DOI: 10.1542/neo.12-3-e1302011;12;e130Neoreviews

Nahed O. ElHassan and Jeffrey R. KaiserParenteral Nutrition in the Neonatal Intensive Care Unit

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Parenteral Nutrition in theNeonatal Intensive Care UnitNahed O. ElHassan, MD,

MPH,* Jeffrey R. Kaiser,

MD, MA

Author Disclosure

Drs ElHassan and

Kaiser have disclosed

no financial

relationships relevant

to this article. This

commentary does

contain a discussion

of an unapproved/

investigative use of a

commercial

product/device.

AbstractNeonatal parenteral nutrition (PN) is readily available in many hospitals and plays anessential role in the management of sick and growing preterm and term infants. PNcan be used as the sole source of nutrition support for infants who cannot be fed or asan adjunct to enteral feeding. Preterm infants are a particularly vulnerable populationbecause they are born at a time, if they had remained in utero, of rapid intrauterinebrain and body growth. The impact of early malnutrition can have long-lastingnegative effects on central nervous system development and growth. Despite this, PNis often provided to preterm infants based on local traditions rather than experimentalevidence. The quality of PN and its early initiation are critical in providing the mostadequate substrates for appropriate development. This article reviews the energy andfluid requirements of infants and presents by component (protein, carbohydrates,lipids, minerals such as calcium and phosphorus, trace elements, and multivitamins)the available literature on neonatal PN and its complications. In addition, suggestedguidelines for PN administration for preterm and term neonates are presented.

Objectives After completing this article, readers should be able to:1. Describe the different components of PN for neonates.2. Review the suggested recommendations for macro/micronutrients in PN for neonates.3. Understand the function and benefits of macro/micronutrients in PN for neonates.4. Discuss the neonatal morbidities and possible complications associated with each of

the PN components.

IntroductionNeonatal PN was first used in 1967 for an infant who had intestinal atresia and postoper-ative weight loss. (1) The goal of PN in preterm neonates has been to approximate the

nutrition they would have received if they have remained inutero for appropriate extrauterine growth and development.(2) PN can be used as the sole source of nutrition support forneonates who cannot be fed or as an adjunct to enteralfeeding. Since its implementation, many lessons have beenlearned about the benefits and complications of PN. Animportant milestone in neonatal nutrition research was therealization of the valuable impact of early initiation onneurocognitive development. Despite this fact, the clinicalpractice of providing PN is often based on local tradition anddogma rather than experimental evidence. (2)(3) Althoughfetuses receive continuous nutrition from the placentathrough the umbilical vein, many preterm newborns haveessential nutrients limited or entirely withheld due totheoretical concerns and previous experiences with olderPN preparations. The quality of PN and its early initiationare critical in providing the most appropriate substrates for

*Assistant Professor of Pediatrics, Department of Pediatrics, Neonatology, University of Arkansas for Medical Sciences, Collegeof Medicine, Arkansas Childrens Hospital, Little Rock, AR.Associate Professor, Departments of Pediatrics and Obstetrics and Gynecology, Neonatology, University of Arkansas forMedical Sciences, College of Medicine, Arkansas Childrens Hospital, Little Rock, AR.

Abbreviations

AA: amino acidALA: alpha-linolenic acidBUN: blood urea nitrogenCa: calciumEFAD: essential fatty acid deficiencyELBW: extremely low birthweightFDA: United States Food and Drug AdministrationFFA: free fatty acidLA: linoleic acidP: phosphorusPN: parenteral nutritionVLBW: very low birthweight

Article parenteral nutrition

e130 NeoReviews Vol.12 No.3 March 2011

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appropriate growth and development. (2)(3) This articleaims to discuss the art and science of PN in neonatesand reviews the benefits and potential complications ofthe multiple components provided in PN for pretermand term neonates. When there is limited evidence, andrecommendations are made, this is stated. Definitions ofpreterm infants for this article are stated in Table 1.

Energy RequirementsKnowing the appropriate energy requirements for neo-nates is fundamental in prescribing PN. Energy is essen-tial for body maintenance and growth. The basal restingmetabolic rate reflects the energy expenditure requiredfor maintenance of vital processes. The resting metabolicrate has been estimated to be 40 to 60 kcal/kg per day inparenterally fed neonates maintained in a thermoneutralenvironment. (4) Each gram of weight gain for growth,including the stored energy and the energy costs ofcomponent synthesis, requires between 3 and 4.5 kcal.(4) Thus, an ideal daily weight gain of 15 g/kg (whichestimates daily fetal growth) requires an additional ca-loric requirement of 45 to 67 kcal/kg above the esti-mated resting metabolic rate. (4) A summary of theenergy requirements during the neonatal period is pre-sented in Table 2. These estimated energy requirementshave been calculated in healthy growing preterm in-fants at 3 to 4 weeks of age. There is relatively minimalinformation, however, on the energy requirements forsick infants and especially extremely low-birthweight(ELBW) infants during early postnatal life. ELBW in-fants are believed to have increased metabolic demandsdue to their large body proportion of metabolically activeorgans, including the heart, liver, kidney, and brain. (4)

