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High-Energy and Protein Diet Increases Brain and Corticospinal Tract Growth in Term and Preterm

Infants After Perinatal Brain Injury Dabydeen etal Ped Jan 2008

• Prospective double blind, randomized, 2 stage group sequential study

• Controlled for gestation, gender, brain lesion ≤ 32 or > 32 weeks • Neonatal encephalopathy or white matter disease

• 120% recommended average intake vs 100% intake

• Study initiated at term and continued for 12 monthsPrimary outcome: OFCOther measures: • growth axonal diameters in corticospinal tract

(transcranial magnetic stimulation)• weight gain• length

ResultsDabydeen etal Ped Jan 2008

• Study terminated after 16 patients (because > 1 SD OFC* at 12 months) with Hi Energy and Protein Intake

• Axonal diameters in corticospinal tract, length/weight also significantly increased

*additional nutrition given early in development to preterm infants which increased OFC >1SD reduced incidence of CP at age 7 – 8 years by ninefold (Lucas etal Lancet 1990, Lucas et al BMJ 1998)

012345678

3 6 9 12

mo. corrected age

axon

al d

iam

eter no consent

groupaverageenergy grouphigh energygroup

.26 .06 .017 .001

µm

normal subjects

RESULTSAXONAL DIAMETER IN THE CORTICOSPINAL PROJECTION TO THE MOTOR

NEURONS OF THE BICEPS

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High Energy and Protein Diet Conclusions

• Infants with significant perinatal/brain damage have increased nutritional requirements in the first postnatal year

• Decreased postnatal brain growth may exacerbate their impairment

• Waiting for measures of cognitive ability in these patients to determine if strategy has lasting benefit.

CATCH-UP GROWTH and METABOLIC SYNDROME RISK

ADULT Onset Disorders

Hypertension Diabetes

Obesity

Heart Disease

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Infant Weight Gain and School-age BP and Cognition in Former Preterm Infants

N=911 IHDP 8 centers, Boston born 1980’s Median BW 1.87, GA 34 weeks

27% <32 weeks (SGA – 37%)

Wts – at term, 4, 12mos CA. Primary predictor wt gain term – 1yrBP x 3 at 6.5 years

WISC III at 8 years (normal ≥ 85)

Linear regression “infant weight gain” as the 12 month weight z scores adjusted for the term weight z score (using CDC curves)

Represents ∆ from term to 12 mos

Belfort et al Ped June 2010

ResultsWT BP @6.5y WISC III @8yrs

±SD ±SD Z score median @ 12 mo -0.7

Interquartile range (-1.5-0.0) 104.2 918.4 18

Adjusting for gender, GA, race, maternal education, income, age, mother’s IQ, smoking

For each Z score additional weight gain from term to 12 monthsSystolic BP 0.7mm Hg higherWISC III 1.9 points higher

Belfort et al Ped June 2010

Infant Weight Gain and School Age BP/Cognition in Former Preterm

Post Discharge Implications• Preterm Infants across the full range demonstrated

better cognitive outcomes with faster weight gains not just ELBW infants. Late Preterm?

• From 4-12 mos better HC growth was associated with better cognition (~3pts)

• Increased weight and length had independent effects on IQ

• Caught up by age 8

Modest neurodevelopmental advantages of more rapid weight gain first year, especially first 4 mos (wt,L) of life and only small BP related effects (only >32weeks)

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Treatment Recommendations

• Formula-fed preterm infants should be fed nutrient-enriched discharge formula in the first year of life to replenish nutrient deficits and promote growth

– Duration of use varies depending on

• Clinical history

• Degree of postnatal growth failure

• Bone health

• Proportional growth

• Growth in breast-fed premature infants should be closely monitored

– Employ individual feeding strategies as needed to optimize proportional growth

Post-discharge Nutrition Choices

with Human Milk

• Human milk

– Human milk alone

– Fortified human milk with post-discharge powder

– Supplemental bottles of post-discharge formula

– Liquid fortifier

Reasons for Fortification

1) Postnatal Growth Failure

2) Metabolic Bone Disease

52

CA = corrected age.Aimone A, et al. J Pediatr Gastroenterol Nutr. 2009;49:456-466.

