Nutrition in Clinical Practice

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Nutrition Management for the Promotion of Growth in Very Low Birth Weight Premature Infants
Allison Prince and Sharon Groh-Wargo
Nutr Clin Pract 2013 28: 659 originally published online 25 October 2013
DOI: 10.1177/0884533613506752
The online version of this article can be found at:
http://ncp.sagepub.com/content/28/6/659

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506752

research-article2013

NCPXXX10.1177/0884533613506752Nutrition in Clinical PracticePrince and Groh-Wargo

Invited Review

Nutrition Management for the Promotion of Growth in

Very Low Birth Weight Premature Infants

Nutrition in Clinical Practice

Volume 28 Number 6
December 2013 659668
2013 American Society
for Parenteral and Enteral Nutrition
DOI: 10.1177/0884533613506752
ncp.sagepub.com
hosted at
online.sagepub.com

Allison Prince, MS, RD, LD1; and Sharon Groh-Wargo, PhD, RD, LD2

Abstract
Premature infants are highly susceptible to extrauterine growth restriction. Without early and adequate nutrition support, nutrition deficits
of energy and protein can quickly accrue. Growth failure has been implicated in poor neurodevelopmental outcomes and long-term
morbidity, creating a major focus on neonatal nutrition alongside medical management. Optimal nutrition is paramount for optimal
growth outcomes. The purpose of this article is to review the implications and long-term effects of growth failure in premature infants,
specifically, those with very low birth weights. In addition, nutrition interventions and treatments will be presented to manage and
improve growth outcomes of the neonate. (Nutr Clin Pract. 2013;28:659-668)

Keywords
neonates; growth; enteral nutrition; parenteral nutrition; infant, newborn; infant, very low birth weight; nutrition therapy; nutritional support

Growth is by far the number one priority for the preterm infant
after medical stability is achieved. The majority of days that a
preterm infant is cared for in the neonatal intensive care unit
(NICU) are spent feeding and growing. In other words, it is
the time medical providers use to provide optimal nutrition
while trying to achieve adequate growth that mimics that of the
third trimester in utero. Expectations for growth of preterm
infants are based on well-documented literature that supports
optimal brain development, head circumference growth, and
neurodevelopmental outcomes in early childhood.1-4
There are 3 times in the lifecycle when growth has long
range effects: the intrauterine period, infancy, and adolescence.
Failure of the neonate to achieve appropriate gestational
growth prenatally is called intrauterine growth restriction
(IUGR). Infants who are born with IUGR are often small for
gestational age (SGA) (weight for gestational age below the
10th percentile), and very low birth weight (VLBW) (<1500
g). For premature infants, whether born SGA or appropriate for
gestational age (AGA), it is the management of growth during
the immediate extrauterine period that has the most impact on
brain development. Postnatal growth failure occurring during
this period is referred to as extrauterine growth restriction
(EUGR). The purpose of this article is to review the implications and long-term effects of growth failure in premature
infants, specifically, those with VLBW. In addition, nutrition
interventions and treatments will be presented to manage and
improve growth outcomes of the neonate.

and iron. Diagnoses of osteopenia of prematurity and anemia of prematurity are common in the neonate. The greatest
period of skeletal development and bone mineralization occurs
in the third trimester where 80% of total fetal mineral accretion
is achieved between 24 and 37 weeks gestation.6,7 Differences
in postnatal calcium and phosphorous accretion coupled with
inefficient metabolism of iron and rapid depletion of intrauterine stores create micronutrient challenges for clinicians caring
for preterm infants.8 The immediate focus of postnatal nutrition, however, is to provide energy substrates to the neonate to
maintain the anabolic state of the fetus and an ideal protein
calorie ratio to promote gain of lean body mass.2
VLBW infants, especially those born SGA, have inadequate
glycogen reserves and may have difficulty maintaining postnatal blood sugars. Likewise, impaired glucose production may
also lead to hypoglycemia. While the majority of premature
infants often receive parenteral nutrition (PN) as the initial
mean of nutrition in the first few days of life and thus a continuous supply of glucose, insufficient energy provision or
cyclic PN may result in hypoglycemia in the growth-restricted

From 1University Hospitals Rainbow Babies & Childrens Hospital,

Cleveland, Ohio; and 2Case Western Reserve University School of
Medicine, Department of Pediatrics, MetroHealth Medical Center,
Cleveland, Ohio.
Financial disclosure: None declared.
This article originally appeared online on October 25, 2013.

