Feeding the Preterm Infant

Sharon Groh-Wargo PhD, RD, LD

Associate Professor Nutrition and Pediatrics Senior Nutritionist Case Western Reserve University School of Medicine MetroHealth Medical Center, Cleveland, Ohio

June 2, 2012

Cleveland, Ohio ~ on The Great North Coast

Surfing in Cleveland: October 15, 2011

Objectives: For the critically ill newborn

Describe elements of ideal nutritional support Discuss safety concerns related to nutritional support Review the what, when, why and how of nutritional support

The impact of prematurity

NICHD Growth Observational Study

2000

Weight (grams)

Extrauterine Growth Restriction

1500

50th

10th

= Return to birth weight

1000
Intrauterine growth (50th and 10th percentile) 24-25 weeks 26-27 weeks 28-29 weeks

500 24

28 Postmenstrual Age 32 (weeks)

36

Ehrenkranz RA, et al. Pediatrics 1999;104:280-9.

Poor Weight Gain Increases Odds for Poor Outcomes

ELBW infants, in-hospital growth: 12.0 vs 21.2 g/kg/day

Cerebral palsy
8.00 (2.0730.78)

Bayley MDI <70

2.25 (1.034.93)

Neurodevelopmental Impairment

2.53 (1.275.03)

0.2
MDI=Mental Development Index

10.0 1.0 Odds Ratio (95% Confidence Interval)

50.0

Ehrenkranz RA, et al. Pediatrics 2006;117:1253-61.

Enteral Protein Intake Associated With Improved Head Circumference Gain

1.40
HC Growth (cm/week)

R2=0.53

1.20 1.00 0.80 0.60 0.40 0.20 0.00 0.0

HC gain 0.08 cm/wk each additional g of protein

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

N=69 infants <1000 g.

Average Protein Intake (g/kg/d)

Ernst KD, et al. J Perinatol 2003;23:477-82.

Initiate parenteral nutrition as soon as the infant is medically stabilized

Improves glucose tolerance Minimizes negative nitrogen balance and improves protein accretion Lower incidence of retinopathy of prematurity Promotes better growth Lowers loss of lean body mass Improves developmental outcomes
Ibrahim HM, 2004; Hellstrom A, et al. 2003; Lofqvist C, et al 2006; Martin CR, et al 2009; Ehrenkranz RA et al, 2006; Pointdexter BB, 2006; Stephens BE et al, 2009; Isaacs EB, et al, 2009

Critical Elements of Enteral Nutritional Support

Human milk and breastfeeding Human milk fortification Initiating and advancing feedings Discharge and follow-up

1. Human milk and breastfeeding

Decreased necrotizing enterocolitis and late onset sepsis [Lucas & Cole 1996; Meinzen-Derr et al 2009; Sisk et al 2007; McGuire & Anthony 2003; El-Mohandes et al 1997; Hylander et al 1998; Furman et al 2003; Schanler et al 1999 and 2005] Faster progression to full feeding [Sisk et al 2007 and 2008; Schanler et al 1999; Simmer et al 1997] Improved cognitive and visual outcomes [Lucas 1989; OConnor 2007; Birch 1992; Vohr, B 2007] Meier P et al Clin Perinatol 2010 37:217-245

Clinical Outcomes by Feeding (MeanSD)

(Schanler et al, 1999) FHM (n=62 ) PTF (n=46) Oxygen (days) NEC, n (%) Late-Onset Sepsis, n (%) 19 21 1 (1.6) 19 (31) 33 41 6 (13) 22 (48) 1.2 1.7 25 (54)

Positive Blood Cultures 0.5 0.9 (no. per infant) NEC or Late-Onset Sepsis, 19 (31) n (%)
P=0.2 P.01 P=.07