Fortified human milk (n=19)

Human milk (n=20)

Study Day 1

0

2000

4000

6000

8000

10000

12000

4 mo CA 6 mo CA 12 mo CA Study Day 1 4 mo CA 6 mo CA 12 mo CA

0

50

60

70

80

90

2635 ± 611

2723 ± 359

5998 ± 1250

6642 ± 678

6800 ± 1299

7564 ± 845

9835 ± 1152

8648 ± 1438

45.0 ± 3.3

46.3 ± 1.8

63.6 ± 2.6

60.9 ± 3.664.1 ± 3.6

67.4 ± 2.5

76.5 ± 2.9

72.7 ± 4.2

Group x time P=0.0035 Group x time P=0.0059

Leng

th (c

m)

Wei

ght (

g)

Weight Length

Fortification of Human Milk Post Dischargen = 19 half of feeds fortified for three monthsn = 20 human milk alone out to 12 mos CA

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53

Fortified Human Milk Improves Head Circumference in the First Year of Life (<1250g)

4 mo CA30

35

40

45

50

6 mo CA 12 mo CAStudy Day 1

Hea

d C

ircum

fere

nce

(cm

)

Group x time P=0.0149

33.5 + 1.4

34.1 ± 1.2

42.6 ± 0.9

41.2 ± 1.8

44.5 ± 0.9

42.8 ± 1.6

46.0 ± 1.4

47.0 ± 1.1

Human milk Fortified human milk

Aimone A, et al. J Pediatr Gastroenterol Nutr. 2009;49:456-466.

Head Circumference (cm)

Nutrition Management Options

for Human-Milk-Fed VLBW

Infants at NICU Discharge

Groh-Wargo and M Thompson ICAN 2014

No longer pumping with Mother – Baby Situation

no stored EBM Still pumping with significant stored EBM

No longer

Baby w/risk factors Baby w/o risk pumping but w/ Still pumping

factors significant stored with little or no

EBM stored EBM Mother interested Mother not interested

PTDF in feeding the baby in feeding the baby at

PF24; transition to Baby w/o risk at the breast the breast

PDF at 3.5 kg Baby w/ risk factors

factors

FHM for several HM alternated

weeks with tran- with PDF with Mother inter- Mother not Baby w/ risk Baby w/o Baby w/ risk Baby w/o

sition to PDF when transition to ested in feed- interested in factors risk factors factors risk factors

stores of EBM PDF when stores ing the baby feeding the

exhausted of EBM at the breast baby at the

exhausted breast

Baby w/ risk Baby w/o risk Baby w/ risk Baby w/o risk

factors factors factors factors

60-90ml/day

PFHP24 from bottle PDF from bottle PFHP24 alt with EBM PDF alt with EBM FHM from a bottle PF30 “booster” FHM from a bottle 60-90ml/day PF30

atl with direct BF; alt with direct BF; from bottle; transition from bottle; cont. For ≥ 1/2 of the (divided) with for≥ ½ of the feed- “booster” (divided)

transition to PDF at lactation support to PDF at 3.5kg; cont pumping 8-10 X the feedings until HM until 3.5kg ings until 3.5 kg then with HM until 3.5

3.5 kg; lactation sup- to get baby to the pumping 8-10 X/day /day to improve 3.5 kg then BF; PDF then plain HM; HM alt with PDF; kg then plain HM;

port to get baby to breast; continue to improve supply supply in 3:1 ratio; lacta- lactation sup- cont. pumping continue pump-

the breast; continue pumping tion support to port to move ing

pumping move from pumping from pumping

to breastfeeding to breastfeeding

FHM for several

weeks with

transition to

PDF when

stores of EBM

exhausted

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Feeding Type

(kcal/oz)

Volume (ml) Protein (g) Calcium (mg) Phosphorus

(mg)

Zn (µg)

HM (20) 180 1.6 40 23 360

Enriched HM (24) 150 1.9 55 32 513

HM alternated with PDF 170 2.6 91 52 910

HM alternated with FHM

(average 22)

165 2.6 122 69 1050

HM alternated with PFHP24

(average 22)

165 3 132 70 1129

HM plus 60 – 120mL PF30

“booster”

165 2.1 – 2.8 84 – 132 48 – 74 726 - 1123

FHM (24) 150 3.4 188 106 1610

Nutritional

recommendations

135 – 200 2.5 – 3.1 70 – 140 35 – 90 1100 - 2000

Comparison of Intake for Selected Nutrients (per kg/d) from Human-Milk Based Feeding Options

for VLBW at NICU Discharge: 2 kg Infant Receiving ~120kcal/kg/day

57

•

Symmetrical EUGR 1) PTF 24 calstrategy for 2 mos then PDF. 2) MBM must be fortied……..