Nutrition Challenges of VLBW Infants

During the third trimester of pregnancy, accretion of protein,
fat, glycogen, and fat soluble vitamins and minerals occurs.5,6
Minerals of particular interest include calcium, phosphorous,

Corresponding Author:
Allison Prince, MS, RD, LD, University Hospitals Rainbow Babies
& Childrens Hospital, 11100 Euclid Ave, Mail Stop: LKSD 5021,
Cleveland, OH 44106, USA.
Email: allison.prince@uhhospitals.org.

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Nutrition in Clinical Practice 28(6)

Figure 1. Average body weight versus postmenstrual age in

weeks for all study infants with gestational ages 24 to 25 weeks
(dotted line), 26 to 27 weeks (short dashes), and 28 to 29 weeks
(long dashes). The reference intrauterine growth curves were
plotted using the smoothed 10th and 50th percentile birth weight
data reported by Alexander et al.15 (Figure from Ehrenkranz et
al.14 Reproduced with permission from Pediatrics, Vol. 104,
Page 287, Copyright 1999 by the AAP).

infant.9 Prospective studies suggest that recurrence of hypoglycemia is correlated to significantly reduced Bayley psychomotor development scores,10 head circumference11 at 18 months
of age, and significant impairment in physical growth and neurodevelopment at 5 years of age.11

Consequences of Growth Failure

Premature infants with growth failure are susceptible to
adverse short and long-term implications. When born 32
weeks gestation, premature neonates miss a very essential time
of growth and development in utero. Growth velocity at a rate
slower than expected for age may have a direct impact on premature infants neurodevelopmental and growth status placing
them at risk for medical problems later in life.12 The desired
outcome for postnatal growth mirrors that of the third trimester
of the fetus.3,4,13,14 Unfortunately, several studies show that
despite in-hospital growth velocity similar to expected intrauterine growth rate, weight at discharge often does not match
that of the median birth weight of a reference fetus of the same
postmenstrual age (Figure 1).14-17
In 1 study, neonates who gained on average 21 g/kg/day vs
12 g/kg/day during hospitalization had significantly decreased
likelihood of developing cerebral palsy.1 The effect of increased
rate of weight gain on neurodevelopmental and growth outcomes may be independent of factors such as gender or race.1
Important hospital comorbidities such as necrotizing enterocolitis (NEC), late-onset sepsis, and bronchopulmonary dysplasia
(BPD) were decreased in infants with greater growth velocity
(21 g/kg/day), thus poorly nourished infants with slower
weight gain may be more prone to developing infections and

BPD.1,18 While poor weight gain is often the first identifiable

marker of nutrition deficit, long-term nutrition deficits of protein and energy can also affect head circumference, brain
development, and length.1,12 Preterm infants with increased
rates of head circumference growth (1.2 cm/week) have significant decreases in the incidence of cerebral palsy, abnormal
neurological examinations, and neurodevelopmental impairment at approximately 18-22 months of life when compared to
preterm infants with slower rates of postnatal head circumference growth (0.7 cm/week).1 The importance of brain development within the first 2 years of life is highlighted in Figure 2.
Critical patterns of visual and auditory development, speech
production, and higher cognitive function are noted.19
Postnatal growth restriction is a powerful predictor of longterm morbidity and poor neurodevelopmental outcome. The
identification of growth failure is crucial to the care of the neonate as it provides an indirect measure of overall health and
nutrition adequacy.20

Identification of Growth Failure

There are several ways to assist clinicians in identifying growth
restrictions in preterm neonates such as calculating growth
velocity, using growth charts, and monitoring growth parameters over time. Growth velocity can be quickly calculated using
weekly weight, length, and head circumference measurements.
Daily weights may be obtained if in-bed scales are used but it
is still important to assess overall velocity vs day-to-day weight
gain. To calculate growth velocity of an infant who is <40
weeks gestational age, the average of 2 weights is summarized
over a particular time period and produced as grams per kilogram per day (g/kg/day). Weight gain velocity calculated as g/
kg/day is commonly used in the neonatal setting because it
accounts for the variability in daily measurements.20 Patel et al
validated an exponential model which estimates growth velocity through a consistent approach; however the calculation can
be quite complex and difficult to calculate. Alternately, a simple-to-use equation that has been validated in extremely low
birth weight (ELBW) infants yields an accurate mean estimate
of growth velocity (Figure 3).20
Results from calculation of growth velocity are compared
to the standards based on reported intrauterine growth data.
Generally accepted growth velocity for a neonate is 15 g/kg/
day in weight gain and 0.9 cm/week each in head circumference and length, although the ideal growth pattern of premature infants is truly undefined.13
Growth charts are the most frequently utilized measurement
tool to assess growth adequacy in neonates. Neonatal growth
charts help clinicians identify not only growth restriction at
birth (intrauterine) but also postnatal growth failure (extrauterine). Table 1 contains examples of growth curves commonly
used in the neonate. Updated growth charts which incorporate
World Health Organization (WHO) growth data25 and other
additional globally representative studies were recently published by Fenton et al.30 The revised growth charts are separate

