate, it also helps in enhancing
Restriction of amino acid load not only affects lipoprotein lipase activity and thus plasma
anabolic reactions and also it influences velocity of clearance.[12] Intravenous lipid emulsion is not only

Journal of Pediatric Sciences 2015; 7; e242

 11

helps in improving nitrogen balance, providing non- to late preterm infants with low birth weight, where
protein energy source, improved weight gain but also severe hypophosphatemia is found in extremely
supplying essential fatty acid to premature preterm infants with extremely low birth weight, as
infants.[13] Brans YW et al. also suggested no shown in Figure 2. Phosphorus is a main component
effects on serum bilirubin with dose of 3 g/kg/day of of Adenosine triphosphate (ATP), membrane
lipid emulsion.[14] phospholipids and nucleic acids. Furthermore, rapid
cell growth can be achieved when sufficient amount
The mean weight gain of premature infants in our
of nitrogen, potassium and phosphorus is provided.
study population is 15.3 g/kg/day, at a rate similar to
Thus, with the aggressive amino acid supply to
the intrauterine weight gain of 15 g/kg/day where as
promote extrauterine growth to premature infants
term infants had weight gain of 11 g/kg/day, at a rate
especially to extremely preterm infants whose growth
higher than reported intrauterine growth of 10
rate is the highest among all premature infants,
g/kg/day at term.[15, 16] ELBW infants have highest
results in high metabolism of phosphorus and high
growth rate if compared to VLBW infants and LBW
uptake of phosphorus into cell, thus affects its plasma
infants.[17] In addition, our sample population had
concentration.[21] In addition, Mizumoto defined this
average weekly increment in length of 1.2 cm and
phenomenon as re-feeding syndrome as nutrition is
OFC of 1 cm, which are corresponded to reported
commenced after intense nutritional deprivation in
intrauterine and postnatal growth of 1 cm/week and
intrauterine.[22]
0.5-1 cm/week respectively.[19]
On the other hand, by extending PN hang time to 48
Growth velocity plays a major role in development
hours instead of 24 hours is associated with
outcomes and as an indicator of well being of infants.
minimizing TPN related cost. The change of practice
Slowest rate of weight gain in ELBW infants has
also resulted in yearly savings of RM 62556.60,
highest morbidity.[19] A recent study by Ehrenkranz
exclusive of labor cost and nursing cost. Another
et al. also found that growth velocity influences
concern about extending hang time is increase risk of
growth and neurodevelopemental outcomes.[19] As
line sepsis; however a study by Kiran Kumar Balegar
the rate of weight gain and OFC increased, the better
V et al. had suggested that no increase in central
the neurodevelopment and the least of
line–associated blood stream infection (CLABSI)
neurodevelopmental impairment.[19] Another
with longer hang time.[23]
concern of providing PN therapy to premature
infants, especially to extremely premature newborns CONCLUSION
is the incidence of metabolic acidosis. In our PN
This single center study has proven that PN therapy is
formulation, sodium acetate is added in to partially
relatively safe to infants. With the standardized PN, it
replace the chloride to reduce the severity of acidosis
achieved goal of postnatal growth velocity and body
and hyperchloraemia. Furthermore, a study by te
composition in premature infants. In addition, the
Braake et al. showed that no significant differences in
serum concentration of phosphate needs to be closely
degree of acidosis in infants who received aggressive
monitored and the amount of phosphorus needs to be
amino acid nutrition.[20]
optimized as to reduce the severity of
Another issue is arising when practice of nurturing hypophosphatemia condition. This study also
premature infants with high amino acid load to demonstrated that the current practice of extending
enhance anabolism and promote growth. Similar to hang time is financially beneficial to hospital and
our result, Francesco Bonsante and colleagues (2013) reduced TPN pharmacy and nursing workload.
also found that incidence of hypophosphatemia is
high with high amino acid supply via PN therapy.[21] ACKNOWLEDGMENT
During our study, all premature infants were We acknowledge Dr Wong Ann Cheng, Dr Olive Lee
instituted with same amount of amino acid, however, and Dr Rita Lau who assisted in this study.
the severity of hypophosphatemia is less in moderate

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References ELBW infants (1000g) in three time periods. J

