Approach To Enteral Nutrition in The Premature Infant

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Approach to enteral nutrition in the premature infant

Author: Amy B Hair, MD
Section Editor: Steven A Abrams, MD
Deputy Editor: Alison G Hoppin, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jul 2019. | This topic last updated: Jan 08, 2019.
INTRODUCTION
Premature infants have greater nutritional needs in the neonatal period than at any other time of their
lives. The nutrient needs are inherently high at this stage of development to match the high rates of
nutrient deposition achieved by infants in utero [1]. In addition, they often have medical conditions
that increase their metabolic energy requirements, including hypotension, hypoxia, acidosis, infection,
and surgery. Additional impediments to growth are physiologic immaturity of the gastrointestinal tract,
including decreased gastrointestinal motility and reduced intestinal enzyme activity and therapies
such as corticosteroids.
Early and adequate nutritional support is needed to achieve appropriate rates of weight gain, which
are almost twice that of a term infant, and to avoid postnatal growth failure [2,3]. Despite intensive
nutritional strategies for premature infants, growth failure remains a major problem [4]. However,
intensive feeding strategies must be balanced with potential risks. As an example, while early
initiation of enteral feedings has been shown to benefit premature infants, very rapid advancements
of enteral feedings may result in feeding intolerance or necrotizing enterocolitis (NEC) [5]. In addition,
it is important to choose feeding practices associated with improved outcomes for premature infants,
such as the use of human milk rather than formula [6]. In some cases, when it is not possible to
provide full enteral feedings due to an infant's medical condition, it may be necessary to provide
partial or total parenteral nutrition. (See "Parenteral nutrition in premature infants".)
Issues related to enteral nutrition in the premature infant are reviewed here. The composition of the
feeding, including human milk, formula, and human milk fortifiers (HMFs) is discussed elsewhere.
(See "Nutritional composition of human milk and preterm formula for the premature infant" and
"Human milk feeding and fortification of human milk for premature infants".)
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NUTRITIONAL GOALS
The nutritional goal for premature infants is to achieve rates of growth and nutrient accretion that
match those achieved by infants of similar gestational age in utero, while avoiding complications that
can be caused by nutritional therapies.
Intrauterine growth and nutrient accretion — A national reference standard for fetal growth was
developed from more than three million singleton births in the United States [7]. A new international
standard (INTERGROWTH-21st Century) was developed in 2014 and is increasingly used [8,9].
Premature infants often are unable to attain this rate. As an example, in a study of 1660 premature
infants with birth weight ≤1500 g at discharge, most infants born below 29 weeks gestation had not
reached the median birth weight of the reference fetus at the same postmenstrual age [10]. Thus,
even in the neonatal intensive care unit (NICU), premature infants did not receive adequate nutrition
to successfully grow at a rate equivalent to the reference standard for fetal growth. Continual
reassessment and delivery of adequate nutritional support are imperative to optimize the growth rate
for premature infants [11]. (See "Growth management in preterm infants", section on 'Normative
growth data'.)
Rates of intrauterine nutrient accretion during the third trimester have been estimated from chemical
analysis of fetal cadavers [12,13]. Data for several minerals have been corroborated by contemporary
noninvasive neutron activation techniques [14].
Energy requirements — The energy (caloric) requirements to achieve optimal growth are calculated
from the estimated resting energy expenditure (REE), plus the energy requirements for activity
(including feeding), thermoregulation, fecal loss, growth, and chronic medical conditions (table 1). In
term infants between 8 to 63 days of postnatal age, REE varies from 49 to 60 kcal/kg per day [15].
For premature infants, the clinical condition and activities dictate the daily energy requirements as
follows:
● For enterally fed premature infants, the average daily energy requirements are 105 to 130
kcal/kg per day [16-19].
● For parenterally fed premature infants, the energy requirements are lower (90 to 100 kcal/kg per
day) because of less fecal energy loss, fewer episodes of cold stress, and somewhat less activity
[20].
● For infants with chronic illness, such as bronchopulmonary dysplasia, energy requirements may
be higher due to increased REE, activity, and possibly fecal losses [21,22].

Nutrient requirements — Suggested enteral intakes for other nutrients are listed in the table (table
2); the requirements for parenterally given nutrients may differ. The appropriate enteral intake for a
particular nutrient can be estimated from established rates of intrauterine accretion, plus estimation of
daily losses, divided by the bioavailability (net absorption) of the nutrient [23].
As an example, this approach can be used to estimate calcium (Ca) requirements as follows:
● Intrauterine accretion rate (bone deposition) − 105 mg/kg per day

● Urinary losses − 5 mg/kg per day
● Cutaneous losses − 2 mg/kg per day
● Subtotal net Ca requirement − 112 mg/kg per day
● Net absorption of dietary Ca − 50 percent
● Total Ca intake to meet requirement − 224 mg/kg per day
Clinical conditions will affect absorption of nutrients. For example, absorption of Ca and phosphorus
is affected by postnatal age and intake of lactose, fat, and vitamin D. However, vitamin D may
contribute little to Ca absorption in premature infants [24]. (See "Management of neonatal bone
health", section on 'Enteral nutrition'.)
NUTRITIONAL ASSESSMENT AND MONITORING
Nutritional assessment of the premature infant requires determination of the daily energy and nutrient
requirements for optimal growth. This assessment requires a knowledge of nutritional biochemistry
and neonatal medical conditions.
The infant's progress is then monitored by the rate of growth and daily assessments of fluid, energy,
and nutrient intake. The nutrient targets are then readjusted if the target growth rate is not met. The
dietitian is a key resource to ensure an intake that meets nutrition goals and is compatible with the
infant's medical condition.
Rate of growth — Growth is monitored by serial measurements of weight, length, and head
circumference and compared with growth standards [10,25-27]:
● Weight is assessed daily, targeting a minimum increment of 15 to 20 g/kg per day from 23 to 36
weeks gestation [10,28]. Traditionally, once the infant reaches 2 kg body weight, the goal can be
a weight gain of 20 to 30 g per day.
● Length is assessed weekly, preferably using a length board, targeting an average increment of 1
cm per week.

