Postnatal growth failure

and its prevention

Ekhard E. Ziegler, M.D. Fomon Infant Nutrition Unit

University of Iowa

Outline Growth failure

Nutritional support - General

Early enteral nutrition = Gut priming

Transition feeding

Late enteral nutrition

Post-discharge nutrition

1995; 26-29 weeks gestation

NICHD Growth Observational Study

Ehrenkranz RA, et al. Pediatrics

1999;104:280-9.

24 28 32 36

Postmenstrual Age (weeks)

We

igh

t (g

ram

s)

500

1000

1500

2000 Extrauterine

Growth

Restriction

Intrauterine growth

(50th and 10th percentile)

24-25 weeks

26-27 weeks

28-29 weeks

50th 10th

4

Postnatal growth failure

Consequences

McCance and Widdowson

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

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

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

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)

From Latal-Hajnal et al., J Pediat 2003;143:163

VLBW infants (<1250 g), N= 219, z-scores for weight

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

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

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

Growth failure and neuro-developmental

outcome Ehrenkranz et al., Pediatrics 2006;117:1253

0

5

10

15

20

25

Q1 Q2 Q3 Q4

Weight Gain

% C

P

Data of Ehrenkranz et al., Pediatrics 2006; 117:1253

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)

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

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

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

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

Inadequate nutrition

Inadequate

nutrition

Growth failure

Impaired

neurocognitive

development

Postnatal growth failure

Cause(s)

Nutrient requirements

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

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

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

Year N BW (GA)

Age 4 weeks

Age 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

Protein and energy intakes (per kg body weight)

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

Postnatal growth failure Cause

• All studies reporting nutrient intakes show inadequate intakes

• Inadequate intakes are linked to poor neurocognitive outcome

Postnatal growth failure Definition

• Falling off of fetal growth trajectory

• AGA at birth, SGA at 36 weeks PMA

(for comparative purposes)

Can we define a degree of growth

failure that is free of adverse effects?

No

Postnatal growth failure

Do we still have it?

Postnatal growth failure

Is alive and well

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

Martin C R et al. Pediatrics 2009;124:649-657

ELGAN study, infants born 2002-2004

2

FIGURE 3

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

Prevention of postnatal growth

failure

Postnatal growth failure

Prevention begins at birth and comes through good nutrition

Objective of nutritional support

To protect the brain

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

Phases of nutritional support

Phase 1: Parenteral

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)

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

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

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

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

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

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

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

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

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

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

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

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

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/d kg/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

The importance of parenteral nutrition

It protects the brain

Good nutrition does not save

lives

It saves brains

Fenton chart