Fluid RequirementsThe percentage of total body water in fetuses decreasesfrom approximately 95% early in development to 80%by 8 months gestation and to 75% at term. (5) Duringthe first day after birth, term infants require a minimum

of 60 mL/kg per day to meet maintenance fluid needs(replacing net losses). As infants mature, fluid needsgradually increase to a total of 120 to 150mL/kg per dayto allow for increased renal solute load, stool wateroutput, and growth. (5) Preterm infants have more in-sensible water losses than term infants due to their largesurface area, skin immaturity, and ensuing increasedevaporation. Thus, fluid needs are higher on the firstpostnatal day at 80 to 100 mL/kg per day and increaseby 10 to 20mL/kg per day to a total of 130 to 180mL/kgper day as preterm infants mature (Table 2). (5)

Infusion RoutesPN may be infused via peripheral and central catheters.Peripheral infusion typically is used for short-term nutri-tion support. Peripheral vein osmolarity tolerance rangesfrom 700 to 1,000 mOsm/L. Osmolarity is calculatedusing the equation: (6)

osmolarity (mOsm/L)([amino acids (g/L) 8] [glucose (g/L) 7] [sodium (mEq/L) 2] [phosphorus (mg/L) 0.2] 50)

The osmolarity of glucose solutions rises from 255 to1,020 mOsm/L with increasing concentration from 5%to 20%, respectively. Generally, glucose concentrationsof 12.5% or less are well tolerated by peripheral veins aslong as no other osmolarity-increasing agents are added.Central infusion of PN is delivered via central venouscatheters and is the preferred route for long-term PN.

Components of Parenteral Nutrition (Table 2)Protein

Previously used intravenous amino acid (AA) prepara-tions were based on casein hydrolysates. Current crystal-line AA solutions have elevated ratios of essential tononessential AAs, leading to the endogenous produc-tion of higher concentrations of the branch amino acids:leucine, isoleucine, and valine. (7) Despite extensiveendeavors to create optimized AA preparations, how-ever, plasma AA concentrations in infants receiving cur-rent intravenous solutions are still reduced comparedwith breastfed infants. (8) This is partly due to the poorsolubility or stability of various intravenous AAs (eg,glutamine, tyrosine, and cysteine). (8) Cysteine is oftenconsidered a semi-essential AA in the newborn periodand is, therefore, routinely added to AA preparationsto circumvent low cysteine synthesis, low plasma concen-trations, and impaired protein synthesis. (9) Cysteine isa major substrate for glutathione, a tripeptide (glutamicacid/cysteine/glycine) antioxidant, and is important inmaintaining redox potential and calcium homeostasis.

Table 1. Classification of PretermInfants Preterm infants are born

Table

2.Su

ggestedRe

commen

dation

sforPa

renteral

Nutrit

ionMacronu

trientsforNeo

nates

Source

Initial

Administration

Advanc

emen

tGo

alNeo

nate

Bloo

dCo

ncen

tration

PotentialC

omplications

Fluid

60to

70mL/kg

perda

y80

to10

0mL/kg

perda

y

10to

20mL/kg

perda

y10

to20

mL/kg

perda

y

130to

150mL/kg

perda

y13

0to

180mL/kg

perda

y

Term

Preterm

TotalE

nergyIntake

90kcal/kgpe

rda

yTerm

120kcal/kgpe

rda

yPreterm

Energy

Expe

nded

40to

60kcal/kg

perda

yRe

stingmetab

olic

rate

40to

50kcal/kg

perda

yAc

tivity

0to

5kcal/kgpe

rda

yTh

ermoreg

ulation

0to

5kcal/kgpe

rda

ySy

nthe

sis

15kcal/kgpe

rda

yEn

ergy

Excreted

15kcal/kgpe

rda

yEn

ergy

Stored

20to

30kcal/kg

perda

yAm

inoAc

ids1

2to

3g/kg

perda

y1g/kg

perda

y3g/kg

perda

yTerm

Ch

olestasis

2to

3g/kg

perda

y0.5to

1g/kg

perda

y3.5to

4g/kg

perda

yPreterm

Dextrose

8mg/kg

perminute

4to

6mg/kg

per

minute2

1to

3mg/kg

perminute

1to

3mg/kg

perminute

12mg/kg

perminute

12mg/kg

perminute

Term

Preterm

>45

to45

to