Schanler, R. J. et al. Pediatrics 1999;103:1150-1157

Copyright 1999 American Academy of Pediatrics

Human Milk (HM) Reduces Time to Full Feeding (Sisk et al Pediatrics 2008)
Prospective study VLBW infants Two groups formed based on HM intake:
High (50%; n=93) and Low (<50%; n=34)

Days to reach 100 ml/kg per day (15 vs.19) and 150 ml/kg per day (22 vs. 27) enteral feeding was significantly lower for High vs. Low groups (p<.01)

Human Milk: Long term benefits

Vohr, B. R. et al. Pediatrics 2007;120:e953-e959 Copyright 2007 American Academy of Pediatrics

Breast is Best Initiative: MetroHealth

Strategies
Within 24 hours of admission, mothers receive electric pump kit, storage containers & labels, and printed materials All nurses are in-serviced Electric pumps on mobile carts are added to electric pumps available in breastfeeding rooms Bedside cards I get my moms milk Scripting developed for physicians

Results after 9 months

Increase from 20% to 70% of babies receiving their own mothers milk

2. Human Milk Fortification

Increasing Lean Body Mass Building strong bones Mixing safely and accurately

Discuss challenges of providing human milk

Macro and micronutrients: content Variability (Weber A et al. Acta Pediatr 2001)
By gestation (preterm vs. term) By stage of lactation (colostrum, transitional, mature) By time of day Between mothers

Breast milk analysis

Creamatocrit Near- and mid-Infrared Ultrasound

Variability of Human Milk

Protein g/dl Preterm DOL #7 Preterm 1st week Foremilk @ 1 mo 1st month Mothers own Mother #1 2.4 2.4 1.3 1.6 1.6 2.3 1.9 1.8 1.4 0.9 1.2 0.6 Full term DOL #7 Preterm 4th week Hindmilk @1 mo 6-12 months Donor Mother #2

Picciano MF, Peds Clin N Am 2001; Wojcik KY JADA 2009; Gross SJ J Peds 1980; Saarela T Acta Pediatr 2005; Groh-Wargo S et al SPR 2011

Analyzers
Calais Milk Analyzer; Metron Instruments

Creamatocrit Plus; Medela

Ultrasonic Milk Analyzer; Milkotronic Inc

Breast Milk Analysis: A Paradigm Shift in Fortification for Preterm Newborns

Pediatric Academic Societies Meeting, Denver 2011 Sharon Groh-Wargo, PhD, RD Jennifer Valentic, BS Sharmeel Khaira, MD Dennis Super, MD, MPH Marc Collin, MD

Objectives
Determine the energy and macronutrient content of breast milk found in 24-hour samples collected longitudinally from mothers of preterm infants Describe variability in breast milk composition within and between mothers Determine how variability could potentially affect nutritional intake of individual infants

Methods
MetroHealth Medical Center (Cleveland, OH) IRB approved Recruited mothers of infants admitted to NICU weighing < 2 kg Collected 24 hour supply Homogenized and removed a 15 ml sample Calais Milk Analyzer (Metron Instruments, Solon, OH)
Preparing a sample

Calais Milk Analyzer

Results: Variability
Variability is greater between mothers than within a mother for all macronutrients

p=0.043

Study Conclusions
High variability between mothers supports use of milk analysis technology in clinical setting Low variability within a mother suggests occasional analysis would be adequate to establish an individualized fortification plan Individualized breast milk analysis is a paradigm shift in fortification for preterm newborns

Discuss options and strategies for human milk fortification (HMF)

WHO WHAT WHEN WHERE WHY

WHY do we give HMF?

