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Developmental Outcomes of Preterm Infants: Emphasis on Nutrition

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Title: Developmental Outcomes of Preterm Infants: Emphasis on Nutrition


1
Developmental Outcomes of Preterm Infants
Emphasis on Nutrition
  • Michael K. Georgieff, M.D.
  • Professor of Pediatrics and Child Development
  • Director, Center for Neurobehavioral Development
  • Director, NICU Follow-up Program
  • University of Minnesota School of Medicine

2
Prematurity in the United States
  • In the year 2000
  • 7.6 of infants born weighed lt 2500 grams
  • 1.4 weighed lt 1500 grams
  • Infant mortality dropped to 6.9 per 1000 births
  • Last 8 years, prematurity rates have increased
  • Role of multiples (IVF)

3
Cognitive Development of Premies in
Infancy/Early Childhood
  • Theme Within the normal range, but significantly
    lower than full term comparisons
  • Specific abilities
  • immature patterns of visual attention
  • memory mostly intact but subtle impairments
  • slight working memory advantage

4
Cognitive Development of Premies in Middle
Childhood/Adolescence
  • Themes IQ drops with birth weight GA
  • lt 2500 g No MR, no group diffs. in IQ
  • lt 1500 g Roughly 10 points below mean
  • lt 750 g Roughly 20 points below mean
  • Specific deficits
  • expressive language - memory
  • sustained attention - working memory
  • visual-spatial abilities - set shifting

5
The Vulnerable Preterm Brain
  • Rapidly growing tissue
  • exaggerated effect of any insult
  • vulnerability outweighs plasticity
  • Vascular instability of the germinal matrix
  • Watershed areas (periventricular area)
  • Selective regional metabolic vulnerability
    (hippocampus)

6
Thompson Nelson, Am Psychol, 2001
7
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8
(No Transcript)
9
Factors Influencing Neurodevelopmental Outcome in
Preterm Infants Which Ones Can We Influence?
1. Degree of Prematurity 2. Size for Dates
(SGA) 3. Intraventricular hemorrhage 4.
(Periventricular) Leukomalacia 5. Socio-economic
Status 6. Postnatal Nutrition
10
Major Factors Influencing Neurodevelopmental
Outcome in Preterm Infants
1. Degree of Prematurity 2. Size for Dates
(SGA) 3. Intraventricular hemorrhage 4.
(Periventricular) Leukomalacia 5. Socio-economic
Status 6. Postnatal Nutrition
11
Percent
10 1 0.1 0.01
24 26 28 30 32 34
36 38 40 42 44
Gestation (week) FIG 59-2. Occurrence of spastic
diplegia as related to gestational age.
12
lt750 g
lt750 - 1499 g
Born at term
Children In Group ()
13
Outcome of 401-1000g Infants Vohr et al, 2000
  • NICHD Network
  • 1151 infants evaluated at 18 months
  • 25 with abnormal neurologic exam
  • 37 with Bayley II MDI lt70
  • 29 with Bayley II PDIlt70
  • Grim news. Is it representative?

14
Factors Influencing Neurodevelopmental Outcome in
Preterm Infants Which Ones Can We Influence?
  • Degree of Prematurity?
  • Minimal Influence
  • Prematurity rates have risen
  • Time to delivery with PTL 4 days
  • - Prematurity prevention programs-gt mixed success

15
Factors Influencing Neurdevelopmental Outcome in
Preterm Infants 1. Degree of Prematurity
2. Size for Dates (SGA) 3.
Intraventricular Hemorrhage 4.
(Periventricular) Leukomalacia 5.
Socio-economic Status 6. Postnatal
Nutrition
16
  • Effect of Size for Dates
  • Term Infants National Collaborative
    Prenatal Data Base
  • 6.8 point IQ deficit at 7y compared to case
    controls
  • Preterm Infants with and without postnatal
    malnutrition
  • 8 point deficit on 1y MDI if postnatal
    malnutrition gt 2 weeks

17
Factors Influencing Neurodevelopmental Outcome in
Preterm Infants Which Ones Can We Influence?
  • Size for Dates (SGA)?
  • A. Moderate potential influence
  • Control maternal BP
  • Deliver more prematurely?
  • Trading IUGR for EUGR

18
Factors Influencing Neurdevelopmental Outcome in
Preterm Infants 1. Degree of Prematurity
2. Size for Dates (SGA) 3.
Intraventricular Hemorrhage 4.
(Periventricular) Leukomalacia 5.
Socio-economic Status 6. Postnatal
Nutrition
19
  • Incidence of Major Handicap with IVH in lt1500g
    Infants
  • No Hemorrhage lt10
  • Grade I or II IVH 12
  • Grade III IVH 36
  • Grade IV IVH 75
  • Is it the lesion or the associated
    circumstances?