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661

Figure 2. Importance of early growth on central nervous system development as illustrated by Thompson and Nelson.19 Reprinted with
permission.

[1000 x (Wn - W1)]

GV =
{(Dn-D1) x [(Wn+W1)/2]}
Where GV = growth velocity, W = weight in grams, D = day,
1 = beginning of time interval, and n = end of
time interval in days.
For example, an infant who weighs 750g (W1) on day of
life 14 (D1) and 850g (Wn) on day of life 21 (Dn),
would have the following calculation:
GV =

[1000 x (850-750)]
{(21-14) x [(850+750)/2]}

Calculated GV = 18 g/kg/day
Expected GV = 15-20 g/kg/day2,13

Figure 3. Equation for calculation of growth velocity.20

for boys and girls and allow clinicians to plot exact age instead
of completed weeks gestation (Figures 4a, 4b).
Tracking along the 50th percentile is not the expectation for
all infants. The slope of the infants curve is more important
than whether the infant plots at the 10th or 90th percentile.
Most neonatal curves do not reflect the decrease in weight that
occurs right after birth, the so-called postnatal nadir. Infants
often cross into lower percentiles and are usually unable to initially track along their intrauterine curve.14,31 Clinicians must
be cautious not to hasten catch-up growth too quickly because
of the discrepancy between catch-up growth in height and adiposity seen in preterm or SGA infants.32 Rapid catch-up growth
can lead to adverse consequences later in life in cardiovascular

health.32-35 The assessment of an infants weight for length is

important, but, unlike the WHO growth curves, neonatal
growth curves do not have a designated curve for weight for
length. The clinician is therefore responsible for making a
physical assessment using clinical judgment to determine
appropriateness of weight for length. Subjective Global
Nutrition Assessment (SGNA) has been validated in infants
who are >1 month corrected gestational age (CGA).36 SGNA
incorporates a physical exam to help identify fat and muscle
wasting as an indicator of malnutrition, but physical assessments may also be used to identify those infants with excessive
adiposity or disproportionate weight for length.
When assessing neonatal growth in the NICU, clinicians
often look for catch-up growth. The term catch-up growth is
used in reference to the period of accelerated linear growth or
weight gain greater than expected for age, which occurs following a period of growth restriction or in infants born SGA.32,37
Although there is much controversy as to how fast catch-up
growth should occur, the majority of opinion promotes catch-up
growth at a rate that mimics intrauterine growth to optimize
brain growth and development.29,38 Increased central fat deposition, insulin resistance, type 2 diabetes, and cardiovascular disease is observed during adulthood in former SGA infants who
experience rapid catch-up growth during the first year of life.34
Systematic reviews suggest that premature infants have a higher
percentage fat mass and much less fat free mass at term compared to healthy term newborns.39 Adequate acquisition of lean
body mass is as important as overall weight gain in infancy.
Both early and late catch-up growth has been described with
improvements into childhood and adolescence but typically
catch up growth is achieved within the first few years of life.32

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Nutrition in Clinical Practice 28(6)

Table 1. Characteristics of Common Growth Curves Used in Preterm Infants.