● Head circumference is assessed weekly, targeting an average increment of 1 cm per week.
Growth parameters are charted on gender-specific growth curves for premature infants [11,29]. We
attempt to keep infants growing at rates above the 10th percentile on these charts whenever possible.
The charts are helpful for monitoring growth, but equally important is the computation of the weekly
rate of growth [27]. (See "Growth management in preterm infants", section on 'Normative growth
data'.)
Laboratory monitoring — The nutritional status of the very low birth weight (VLBW) infant (birth
weight ≤1500 g) is monitored by serial evaluations of biochemical indices.
At our institution, we perform these measurements as indicated in the table (table 3) until the values
are in the target range and stable. Other neonatal intensive care units (NICUs) may monitor more (or
less) frequently. These assessments include the following:
● Hemoglobin is monitored to assess for anemia, which may affect rate of growth. However, in the
NICU anemia generally is not caused by nutritional deficiencies. (See "Anemia of prematurity".)
● Bone mineral status is assessed by monitoring levels of serum calcium (Ca), serum phosphorus,
and serum alkaline phosphatase. Infants with persistently abnormal results suggesting the
possibility of rickets (low serum phosphorus and increased alkaline phosphatase activity) should
be further evaluated. In our practice, an alkaline phosphatase value >800 international units/L (on
two measurements one week apart) or alkaline phosphatase value >1000 international units/L
(on a single occasion) requires further evaluation including wrist radiographs. (See "Management
of neonatal bone health", section on 'Assessment and management'.)
● Protein status is assessed by monitoring levels of blood urea nitrogen (BUN). BUN >10 mg/dL
suggests protein sufficiency. There is no defined upper limit for a safe BUN, but some clinicians
are concerned if the value is >60 mg/dL (assuming normal creatinine and urine output), which
may occur in the setting of inadequate caloric input. Serum albumin reflects long-term protein
intake (half-life of 21 days) so it is usually not helpful as a marker of protein status in the NICU.
(See "Laboratory and radiologic evaluation of nutritional status in children", section on
'Transthyretin and albumin'.)
● Electrolytes (serum sodium, chloride, and bicarbonate) are evaluated in selected infants who
receive diuretics, who are fed unfortified human milk, whose intakes are limited, or who have
slow growth. Infants with abnormal results may require more frequent monitoring and potentially
supplementation.
● Zinc and copper may be measured in infants with unusual intestinal losses, such as those with
enterostomies or short bowel syndrome. These measurements are not needed in premature
infants without these conditions. (See "Chronic complications of short bowel syndrome in
children", section on 'Nutrient deficiencies'.)
The trend in biochemical indices may be more reflective of nutritional status than isolated values.
Infants who are receiving parenteral nutrition require more frequent monitoring, especially of
electrolytes and glucose. (See "Parenteral nutrition in premature infants", section on 'Monitoring'.)
INFANTS REQUIRING TUBE FEEDING
Infants weighing ≤1800 g birth weight (usually ≤32 weeks gestation) typically require tube feeding
until they are sufficiently mature to feed directly from the breast or artificial nipple. The approach
depends upon the infant's maturity and clinical condition. Our general approach is outlined below,
followed by sections providing the rationale.
Oral feeding should be initiated when the infant demonstrates signs of readiness, which typically
occurs when the tube-fed infant is between 32 and 34 weeks gestational age. (See 'Infants who can
feed orally' below.)
Overview of initiation and advancement of feeds — All neonatal intensive care units (NICUs)
should adopt a protocol to ensure prompt initiation and advancement of feeds; the details of timing,
composition, and rate of advancement vary. Our NICU's protocol for stable infants requiring tube
feedings (typically ≤1800 g birth weight) is outlined below (table 4). Infants with significant feeding
intolerance or other medical problems may progress more slowly.
● Colostrum – Beginning immediately after birth, we swab the oropharyngeal mucosa with
expressed colostrum every three hours. We continue to swab the oropharynx with mother's milk
until the infant is taking some feeds orally. Oropharyngeal colostrum provides immune benefits to
the infant as well as an early initiation of maternal milk expression, which favors overall milk
production [30-32].
● Parenteral nutrition – For infants ≤1500 g birth weight, "starter" parenteral nutrition (glucose,
amino acids, calcium [Ca], and lipids) is started within a few hours after birth to supply part of the
energy and nutrient needs. Other high-risk infants such as those with congenital bowel
anomalies, congenital heart disease, or congenital diaphragmatic hernia may also require early
parenteral nutrition. (See "Parenteral nutrition in premature infants", section on 'Parenteral
nutritional requirements'.)
● Trophic feeds – For all infants, small-volume ("trophic") feeds are started within the first day of
life and ideally within six hours of life if medically stable.

• The feeds are given via oropharyngeal or nasogastric tube at 15 to 20 mL/kg per day,
divided into boluses given every three hours. (See 'Trophic feeds' below and 'Bolus versus
continuous' below.)
• Feeding is begun with unfortified mother's own milk. If mother's own milk is not available, we
use pasteurized donor human milk for infants ≤1500 g birth weight; premature infant formula
may be used for those >1500 g birth weight [20,33]. (See 'Milk strength and content' below.)
• Trophic feeds may be given to infants who have an umbilical artery catheter (UAC) in place
or are undergoing medical treatment for patent ductus arteriosus (PDA). (See 'Adjustment
for concurrent medical conditions' below.)
● Advancement of feeds – Feeding volume is advanced gradually. As feeds are advanced, a

human milk fortifier (HMF) is added to boost the nutrient intake. In our NICU, the timing of
advancement and fortification depends upon the infant's birth weight; our protocol is outlined in
the tables (table 5A-C). The rate of advancement also depends on feeding tolerance, which is
assessed by serial monitoring of clinical signs and symptoms. (See 'Rate of volume increase'
below and 'Fortification of feeds' below and 'Feeding intolerance' below.)
As enteral feeds are advanced, the parenteral nutrition solution is gradually decreased. Because
energy needs are greater for enterally fed infants, the parenteral nutrition should not be
decreased isocalorically as enteral feeds are advanced (see 'Energy requirements' above). The
parenteral nutrition is discontinued when the enteral feeds reach 100 mL/kg per day.
● Target volume – The target volume for feeds is 160 mL/kg per day of fortified human milk. (See
'Target volume' below.)
Milk strength and content — Full-strength milk should be used throughout the feeding protocol,
based on a preponderance of evidence and clinical experience; whenever possible, human milk
should be used rather than formula. If mother's own milk is not available and the infant is <1500 g
birth weight, we use pasteurized donor human milk (with an HMF as described below) until the infant
is approximately 34 weeks postmenstrual age and preterm formula thereafter. There is evidence to
suggest that donor human milk is associated with lower rates of necrotizing enterocolitis (NEC) and
feeding intolerance in very low birth weight (VLBW) infants compared with preterm formula [33]. (See
'Fortification of feeds' below and "Human milk feeding and fortification of human milk for premature
infants", section on 'Donor human milk'.)
Feeding full strength formula triggers earlier and more consistent intestinal motility responses to
feeding compared with diluted formula [34] or water [35]. In addition, full enteral feeds may be
achieved more rapidly using a diet of human milk compared with formula. In a study of 127 premature

infants (birth weight ≤1250 g), infants fed at least 50 percent human milk achieved full enteral feeds
more rapidly than those fed formula alone [36].
Trophic feeds — We suggest early initiation of low-volume enteral feeds known as "trophic" feeds or
"gastrointestinal priming." For infants who are very premature or ill, the low-volume feeds usually are
continued for several days before advancing the milk volume [37]. Some providers may be
comfortable with a more rapid advancement of feeds, such as giving trophic feeds for only one to
three days, and adding HMF to human milk feeds early in the course of feeding advancement (see
'Fortification of feeds' below). Limited evidence supports this approach [38].
The safety of early trophic feeds was supported by a meta-analysis, which concluded that early
initiation of trophic feeds was not associated with an increased risk of NEC or all-cause mortality in
VLBW infants [5]. A separate meta-analysis also found no safety concerns with trophic feeding,
although it was unable to establish that this approach is advantageous because each study used
different outcome measures [39].
The rationale for early introduction of feeds is that lack of enteral nutrients impairs intestinal
development, manifested by diminished intestinal size and weight, atrophy of mucosa, and delayed
maturation of intestinal enzymes and motility; some of these effects may be mediated by diminished
production of gastrin, which is a trophic hormone for intestinal growth. In addition, lack of enteral
nutrients increases intestinal permeability and bacterial translocation, suggesting that it might
predispose to sepsis or other infectious complications [40-43].
Clinical benefits of early feeding in premature infants have been demonstrated in several randomized
trials [37,40,44-48]:
● Better feeding tolerance, permitting more rapid advances in feeding volume [44-46]
● More rapid maturation of intestinal motility patterns [40]
● Increased lactase activity [47]
● Higher serum levels of gastrointestinal hormones, including gastrin, gastric inhibitory polypeptide,
and enteroglucagon [40,43,44]
● Reduced intestinal permeability [48]
● Decreased risk of late-onset sepsis [49]
● Lower incidence of conjugated hyperbilirubinemia [45]
● Greater absorption of Ca and phosphorus [37], with lower serum alkaline phosphatase activity,
suggesting less osteopenia of prematurity [45]
Of note, most of these studies focused on a selected population of premature neonates with
particularly high risk of feeding intolerance and NEC. For example, in some studies, feedings were
administered during mechanical ventilation and while umbilical arterial and venous catheters were in

