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

1. Postnatal growth failure
and its prevention
Ekhard E. Ziegler, M.D.
Fomon Infant Nutrition Unit
University of Iowa

2. Outline
Growth failure
Nutritional support - General
Early enteral nutrition = Gut priming
Transition feeding
Late enteral nutrition
Post-discharge nutrition

3. 1995; 26-29 weeks gestation

4. NICHD Growth Observational Study
2000
Extrauterine 50th 10th
Growth
Restriction
1500
Weight (grams)
1000
Intrauterine growth
(50th and 10th percentile)
24-25 weeks
26-27 weeks
28-29 weeks
500
24 28 32 36
Ehrenkranz RA, et al. Pediatrics
Postmenstrual Age (weeks) 4
1999;104:280-9.

5. Postnatal growth failure
Consequences

6. McCance and Widdowson

7. Postnatal growth failure
Consequences – human studies
• Multiple studies show associations of
slow growth with poor neurocognitive
development and with ROP
• All studies are observational with the
exception of the trial by Lucas and
coworkers

8. Postnatal growth failure and
neurocognitive outcome 8-20-12
Birth year Age at FU
Weisglas-Kuperus 2009 1983 19 yr
Hack 1991 1977-79 8 yr
Lucas 1998 1982-84 8 yr
Kan et al. 2008 1991-92 8 yr
Claas 2011 1996-2005 5.5 yr
Franz 2009 1996-99 5 yr
Latal-Hajnal 2003 1983-94* 2 yr
Ehrenkranz 2006 1994-95 2 yr
Belfort 2011 2001-06 2yr
Rozé 2012 2003-08 2 yr
Georgieff 1985 1983 1 yr

9. Postnatal growth failure and
neurocognitive outcome 8/20/12
Birth year Age at FU
Hack 1991 1977-79 8 yr
Lucas 1998 1982-84 8 yr
Weisglas-Kuperus 2009 1983 19 yr
Latal-Hajnal 2003 1983-94 2 yr
Georgieff 1985 1983 1 yr
Kan et al. 2008 1991-92 8 yr
Ehrenkranz 2006 1994-95 2 yr
Franz 2009 1996-99 5 yr
Claas 2011 1996-05 5.5 yr
Belfort 2011 2001-06 2yr
Rozé 2012 2003-08 2 yr

10. Slower vs faster growth
Follow-up at 7.5-8 years of age
Neurocognitive development
Feeding Faster Slower p
growth growth
Average IQ 99.4 94.8 0.05
% with IQ <85 14 31 0.02
% with CP 1.5 12 0.03
% with IQ <85 and/or CP 15 38 0.003
Lucas et al., BMJ 317:1481 (1998)

11. VLBW infants (<1250 g), N= 219, z-scores for weight
From Latal-Hajnal et al., J Pediat 2003;143:163

12. Extrauterine growth failure
B. Latal-Hajnal et al., J Pediat 2003;143:163-70
MDI at age 2 yr
AGA, no growth failure 101.7
SGA, catch-up 98.2
AGA, growth failure 94.9
SGA, no catch-up 94.7

13. Growth failure and neuro-
developmental outcome
Ehrenkranz et al., Pediatrics 2006;117:1253
Setting: NICHD Neonatal Network
Subjects: Infants born September 1994 and August 1995
with birth weight 500–1000 g (N=600 discharged)
Outcomes: 1. Follow-up at 18-22 months (MDI,
PDI, neurologic assessment (N=495)
2. Weight gain from regained birth weight to
discharge

14. Growth failure and neuro-developmental
outcome
Ehrenkranz et al., Pediatrics 2006;117:1253
Q1 Q2 Q3 Q4
Weight gain (g/kg/d) 12.0 15.6 17.8 21.2
Head circ. gain (cm/week) 0.77 0.90 0.96 1.07
Cerebral palsy (%) 21 13 13 6
MDI <70 (%) 39 37 34 21
PDI <70 (%) 35 32 18 14
Neurodev. impairm. (%) 55 49 41 29

15. 25
20
15
% CP
10
5
0
Q1 Q2 Q3 Q4
Weight Gain
Data of Ehrenkranz et al., Pediatrics 2006; 117:1253