Growth Curve
Fenton

21

Year

Age

2003

22-50 weeks

Olsen et al26

2010

23-41 weeks

Lubchenco et al13

1966

24-43 weeks

Infant Health and

Development
Program27

1991

40 weeks CGA36 months

WHO25

2006

Birth-5 years

In progress

23-36 weeks

Intergrowth-21st
Project28
Fetal Infant Growth
Charts29

2013

22 weeks GA92 weeks

PCA

Revised, Fenton
et al30 growth
charts

2013

22 weeks GA50 weeks

PCA

Description
Cross-sectional data points inclusive of weight,22 head circumference, and
length23,24 measured at all live births < 40 weeks gestation
In other words, infants born at 30 weeks are plotted on a curve reflective of the
weight of all other infants born at 30 weeks gestational age
Mimics intrauterine growth
Assumes the ideal velocity of weight gain is equivalent to fetal growth
Growth curves from 40-50 weeks are equal to the average male and female
WHO Growth standards25 as the Fenton curves are not gender specific
Gender-specific weight-, length-, and head-circumference-for-age curves
taken from a large, racially diverse sample
Does not allow for tracking past term
Compilation of recent data, which may be reflective of advances in prenatal
care allowing for longer extension of high-risk pregnancies
Includes curves for weight, length, and head circumference for age
All created from the same sample; based on U.S. data
May underestimate percentage of SGA infants31
Data from babies born at high elevation and may not be appropriate for use
with babies born at sea level
Not a good reflection of the population at GA < 27 weeks due to extremely
small sample sizes at 24-26 weeks
Longitudinal charts which plot birth data of very low birth weight infants as
well as the actual growth of the infants over time
Not commonly used in practice
Does not show an infants growth velocity relative to fetal growth
Infants who are plotted and/or tracked on such growth curves are directly
compared to other very low birth weight babies, which cannot be used as an
indicator of ideal growth26
Provides a set of data indicative of optimal growth
Subjects were predominantly breastfed infants who were still being breastfed
at 12 months (the gold standard in infant nutrition)
Longitudinal growth data inclusive of weight-, length-, and headcircumference-for-age curves as well as weight for length
Demonstrates how an infant should grow, not how they have growth in the
past
Longitudinal growth data from cohort of healthy pregnancies to identify
adequate growth of the fetus
Assesses intrauterine growth utilizing intermittent state-of-the-art technology
Gender-specific; combined Olsen et al26 and WHO25 growth curves
Allows continuity of plotting on 1 growth chart from initial hospital course
through early discharge period
Identifies 1 and 2 standard deviations from the mean
Gender-specific; smoothed data from Fenton et al,21 6 multinational studies,
and WHO25
Allows infants to be plotted at actual age instead of completed gestation

CGA, corrected gestational age; GA, gestational age; PCA, postconceptual age; SGA, small for gestational age; WHO, World Health Organization.

Nutrition Support and the VLBW infant

Preterm infants require excellent nutrition to achieve the
growth velocity and body composition of the third trimester
fetus.2 The challenge of estimating nutrient requirements is
complicated by the incomplete absorption of the preterm

infants immature gastrointestinal tract, the rapid accretion of

tissue, the high energy cost for growth, and the presence of
nutrition deficits acquired during the early days or weeks of
life.2,12,40 An increment above the normal nutrient recommendation for maintenance of expected growth for age is indicated
for the baby who has experienced EUGR.29

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663

Figure 4. Revised preterm growth charts for boys and girls from Fenton et al.30

Parenteral Nutrition
Recommendations for protein and calories vary depending on
the reference used but all agree that growth of the preterm
infant is not possible without adequate calories and protein.2,41-43 PN is recommended almost immediately after birth,
or within the first 2 hours after birth. Early and adequate nutrients, especially protein, are crucial to promote anabolism and
mimic fetal growth. The length of time for an infant to achieve
full enteral feedings is significantly shorter when PN starts
within the first 24 hours of life compared to >24 hours after
birth.44 Amino acids are initially provided at a minimum of 2 g/
kg/day and advanced to 3.5 g/kg/day.2 Infants who receive
early amino acid administration of 3 g/kg/day immediately
after birth have decreased growth restriction at 36 weeks postconceptional age when compared to infants who receive identical amounts of amino acids after 48 hours of life.44 A significant
protein deficit accrues within the first week of life with any
delay in providing optimal protein and can be difficult to
recoup prior to hospital discharge.12
Total energy, inclusive of calories provided by amino acids,
dextrose, and lipids, is provided at 90-100 kcal/kg for VLBW

infants and 105-115 kcal/kg for ELBW infants within several

days after birth.2,41 Promptly providing calories greater than
basal energy expenditure (assumed to be 45 kcal/kg/day in
infants <900 g and 50 kcal/kg/day in larger infants) prevents
postnatal growth failure and produces postnatal growth above
the 10th percentile.2,45 Aggressive early PN shortens the duration of exclusive PN44,46 and enhances postnatal growth in
infants at high risk of growth failure such as those with BPD.47