Inadequate concentration of
Protein Minerals, for example
Calcium Phosphorus Zinc Sodium

Intake for 1 kg infant @ ~120 kcal/kg/d

Nutrient Volume, mL/kg Protein, g/kg Calcium, mg/kg Phos, mg/kg Zinc, mcg/kg Vitamin D, IU/d Human Milk (PT) 180 2.5 45 23 612 4 HMF 1:25 150 3.6 190 118 1776 178 HM:PT HP 1:1 165 3.3 125 71 1286 102 HM:PT 30 1:1 145 3.2 150 71 1351 112 Prolact+ 4 150 3 192 94 1110 41

Estimated needs: Protein (3-4 g/kg); Ca (100-220 mg/kg); P (60140 mg/kg); Zn (1000-3000 mcg/kg); Vitamin D (>400 IU/d)
30

% Fat mass: preterm (PT) infants at or near term vs. term newborns
20 18 16 14 12 10 8 6 4 2 0 Butte '00 Ramel '11 Bolt '02 Term PT PT G-W '05 PT Walyat '12 PT Roggero '10 PT % Fat at Term

WHAT are the options for human milk fortification?

Commercial human milk fortifier (1:25) (powder and concentrated liquid) (Kuschel CA, Harding JE.
Cochrane Database Syst Rev. 2004;(1):CD000343)

Commercial nutrient dense preterm formula (1:1 etc) (liquid) (Moyer-Mileur L et al JPGN 1992; Lewis J et al J
Invest Med 2010)

Concentrated donor human milk enriched with minerals (frozen liquid) [Prolacta Bioscience
http://prolacta.com accessed 8/23/11] (~$40/oz) (Sullivan S et
al. J Pediatr 2010)

HMF Meta-Analysis: Weight Gain

HMF Meta-Analysis: Length Gain

HMF Meta-Analysis: HC Gain

HMF Meta-Analysis: BMC

HMF Meta-Analysis: N Retention

HMF Meta-Analysis: NEC

HMF Meta-Analysis: Development

WHAT are the options for human milk fortification? (continued)

Individualized:
Based on milk analysis (Polberger S et al. JPGN 1999; deHalleux V et al. Arch Pediatr 2007) Based on nutrient content (Pohlandt F Pediatr Res 1993)

Adjustable: based on BUN (Arslanoglu S et al. J

Perinatol 2006)

Weight gain (g/kg/d): Standard Fortification

(Classique) vs. Preterm Formula vs. Individualized Fortification (A la carte)

de Halleux V et al 2007

Average protein intakes: STD vs. ADJ compared with OPTIMAL intrauterine protein intakes
(Arslanoglu S et al. J Perinatol 2006)

Weight, Length and HC Gains

(Arslanoglu S et al. J Perinatol 2006)

STD Weight gain 24.8 4.8 (g/day) g/kg per 14.4 2.7 day Length gain 1.1 0.4 (mm/day) HC gain mm/day 1.0 0.3

ADJ 30.1 5.8 17.5 3.2 1.3 0.5 1.4 0.3

P-value <0.01 <0.01 >0.05 <0.05

WHO should receive human milk fortification? Indications include

34 weeks gestation 1500 g birth weight Parenteral nutrition > 2 weeks > 1500 g birth weight with suboptimal growth and/or feeding volume restriction and/or significant medical/surgical complications

[Schanler RJ and Abrams SA, 1995; Schanler RJ et al, 1999; Atkinson SA, 2000]

WHEN should human milk fortification start and stop?

Start
As early as 25 ml/day of human milk As late as attainment of full enteral feedings (150 ml/kg per day) Most usual start time is attainment of 80-100 ml/kg per day enteral feedings

Stop
As early as a few days prior to NICU discharge (most usual) As late as 52 weeks post-conceptional age or weight of 3.5 kg, whichever comes first

WHERE should human milk fortifier be added to human milk?

