Nutritional Management of Premature

Infants

Ekhard E. Ziegler, M.D.

Fomon Infant Nutrition Unit Department of Pediatrics

University of Iowa

Acknowledgement

Dr. Ziegler receives grant support form

Abbott, Mead Johnson and Nestlé

Dr. Ziegler gives talks, for which he

sometimes receives payment, on

behalf of Abbott, MeadJohnson and

Nestlé

Phases of nutritional support

Phase 1: - Parenteral nutrition

- Gut priming

Phase 2: Transition feeding: Enteral

phased in, parenteral phased

out

Phase 3: Enteral (late)

Phase 4: Post-discharge

Early nutrition period

Gut priming

Dealing with an immature and unused gut

Objective: Maturation of immature gut

The immature gut

• Diminished cell mass, enzyme activity

• Increased permeability

• Disordered, immature motility

• Susceptibility to NEC

• Absent or abnormal microbiota

A Walker J Pediat 2010; 156: S3-7

Small intestinal motility Term infant

From: C.L.Berseth, J Pediatr 1990;117:777

Small intestinal motility Premature infant (32 weeks)

From: C.L.Berseth, J Pediatr 1990;117:777

From: Cormack & Bloomfield, J Paed Child Health 2006;42:458-63

Gastric residuals

• Are normal in the first 2 weeks of life

• Are sometimes green or yellow

• Consist mostly of gastric secretions

• Do not indicate "intolerance"

• Indicate immature motility

• Do not indicate NEC, or impending NEC,

unless there are other signs of NEC

Clinical manifestations of GI

tract immaturity

1. Gastric emptying slow and erratic and

strongly dependent on body position

2. Duodenal reflux common (bilious residuals)

3. Susceptibility to NEC

4. Intestinal transit time long

5. Bowel movements irregular

Gut priming

Q: Start when?

A: On day of birth or next day

Q: Why early?

A: Delay only postpones maturation and

induces atrophy

Q: Doesn't early start increase risk of NEC?

A: No, it does not increase risk of NEC, it

actually decreases it and that of sepsis

Gut priming

Q: Priming with what?

A: Human milk

Q: Why?

A: Human milk primes the gut more efficiently

and more safely than anything else

Gut priming

Q: Priming with how much?

A: Very small volumes, 1-2 cc every 8 hrs

Q: Start to advance?

A: When residuals begin to decrease

Why is human milk so important

for gut priming?

• Strong trophic effects

• Strong anti-infectious effects

• Protects against sepsis, NEC and death

Human milk and GI priming

Relevant properties

• Trophic effects

• Anti-infective effects

• Ant-inflammatory effects

• (Prebiotic effects)

• (Anti-NEC effect)

Human milk Trophic factors

EGF (epidermal growth factor)

TGFα

Insulin

IGF-1

Lactoferrin

Heat-stable factor(s)

Trefoil factors

Human milk in the VLBW infant Trophic effects

• Stimulates cell proliferation

• Decreases permeability

• Enhances motility maturation

• Protects from NEC

Clinical correlates of trophic

effects of human milk

1. Fewer and smaller residuals

2. Rapid feeding advancement, full feeds

sooner

3. Absence of abdominal distention episodes

4. Rapid gastric emptying

5. Low susceptibility to NEC

Human milk Anti-infectious components

• Cells (macrophages, T and B cells)

• Secretory IgA

• Lactoferrin

• Lysozyme

• Bactericidal substances

• Fatty acids

• Oligosaccharides anti-adhesive

• Mucins effects

Human milk oligosaccharides (2)

Effects

• Anti-infectious: Inhibit pathogen binding

• Anti-inflammatory

• Prebiotic: Foster colonization by fucose-

utlizing bacteria

Human milk & the premature infant

Sepsis

El-Mohandes et al., 1997

Hylander et al., 1998

Furman et al., 2003

Schanler et al., 2005 not for donor milk

Sepsis + NEC Schanler et al., 1999

Meinzen-Derr et al., 2008

Human milk protects ELBW infants

against NEC or death

The likelihood of NEC or death was

decreased by a factor of 0.87 for each 100

ml/kg increase in human milk intake during

the first 14 days

Meinzen-Derr et al. for the NICHD Neonatal Research Network

From: J Meinzen-Derr et al., J Perinatol 2009;29:57-62

The huge advantages of human

milk for the premature infant

1. Protects against sepsis, NEC and

death

2. Leads to higher IQ later in life

3. Primes the gut better than anything

else

The disadvantages of human milk

for the premature infant

1. Nutritionally inadequate

2. There is not always enough of it, not

all mothers pump

3. The nutrient composition is not known

Securing human milk

Because of its important protective effects, we

must make every effort to secure human milk:

1. Educate mothers before delivery, explain

how expressed milk is stored and used

2. Support and encourage mothers after

delivery

3. Obtain donor milk if the mother's milk

supply is insufficient

Feeding advancement in VLBW infants Guidelines

1. Start feeds on day 1 or 2

2. Start with low volume, e.g., 2 cc/8hrs

3. Monitor gastric residuals

4. Increase feeds slowly in frequency and/or

size as residuals subside

5. Do not hold feedings because of occasional

large residuals

6. Pay attention to passage of meconium

Transition feeding

Issues

How fast to advance

When to start fortification

When to stop TPN

Advancement of feedings

1. Kennedy & Tyson 2009 Cochrane

3 studies; 10 – 20 cc/kg/d vs 30 – 35 cc/kg/d

No effect on NEC, reached full feeds sooner

2. Morgan et al. 2011 Cochrane

4 studies; 15-20 cc/kg/d vs 30 – 35 cc/kg/d

No effect on NEC or mortality; full feeds

sooner (2-5 days)

3. At least 2 newer studies, same findings

Early feeding advancement Härtel et al., J Ped Gast Nutr 2009;48:464-470

Slow p Rapid

Late-onset sepsis 20.4% 0.002 14.0%

Central line 48.6% <0.001 31.1%

Antibiotics 92.4% <0.001 77.7%

Copyright ©2005 American Academy of Pediatrics

Ronnestad, A. et al. Pediatrics 2005;115:e269-e276

When to start fortification

1. At Iowa we start when the feeding

volume reaches 25 ml/day (= 1 packet

of powder fortifier)

2. Most commonly started at 100

ml/kg/day. Why so late?