Enteral Nutrition
Within the first few days of life, trophic feeds are initiated to
stimulate gut motility and maturation. Enteral feeding is the
preferred method of nutrition support, but can be complicated
by barriers such as feeding intolerance, infections, gastrointestinal anomalies, or renal function. Commonly both PN and
enteral nutrition (EN) are used in combination until full enteral
feeds can be achieved. Human milk is the first choice for early
feeding due to its trophic effects on the gastrointestinal tract
and anti-infectious effects; human milk has also been shown to
protect infants against NEC.2,48 Preterm human milk differs in
nutrition composition from that of term human milk, with

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Nutrition in Clinical Practice 28(6)

initially higher quantities of calories and protein; however,

quantities of all nutrients are still inadequate for the preterm
infant (Table 2). Practitioners use human milk fortifiers
(HMFs) added either to preterm or donor human milk to meet
the higher nutrition requirements of the neonate.49 All infants
born before 32 weeks gestation, and some infants born at 32-36
weeks gestation, benefit from fortification.50 Table 2 compares
intake of key nutrients from common methods of human milk
fortification against generally accepted nutrient needs. The
composition of preterm human milk changes over time with
the most notable difference being a decrease in protein content.
Low protein intake is a limiting factor in achieving adequate
growth.51 Table 2 contains estimated nutrient values in preterm
human milk; however after several weeks of lactation, the protein content significantly decreases by approximately 25%.50
Protein intake from all fortification options in Table 2 are based
on the assumed protein content of preterm human milk and
should be adjusted downward if more mature milk is fed.
HMF. HMFs are currently available in both concentrated liquid and powder form. Although liquid HMFs are generally preferred because they are sterile, they add volume and slightly
dilute the human milk. A study by Moya et al compared a liquid HMF which provided 20% more protein to powder HMF.52
The liquid HMF appeared safe and supported significantly
greater weight, length, and head circumference growth compared to the powder HMF.52 Unfortunately, due to the rapid
decline in protein content of preterm human milk, even fortified human milk is often insufficient to meet the protein needs
of a growing preterm infant. Additional protein fortification
may be necessary. Some practitioners add 5 packets of HMF,
instead of 4, to 100 ml expressed human milk creating an
approximately 25 kcal/oz feeding. This is considered off-label
use of the HMF product. Depending on the nutrient density of
the HMF chosen, this practice may deliver either excessive
protein or calcium. Close monitoring of the babys tolerance is
recommended. Preterm discharge formulas (PDFs) are added
sometimes to human milk, often around the time of discharge
and during the immediate postdischarge period, to increase
caloric density. PDFs used in this way do not fortify human
milk but rather produce an enriched feeding. Enriched
human milk may not provide adequate protein and minerals
when used as a sole source of nutrition in the growing preterm
infant. Alternating human milk with PDF provides a more
nutrient dense diet but the formula displaces some of the
human milk.
There are 2 methods of individualized EN that optimize
human milk fortification: adjustable fortification and targeted fortification. While neither method is current standard
of practice, there is increased interest in an individualized
approach. Targeted fortification uses data from nutrient analysis of human milk. Amounts of fortifier are added based on the
specific composition of the human milk to satisfy, for example, the infants target protein goal, that is, 3.5 g/kg/day. With