The addition of human milk fortifier to expressed human milk at the bedside is not advised (Ohio Department of Health, The American Dietetic Association, ASPEN) A NICU Milk lab as a separate location is ideal to insure
Safety of expressed human milk Accuracy and adequacy of mixing

Human Milk, Thickeners and Reflux

Effectiveness controversial for healthy infants; little evidence for preterm infants
Horvath A et al Pediatrics 2008 (meta-analysis) BMJ 2010;341:c4420 (Drug and Therapeutics Bulletin) Birch JL, Newell SJ (Arch Dis Child Fetal Neonatal Ed 2009)

Xanthan gum (Simply Thick and HydraAid); polysaccharide produce by plant pathogen Xanthomonas campestris
Withdrawn from the market for suspected cause of NEC; FDA safety alert & related resources: www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHuma nMedicalProducts/ucm256257.htm [accessed 2/14/12]

Simply Thick and NEC (Woods CW et al 2012)

Three Case Studies Presentation: Late-onset (2nd postnatal month) presentation with colon involvement Probable physiological basis: increased intraluminal water, sugars, H2, SCFA and bile acids in distal small intestine and colon triggering an inflammatory cascade and bowel injury Recommendations: Xanthan gum thickeners should not be used in premature infants

3. Initiating and advancing feedings

Breastfeeding
Colostrum oral wash Kangaroo care Scoring systems

Priming and progressive feedings Cue-based feedings

Colostrum as an oral wash for the highrisk newborn (Meier P 2010)

Colostrum is secreted in the early days postpartum & is rich in protective components especially from mothers of PF infants Especially important for PT infants who have a shortened exposure to amniotic fluid and its trophic effects on the GI tract Oropharyngeally administered colostrum is
Safe and feasible (Rodriguez NA, 2009 and 2010) May have additive effects to trophic feedings May protect against ventilator-associated pneumonia

Kangaroo Care Skin-to-Skin

Shown to
Empower mothers Increase success of breastfeeding Reduce neonatal morbidity and mortality Reduce length of hospital stay

Conde-Agudelo A, et al Kangaroo mother care to reduce morbidity and mortality in low birthweight infants. Cochrane Database of Systematic Reviews 2011,Issue 3.Art.No.:CD002771.DOI: 10.1002/14651858.CD002771.pub2.

Assessing breastfeeding adequacy

Latch
Latch, Audible swallowing, Type of nipple, Comfort, Hold/positioning Jensen D et al. LATCH: a breastfeeding charging system and documentation tool. JOGNN 23:27-32:1994.

PIBBS
The Preterm Infant Breastfeeding Behavior Scale Nyqvist KH et al. Early Human Development 55:247-264, 1999.

MBA
Mother/Baby Assessment: for the mother and baby learning to breastfeed J Human Lactation 8(2),1992.

0 L (Latch) A (Audible
swallowing)
Too sleepy or reluctant; No latch achieved None

1
Repeated attempts; holds nipple in mouth; stimulate to suck A few with stimulation Flat

2
Grasps breast; tongue down; lips flanged; rhythmic sucking Spontaneous and intermittent <24(frequent >24) Everted (after stimulation) Soft Tender

T (Type of nipple) C (Comfort) H (Hold/

Positioning)

Inverted

Engorged; cracked/bleeding, large blisters,buises. Severe discomfort Full assist (staff holds infant at breast)

Filling; reddened/ small blisters, bruises; mild/ moderate discomfort

Minimal assist (elevate head of bed; place pillows); teach one side, mother does other; staff holds and then mother takes over

No assist from staff; mother able to position/hold infant

Breastfeeding Scoring Systems

MBA: Two steps in each of five stages: 1. Signaling, Readiness 2. Positioning 3. Fixing, latches 4. Milk transfer 5. Ending: breast softens, satiety PIBBS: Several maturational steps in each of six stages: 1. Rooting 2. Areolar grasp 3. Latching and fixed 4. Sucking 5. Longest sucking burst 6. Swallowing

Initiation and progression of enteral feedings in preterm infants

Initiation: Priming Feeds @ low volumes of ~ 10-15 ml/kg/d by DOL # 3-7 and continued for 3-5 days Progression: Increase by ~ 10-20 ml/kg/d but no more than 35 ml/kg per day Common methods of feeding include
NG and OG gavage feeding continuous and intermittent schedules

