DOI: 10.7860/IJNMR/2019/41780.

2250 Original Article

Safety and Outcome of High Dose Parenteral

Paediatrics Section

Amino Acid Supplementation for VLBW

Neonates on Partial Parenteral Nutrition:
A Randomised Controlled Study
RAKESH GAMI, MANISHA BHANDANKAR

ABSTRACT The other group received 3 g/kg/day of parenteral AA on day

Introduction: Total Parenteral Nutrition (TPN) is prescribed 1, which was increased to 4 g/kg/day on the next day. Both
to meet a neonate’s requirement for growth and development the groups were continued on AA till they reached 75% of
when his/her condition and/or gestation prevents complete enteral feeds. Independent sample and chi-square test were
enteral feeding. In India Partial Parenteral Nutrition (PPN) is used used to analyse the data.
in neonatal units with inadequate facilities to prepare TPN. Results: With similar baseline characteristics, serum sodium
Aim: To evaluate the effect of supplementation of high dose (p = 0.001) and blood urea (p = 0.041) levels were higher during
parenteral Amino Acid (AA) on growth and biochemical 1st week of hospital stay. The daily physiological weight
parameters of Very Low Birth Weight (VLBW) neonates loss was more in neonates who received high AA from day
receiving PPN in first week of life. 1 of life. There was no significant difference in weight gain
(p>0.05) between the two groups during the hospital stay.
Materials and Methods: This was a Randomised controlled
The mean hospital stay was 23±4.5 days for Group A and
study, conducted in a tertiary care medical center. Sixty
22.4± 3.6 days for Group B.
VLBW newborns with birth weight of <1500 gm admitted
to level III NICU within 24 hour of life were included and Conclusion: Supplementation of high dose parenteral AA in
Randomised into two groups of AA supplementation: One VLBW infants receiving PPN does not help in weight gain
group received 1  g/kg/day of parenteral AA (Aminoven) on during hospital stay, although well tolerated.
day 1, which was increased by 1g/kg/day till 4  gm/kg/day.

Keywords: Birth weight, Blood urea nitrogen, Sodium, Tertiary healthcare, Weight gain, Weight loss

Introduction to withholding of enteral feeding in first few days of life [2]. In

The VLBW infants (weighing <1.5 kg) are vulnerable to India, use of TPN solutions have improved substantially since
increased  mortality and morbidity during neonatal period, the early days and complications are now less common due
infancy, and childhood due to susceptibility to infections, early to the administration of amino acids (AAs) and lipids in the
growth retardation, and developmental delay [1]. VLBW neonate Neonatal Intensive Care Unit (NICU) [3,4]. However, the use
could be born preterm, small size for gestational age, or of TPN is still influenced by affordability of parents, availability
sometimes both. of trained nursing staff, and willingness of the neonatologist to
prescribe it [3,4].
TPN is a delivery of nutrition through parenteral route for
growth and metabolic requirements. TPN is prescribed to Premature VLBW neonates are devoid of fetal accretion of
meet a neonate’s requirement for growth and development nutrients in last trimester leading to limited glycogen and
when his/her condition and/or gestation prevents complete fat reserve and have slow postnatal weight gain. Postnatal
enteral feeding. Although, early aggressive enteral nutrition growth of VLBW neonates has remained a major challenge
is recommended in VLBW neonates, need for high ventilator in the NICU [5]. There is enough evidence to support that
settings, ionotropic support, immature gastrointestinal system, administration of early and aggressive parenteral nutrition and
surgery, and infection are some of the main factors that lead enteral nutrition is beneficial [6,7]. Administration of high dose
12 Indian Journal of Neonatal Medicine and Research. 2019 Apr, Vol-7(2): PO12-PO17
 www.ijnmr.net  Rakesh Gami and Manisha Bhandankar, Safety and Outcome of Low Dose vs. High Dose AA Supplementation in VLBW Neonates