Perinatol; 2009; 29:433–437.
1. Moyses HE, Johnson MJ, Leaf AA, 11. Roggero P, Gianni ML, Morlacchi L. Blood
Cornelius VR. Early parenteral nutrition and growth urea nitrogen concentrations in low-birth-weight
outcomes in preterm infants: a systematic review preterm infants during parenteral and enteral
and meta-analysis. Am J ClinNutr; 2013; 97(4):816- nutrition. J Pediatr Gastroenterol Nutr; 2010; 51:213–
26. 215.
2. Usmani SS, Cavaliere T, Casatelli J, Harper 12. John A. Kerner Jr, Robert L. Poole. The use
RG. Plasma ammonia levels in very low birth weight of IV fat in neonates. Nutr Clin Pract; 2006; 21;
preterm infants. The Journal of pediatrics; 1993; 4374-380.
123:797-800. 13. Lipids. European society of paediatric
3. Christmann V, Visser R, Engelkes M, de gastroenterology, hepatology and nutrition
Grauw A, van Goudoever J, van Heijst A. The (ESPGHAN). Journal of Pediatric Gastroenterology
enigma to achieve normal postnatal growth in and Nutrition; 2005; 41: S19–S27.
preterm infants - using parenteral or enteral nutrition? 14. Brans YW, Ritter DA, Kenny JD, Andrew
ActaPaediatr; 2013; 102(5):471-9. DS, Dutton EB, Carrillo DW. Influence of
4. Guidelines on paediatric parenteral nutrition intravenous fat emulsion on serum bilirubin in very
of the european society of paediatric low birthweight neonates; Arch Dis Child; 1987;
gastroenterology, hepatology and nutrition 62(2):156-60.
(ESPGHAN). J PediatrGastroenterolNutr; 2005; 41 15. Aloka LP, Janet LE, Paula PM, Briana JJ,
(2):81-84. and Robert EK. Calculating postnatal growth velocity
5. Koletzko B, Goulet O, Hunt J, Krohn K, in very low birth weight (VLBW) premature infants.
Shamir R. Guidelines on paediatric parenteral J Perinatol; 2009; 29(9): 618–622.
nutrition of the european society of paediatric 16. Velaphi S. Nutritional requirements and
gastroenterology, hepatology and nutrition parenteral nutrition in preterm infants. S Afr J Clin
(ESPGHAN) and the european society for clinical Nutr; 2011; 24(3): S27-S31
nutrition and metabolism (ESPEN), Supported by the 17. De Onis M, Blossner M. The world health
european society of paediatric research (ESPR). organization global database on child growth and
Journal of pediatric gastroenterology and nutrition; malnutrition: methodology and applications. Int J
2005; 41(2):S1-87. Epidemiol; 2003; 32 (4): 518-26.
6. Kleinman RE. AAP. Pediatric Nutrition 18. Fenton TR. A new growth chart for preterm
Handbook. 2009; 6th Ed. babies: babson and benda's chart. BMC Pediatrics;
7. De Onis M, Blossner M. The world health 2003; 10:3-13.
organization global database on child growth and 19. Richard AE, Anna MD, Betty RV, Linda L
malnutrition: methodology and applications. Int J W, Lisa AW, Kenneth WP. Growth in the neonatal
Epidemiol; 2003; 32 (4): 518-26. intensive care unit influences neurodevelopmental
8. Emily Z, Kristin K, Melanie NAL. Weight and growth outcomes of extremely low birth weight
gain velocity in very low-birth-weight infants: effects infants. Pediatrics; 2006; 117;1253-1261
of exposure to biological maternal sounds. American 20. te Braake FW, van den Akker CH,
journal perinatology; 2012; 0735-1631 Wattimena DJ, Huijmans JG, van Goudoever JB.
9. Ridout E, Melara D, Rottinghaus S, Thureen Amino acid administration to premature infants
PJ. Blood urea nitrogen concentration as a marker of directly after birth. J Pediatr; 2005; 147: 457–461.
amino-acid intolerance in neonates with birthweight 21. Francesco B, Silvia I, Giuseppe L, Jacques
less than 1250g. J Perinatol; 2005; 25:130–133 Rigo, Claudio DF, Pierre YR, Jean BG. Initial amino
10. Radmacher PG, Lewis SL, Adamkin DH. acid intake influences phosphorus and calcium
Early amino acids and the metabolic response of homeostasis in preterm infants – it is time to change

Journal of Pediatric Sciences 2015; 7; e242

 13

the composition of the early parenteral nutrition.

PLOS ONE; 2013;8(8)
22. Mizumoto H, Mikami M, Oda H, Hata D.
Refeeding syndrome in a small-for-dates micro-
preemie receiving early parenteral nutrition. Pediatr
Int. 2012; 54: 715-717.
23. Kiran KBV, Mohammad IA, Kaye S, Nadia
B. Extending total parenteral nutrition hang time in
the neonatal intensive care unit: is it safe and cost
effective? Journal of Paediatrics and Child Health.
2013; 49: E57–E61

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