International conference «Actual approaches to the extremely preterm babies: International experience and Ukrainian realities» (Kyiv, Ukraine, March 5-6, 2013)

1. Nutritional Management of Premature
Infants
Ekhard E. Ziegler, M.D.
Fomon Infant Nutrition Unit
Department of Pediatrics
University of Iowa

2. 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

3. 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

4. Early nutrition period

5. Gut priming
Dealing with an immature and unused gut
Objective: Maturation of immature gut

6. The immature gut
• Diminished cell mass, enzyme activity
• Increased permeability
• Disordered, immature motility
• Susceptibility to NEC
• Absent or abnormal microbiota

7. A Walker J Pediat 2010; 156: S3-7

8. Small intestinal motility
Term infant
From: C.L.Berseth, J Pediatr 1990;117:777

9. Small intestinal motility
Premature infant (32 weeks)
From: C.L.Berseth, J Pediatr 1990;117:777

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

11. 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

12. 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

13. 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

14. 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

15. 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

16. Why is human milk so important
for gut priming?
• Strong trophic effects
• Strong anti-infectious effects
• Protects against sepsis, NEC and death

17. Human milk and GI priming
Relevant properties
• Trophic effects
• Anti-infective effects
• Ant-inflammatory effects
• (Prebiotic effects)
• (Anti-NEC effect)

18. Human milk
Trophic factors
EGF (epidermal growth factor)
TGFα
Insulin
IGF-1
Lactoferrin
Heat-stable factor(s)
Trefoil factors

19. Human milk in the VLBW infant
Trophic effects
• Stimulates cell proliferation
• Decreases permeability
• Enhances motility maturation
• Protects from NEC

20. 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

21. Human milk
Anti-infectious components
• Cells (macrophages, T and B cells)
• Secretory IgA
• Lactoferrin
• Lysozyme
• Bactericidal substances
• Fatty acids
• Oligosaccharides anti-adhesive
• Mucins effects

22. Human milk oligosaccharides (2)
Effects
• Anti-infectious: Inhibit pathogen binding
• Anti-inflammatory
• Prebiotic: Foster colonization by fucose-
utlizing bacteria

23. 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

24. 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

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

26. 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

27. 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

28. 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

29. 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

31. Transition feeding
Issues
How fast to advance
When to start fortification
When to stop TPN

32. 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

33. 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%

34. Ronnestad, A. et al. Pediatrics 2005;115:e269-e276
Copyright ©2005 American Academy of Pediatrics

35. 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?

36. 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

37. Transition feeding
Q: When to stop parenteral nutrition?
A: When enteral feeds are >90% of full

38. Late enteral feeding
Enteral feedings are sole source of
nutrients

39. Late enteral feeding
Objective: Deliver adequate amounts of
nutrients for normal* growth
Main problem: Fortification of human
milk
* normal = like fetus +- catch-up

40. Late enteral feeding
The key issue:
How to consistently provide adequate
protein intakes

41. 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

42. 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

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

45. 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)

46. 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)

47. 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)

48. 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

49. Alternative to fortification
Alternate feeding of mother's milk
with feeding of formula (HiPro)

50. 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)

51. 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

52. 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

53. Fenton chart

54. 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

55. 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

56. Selected Nutrient Levels of Formulas
(per 100 kcal)
Premature Post- Term
formula discharge formula
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

57. 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

58. Good nutrition does not save
lives
It saves brains