AAs, from day 1, in VLBW neonates have resulted in better

plasma AA profile and nitrogen accretion and are well tolerated.
However, its role in improving postnatal growth rate and long-
term neurodevelopment is still not clear [8-12]. In India, due to
Where, Za = type 1 error =1.96; Zβ= type 2 error = 0.84; S1=
resource-limited settings, the use of micronutrients and lipids is
5; S2= 4; n1 = 13; n2= 9
restricted in parenteral nutrition [13]. Hence, PPN comprising of
glucose, AAs, and electrolytes without lipids is prescribed to the Considering power of the study as 80%, the sample size per
preterm neonates. The role of clinical pharmacist is limited and group was 26. Total sample size including 10% drop out.
most of the units prepare their parenteral nutrition by training Hence, the sample size of 30 was included per each group.
the nursing staff. Parenteral nutrition can be used only if trained
This NICU followed the protocol of starting AA at 1 g/kg/day
nursing staff are available, who can prepare and administer PN
from day one. During the study, neonates were Randomised
with proper aseptic precautions and if facilities are available for
into two groups. Group A and Group B by on-duty postgraduate
monitoring biochemical parameters regularly.
with odd and even numbers to receive two different doses of
Postnatal growth restriction in preterm infants is mainly due to parenteral AA preparation. On day one, PPN was administered
a low caloric intake during the first few weeks of life [14,15]. to the neonates in both groups, which composed of dextrose
Randomised controlled studies are conducted which reported (glucose infusion rate (GIR) 6-8  mg/kg/min), AAs, calcium,
that early AA supplementation (starting within few hours of birth) and multivitamin (1  ml/kg) either through peripheral line or
as compared to AA supplementation after 3-5 days of life resulted
Peripherally Inserted Intravenous Catheter (PICC) line. Group
in better postnatal growth in preterm LBW neonates [13,16,17].
A received 1 g/kg/day of parenteral AA on day one and dose
Early administration of AA can promote anabolism through
was increased by 1  gm/kg/day every day till maximum of
positive nitrogen balance [14,15]. In recent times, it has become
4  gm/kg/day. Group B received 3  gm/kg/day of parenteral
evident that protein delivery of 3  g/kg/day beginning on day
AA on day one and dose was increased to 4  gm/kg/day on
one of life is safe and associated with plasma AA concentration
next day. Total fluids were calculated as per the standard
similar to those of second and third trimester fetuses. However,
recommendations (80 mL/kg on day 1, increased gradually to
most of these studies were performed in neonates who received
TPN [7]. Therefore, we undertook this study to evaluate the maximum 150  mL/kg). Rest of the care in both the groups
safety of administering a higher dose (3  g/kg/day) from day 1 was provided as per standard neonatal practices, including
of life in comparison to gradual increments in dose of parenteral ventilation, use of antibiotics, and Kangaroo mother care [16].
AAs in the PPN regimen and its effect on weight loss in the first Trophic feeding was started within 48 hour of life, except where
week of life. The primary outcome measured safety. Secondary contraindicated and increased as per the unit protocols and as
outcomes measured growth parameters (weight, length, tolerated by the preterm infants till 130-150  mL/kg. Trophic
and head circumference) and biochemical variables (sodium, feeds were given once the baby was stabilized after birth and
potassium, blood urea, serum calcium, blood urea nitrogen). gradually increased everyday i.e., 10-15 mL/kg/day till baby
reached full target feeds of 140 mL/kg/day. The follow-up was
MATERIALS AND METHODS done and data was collected till 40th week [16]. Both groups
The Randomised controlled study was conducted from were continued on AA till they reached 75% of enteral feeds.
January 2015 to February 2016 at level III NICU, Department of Weight, length, and head circumference were measured at
Paediatrics, KLE University’s Jawaharlal Nehru Medical College, admission and every week during hospital stay. Biochemical
Belgaum Karnataka, India. All out born and inborn neonates parameters, including serum sodium, serum potassium, serum
weighing < 1500  g admitted within 24  hours of life in NICU calcium, blood urea, and total calcium were monitored weekly
were included. Neonates with congenital anomalies or inborn during hospital stay.
errors of metabolism (IEM), needing surgery, discharged as
AMA, and death during NICU stay were excluded from study. Statistical analysis
A written consent was obtained from the parents/caregivers The data were analysed using SPSS 20.0 statistical software.
before enrolment. The study was approved by the Institutional Continuous data were expressed as mean ± standard
Ethics Committee.The sample size was calculated based on deviation (SD). Independent sample t-test was used to
the following formula. assess the significance of study parameters on continuous
scale between two groups. Chi-square test was used to find
association between the classes of variables. A p-value ≤ 0.05
at 95% confidence interval (CI) was considered as statistically
significant.
Indian Journal of Neonatal Medicine and Research. 2019 Apr, Vol-7(2): PO12-PO17 13
 Rakesh Gami and Manisha Bhandankar, Safety and Outcome of Low Dose vs. High Dose AA Supplementation in VLBW Neonates www.ijnmr.net

RESULTS Demographic data and clinical characteristics

Between January 2015, and February 2016, although 98 VLBW The demographic and clinical characteristics of the neonates
neonates admitted, 60 neonates completed follow-up after are shown in the [Table/Fig-2]. No significant difference was
discharge at 40 weeks, hence only 60 were included with 30 in observed in gender, gestational age, mode of delivery, birth
each group [Table/Fig-1]. weight, and characteristics of study population between the
two groups. Three neonates in group B weighed <1000 g.
The mean hospital stay was 23±4.5 days for Group A and
22.4±3.6 days for Group B.