16. Growth 1 Week to Term and
18-month Bayley scores
Belfort et al., Pediatrics 2011;128:e899-e906
(Data from Australian DINO study [high-dose DHA] conducted by
Makrides & Gibson 2001-2005; infants <33 wks)
Points per 1 z-score increment
MDI PDI
All infants 2.4 (0.8 - 3.9) 2.7 ( 1.2 - 4.2)
<1250 g 4.7 (2.1 - 7.4) 5.9 ( 3.2 - 8.6)
>1250 g 1.0 (-0.8 - 2.8) 0.8 (-0.9 - 2.5)
AGA 1.6 (0.0 - 3.3) 1.9 (0.3 - 3.5)
SGA 11.7 (4.5 - 18.8) 11.2 (1.8 - 20.7)

17. Does slow growth have positive
effects?
Slow growth may lead to more favorable
cardiovascular health outcomes
It definitely leads to bad neurocognitive
outcomes
Therefore, slow growth is unequivocally
worse than faster growth
Disadvantages clearly outweigh advantages

18. Slow weight gain and ROP
The relative risk of Severe ROP for each
10 g/day lowering of weight gain was
1.15 (CI 1.06-1.24)
Binenbaum et al., Pediatrics 2011;127:e607-14
ELBW Infants enrolled in Need of Transfusion study
2000-2003

19. Early growth and risk of ROP
1. Wallace et al., J AAPOS 2000;4:343-7
Threshold ROP was associated with GA at
birth, weight gain, volume of transfused
RBC, sepsis
2. Allegaert et al., J AAPOS 2003;7:34-37
IUGR and postnatal weight gain are risk
factors for threshold ROP

20. Postnatal growth failure
Q: How does growth failure cause poor
neurocognitive development, ROP?
A: It does not
Q: Then how is the association explained?
A: Both have the same cause – inadequate
nutrition

21. Inadequate nutrition
Growth failure
Inadequate
nutrition
Impaired
neurocognitive
development

22. Postnatal growth failure
Cause(s)

23. Nutrient requirements

26. Protein and energy requirements of
preterm infants (parenteral)
Body weight (g) Protein Energy Prot/Energy
(g/kg/d) (kcal/kg/d) (g/100 kcal)
500- 700 3.5 89 3.9
700- 900 3.5 92 3.8
900-1200 3.5 101 3.5
1200-1500 3.4 108 3.1
1500-1800 3.2 109 2.9
1800-2200 3.0 111 2.7

27. Protein and energy requirements of
preterm infants (enteral)
Body weight Protein Energy Prot/Energy
(g) (g/kg/d) (kcal/kg/d) (g/100 kcal)
500-700 4.0 105 3.8
700-900 4.0 108 3.7
900-1200 4.0 119 3.4
1200-1500 3.9 125 3.1
1500-1800 3.6 128 2.8
1800-2200 3.4 131 2.6

28. Recommended Intakes
ESPGHAN 2010*
Protein
g/kg/d g/100 kcal
Weight <1000g 4.0-4.5 3.6-4.1
Weight 1000-1800 g 3.5-4.0 3.2-3.6
Energy
110-135 kcal/kg/d
*J Pediat Gast Nut 2010;50:85-91

29. Protein and energy intakes (per kg body weight)
Year N BW Age Age
(GA) 4 weeks 6 weeks
g Energy Protein Energy Protein
Simmer Aus 92-94 90 <2078 109 2.5 114 2.7
Carlson US 95 39 <1300 97 2.6 103 2.7
Olsen US 94-96 564 <1500 102 2.5 - -
Radmacher US 97-00 220 <1000 98 2.8 108 2.9
Regan NZ 98 37 <32 wk 108 2.3 149 3.0
Embleton UK 99 38 <1750 121 3.1 - -
Carlson US 01 46 <1000 107 3.1 116 3.2
Cormack NZ 03-04 34 <1790 140 2.8 - -
Carlson US 06 68 <1000 110 3.3 118 3.4

30. Postnatal growth failure
Cause
Q: How do we know that inadequate protein
intakes is causing growth failure?
A: 1. Protein is limiting for growth
2. Calories are not limiting if >100 kcal/kg
3. Protein intakes are generally less than
required for growth similar to the fetus

31. Postnatal growth failure
Cause
• All studies reporting nutrient intakes
show inadequate intakes
• Inadequate intakes are linked to poor
neurocognitive outcome