20
Factors Influencing Neurodevelopmental Outcome in
Preterm Infants Which Ones Can We Influence?
  • Intraventricular hemorrhage?
  • A. Almost no influence
  • Still unknown etiology
  • 60 happen at birth
  • Prophylactic Indocin?

21
Factors Influencing Neurdevelopmental Outcome in
Preterm Infants 1. Degree of Prematurity
2. Size for Dates (SGA) 3.
Intraventricular Hemorrhage 4.
(Periventricular) Leukomalacia 5.
Socio-economic Status 6. Postnatal
Nutrition
22
(Periventricular) Leukomalacia
  • Hypoxic-ischemic etiology
  • Periventricular echodensities are common on
    early ultrasound and are not prognostic
  • gt2mm cysts at 1 month are 95 predictive of
    CP if lesions extend from anterior to posterior
  • Most common CP is spastic diplegia

23
Periventricular Hemorrhagic Necrosis
24
Factors Influencing Neurodevelopmental Outcome in
Preterm Infants Which Ones Can We Influence?
  • (Periventricular) Leukomalacia?
  • A. Questionable influence
  • - Keep neonatal blood pressure higher
    (hypothetical)
  • - Reduce fetal hypoxia (earlier delivery?)

25
Factors Influencing Neurdevelopmental Outcome in
Preterm Infants 1. Degree of Prematurity
2. Size for Dates (SGA) 3.
Intraventricular Hemorrhage 4.
(Periventricular) Leukomalacia 5.
Socio-economic Status 6. Postnatal
Nutrition
26
Combined Effect of SES and Prematurity
27
Moderating Factors
  • For the youngest and smallest infants
  • biological factors best predict long-term
    outcomes
  • For the moderately preterm
  • biological factors related to early developmental
    status, but decline in influence
  • environmental factors become important after
    first year of life

28
Home Environment and the Brain
  • The quality of a childs home environment is
    associated with global cognitive outcomes
  • Experience with a stimulating environment has
    been shown to promote synaptogenesis
  • Experience with a stimulating environment also is
    related to better performance on a range of
    learning tasks

29
Factors Influencing Neurodevelopmental Outcome in
Preterm Infants Which Ones Can We Influence?
  • Socio-economic Status?
  • A. No Influence (short-term or individual)
  • - Clear economic data that SES changes in lt20
    of people

30
Major Factors Influencing Neurdevelopmental
Outcome in Preterm Infants
1. Degree of Prematurity 2. Size for Dates
(SGA) 3. Intraventricular Hemorrhage 4.
(Periventricular) Leukomalacia 5.
Socio-economic Status 6. Postnatal Nutrition
31
General Principles
The goal of nutritional management of the sick
premature infant in the first months of life is
to promote normal growth velocity and body
composition relative to age matched, healthy
infants
32
Canadian Pediatric Society Growth Stages in
Prematures
  • Transition (0-10 days)
  • Premie Grower (10 days- 34 weeks PCA)
  • Post-discharge (gt34 weeks PCA)
  • Each stage has different metabolic physiology and
    nutritional needs

33
Transition Nutritional and Metabolic Risks
  • Nutrient Source TPN Minimal Feeds (Fluid
    Restriction)
  • Catabolism gt High protein turnover
  • Goal
  • 2-3g/kg on day 1
  • 3.8 g/kg average daily intake
  • Insulin Resistance gt Energy substrate handling
  • Glucose and lipid intolerance
  • Goals
  • Meet REE (60-70 kcal/kg daily) OR
  • Provide energy for weight gain/ growth (120
    kcal/kg daily)
  • Can sick babies grow?

34
1. Transition
Ehrenkranz et al, 2000
35
Premie Grower
  • 10 days to 34 weeks PCA
  • Start time varies based on end of illness (could
    be 30 days or more)
  • Stable, anabolic
  • Immature gut physiology
  • Accrued deficits from previous phase
  • Nutrient Source Fortified OMM, PT Formula

36
Premie Grower Nutritional Risks
  • Protein gt Intrauterine rate deficit from
    transition
  • Target 4g/kg daily
  • Considerations
  • Unknown maternal milk composition
  • Renal status
  • Energy gt Intrauterine weight gain deficit
  • Target 135 kcal/kg daily
  • Considerations
  • Fuel source balance (CHO/Fat)
  • OMM composition
  • Iron gt Phlebotomy losses Rapid Growth
  • Target 2-4 mg/kg daily
  • Is anemia of prematurity iron deficiency?