place [45,46,50]. Many of the infants also had the common comorbidities of prematurity including
PDA, intraventricular hemorrhage, and systemic hypotension. These data suggest that even infants
who are ill generally benefit from early introduction of low-volume feeds (ie, 10 to 25 mL/kg per day),
provided that they do not have major cardiovascular instability (severe acidosis, hypotension, or
hypoxemia).
Rate of volume increase — Feeding protocols are important tools to support progressive
advancement of feeds, combined with close monitoring of an infant's feeding tolerance, which in turn
varies with the infant's age and state of health.
The details of such protocols vary among centers, and the optimal rate for feeding advancement has
not been established. Traditionally, most protocols advance feeds at rates of 15 to 25 mL/kg/day for
VLBW infants who are healthy and who show no signs of feeding intolerance [51]. In our NICU, we
use this cautious approach (20 mL/kg/day) in the smallest infants but advance at rates of 25
mL/kg/day or more in infants weighing >1500 g, if tolerated (table 4).
There is some evidence that more rapid advancement of feeds can be successful when used with a
carefully managed protocol [52-56]. As an example, a systematic review concluded that for VLBW
infants (1000 to 1500 g), advancing feeding volume by 30 to 40 mL/kg/day (compared with 15 to 24
mL/kg/day) does not increase the risk for NEC [57]. Similarly, results from a meta-analysis suggested
that earlier advancement of enteral feedings (before the fourth day of life) compared with later
advancement of feedings (after four to seven days of life) leads to earlier achievement of full feeds
without increasing the risk of NEC [5]. A subsequent randomized trial evaluated outcomes of even
earlier advancement of feeds, in which all infants began trophic feeds on the first day of life, and
feedings were advanced by 20 to 24 mL/kg/day starting on the second (early feeding) or fifth (later
feeding) day of life [58]. Safety outcomes were similar among those managed with early versus later
progressive feeding. (See "Neonatal necrotizing enterocolitis: Prevention", section on 'Timing and
advancement of feeding'.)
Most protocols provide enteral feeds every three hours. However, one study suggests that a more
frequent feeding schedule improves feeding tolerance and reduces the time to attain full feedings.
This was illustrated in a study of VLBW infants that compared every two-hour with three-hour
feedings [59]. Infants receiving feedings every two hours had a shorter time to reach full enteral
feedings, a greater weight gain, fewer days when feedings were held, and fewer days of receiving
total parenteral nutrition. The magnitude of the effect was greater in infants who were less than 28
weeks gestation.
Fortification of feeds — Initial feeds are with unfortified human milk (mother's own milk or
pasteurized donor milk). As feeds are advanced, an HMF is added to boost the nutrient intake:

● In many NICUs, a bovine-derived HMF is used. In this case, we suggest using unfortified breast
milk until feeding volume reaches approximately 100 mL/kg per day, then begin fortifying feeds
with the HMF, providing 24 kcal/ounce. However, this reflects a traditional approach, and there
are no data to suggest that it is safer than earlier introduction of bovine-derived HMF. As an
example, some NICUs may choose to introduce bovine HMF when feeding volume reaches 60
mL/kg/day or even earlier, as a method to increase nutrient intake while weaning total parenteral
nutrition. Limited evidence suggests that this is safe [38].
● In other NICUs, an HMF derived from donor human milk may be available (eg, Prolact+6). In our
NICU, we use this type of HMF for infants ≤1250 g birth weight because of evidence that it leads
to fewer complications and improved growth compared with bovine-derived HMF. When using
this type of HMF, we start fortification when enteral feeds reach 60 mL/kg per day because early
introduction of this type of HMF was found to be safe in controlled trials. Some NICUs may
choose to introduce human milk-derived HMF start even earlier (eg, when feeding volume
reaches 20 to 40 mL/kg/day). Anecdotal experience suggests that early introduction of fortified
feeds is well tolerated when using an all human milk diet.
The thresholds for fortification and advancement of feeds vary among NICUs. The protocol that we
use in our NICU is shown in the tables (table 5A-C). Studies of different types of fortifiers are
summarized in a separate topic review. (See "Human milk feeding and fortification of human milk for
premature infants", section on 'Type of fortifier'.)
Target volume — The target volume for feeds is 160 mL/kg per day of fortified human milk. If the
HMF provides 4 kcal/ounce (typical for bovine-derived HMF), these feeds provide approximately 128
kcal/kg/day (table 6). If the HMF provides 6 kcal/ounce (typical for a human milk-derived fortifier),
these feeds provide approximately 130 kcal/kg/day. This target volume generally supports a weight
gain of 15 to 20 g/kg per day.
Feeding intolerance — Difficulty tolerating enteral feedings is a major problem for premature infants,
especially in those with gestational age below 28 weeks, those who require positive pressure support,
or those who have positive blood cultures [60]. Factors that affect feeding tolerance include intestinal
motility, gastric emptying, stool output, digestive enzymes, type of feeds (formula or human milk),
rapidity of feeding, volume of feeding, concentration of milk, concomitant medications, and medical
conditions. An infant's intolerance of enteral feeding is a primary factor for clinical decision-making to
initiate, advance, and discontinue feedings. Thus, feeding intolerance may be a major determinant of
the duration of hospitalization.
Clinical assessment — Serial assessment of feeding tolerance is important to management of

enteral feeding protocols, but there are no universally agreed upon criteria on which to base this