adjustable fortification, protein is provided in amounts

required to promote growth and maintenance of the infants
metabolic response. Blood urea nitrogen (BUN) is closely
monitored and the protein intake titrated based on the change
in the BUN.40 BUN levels are available in most NICUs and
monitoring BUN prevents excessive protein intake. Regardless
of which method is chosen, an individualized nutrition prescription accounts for the variability in the protein and fat content of human milk, and adjusts the caloric density and/or the
protein calorie ratio when treating growth failure in preterm
infants fed human milk.29,40
Donor milk.Donor milk is often used when mothers own
milk is unavailable or in short supply; however there is some
controversy about whether it offers the same protection against
NEC as mothers own milk and donor milk may not support
acceptable weight gain in VLBW infants.49 Protein content
varies less over time, but is almost always lower than that of
mothers own milk.2 Alternatively, when infants are fed formula, the nutrient bioavailability from hydrolyzed protein and/
or sterilized preterm formulas is reduced compared to human
milk.29
Preterm formulas.Preterm formulas (PF) are more nutrient
dense than standard term formulas, have sources of macronutrients that match the digestive capacity of preterm infants, and
support weight gain and bone mineralization at near intrauterine rates.49 PDFs contain lower nutrient density than PFs but
greater nutrient density than standard formulas intended for
healthy term infants. PDFs promote increased fat-free and
peripheral fat mass (but not central adiposity) in premature
infants as well as better growth at 4 and 12 months and bone
mineralization at 4 months when compared to premature
infants fed term formulas.29,53,54 Standard milk-based formulas
intended for term, healthy newborns are not generally fed to
VLBW infants. Tolerance formulas, such as soy protein-based,
protein hydrolysate, and amino acid-based formulas, are used
if feeding intolerance to milk-based formulas occurs but tolerance formulas do not meet the nutrition needs of the preterm
infants as well as PFs or PDFs and may not support acceptable
growth. Increasing the caloric density of tolerance formulas
improves energy intake but may not raise the intake of protein
and minerals to the recommended ranges. Vitamin needs are
assessed and appropriate supplementation provided. Table 3
lists the intake of key nutrients from selected infant formulas
fed to preterm infants.
Recommendations for enteral nutrient intake for VLBW
infants are available. To promote positive nitrogen balance and
prevent use of protein as an energy source, sufficient energy is
provided with an adequate protein-energy ratio (PER).
Requirements based on postconceptional ages between 26-36
weeks and including babies both with and without the need for
catch-up growth are published.42 Recommendations for protein
are 3.4-4.4 g/kg/day while those for the PER are 2.8-3.3 grams

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665

179
2.5
2.1
7
12
697
4
2
44
23
5.5
220
610

700-1500
150-400
6-12

100-220
60-140
7.9-15
2000-4000
1000-3000

PTHM

160-220
3.4-4.4
2.8-3.3
6.2-8.4
9-20

Nutrient
Needs41-43

59
32
6.3
530
730

662
17
2

150
2.7
2.3
6.9
12

45 ml PTHMc +
tsp PDFd

174
94
6.1
2320
1610

1915
235
8

150
4.5
3.8
7.7
10

4 vials
EHMFAL
+ 100 ml
PTHMc

180
94
10.6
290
1420

546
40
2

146
3.4
2.8
7.2
10

Prolact+4
H2MFe

24 kcal/oz

210
118
14.9
700
1980

1496
180
6

150
3.6
3
6.3
13

SHMF

204
115
14.5
680
1920

1455
175
6

153
4.3
3.6
6.1
12

SHMFf+
1 ml
Liquid
Proteing

237
134
16.5
780
2200

1628
209
7

148
3.7
3.1
6.2
13

SHMF

25 kcal/oz

167
88
10.9
1690
1510

1307
176
5

133
3.3
2.8
7.1
11

PTHMc +
30 kcal PFd 1:2

27 kcal/oz

209
114
13.7
1430
1890

1498
207
6

133
3.6
3
6.7
12

SHMFf + 30
kcal PFd 1:1

EHMFAL, Enfamil Human Milk Fortifier Acidified Liquid (Mead Johnson Nutrition, Evansville, IN); PDF, preterm discharge formula; PF, preterm formula; PTHM, preterm human milk; SHMF,
Similac Human Milk Fortifier Concentrated Liquid or Similac Human Milk Fortifier Powder (Abbott Nutrition, Columbus, OH).
a
Based on 120 kcal/kg for a 1 kg infant.
b
Nutrients are per kg unless otherwise noted.
c
Values obtained from Pediatric Nutrition Product Guide 2013, Abbott Nutrition, Columbus, OH, 84805/October 2012.
d
Average of products commercially available.
e
Prolacta Human Milk Fortifier (Prolacta Bioscience, City of Industry, CA).
f
Preparation: 1 packet of concentrated liquid or powder SHMF: 25 ml of preterm human milk.
g
Liquid Protein Fortifier (Abbott Nutrition, Columbus, OH).
h
Preparation: 5 packets concentrated liquid or powder SHMF: 100 ml preterm human milk.