Monitoring tolerance to enteral feedings

Acceptable residuals Less than 50% of previous intermittent feeding Less than 2 times the hourly feeding rate for continuous feedings Stable abdominal girth Minimal episodes of emesis Regular stooling

Cue-based feeding
Feeding readiness Focus on infant cues vs. bottle or clock Effective eating:
Organization Physiology Motor Caregiver attributes

Changing Feeding Documentation to Reflect Infant-Driven Feeding Practice (Ludwig SM and Waitzman KA, Newborn & Infant Nursing Reviews 2007:7(3), 155-159)
Feeding Readiness Scale Quality of nippling scale Caregiver technique scale

Feeding Readiness Scale

1 Drowsy, alert or fussy prior to care. Rooting and/or hands to mouth/takes pacifier. Good tone 2 Drowsy or alert once handled. Some rooting or takes pacifier. Adequate tone 3 Briefly alert with care. No hunger behaviors. No change in tone. 4 Sleeping throughout care. No hunger cues. No change in tone. 5 Needs increased O2 with care. Apnea and/or bradycardia and/or tachypnea over baseline with care.

Quality of nippling scale

1 2 3 Nipples with strong coordinated suck throughout feed. Nipples with a strong coordinated suck initially, but fatigues with progression. Nipples with consistent suck, but difficulty coordinating swallow; some loss of liquid or difficulty pacing. Benefits from external pacing. Nipples with a weak/inconsistent suck. Little to no rthythm. May require some rest breaks. Unable to coordinate suck/swallow/breathe pattern despite pacing. May result in frequent or significant A/Bs or large amounts of liquid loss and/or tachypnea significantly above baseline with feeding.

4 5

Caregiver technique scale

A B C D E External pacing Modified Side-lying Chin Support Cheek Support Oral Stimulation

Support for feeding advancement

Pacifier dips initially Non-nutritive sucking at breast Kangaroo care continues Nipples:
Slow flow best Progress to standard Orthodontic and cross cut nipples not usually recommended

4. Discharge and follow-up

Human milk and breastfeeding Formula choice Vitamin and mineral supplements Feeding Progressions of the first year

Nutrition Goals for Breastfeeding

Promote adequate weight gain, including necessary catch-up growth Ensure good nutritional status of protein, calcium, phosphorus, and other micronutrients Maintain or build breast milk supply Sustain or improve feedings at the breast Limit bottle and formula feeding to that required for the first and second goals

Intake for 2 kg infant @ 120 kcal/kg/d

Nutrient Volume, mL/kg Protein, g/kg Ca, mg/kg P, mg/kg Zn, mcg/kg Vit D, IU/d Human Milk (HM) 175 1.6 49 26 210 4 HM enriched with PDF* 150 1.9 64 35 412 36 HM alternated with PDF* 165 2.5 92 52 848 95 HM with HMF 1:50 155 2.2 124 69 852 216 HM with HMF 1:25 150 2.9 197 110 1470 411

*PDF: post-discharge formula

Estimated needs at D/C: Protein (2.8-3.4 g/kg); Ca (100-220 mg/kg); P (60-140 mg/kg); Zn (1000-3000 mcg/kg); Vitamin D (>400 IU/d)

Human Milk (HM) After Discharge: Evidence

Feeding HM is associated with improved neurocognitive outcomes but decreased growth (OConnor DL 2003, Lucas A 2001) Feeding fortified HM improves nutrient intake, bone mineralization, and length and head growth compared to feeding HM without fortification (OConnor DL 2008, Aimone A 2009) Feeding fortified HM may not improve overall growth compared to feeding preterm formula (Zachariassen G 2011) Fortification of HM following discharge does not interfere with breastfeeding success (OConnor DL 2008; Zachariassen G 2011)