judgment.
● Symptoms and signs suggesting feeding intolerance – Symptoms of feeding intolerance are
nonspecific and vary between patients. Most clinicians use a composite of the following clinical
symptoms to determine feeding intolerance [61]:
• Emesis
• Abdominal examination – Distention or tenderness, bowel sounds increased or absent
• Gastric residual fluid − Change in quantity of fluid (usually increased volume) or change in
color to green (bilious) or red (blood)
• Stool output − Any change in the frequency of stool output and presence of blood in stools
• Other – Increased episodes of apnea and bradycardia, diminished oxygen saturation
(desaturation events), and lethargy
Any of these symptoms should prompt the clinician to reassess the infant to evaluate the possibility of
feeding intolerance and/or underlying pathology.
● Gastric residual fluid – The gastric residual volume (GRV) is the amount of milk left in the
stomach several hours after a feeding and is typically measured just prior to a scheduled feeding
[62]. It is an indirect measure of gastric emptying and intestinal function and/or pathology, but is
nonspecific because it may be affected by the position of infant or position of feeding tube.
Although some NICUs routinely measure GRVs in asymptomatic infants, there is no evidence
that practice is a useful guide for feeding advancement or helps to avoid or detect the onset of
NEC [63,64]. As a result, many NICUs have abandoned the routine measurement of GRV
entirely. However, measurement of GRV may still be useful as part of the assessment of an
individual infant with symptoms of feeding intolerance, especially abdominal distension or
vomiting.
● Bloody or bilious gastric fluid – The appearance of the gastric residual fluid also provides
information about feeding tolerance. Gastric fluid that is green (bilious) could indicate intestinal
obstruction, but more often indicates overdistention of the stomach and retrograde reflux of bile
into the stomach [62]. Blood-tinged gastric fluid could indicate an inflammatory process or may
be due to a slight mucosal irritation from the indwelling gastric tube.
● Stool output – Stool output provides an index of intestinal motility. Some clinicians withhold the
initial enteral feeding until after the immature infant has passed a stool; some clinicians use a
small glycerin suppository to stimulate stool output. More rapid evacuation of meconium during
the first week of life is associated with improved feeding tolerance in extremely low birth weight
(ELBW) infants [65]. Most clinicians perform imaging before considering giving a suppository, to
rule out intestinal obstruction.
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● Blood in stools – The presence of gross blood in stools is usually interpreted as a sign of
feeding intolerance and should also raise concern for NEC, especially if combined with other
symptoms such as abdominal distension, temperature instability, or increased apneas (see
"Neonatal necrotizing enterocolitis: Clinical features and diagnosis"). Measurement of occult
blood is not supported by the data and is not recommended. Occult blood in the stool is common
in infants in an NICU, and its clinical implications are unclear. As an example, in a study of 95
infants with birth weights ≤1800 g, 58 percent had at least one occult blood positive stool during
the first six weeks of life [66]. Six of the infants developed NEC, two of whom had occult blood in
their stool and four of whom had no blood in their stool.
Several conditions other than NEC also may cause gross blood in stool and should be
considered when evaluating an infant with this finding:
• Swallowed blood from delivery, suctioning, intubation, gastric tubes, and breast milk from
mothers with nipple trauma.
• Anal excoriation or fissures.
• Colitis due to infection (such as cytomegalovirus) or milk protein sensitivity. (See "Food
protein-induced allergic proctocolitis of infancy".)
• Coagulopathy or thrombocytopenia.
• Abnormality of the gastrointestinal tract. These are rare and include Meckel's diverticulum,
duplication of the small intestine, hemangiomas, lymphangiomas, gastric and duodenal
ulcers, intestinal stricture, volvulus, and intussusception. (See "Lower gastrointestinal
bleeding in children: Causes and diagnostic approach", section on 'Neonatal period'.)
Management
● Adjustment of feedings – When one or more of the above signs raise significant concerns for
feeding intolerance, the clinician may choose to withhold feedings. In this case, the infant should
be carefully reassessed and examined prior to the next feeding to aid the decision whether to
resume feedings and/or to make changes in the regimen. Minor or isolated symptoms of feeding
intolerance often can be corrected by reducing the volume of feeds or postponing advances in
feeding volume. Diluting feeds is not a useful strategy. Multiple or severe symptoms usually
require a full evaluation for an underlying problem such as NEC and stopping feeds temporarily.
It is important to avoid withholding feeds for prolonged periods of time because lack of enteral
feeding hastens the complications of parenteral nutrition and intestinal atrophy.

● Pharmacotherapy – Pharmacotherapy is not recommended as a strategy to manage feeding

intolerance in premature infants because there is little evidence that any agent is effective for this
purpose and each is associated with risks.
• Acid suppressants – Acid-suppressing medications such as histamine type 2 receptor

antagonists should not be used to treat feeding intolerance. Although these agents were
historically used to treat preterm infants with feeding intolerance, they appear to be
associated with higher rates of NEC [67]. Similar considerations may apply to acid
suppression with proton pump inhibitors [68]. (See "Neonatal necrotizing enterocolitis:
Pathology and pathogenesis", section on 'Agents that reduce gastric acidity'.)
• Erythromycin – Evidence does not support the use of erythromycin for treatment of feeding
intolerance in preterm infants. Although erythromycin has prokinetic properties, the results of
clinical trials in this population are inconsistent, and it is unclear if it is effective [69,70]. As
an example, a meta-analysis that included 10 randomized studies found no overall evidence
of efficacy, except perhaps for higher treatment doses [71]. Moreover, there are reports of an
association between early use of this drug (in the first month) and the development of
infantile hypertrophic pyloric stenosis [72]. (See "Infantile hypertrophic pyloric stenosis",
section on 'Macrolide antibiotics'.)
Techniques for tube feeding — Tube feeding is an essential tool in enteral nutrition because
premature infants less than 32 weeks gestation at birth typically are unable to suck and/or coordinate
sucking and swallowing with breathing. Tube feeding varies by method (intermittent bolus versus
continuous feeds) and by route (orogastric, nasogastric, transpyloric, or gastrostomy).
The device used for tube feeding also depends on the duration of the proposed therapy. For infants
who are tube-fed only because of their prematurity, a temporary orogastric or nasogastric tube is
used because they will eventually be able to orally feed. Infants with major congenital anomalies may
require a semipermanent gastrostomy.
Bolus versus continuous — Most premature infants can and should be fed with bolus
(intermittent) feeds. The bolus feeding method mimics the typical feeding routine of term infants and
children and stimulates greater hormonal responses than continuous infusions [73]. The bolus
technique also has practical advantages because it does not require an infusion pump.
The continuous feeding technique may be useful for infants with underlying gastrointestinal disease,
in whom it has been associated with increased nutrient absorption [74]. Continuous feeds are usually
used for infants who are fed via the transpyloric route (to avoid "dumping syndrome," which is seen in
older individuals when formula enters rapidly into the jejunum), and for those who have had intestinal
surgery. An alternative option is to increase the duration of time that bolus feedings are administered

(ie, slow bolus feeds). In a small group of infants who appeared intolerant to bolus feedings, duodenal
motility and gastric emptying appeared to improve following the lengthening of the bolus feeding from
30 min to up to 2 hours [75].
Studies comparing bolus with continuous feeds in infants without underlying gastrointestinal disease
generally show no nutritional advantage of either technique. One review of seven trials involving 511
premature infants with birth weights ≤1500 g compared continuous versus intermittent bolus feeds
[76]. Overall, there was no difference in the time to achieve full enteral feeds or regain birth weight, or
in growth rates or days to discharge, except that a subgroup analysis suggested a slight possible
advantage of continuous feeds on growth rate for infants ≤1000 g. In addition, there was no difference
in the rate of NEC. However, it is difficult to make universal recommendations based upon this review
because of the small sample sizes, methodologic limitations, inconsistencies in controlling variables,
and the conflicting results of the studies that were included.
Another possible advantage of bolus feeds is that this method may reduce the loss of human milk fat
in the feeding tube. In one study, fat loss was greater (up to 40 percent) with continuous feedings
[77].
Gastric versus transpyloric — Most premature infants can and should be given gastric rather
than transpyloric feeds. Transpyloric feeding is used in some institutions for selected infants with
persistent gastric residuals or emesis in the absence of obvious intestinal pathology, but selection of
infants for transpyloric feeds varies among institutions and clinicians.
The potential benefits and risks of transpyloric feeds were evaluated in a systematic review of nine
trials [78]. There was no difference in the rate of short-term growth (ie, weight, length, head
circumference, and skinfold thickness) between transpyloric versus intragastric feeds. Although there
was an increased risk of gastrointestinal disturbance and mortality associated with the transpyloric
approach, this may have been due to selection bias, with allocation of the less mature and sicker
infants to transpyloric feeds. There was no difference in the incidence of adverse events including
NEC, intestinal perforation, and aspiration pneumonia. The authors concluded that there was no
benefit to the routine use of transpyloric feeding in preterm infants, while acknowledging
methodologic weaknesses in all of the included trials.
Adjustment for concurrent medical conditions — Enteral feeds usually can be implemented and
advanced regardless of other medical interventions, as long as the infant is stable. Specific
considerations are:
● Infants with an umbilical artery catheter (UAC) – Enteral feeds can be initiated and advanced
in infants who have a UAC in place, as long as the UAC is functioning properly. In the past,
concerns were raised about proceeding with enteral feeding in infants who have an indwelling