Volume, mL
Protein, g
g protein:100 kcal
Fat, g
Carbohydrate, g
Vitamins
Vitamin A, IU
Vitamin D, IU
Vitamin E, IU
Minerals
Calcium, mg
Phosphorous, mg
Magnesium, mg
Iron, mcg
Zinc, mcg

Nutrients

20 kcal/oz

Table 2. Intake of Key Nutrients From Preterm Human Milk and Common Fortification Options.a

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180
2.5
2.1
6.4
13
360
81
2
94
51
8.4
2160
1050

700-1500
150-400
6-12

100-220
60-140
7.9-15
2000-4000
1000-3000

Milk-Basedc

160-220
3.4-4.4
2.8-3.3
6.2-8.4
9-20

Nutrient
Needs41-43

126
86
9.3
2160
1170

360
72
2

180
3
2.5
6.5
13

Soy ProteinBasedc

HP, high protein; PDF, preterm discharge formula; PF, preterm formula.
a
Based on 120 kcal/kg for a 1 kg infant.
b
Nutrients are per kg unless otherwise noted.
c
Average of products commercially available.
d
Preparation: 1 part High Protein 24 kcal/oz PF + 1 part 30 kcal/oz PF.

Volume, mL
Protein, g
g protein:100 kcal
Fat, g
Carbohydrate, g
Vitamins
Vitamin A, IU
Vitamin D, IU/d
Vitamin E, IU
Minerals
Calcium, mg
Phosphorous, mg
Magnesium, mg
Iron, mg
Zinc, mg

Nutrientsb

117
72
9.4
2160
1100

380
64
4

180
3.3
2.8
6.6
12

Protein
Hydrolysatec

20 kcal/oz

Table 3. Intake of Key Nutrients From Selected Infant Formulas Fed to Preterm Infants.a

134
92
12.7
2180
1520

393
68
2

180
3.6
3
5.8
13

Amino Acid
Basedc

135
77
10.2
2160
1470

480
84
5

164
3.4
2.8
6.5
12

PDFc

22 kcal/oz

207
110
12.6
2160
1800

1500
234
6

150
3.6 (4.1)
3 (3.4)
6.3
13

PF (HP)c

24 kcal/oz

207
110
12.6
2160
1800

1500
234
6

133
3.9
3.3
6.7
12

PFc,d

27 kcal/oz

207
110
12.6
2160
1800

1500
234
6

120
3.6
3
7
11

PFc

30 kcal/oz

Prince and Groh-Wargo

667

Table 4. Enteral Protein and Energy Requirements (and Need for Catch-Up Growth).
Study

kcal/kg/day

g Protein/kg/day

g Protein/100 kcal

105-118
119-127

4
3.9-4

3.7-3.8
3.1-3.4

130-150
110-130

3.8-4.4
3.4-4.2

3.8-4.2 (4.4)
3.4-3.6 (3.6-4)

3 (3.3)
2.8 (3)

120-140
110-130

3.5-4.5
3.5-4.2

Ziegler (2011)
<900 g
<1500 g
Tsang et al (2005)41
<1000 g
<1500 g
Rigo and Senterre (2006)42
26-30 weeks
30-36 weeks
Berseth and Uauy (2013)43
29 weeks
34 weeks

of protein per 100 kcal. A summary of current recommendations for energy, protein, and PER is provided in Table 4.
Suggested intakes of micronutrients for preterm infants have
changed over time.41,42,55 Evidence of reduced calcium retention reflecting postnatal adaptation to bone mineralization suggests target calcium and phosphorous requirements are less
than previously published. Calcium and phosphorus recommendations range from 110-220 mg/kg/day and 60-140 mg/kg/
day, respectively41 to 100-160 mg/kg/day and 60-90 mg/kg/
day, respectively.42,55
In summary, we have reviewed several elements surrounding
growth failure in the premature infant highlighting the identification of growth failure and its short and long-term impact on
the neonate. Nutrition management with adequate protein and
PER is mandatory to promote gain of lean body mass. Attention
to common barriers to ensure adequate nutrition support is
important. Human milk is the preferred feeding for VLBW
infants but requires fortification to meet nutrient needs. The
development of reference intrauterine growth curves and gender-specific fetal infant growth charts increases options for monitoring growth.29,30 Despite abundant knowledge and research
encompassing both the prevention and treatment of growth failure, challenges to neonatal nutrition remain. The novel idea of
an individualized nutrient prescription utilizing human milk
analysis is gaining popularity but still needs evidence of efficacy. The optimal amount of protein and other key nutrients for
individual infants of various postnatal ages is not defined. The
relationship between growth and under- and overnutrition, and
the relative risks of metabolic consequences vs neurodevelopmental outcomes later in life remain controversial.33

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