CriticalGrowth Epoch

Biochemical Markers To Follow

Post DischargeTarget Value

BUN ≥ 5 4-6 wks after d/c

Alkaline phosphatase* < 400 4-6 wks after d/c

Phosphorus > 4.5 4-6 wks after d/c

Hemoglobin >10 4-6 wks after d/c

& 3 months after d/c

Reticulocyte count With hemoglobin

Ferritin 50-250 3 mos after d/c

Lucas A, Brooke OG, Baker BA, Bishop N, Morley R. High alkaline phosphatase activity and growth in preterm neonates. Arch Dis Child. Jul 1989;64(7 Spec No):902-909

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Nutrition Discharge of the Preterm

Infant

What to consider for nutritional management?

• Anthropomorphic growth

• Body composition

• Bone status

• Iron status

• Vitamin status

• Neurodevelopmental outcomes

THE END

NEAR TERM INFANT

LATE PRETERM INFANT

X

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Definitions AAP

� Preterm

� <37 weeks’ gestation

� Late preterm

� 34-366/7 weeks’ gestation

� Early Term

� 37-38 weeks’ gestation

� Full term

� 37 – 41 6/7 weeks’ gestation

The late preterm infant is often treated like a full-term infant.

The late preterm infant is not a full-term infant!

“THE GREAT IMPOSTOR”

AAP = American Academy of Pediatrics

Engle WA et al Pediatrics 2007;120:1390-1401

“Late Preterm” Infants*

First day of LMP

1

0/7

Day #

Week #

259 260 274

36 6/7

294

41 6/7

Preterm Term Post term

239

34 0/7

Late Preterm

* Raju TNK. NIH Consensus Conference on “Optimizing Care and Outcome of the Near-Term Pregnancy and the Near-Term Newborn Infant”, 2005

Early Term

LPT “Quick Facts”• 3 x mortality rate vs term (7.7/1000 LB vs

2.5/1000)• 74% of all PTB’s; 8-9% births in US • 4 x risk of death from congenital anomalies

LPT vs Term• IUGR more common in LPT vs Term

• Resp complications prime morbidities of LP• IVH 0.2-1.4%; Term, not routinely screened

• CP increase 3 x vs Term

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The Late Preterm Infant

The Most Rapid Brain Weight Gain Is

Around 40 Weeks’ Gestation

Morgan PJ etal neurosci Biobehav Rev, 2002;26:471-483

Kinney HC Semin Perinatol, 2006;30:81-88

At 34 Weeks the Brain Is Two Thirds Of

Its Weight At Term

Adams-Chgapman I, Clin Perinatol 2006;33:947-954 Kinney HC Semin Perinatol 2006;30:81-88

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NUTRITION IN LATE PRETERM

(1) Consider fetal growth as appropriate for a particular gestational age

(2) Focus on LBM

(3) Consider age-appropriate accretion rates of protein, minerals and various essential nutrients

(4) Understand GI-tract development

(5) Consider cumulative nutrient deficit that accrues in the early days or weeks of life

(6) Adopt recommendations relative to PCA Lapillonne et alJofPed 2013

Nutritional Recommendations for Preterm Infants

Variables (per kg/d)

GA, weeks

<28 28-31 32-33 34-36 37-38 39-41

Fetal growth

Weight gain, g 20 17.5 15 13 11 10

Lean body mass gain, g

17.8 14.4 12.1 10.5 7.2 6.6

Protein gain, g 2.1 2 1.9 1.6 1.3 1.2

Requirements

Energy, kcal 125 125 130 127 115 110

Proteins, g 4 3.9 3.5 3.1 2.5 2

Calcium, mg120-140

120-140

120-140 120-140 70-120 70-120

Phosphorus, mg 60-90 60-90 60-90 60-90 35-75 35-75

Nutritional needs by GA (weeks)