UAC. However, studies of trophic feeds included many infants with a UAC in place, and no
untoward events were reported [37,45]. Furthermore, a randomized trial found no increased risk
of enteral feeding with a UAC in place [50].
● Infants receiving treatment for patent ductus arteriosus (PDA) – In our NICU, we generally
provide trophic feeds during medical treatment for PDA if the infant was already receiving feeds
prior to starting treatment, although we do not advance feeds until the PDA treatment is
completed. This strategy is supported by a study in infants <1250 g birth weight that showed that
premature infants who received trophic feedings during ibuprofen or indomethacin treatment for a
PDA did not have an increased risk of adverse events, including NEC. Infants who received
trophic feeds achieved their target for enteral feedings sooner compared with those who did not
[79].
● Infants receiving red blood cell transfusions – In many NICUs, feeds are held for several
hours during and after a red blood cell transfusion, although there is no strong evidence to guide
this practice. Several studies (primarily retrospective) have suggested an association between
red blood cell transfusions and NEC (transfusion-associated NEC) [80,81]. However, it is
possible that the risk of NEC might be related to the degree of anemia rather than the red blood
cell transfusion [82]. (See "Neonatal necrotizing enterocolitis: Prevention", section on 'Severe
anemia and transfusion'.)
INFANTS WHO CAN FEED ORALLY
Readiness — Oral feeding should be initiated as soon as the infant demonstrates signs of readiness,
which typically occurs when the tube-fed infant is between 32 and 34 weeks gestational age. Initiating
oral feeds including breastfeeding is discussed in a separate topic review. (See "Breastfeeding the
preterm infant".)
Although there is some variability, many preterm infants born at >34 weeks gestation can be
completely fed orally from birth; others require only a brief period of tube feeding.
Diet — Infants with very low birth weights (VLBWs) generally benefit from an enriched diet before and
after discharge, especially if there is slow growth or evidence of protein insufficiency or osteopenia on
laboratory monitoring [83,84].
Enriched diet
● Indications – Some neonatal intensive care units (NICUs) routinely use an enriched diet for
VLBW infants, with careful monitoring to avoid excessive growth. In our institution, we provide
this diet to any infant with any of the following characteristics:
• Birth weight ≤1800 grams.
• Unable to consume at least 180 mL/kg/day due to fluid restriction or poor feeding.
• Abnormalities in routine laboratory tests suggesting suboptimal bone health, such as low
serum phosphorus or elevated alkaline phosphatase activity with a persistently abnormal
trend, or low blood urea nitrogen (BUN) suggesting inadequate protein intake. (See
"Management of neonatal bone health", section on 'Assessment and management'.)
● Implementation – Several approaches can be used to enrich the diet; the choice depends upon
the available products and whether the infant is feeding directly from the breast or from an
artificial nipple:
• For infants who are feeding at the breast, provide two or three feedings daily with a
transitional "post-discharge" formula (22 kcal/ounce) or premature infant formula (30
kcal/ounce). These feeds generally substitute for the breast milk feed for a total of at least
eight feeds daily (ie, two formula feeds with at least six feeds at the breast or three formula
feeds with at least five feeds at the breast).
• For infants who are feeding from an artificial nipple, add bovine milk-based fortifier to breast
milk (to provide 22 or 24 kcal/oz); or mix the premature infant formula with mother's milk. Do
not use powdered forms of fortifier or formula until the infant is at least 44 weeks
postmenstrual age.
• For infants fed only formula, we use a transitional "post-discharge" formula (22 kcal/oz).
A comparison of the nutrients provided by these different discharge feeding strategies is shown
in the table (table 7). We change to the discharge diet three to four days prior to the discharge
date to ensure tolerance and observe growth. Management of feeds after discharge is discussed
in more detail in a separate topic review. (See "Growth management in preterm infants", section
on 'Routine nutrient supplementation'.)
Standard diet — For infants who do not meet the above criteria for an enriched diet, we provide
feedings of unfortified human milk or term infant formula at 20 kcal/oz, with target volumes of 180
mL/kg/day, and monitor growth closely.
DISCHARGE PLANNING
Discharge criteria — We begin planning for nutrition after discharge when the premature infant has
attained approximately 50 percent of the target for full oral enteral feeds. We consider discharge from

the neonatal intensive care unit (NICU) when the premature infant is maintaining body temperature in
a crib and meets both of the following nutritional milestones:
● Feeding by mouth with good documented intake of one of these diets:
• Standard diet (20 kcal/oz) at >180 mL/kg/day

• Enriched diet (usually 22 kcal/oz, but it is also reasonable to use 30 kcal/oz, to provide
maximum nutrition with the smallest amount of non-breast milk diet) at >160 mL/kg/day
• Breastfeeding with complementary formula feeds of 22 to 30 kcal/oz
• Exclusive breastfeeding
● Established growth rate on the above feeds:
• Infants ≤2 kg – Gaining at least 15 to 20 g/kg per day

• Infants >2 kg – Gaining 20 to 30 g per day (not g/kg per day)
Ongoing monitoring of growth after discharge is important to verify whether optimal growth will
continue on ad libitum breastfeeding or standard term formula. When an enriched diet is used, we
suggest continuing it for at least six months post-discharge, as long as the infant does not gain too
rapidly and cross growth percentiles upward. It is important to communicate the plan for an enriched
diet to the clinician who will manage the infant's care after discharge. (See "Growth management in
preterm infants", section on 'After discharge'.)
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions around
the world are provided separately. (See "Society guideline links: Nutrition support (parenteral and
enteral nutrition) in infants and children" and "Society guideline links: Breastfeeding and infant
nutrition".)
SUMMARY AND RECOMMENDATIONS
● The goals of nutritional management for premature infants are to mimic intrauterine rates of
growth and nutrient accretion. The initial assessment calculates a target for energy (calories) and
other nutrients needed to achieve optimal growth, and targets are then adjusted based on the
infant's progress. (See 'Nutritional assessment and monitoring' above.)
● Tube feeding is typically needed for infants weighing ≤1800 g at birth (usually ≤32 weeks
gestation). In our neonatal intensive care unit (NICU), we use the following protocol for