Anthropometric measurements
Changes in the mean weight of the neonates in both groups at
weekly intervals was not significantly different as shown in the
[Table/Fig-3]. Similarly, the changes in head circumference and
length were comparable. [Table/Fig-4] shows the mean daily
weight change in both the groups. Interestingly the daily weight loss
in group B was significantly more than that in group A in the first
week of life. However, during the rest of the hospital stay, the daily
weight gain was more in this group of neonates. There were three
neonates with birth weight <1000 g in group B. This could have
affected the change in mean weight that is observed in group B.

Biochemical profile
The mean sodium, potassium, blood urea, serum calcium, and
[Table/Fig-1]: Flowchart representing patients in the study. blood urea levels from first week to fourth week are shown in

Variable Group A (n=30) Group B (n=30) p-value

Gender

Male 16 (53.33%) 14 (46.67%)

0.606
Female 14 (46.67%) 16 (53.33%)

Gestational age (weeks)

28 weeks-31 week 6 days 9 (30%) 10 (33.33%)

32 weeks-36 week 6 days 19 (63.33%) 19 (63.33%) 0.824

37 weeks-39 week 6 days 2 (6.67%) 1 (3.34 %)

Mode of delivery

Caesarean 25 (83.33%) 24 (80%)

0.739
Vaginal 5 (16.67%) 6 (20%)

Birth weight (gm)

<1000 0 3 (10%)
0.237
1000–1500 30 (100%) 27 (90%)

Characteristics of study population

Gestational age (week) 32 ± 2.32 32.90±2.10

Birth weight (gm) 1351.67±124.40 1326.93 ±189.11

> 0.050
Head circumference at the time of admission (cm) 28.57±1.25 28.40±1.43

Length at the time of admission (cm) 37.70±2.60 39.15±3.27

[Table/Fig-2]: Demographic and baseline characteristics of neonates.

14 Indian Journal of Neonatal Medicine and Research. 2019 Apr, Vol-7(2): PO12-PO17
 www.ijnmr.net  Rakesh Gami and Manisha Bhandankar, Safety and Outcome of Low Dose vs. High Dose AA Supplementation in VLBW Neonates

Weight (g) Head circumference (cm) Length (cm)

Interval (week)
Group A Group B Group A Group B Group A Group B

1 1331.60 ±131.45 ns
1297.50±179.92 ns
28.60±1.16 ns
28.37±1.40 ns
37.55±2.86 ns
38.82±2.89ns

2 1330.46 ±162.71ns 1242.90±194.40ns 28.61±1.10ns 28.45±1.38ns 37.61±2.91ns 39.03±2.77ns

3 1324.93 ±185.53ns 1262.1±217.4ns 29.10±1.39ns 28.60±1.50ns 37.73±3.22ns 38±2.33ns

4 1270 ±151ns 1205.75±214.19ns 28.86±1.07ns 27.88 ±1.13ns 37.29±3.15ns 38.63±2.56ns

[Table/Fig-3]: Comparison of anthropometric measurements in neonates at weekly intervals.
ns: p> 0.05; s: p< 0.05

Interval Number of babies Group A (Mean±SD) Number of babies Group B (Mean±SD) p-value

Birth to week 1 30 -2.87± 9.91 30 -4.20 ±7.73 0.012

Week 1 to week 2 28 1.35±10.48 29 3.81± 9.10 0.047

Week 2 to week 3 15 7.29±8.45 15 9.04±4.11 0.012

[Table/Fig-4]: Comparison of change in weight per day during hospital stay.