37
2. Premie Grower
Ehrenkranz et al, 2000
38
Post-Discharge
  • After 34 weeks PCA
  • Stable, anabolic, mature gut
  • Nutrient Sources OMM, Fortified OMM,
    Post-discharge formula

39
Post-Discharge Nutritional Risks
  • Protein- daily needs 25 g/kg deficit
  • Target 3.2 g/kg daily
  • Considerations
  • OMM commonly used as base unknown protein
    content
  • Energy- term growth 1000 Kcal/kg deficit
  • Target 110 kcal/kg daily
  • Considerations
  • Issue of body proportionality (from low W/L to
    high W/L slow linear growth)
  • Fe- growth status at discharge
  • Target 2.25 mg/kg daily
  • Considerations
  • Issue of wide range of iron status at discharge
  • Recent data that 2.25 mg/kg daily is probably low

40
3. Post-discharge
Ehrenkranz et al, 2000
41
3. Post-discharge
2. Premie Grower
1.Early
Ehrenkranz et al, 2000
42
Prematures Evidence for Post-Discharge Nutrient
Deficits
  • Poor first year growth (protein-energy)
  • Poorer developmental outcome-related to growth
    failure
  • Anemia (Iron)

43
Effect of Mild to Severe Postnatal Malnutrition
on Head Growth in the NICU and at One-Year
Follow-up
44
Effect of No Prenatal and Mild Postnatal
Malnutrition on Head Size and Development
No DQ Differences
45
Effect of No Prenatal and Moderate Postnatal
Malnutrition on Head Size and Development
3 point DQ difference
46
The effect of combined pre- and postnatal
malnutrition on neonatal and follow-up head growth
47
Effect of Pre and Postnatal Malnutrition on Head
Size and Development
-8 DQ Points
48
Factors Influencing Neurodevelopmental Outcome in
Preterm Infants Which Ones Can We Influence?
  • Postnatal Nutrition
  • A. Large potential influence!!
  • - Limit degree and duration of initial illness
  • Prenatal steroids, control infections
  • - Initiate early nutrition
  • Early protein, trophic feeds

49
Factors Influencing Neurodevelopmental Outcome in
Preterm Infants Which Ones Can We Influence?
  • Postnatal Nutrition
  • - Make up deficits during premie growth
  • Calculate and replace deficits adequate
    monitoring of key brain nutrient status
  • - Continue nutritional management post-discharge

50
Conclusions
  • Outcomes of preterm infants are generally better
    than anticipated based on the biologic lesions
  • Outcomes still poor in lt25 week babies
  • NICHD network data are overly pessimistic
  • Use more pathophysiologically precise tools in
    preterm follow-up studies to better identify
    factors that can be altered in the NICU
  • Pay closer attention to nutrition from birth to
    post-discharge

51
The effect of chronic illness (BPD) on weight
gain and head growth
52
1 0 -1 -2 -3 -4

Weight
Control
BPD
Weight z-score
0 1 2 3 4
5 6 7 8 9
10
Postnatal Age (weeks)
deRegnier et al, 1996
53
1 0 -1 -2 -3 -4
Head Circumference
OFC Z-score
0 1 2 3 4
5 6 7 8 9
10
Postnatal Age (weeks)
deRegnier et al, 1996
54
Major Factors Influencing Neurodevelopmental
Outcome in Preterm Infants
1. Degree of Prematurity 2. Size for Dates
(SGA) 3. Intraventricular hemorrhage 4.
Periventricular Leukomalacia 5. Socio-economic
Status 6. Postnatal Nutrition
55
What the brain does with protein
  • DNA, RNA synthesis and maintenance
  • Neurotransmitter production (synaptic efficacy)
  • Growth factor synthesis
  • Structural proteins
  • Neurite extension (axons, dendrites)
  • Synapse formation (connectivity)

56
Why the brain needs fats
  • Cell membranes
  • Synapse formation
  • Myelin

57
Iron A Critical Nutrient for the Developing
Human Brain
  • Iron containing enzymes and hemo-proteins are
    involved in important cellular processes in
    developing brain
  • Delta 9-desaturase, glial cytochromes control
    oligodendrocyte production of myelin
  • Cytochromes mediate oxidative phosphorylation and
    determine neuronal and glial energy status
  • Tyrosine Hydroxylase involved in monamine
    neurotransmitter synthesis (dopamine, serotonin,
    norepi)

58
Thompson Nelson, Am Psychol, 2001
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