introducing and advancing feeds, which varies depending on the size and maturity of the infant
(table 4):
• Expressed colostrum or breast milk is swabbed onto the oropharyngeal mucosa, starting
after birth and continuing until the infant is taking some feeds orally.
• Parenteral nutrition solutions (glucose, amino acids, calcium [Ca], vitamins, and lipids) are
started as early as feasible and gradually decreased as enteral feeds increase. (See
"Parenteral nutrition in premature infants".)
• Trophic feeds are given at 15 to 20 mL/kg per day, ideally starting within six hours after birth
(when medically feasible), using mother's own milk or pasteurized donor human milk.
Trophic feeds are traditionally given for three to seven days, depending on the infant's birth
weight, before advancing. However, the optimal duration of trophic feeds has not been
established, and limited evidence suggests that more rapid advancement of feeds is
probably safe. As an example, for very low birth weight (VLBW) infants who are stable and
on an exclusively human milk diet, some NICUs may give trophic feeds for only one to three
days and add human milk fortifier (HMF) to human milk feeds early in the course of feeding
advancement, without increasing rates of complications. When donor human milk is used,
we generally switch to premature formula around 34 weeks postmenstrual age. (See 'Milk
strength and content' above and 'Trophic feeds' above.)
• The volume of feedings is commonly advanced by 20 mL/kg per day in the smallest infants
and 25 to 40 mL/kg per day in infants >1500 g birth weight. The feeding volumes and rate of
advancement depend upon the size, maturity, and feeding tolerance of the infant; our
protocol is outlined in the tables (table 5A-C). (See 'Rate of volume increase' above.)
• The target volume for feeds is 160 mL/kg per day of fortified human milk, which provides
approximately 24 kcal/ounce if a bovine fortifier is used, or 26 kcal/ounce if a typical donor
human milk-derived fortifier is used (table 6). The target volume generally is one that
supports a weight gain of more than 15 to 20 g/kg per day. (See 'Target volume' above.)
(See 'Overview of initiation and advancement of feeds' above.)
● Although there are no universally agreed upon criteria to judge feeding intolerance in premature
infants, we use the following clinical criteria (see 'Feeding intolerance' above):
• Emesis
• Presence of bile or blood
• Changes in stool output and presence of blood
• Abdominal distention, tenderness, and bowel sounds
• Increased episodes of apnea and bradycardia, diminished oxygen saturation, or lethargy
Most clinicians use a composite of the above criteria as opposed to a single factor. When
present, these parameters should prompt the clinician to evaluate the infant for causes of feeding
intolerance. On occasion, the clinician may choose to withhold feedings because of one or more
of the above signs. Careful assessment and examination prior to the next feeding generally aid
the decision whether to resume feedings and/or to make changes in the feeding regimen. (See
'Feeding intolerance' above.)
● Oral feeding should be initiated as soon as the infant demonstrates signs of readiness, which
typically occurs when the tube-fed infant is between 32 and 34 weeks gestational age. Although
there is some variability, most preterm infants born at >34 weeks gestation do not require a
prolonged period of tube feeding, and many can be completely fed orally from birth. Discharge
feeding strategies depend on birth weight, infant growth, and whether the infant is breastfeeding
or solely formula-fed (table 7). (See 'Infants who can feed orally' above.)
ACKNOWLEDGMENT
The editorial staff at UpToDate would like to acknowledge Richard J Schanler, MD, who contributed to
an earlier version of this topic review.
Use of UpToDate is subject to the Subscription and License Agreement.
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Topic 5014 Version 44.0

GRAPHICS
Estimated daily energy requirements for growing premature infants
Factor Kcal/kg Comment
Resting energy expenditure 50 Resting metabolic rate
Activity 15 30 percent above resting
Cold stress 10 Thermoregulation
Synthetic effect of feeding 8 Dietary thermogenesis
Fecal loss 12 10 percent of intake
Growth 25 Calories stored
Total caloric requirement 120
Adapted from: Sinclair JC. Clin Obstet Gynecol 1971; 14:840.
Graphic 59766 Version 4.0

Recommended daily requirements for enteral nutrition in premature infants
Component (unit) Enteral intake, unit/kg
Water (mL) 135 to 200
Energy (kcal) 105 to 130
Protein (g) 3.5 to 4.5
Fat (g) 5 to 7
Carbohydrate (g) 7 to 20
Electrolytes, minerals, and trace elements

Sodium (mEq) 3 to 5
Potassium (mEq) 2 to 3
Chloride (mEq) 3 to 7
Calcium (mg) 100 to 220
Phosphorus (mg) 60 to 140
Magnesium (mg) 7.9 to 15
Zinc (mcg) 1000 to 3000
Copper (mcg) 120 to 150
Chromium (mcg) 0.1 to 2.25
Manganese (mcg) 0.7 to 7.75
Vitamins
Vitamin A (int. unit) 700 to 1500
Vitamin D (int. unit) 400*
Vitamin E (int. unit) 6 to 12
Vitamin K ¶ (mcg) 8 to 10
Folic acid (mcg) 25 to 50
Niacin (mg) 3.6 to 4.8
Pyridoxine (mcg) 150 to 210
Riboflavin (mcg) 250 to 360
Thiamine (mcg) 180 to 240
Vitamin B12 (mcg) 0.3
Vitamin C (mg) 18 to 24
* Intake is not adjusted for weight.

¶ Does not include 0.5 to 1 mg vitamin K given at birth.
Adapted from:
1. Kleinman RE, Greer KF (eds). American Academy of Pediatrics. Committee on Nutrition. Pediatric Nutrition Handbook
7th edition. American Academy of Pediatrics, Elk Grove Village, Illinois. 2014.
2. Koletzko B, Poindexter B, Uauy R. Nutritional Care of Preterm Infants. Scientific Basis and Practical Guidelines. World
Review of Nutrition and Dietetics Vol. 110. Switzerland. 2014.

Nutritional assessment of infants <1500 grams birthweight - Laboratory monitoring
Laboratory
Frequency
test
Hemoglobin, After the infant is receiving enteral iron supplementation, measure every 2 weeks until results are
hematocrit stable. Recheck prior to hospital discharge.
Calcium, In infants <1500 g birth weight, measure starting at 5 to 6 weeks of age. Measure weekly until
phosphorus, alkaline phosphatase is <600 IU/L and serum phosphorus is >4.5 mg/dL. Once stable beyond
alkaline these thresholds, no need to repeat.
phosphatase
Blood urea Measure in infants with poor growth. BUN <10 mg/dL may suggest the need for more protein
nitrogen (BUN) intake.
Serum In selected infants (those receiving diuretics, or feeds of unfortified human milk, or limited intake,
electrolytes or slow growth).
VLBW: very low birthweight (birthweight ≤1500 g).
Adapted from: Anderson D and E Bacon. Nutrition Assessment. In: Nutrition: Guidelines for Acute Care of the Neonate 26th
Ed., Anderson D, Hair AB (Eds), Baylor College of Medicine, Section of Neonatology, Department of Pediatrics. 2018.

Suggested feeding schedules for infants in the neonatal intensive care unit (NICU)
based on birth weight
Initiation rate Advancement rate

Birth weight (g) When to advance
(mL/kg/day) (mL/kg/day)
≤750 15 to 20 Maintain for 3 to 5 days 10 to 20
751 to 1250 15 to 20 Maintain for 3 days 10 to 20
1251 to 1500 20 If feeds tolerated, may 20

advance after 24 to 48
hours
1501 to 2000 20 If feeds tolerated, may 25 to 40

advance after 24 to 48
hours
2001 to 2500 25 to 30 Advance daily 25 to 40
>2500 and stable 50 or ad-lib with minimum Advance daily 25 to 40

(Infants with symptomatic (Infants with symptomatic
or cyanotic congenital heart or cyanotic congenital heart
disease: 20) disease may need 20 mL/kg
for a longer period of time)
Individual initiation and advancement rates based on patient's weight, age, and clinical status. Feedings for infants
<1500 g are usually best given on a pump, distributed over 30 to 60 minutes.
Reproduced with permission from: Guidelines for Acute Care of the Neonate, 26th edition (2018-2019), Fernandes CJ, Pammi
M, Katakam L, et al (Eds), Baylor College of Medicine, Houston 2014. Copyright © 2018 Baylor College of Medicine.