32. Postnatal growth failure
Definition
• Falling off of fetal growth trajectory
• AGA at birth, SGA at 36 weeks PMA
(for comparative purposes)

33. Can we define a degree of growth
failure that is free of adverse effects?
No

34. Postnatal growth failure
Do we still have it?

35. Postnatal growth failure
Is alive and well

37. Henriksen et al. Br J Nutr 2009;102;1179-86 VLBW infants born 2003-2005

38. ELGAN study, infants born 2002-2004
Martin C R et al. Pediatrics 2009;124:649-657

39. FIGURE 3
Senterre & Rigo, JPGN 2011;53:536-542 Group D: GA=27.0±1.1 wks 2

40. Prevention of postnatal growth
failure

41. Postnatal growth failure
Prevention begins at birth and
comes through good nutrition

43. Objective of nutritional support
To protect the brain

44. 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

45. Early nutrition period

46. Phases of nutritional support
Phase 1: Parenteral

47. Parenteral nutrition of premature
infants
Q: Why parenteral nutrition?
A: Because immaturity of the gut precludes
enteral nutition in adequate amounts
Q: Who needs parenteral nutrition?
A: All infants weighing <1800 g (optional for
infants >1800 g)

48. Parenteral nutrition
Recent history
Before 1999: - Glucose only from birth
- Amino acids started on Day 3-4, low
dose, gradually increased
- Lipids Day 4-5, low dose, slowly increased
About 1999: Amino acids Day 1-2, still low dose
About 2002: Amino acids at time zero, 1.5 g/kg/d
2005: te Baake et al., time zero at 2.6 g/kg/d
2010: Transition to time zero nearly complete,
dose 3.0 to 3.5 g/kg/d

49. Data of B E Stephens et al., Pediatrics 2009;123:1337 124 ELBW infants born in 2000 and 2001

50. Data from BE Stephens et al., Pediatrics 2009;123:1337

51. Data of B E Stephens et al., Pediatrics 2009;123:1337 124 ELBW infants born in 2000 and 2001

52. Data from BE Stephens et al., Pediatrics 2009;123:1337

53. Parenteral nutrition of premature
infants
Principles
• Start AA at birth, lipids within 24 hrs
• Push GIR
• Keep as short as possible but as long as
necessary

54. Parenteral nutrition of the premature
infant
Starter NVN at Iowa
• First intravenous fluid
• (30 -) 60 ml/kg/d
• 10% glucose, 5% amino acids,
• Na 10 mEq/L (as phosphate)
• Ca 20 mEq/L (as gluconate)
• Mg 4 mEq/L
• No potassium, trace elements, vitamins
3/12/10

55. Parenteral nutrition
Full NVN as soon as possible
• 10% Glucose, increase GIR q 12 hrs
• 3.5 g/kg/d of amino acids (no need to go
to 4 g/kg/d)
• Full electrolytes, minerals, trace minerals,
vitamins
• Don't look at BUN

56. From: Ridout et al., J Perinatol. 2005;25:130

57. Parenteral nutrition of premature
infants
Amino acids
• No need to go higher than 3.5 g/kg/day
• No need (excuse) for going below 3.5 g/
kg/day
Glucose
• Push GIR

58. Parenteral nutrition
Lipids
• Start within 24 hrs of birth
• Primary reason is DHA
• Dose 1 g/kg/d
• Give slowly
• No need to monitor triglycerides

59. Intralipid
Soybean oil 20 g/dl
Egg yolk phospholipids 1.2 g/dl
Fatty acids
Linoleic acid 50 % bad
Linolenic acid 7%
Arachidonic 0.3 %
DHA 0.34 % good
Alpha-tocopherol 1.45 mg/dl

60. Parenteral nutrition of VLBW infants
Good practice 2011
• Start amino acids within 2 hrs of birth
• Start with 3 g/kg/d (minimum of 1.5 g/kg/dkg/d)
and increase to maximum 3.5 g/kg/d
• Start lipids within 24 hrs of birth at 1.0 g/kg/d and
increase to 2.0 g/kg/d
• Start glucose at 4 mg/kg/min and increase daily by
1-2 mg/kg/min if maintaining euglycemia
• Don’t stop TPN until enteral feeds are >90% of full

61. The importance of parenteral nutrition
It protects the brain

62. Good nutrition does not save
lives
It saves brains

63. Fenton chart