3. 9=

Fortification of human milk

Initiation

1. Most commonly at 80 or 100 cc/kg/day

enteral feeding volume

2. At Iowa: At feeding volume of 25 cc/kg/d

Advantages: - Probably decreases need for

PN

- Baby still has gastric

residuals

Transition feeding

Q: When to stop parenteral nutrition?

A: When enteral feeds are >90% of full

Late enteral feeding

Enteral feedings are sole source of

nutrients

Late enteral feeding

Objective: Deliver adequate amounts of

nutrients for normal* growth

Main problem: Fortification of human

milk

* normal = like fetus +- catch-up

Late enteral feeding

The key issue:

How to consistently provide adequate

protein intakes

Human milk fortification

Why fortification?

Human milk provides about 1/3 of the protein and

only a fraction of most other nutrients needed by

the premature infant

Meeting the need for protein with human milk alone

would require feed volumes of >300 ml/kg/d and

provide 3x the amount of energy needed, and

would still not meet the needs for most other

nutrients

Human milk fortification

Objective

Increase concentration of protein and minerals

so that we can meet the requirements for

protein and minerals without feeding huge

amounts of calories

Data of Lemons et al., Ped. Res. 16:113 (1982)

Fortified Human Milk

Protein (g/100 mL)

Human milk, 2 weeks 1.5

Fortifier 1.0

Total 2.5

Protein/energy = 3.1 g/100 kcal

Protein intake = 3.4 g/kg/d (at 110 kcal/kg/d)

Fortification of Mother’s Milk

Protein (g/100 mL)

Mother’s milk, 4 weeks 1.1

Powder fortifier 1.0

Total 2.1

Protein/energy = 2.6 g/100 kcal

Protein intake = 3.1 g/kg/d (at 120 kcal/kg/d)

Fortification of Mother’s Milk

Protein (g/100 mL)

Mother’s milk, 4 weeks 1.1

Powder fortifier 1.0

Extra fortifier 0.5

Total 2.6

Protein/energy = 3.25 g/100 kcal

Protein intake = 3.9 g/kg/d (at 120 kcal/kg/d)

Human milk fortifiers (amounts of nutrients added to each100 ml human milk)

Powder A Powder B Liquid

Calories (kcal) 14 14 14

Protein (g) 1.0 1.1 1.8

Na (meq) 0.65 0.5 0.5

Ca (mg) 117 90 90

Iron (mg) 0.35 1.4 1.4

Plus all other minerals, trace minerals and vitamins in

adequate amounts

Alternative to fortification

Alternate feeding of mother's milk

with feeding of formula (HiPro)

Formulas for premature infants

Caloric density: Standard 80 kcal/dl (some also

available at 90 kcal/dl and 100 kcal/dl)

Protein: 3.0 or 3.3g/100 kcal

Lipid: 40% MCT oil; DHA, ARA

Carbohydrate: 40% lactose, 60% glucose polymers

Minerals (per 100 kcal): Ca 165, P 83

Iron: 14 mg/L (or 4 mg/L)

Formulas for preterm infants

protein content (g/100 kcal)

Body weight Requir. Formula Formula (g) Standard Hi-protein

500-700 3.8 3.0 3.3 3.5

700-900 3.7 3.0 3.3 3.5

900-1200 3.4 3.0 3.3 3.5

1200-1500 3.1 3.0 3.3

1500-1800 2.8 3.0

1800-2200 2.6 3.0

2200-2800 2.5 2.8

2800-3500 2.3 2.8

3500+ 1.8 2.2

What can you do to ensure

adequate nutrition?

Monitor protein intakes

Monitor growth: Plot infant weight

on chart (or use target weight

gains), make sure growth runs

parallel to fetal percentiles, or

crosses them upwards

Fenton chart

Human milk fortification

Adding calories alone to mother's milk

lowers the protein/energy ratio to <1.6

g/100 kcal

Therefore

Fat (canola oil, MCT oil) or

carbohydrate

must never be added to mother's milk

Going home

When the premature infant leaves the hospital, his/her protein needs are still much higher than those of the term infant

Also, the infant has almost always undermineralized bones

Hence the infant needs more protein and more minerals than plain mother's milk or term formula can provide

Selected Nutrient Levels of Formulas

(per 100 kcal)

Premature

formula

Post-

discharge

formula

Term

formula

Kcal/dl 80 74 67

Protein 3.0-3.5 2.8 2.1

Vitamin A 1250 460 300

Vitamin B6 250 100 60

Ca 180 105 78

Fe 1.8 1.8 1.8

Post-discharge nutritional

management of the VLBW infant

Summary

• Formula-fed infants: Special post-discharge

formulas (provide adequate protein, Ca, P; Fe)

• Breast-fed infants: Fortification

(supplementation) indicated, but not practiced

regularly, difficult to perform; special attention

to Fe supplementation

Good nutrition does not save

lives

It saves brains