Guidelines for feeding advancement – Newborn infants with birth weight ≤750 g
Day Feeding
PN Lipids Total fluid*
of Feeding kcal/oz volume
(mL/kg/day) (mL/kg/day) (mL/kg/day)
life (mL/kg/day)
1 EBM 20 15 to 20 ¶ 100 2.5 Δ 130
2 EBM 20 15 to 20 100 2.5 to 5 140
3 EBM 20 15 to 20 100 5 to 10 140
4 EBM 20 15 to 20 100 10 to 15 140
5 EBM 20 15 to 20 110 15 150
6 EBM 20 40 95 15 150
EBM 20 60 75 15 150
OR EBM with 26 60 75 15 150

7 donor human
milk-derived
HMF ◊
EBM 20 80 55 to 70 15 or off lipids 150
OR EBM with 26 80 55 to 70 15 or off lipids 150

8 donor human
milk-derived
HMF ◊
EBM 20 100 50 0 150
OR EBM with 26 100 50 0 150

9 donor human
milk-derived
HMF ◊
EBM with 24 100 50 0 150

bovine HMF §
10 OR EBM with 26 120 Off PN 0 120

donor human
milk-derived
HMF ◊
EBM with 24 120 Off PN 0 120

bovine HMF §
11 ¥ OR EBM with 26 140 0 0 140

donor human
milk-derived
HMF ◊
EBM with 24 140 0 0 140

bovine HMF §
12 OR EBM with 26 150 to 160 0 0 150 to 160

donor human
milk-derived
HMF ◊
EBM with 24 150 to 160 0 0 150 to 160

bovine HMF §
13 OR EBM with 26 150 to 160 0 0 150 to 160

donor human
milk-derived
HMF ◊

This table outlines the protocol used for stable infants in the NICU at Texas Children's Hospital. Protocols used in other
NICUs are similar, but the details of timing, composition, and rate of advancement vary. Infants with significant
feeding intolerance or other medical problems may progress more slowly.
PN: parenteral nutrition; EBM: expressed breast milk; HMF: human milk fortifier; NICU: neonatal intensive care unit.
* Anticipated total fluids include PN, lipids, any other intravenous fluids, medications and flushes. Volume available for PN may
differ depending on volume of medications, flushes, etc. Trophic feeds (15 to 20 mL/kg/day) generally do not count towards
total fluid.
¶ Begin enteral feeds within the first day of life if the infant is medically stable (ie, not requiring pressors except low dose
dopamine).
Δ For infants ≤750 g birth weight, initiate lipids at 2.5 mL/kg/day.
◊ Donor human milk-derived HMF (Prolacta+6) is preferred for infants <1250 g birth weight (rather than bovine HMF). If this
is available, add it to EBM when the feeding volume reaches 60 mL/kg. This increases the caloric density from 20 kcal/oz to 26
kcal/oz.
§ If donor human milk-derived HMF is not available, then continue on unfortified EBM until feeding volume reaches 100
mL/kg, then begin to fortify feeds with liquid or bovine HMF (eg, Similac HMF, Enfamil HMF, or Nestle products). These bovine
HMFs add 4 kcal/oz. The protein and nutrient content varies somewhat among brands.
¥ After PN is discontinued, add a liquid multivitamin (eg, Poly-vi-sol) unless the HMF includes multivitamins (as examples,
Similac HMF contains multivitamins, and Prolacta+6 HMF does not). After 14 days of age, add liquid iron (eg, Fer-in-sol),
providing 2 to 3 mg/kg of elemental iron (for infants <1500 g birth weight not on PN).
Adapted with permission from: Guidelines for Acute Care of the Neonate, 26th edition (2018-2019), Fernandes CJ, Pammi M,
Katakam L, et al (Eds), Baylor College of Medicine, Houston 2014. Copyright © 2018 Baylor College of Medicine.

Guidelines for feeding advancement – Newborn infants with birth weight 751 to
1250 g
Day Feeding
life (mL/kg/day)
1 EBM 20 15 to 20 ¶ 80 5 to 10 Δ 80 to 110
2 EBM 20 15 to 20 80 to 100 5 to 10 120 to 130
3 EBM 20 15 to 20 80 to 100 10 to 15 120 to 130
4 EBM 20 40 80 15 120 to 135
EBM 20 60 70 15 150
OR EBM with 26 60 70 15 150

5 donor human
milk-derived
HMF ◊
EBM 20 80 50 to 70 15 or off lipids 150
OR EBM with 26 80 50 to 70 15 or off lipids 150

6 donor human
milk-derived
HMF ◊
EBM 20 100 50 0 150
OR EBM with 26 100 50 0 150

7 donor human
milk-derived
HMF ◊
EBM with 24 100 50 0 150

bovine HMF §
8 OR EBM with 26 120 Off PN 0 120

donor human
milk-derived
HMF ◊
EBM with 24 120 Off PN 0 120

bovine HMF §
9¥ OR EBM with 26 140 0 0 140

donor human
milk-derived
HMF ◊
EBM with 24 140 0 0 140

bovine HMF §
10 OR EBM with 26 150 to 160 0 0 150 to 160

donor human
milk-derived
HMF ◊
EBM with 24 150 to 160 0 0 150 to 160

bovine HMF §
11 OR EBM with 26 150 to 160 0 0 150 to 160

donor human
milk-derived
HMF ◊

total fluid.
¶ For infants <1000 g, begin enteral feeds on the first day of life if the infant is medically stable (eg, not requiring pressors
except low dose dopamine). For those >1000 g, begin enteral feeds within 6 to 12 hours of birth if the infant is medically
stable.
Δ For infants 751 to 1000 g birth weight, initiate lipids at 5 mL/kg/day.
◊ Donor human milk-derived HMF (Prolacta+6) is preferred for infants <1250 g birth weight (rather than bovine HMF). If this
is available, add it to EBM when the feeding volume reaches 60 mL/kg. This increases the caloric density from 20 kcal/oz to 26
kcal/oz.
§ If donor human milk-derived HMF is not available, then continue on unfortified EBM until feeding volume reaches 100
mL/kg, then begin to fortify feeds with liquid or bovine HMF (eg, Similac HMF, Enfamil HMF, or Nestle products). These bovine
HMFs add 4 kcal/oz. The protein and nutrient content varies somewhat among brands.
¥ After PN is discontinued, add a liquid multivitamin (eg, Poly-vi-sol) unless the HMF includes multivitamins (as examples,
Similac HMF contains multivitamins, and Prolacta+6 HMF does not). After 14 days of age, add liquid iron (eg, Fer-in-sol),
providing 2 to 3 mg/kg of elemental iron (for infants <1500 g birth weight not on PN).

Guidelines for feeding advancement – Newborn infants with birth weight 1251 to
1500 g
Day Feeding
life (mL/kg/day)
1 EBM 20 20 ¶ 70 10 80
2 EBM 20 40 60 15 100 to 120
3 EBM 20 60 40 15 100 to 120
4 EBM 20 80 40 Off lipids 100 to 120
5 EBM 20 100 50 0 150
6 EBM with 24 100 50 0 150

bovine HMF Δ
7 EBM with 24 120 Off PN 0 120

bovine HMF
8 EBM with 24 140 0 0 140

bovine HMF
EBM with 24 150 to 160 0 0 150 to 160

9◊
bovine HMF
total fluid.
¶ Begin enteral feeds within 6 to 12 hours of birth if the infant is medically stable (eg, not requiring pressors except low dose
dopamine).
Δ After one day on feeding volume 100 mL/kg, begin to fortify feeds with liquid or bovine HMF (eg, Similac HMF, Enfamil HMF,
or Nestle products). These bovine HMFs add 4 kcal/oz. The protein and nutrient content varies somewhat among brands.
◊ Add liquid iron (eg, Fer-in-sol), providing 2 to 3 mg/kg of elemental iron (for infants <1500 g birth weight). The infant
should be at least 14 days of age for iron supplementation.