The Journal of Pediatrics Volume 162, Issue 3, Supplement , Pages S90-S100, March 2013

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71

Range of Protein Intakes

2.1

3.1

3.6

4.0

“g protein/kg/d at150 mL/kg/d”“g protein/kg/d at150 mL/kg/d”

Term formula

Nutrient-enriched formula

Preterm formula 24

High-proteinpreterm formula 24

Prot req 2.0-3.1g/k/d

Human milk provides ~1.5 g/kg/d of protein

Infant Weight Gain and School-age BP and Cognition in Former Preterm Infants

N=911 IHDP 8 centers, Boston born 1980’s Median BW 1.87, GA 34 weeks

27% <32 weeks (SGA – 37%)

Wts – at term, 4, 12mos CA. Primary predictor wt gain term – 1yrBP x 3 at 6.5 years

WISC III at 8 years (normal ≥ 85)

Linear regression “infant weight gain” as the 12 month weight z scores adjusted for the term weight z score (using CDC curves)

Represents ∆ from term to 12 mos

Belfort et al Ped June 2010

ResultsWT BP @6.5y WISC III @8yrs

±SD ±SD Z score median @ 12 mo -0.7

Interquartile range (-1.5-0.0) 104.2 918.4 18

Adjusting for gender, GA, race, maternal education, income, age, mother’s IQ, smoking

For each Z score additional weight gain from term to 12 monthsSystolic BP 0.7mm Hg higherWISC III 1.9 points higher

Belfort et al Ped June 2010

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Infant Weight Gain and School Age BP/Cognition in Former Preterm

Post Discharge Implications• Preterm Infants across the full range demonstrated

better cognitive outcomes with faster weight gains not just ELBW infants. Late Preterm?

• From 4-12 mos better HC growth was associated with better cognition (~3pts)

• Increased weight and length had independent effects on IQ

• Caught up by age 8

Modest neurodevelopmental advantages of more rapid weight gain first year, especially first 4 mos (wt,L) of life and only small BP related effects (only >32weeks)

Human Milk Feeding For Preterm

Infants

Healthy

microbiome

Increased

immunologic

function

Decrease NEC

Breastfeeding And CognitionInfant feeding and childhood cognition at ages 3 and 7 years: effects

of breastfeeding duration and exclusivity. JAMA Pediatr 2013

• Prospective cohort (project ViVa) US Prebirth Cohort enrolled

mothers from 1999-2012, n=1312

• Duration of any breastfeeding to age 12 months

• Adjusted for sociodemographics, maternal intelligence, home

environment factors in linear regression

RESULTS IQ BENEFIT

• 0.35 points per month breastfeeding Verbal scale

• 0.29 points per month breastfeeding Nonverbal

• 0.24 points per month Visual Motor Abilities at age 3 greater with

women who consumed 2 or more servings fish/week

Breastfeeding an infant for the first year of life would be expected to

increase his or her IQ by about 4 points (0.3SD)

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Verbal IQ

Breastfeeding Failure in Late Preterm Infants

Jain (SAN)

Problems Establishing Breastfeeding in Late Preterm

• Sleeper, less stamina• Latch, suck, swallow difficulty• Difficulty maintaining body temperature• Delays in Bilirubin excretion• Respiratory instability

“R/O sepsis”…. Because they are acting like preterm

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Potential Risks Late Preterm Breastfeeding

– Hypothermia – Hypoglycemia– Excessive wt. loss – Exaggerated jaundice

– Kernicterus – Dehydration– Fever secondary to dehydration

– Breastfeeding failure– Rehospitalization

What Should We Feed LPT?• Those infants 34 -36 weeks can use a

Post Discharge Formula through term equivalent age.

• Would not routinely fortify breast fed• Consider fortification in the 34,35 weekers

who have been more ill and have growth faltered.

• Discharge these infants on MBM/PDF supplement if growth failure in place

DHA opinion