1st week 2nd week 3rd week 4th week

Variables
Group A Group B Group A Group B Group A Group B Group A Group B

Sodium
131.17±3.66S 140.5±3.15S 135.3±3.15ns 135.8±4.38ns 133.7±5.40ns 133.5± 3.71ns 133.3± 8.08ns 136.20±6.87ns
(meq/L)

Potassium
4.89±0.84ns 4.92±0.83ns 4.67±0.64ns 5.12±0.89ns 4.52±0.34 4.75 ± 0.56ns 4.30±0.53ns 4.42±0.69ns
(meq/L)

Blood urea
25.79±14.86s 32.31±8.26s 36.46±22.3ns 33.59±19.3ns 39.91±27.84 26.20 ± 11.44ns 19.40±4.50ns 21.04±8.63ns
(mg/dL)

Serum
calcium 8.56±0.66ns 8.66±0.77ns 9.07±0.52ns 9.13±0.88ns 9.20±0.49 9.19 ± 0.5ns 8.90±0.17ns 9.08±0.70ns
(mg/dL)

Blood urea
nitrogen 12.04±6.94S 15.08±3.86S 17.02±10.41ns 15.67±9.01ns 18.63±12.99ns 12.33 ± 5.34ns 9.05±2.10ns 9.82±4.03ns
(mg/dL)
[Table/Fig-5]: Comparison of biochemical parameters.
ns: p >0.05; s: p <0.05

the [Table/Fig-5]. Although, mean values of sodium (p <0.001), infusion rate was 12 mg/kg/hour to maintain blood glucose
blood urea (p = 0.041), and Blood Urea Nitrogen (BUN) showed level between 80-120 mg/dL. This did not improve the ratio
statistically significant difference in both groups, they were of non-protein caloric intake to calories from protein to the
within normal range. Rest of the biochemical parameters were desired level of 100-200 Cal/g of protein needed for adequate
comparable. However, weekly monitoring of these parameters postnatal growth. VLBW neonates who receive only glucose
during rest of the hospital stay were comparable between the can have protein loss of 0.5-1 g/kg/day. It has been shown
two groups. that early administration of AA may in fact lead to decreased
glucose levels due to stimulation of insulin secretion [13].
DISCUSSION Although, the neonates received higher amounts of protein in
It was found that PPN consisting of 3 g/kg/day of parenteral AA
group B as compared to group A, it was not used for growth
on day 1 and increased to 4 g/kg/day is well-tolerated by VLBW
and accretion of protein. Studies in preterm neonates suggest
neonates than the gradual increments in parenteral amino acid
that the effect of AA intake on protein accretion occurs
supplementation (i.e., 1g/kg/d on day 1 of life).
through increased protein synthesis rather than inhibition of
In TPN, the ratio of protein: nonprotein caloric intake is important protein breakdown [7]. A study conducted by Denne SC et al.,
to prevent oxidation of AAs [3]. In this study, parenteral lipids demonstrated an increase in protein synthesis with PN [18];
were not used due to resource limitations. Maximum Glucose however, there was significantly less suppression of protein
Indian Journal of Neonatal Medicine and Research. 2019 Apr, Vol-7(2): PO12-PO17 15
 Rakesh Gami and Manisha Bhandankar, Safety and Outcome of Low Dose vs. High Dose AA Supplementation in VLBW Neonates www.ijnmr.net

breakdown in the preterm neonates. Further, the mechanism day is well tolerated by VLBW neonates. To ensure adequate
of action by which AA intake promotes protein accretion in postnatal growth, it is essential to use TPN from day 1 of life for
neonates is not clearly reported [7]. Balasubramanian H et al., very and extreme low birth weight neonates. Administration of
reported that 1 g/kg/ day of parenteral AAs on day 1 with gradual high dose of AA with PPN does not serve the purpose of protein
increments of 1 g/ kg/day till a maximum of 4 g/kg/day resulted anabolism and growth of the baby.
in better growth (weight, length, and head circumference) than
early aggressive parenteral AA supplementation (3 g/kg on Acknowledgements
day 1 of life) in VLBW neonates [13]. Randomised controlled All the authors have contributed equally in the development of
trial (RCT) conducted by Bulbul A et al., reported no significant manuscript.
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AUTHOR(S): NAME, ADDRESS, E-MAIL ID OF THE
1. Rakesh Gami CORRESPONDING AUTHOR:
2. Manisha Bhandankar Dr. Manisha Bhandankar,
Department of Paediatrics, KAHER’s Jawaharlal
PARTICULARS OF CONTRIBUTORS: Nehru Medical College, Belgaum-590010, Belagavi,
1. Postgraduate Student, Department of Paediatrics, Karnataka, India.
KAHER’s Jawaharlal Nehru Medical College, Belagavi, E-mail: manishabhandankar@yahoo.com
Karnataka, India.
2. Professor, Department of Paediatrics, KAHER’s Financial OR OTHER COMPETING INTERESTS:
Jawaharlal Nehru Medical College, Belagavi, None.
Karnataka, India. Date of Publishing: Apr 01, 2019

Indian Journal of Neonatal Medicine and Research. 2019 Apr, Vol-7(2): PO12-PO17 17