Intakes of key nutrients from various enteral nutrition feedings for preterm infants,
assuming milk intake of 160 mL/kg per day [1,2]
EBM + donor
EBM + bovine EBM + bovine
human milk-
Nutrients per Recommended fortifier fortifier
derived
kg/day targets (powder)* at (liquid)* at 24
fortifier ¶ at 26
24 kcal/oz kcal/oz
kcal/oz
Energy (kcal) 105 to 130 128 128 130
Protein (g) 3.5 to 4.5 3.0 to 3.2 3.9 to 4.1 3.9
Calcium (mg) 100 to 220 176 to 218 185 to 191 195
Phosphorus (mg) 60 to 140 98 to 125 101 to 108 102
Iron (mg) 2 to 4 0.6 to 2.4 0.7 to 2.4 0.3
EBM: expressed breast milk.

* Bovine human milk fortifiers (powdered or liquid) are designed to provide 24 kcal/oz when mixed with human milk. This
table shows the range of protein and mineral content among different commercial brands commonly used in the United States.
The protein is derived from cow's milk. Depending on the brand used, the protein may be intact or hydrolyzed.
¶ Prolacta is the brand name for a liquid fortifier derived from donor human milk. When prepared as directed, EBM
supplemented with Prolacta +6 provides approximately 26 kcal/ounce.
References:
1. Pediatric Nutrition Handbook, 7th ed, Kleinman RE, Greer FR (Eds), Academy of Pediatrics, Elk Grove Village, Illinois
2014. p.83.
2. Nutritional Care of Preterm Infants. Scientific basis and practical guidelines, Koletzko B, Poindexter B, Uauy R (Eds),
World Review of Nutrition and Dietetics, Switzerland 2014.

Intakes of key nutrients from typical enriched post-discharge feedings for preterm
infants, assuming milk intake of 160 mL/kg per day
Feeding Breastfeeding (or bottle feeding with expressed

Formula
strategy breast milk)
Breast milk × 6 Breast milk × 5

Breast milk × 6
feeds feeds
feeds Premature
- and - - and -
Strategy for - and - discharge
premature premature
enrichment premature formula (22
discharge discharge
formula [3] (30 kcal/oz)
formula [1,2] (22 formula [1,2] (22
kcal/oz) × 2 feeds
kcal/oz) × 2 feeds kcal/oz) × 3 feeds
Energy 112 113 120 117

(kcal/kg/day)
Protein (g/kg/day) 1.9 2.2 2.3 3.4
Calcium 59 to 64 70 to 76 94 to 100 125 to 144

(mg/kg/day)
Phosphorus 34 to 35 41 to 42 49 to 56 74 to 80
(mg/kg/day)
This table uses the following assumptions:

Feeding intake is 160 mL/kg/day.
Each feed is 20 mL (and breastfeeds are assumed to provide about 20 mL per feed).
Breast milk provides 20 kcal/oz with 0.9 g/dL of protein. [4]
For infants who are less than 44 weeks gestational age, a liquid formulation of premature discharge formula [1,2] or
premature formula [3] should be used rather than a powdered formulation. Nutrient composition of these formulas are
based upon commonly used commercial brands, as cited.
References:
1. Similac Neosure (premature discharge formula). Nutrition information available at: https://abbottnutrition.com/similac-
neosure (Accessed on August 16, 2018).
2. Enfamil Enfacare (premature discharge formula). Nutrition information available at:
https://www.meadjohnson.com/pediatrics/us-en/product-information/products/premature/enfamil-enfacare (Accessed
on August 16, 2018).
3. Similac Special Care 30. Nutrition information available at: https://abbottnutrition.com/similac-special-care-30
(Accessed on August 16, 2018).
4. Pediatric Nutrition Handbook, 7th ed, Kleinman RE, Greer FR (Eds), American Academy of Pediatrics, Elk Grove Village,
Illinois 2014.

Contributor Disclosures
Amy B Hair, MD Grant/Research/Clinical Trial Support: Prolacta Bioscience [Research support (Human milk
cream study and human milk cardiac study)]; Fresenius Kabi [Research support (Randomized SMOF
trial)]. Steven A Abrams, MD Grant/Research/Clinical Trial Support: Fresenius Kabi [Parenteral nutrition-
associated liver disease (Intravenous lipid emulsions)]. Consultant/Advisory Boards: MilkPep [Childhood nutrition
(Dairy)]. Alison G Hoppin, MD Nothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform to
UpToDate standards of evidence.
Conflict of interest policy

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11/8/2019 Approach to enteral nutrition in the premature infant - UpToDate

Official reprint from UpToDate®

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● Intrauterine accretion rate (bone deposition) − 105 mg/kg per day

NUTRITIONAL ASSESSMENT AND MONITORING

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● Head circumference is assessed weekly, targeting an average increment of 1 cm per week.

INFANTS REQUIRING TUBE FEEDING

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● Advancement of feeds – Feeding volume is advanced gradually. As feeds are advanced, a

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Clinical assessment — Serial assessment of feeding tolerance is important to management of

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• Anal excoriation or fissures.

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● Pharmacotherapy – Pharmacotherapy is not recommended as a strategy to manage feeding

• Acid suppressants – Acid-suppressing medications such as histamine type 2 receptor

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INFANTS WHO CAN FEED ORALLY

• Birth weight ≤1800 grams.

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● Feeding by mouth with good documented intake of one of these diets:

• Standard diet (20 kcal/oz) at >180 mL/kg/day

● Established growth rate on the above feeds:

• Infants ≤2 kg – Gaining at least 15 to 20 g/kg per day

SOCIETY GUIDELINE LINKS

SUMMARY AND RECOMMENDATIONS

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(See 'Overview of initiation and advancement of feeds' above.)

• Increased episodes of apnea and bradycardia, diminished oxygen saturation, or lethargy

Use of UpToDate is subject to the Subscription and License Agreement.

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5. Morgan J, Young L, McGuire W. Delayed introduction of progressive enteral feeds to prevent

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21. Weinstein MR, Oh W. Oxygen consumption in infants with bronchopulmonary dysplasia. J

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69. Patole S, Rao S, Doherty D. Erythromycin as a prokinetic agent in preterm neonates: a

70. Nuntnarumit P, Kiatchoosakun P, Tantiprapa W, Boonkasidecha S. Efficacy of oral erythromycin

74. Parker P, Stroop S, Greene H. A controlled comparison of continuous versus intermittent

81. Jasani B, Rao S, Patole S. Withholding Feeds and Transfusion-Associated Necrotizing

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Topic 5014 Version 44.0

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Estimated daily energy requirements for growing premature infants

Factor Kcal/kg Comment

Resting energy expenditure 50 Resting metabolic rate

Activity 15 30 percent above resting

Cold stress 10 Thermoregulation

Synthetic effect of feeding 8 Dietary thermogenesis

Fecal loss 12 10 percent of intake

Growth 25 Calories stored

Total caloric requirement 120

Adapted from: Sinclair JC. Clin Obstet Gynecol 1971; 14:840.

Graphic 59766 Version 4.0

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