Human Milk After Discharge: Evidence

Anthropometric measurements of human milk-fed infants sent home (study day 1) fed human milk alone (- -) or with approximately half of the human milkfed mixed with a multi-nutrient fortifier () for 12 weeks. Asterisks denote a significant difference between feeding groups at a specific time point. (Aimone A et al 2009)

Preterm Formula (PF) and/or Post-Discharge Formula (PDF) for Feeding PT Infants after Discharge: Advantages
Improved nutritional intake of key nutrients Increased weight, length and head circumference growth Improved bone mineral content (BMC) Enhanced lean body mass accretion Normalization of biochemical indices of nutritional status

Selected Nutrient Levels (per 100 kcal) for Three Formulas

Preterm Formula
Kcal/oz Pro (gm) A (IU) B6 (g) Ca (mg) Zn (mg) 24 3 1250 250 180 1.5

Post- Discharge (Enriched) Formula

22 2.8 460 100 105 1.2

Standard Term Formula

20 2.1 350 60 78 0.75

Enriched Formula & Lean Body Mass

Brunton JA et al 1998

Enriched Formula & Bone Mineral Content

Brunton JA et al 1998

According to the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists (AAP/ACOG, 2007)
their

use has been shown to result in greater linear growth, weight gain, and bone mineralization when compared with the use of term formula. Small, preterm neonates (born at or before 34 weeks of gestation, with a birth weight less than or equal to 1,800 g) and neonates with other morbidities (eg, BPD) may benefit from the use of such formulas for up to 9 months after hospital discharge.

AAP/ACOG, Guidelines for Perinatal Care, 6th Edition 2007

Suggested Schedule: Use of Post-discharge Formula

Birthweight:
< 750 g 750-1000 g 1000-1500 g 1500-2000 g 2000-2500 g > 2500 g
MetroHealth Medical Center, Cleveland, OH

Length of use (CA*):

12 months 9 - 12 months 6 - 9 months 3 - 6 months 1 - 3 months term - 1 month
*CA=corrected age

Supplements: Preterm (PT) Infants at Discharge

Multivitamin consider for PT infants discharged on PDF and continue until full term size HM or non-preterm formula Zinc consider for PT infants discharged on HM Vitamin D all newborns; 400 IU/day Iron by 1 month; 2 mg/kg per day (Baker RD, Greer FR
and The Committee on Nutrition. Pediatrics 2010;126:10401050)

Fluoride at 6 months for selected infants (AAP,

Committee on Nutrition. Fluoride supplementation for children: interim policy recommendations. Pediatrics 1995;95:777)

Vitamin D Recommendations
WHO: All Breastfed infants and any formula fed infant taking < 1 quart or liter per day WHEN: Within the first few days of life WHAT: 400 IU vitamin D per day supplement HOW: Infant ADC drop 1 ml per day WHY: Increasing incidence of vitamin D deficiency in the maternal population has resulted in deficiency in newborns Reference: Wagner C, Greer FR, Section Breastfeeding and CON. Pediatrics 2008 122:1142-1152; Taylor SN et al, Vitamin D Needs of Preterm Infants. NeoReviews 2009;10;e590-e599

NICU Screening MetroHealth 2009 (n=186)

Mean SD (range)
Birth weight (g): 2061 936 (462-4499) Gestational Age (wk): 32.8 4.3 (23-41) Day of life: 33 42 (2-343)

Serum 25 (OH) vitamin D at discharge

Normal >30 ng/ml Mean SD (range) 27.7 18.2 (6.4-118.8)

Feeding recommendations for former preterm infants at term and term Infants
Breastfeeding on demand Commercial infant formula until one year if breastfeeding not chosen or stopped early Vitamin D (400 IU/day) supplement Iron by 4-6 months as iron supplement 1 mg/kg/d to maximum of 15 mg/d or as iron fortified formula

Feeding Recommendations for Term Infants (continued)

Fluoride supplement AFTER 6 months if water is not fluoridated (0.25 mg/d) Solid foods by 4-6 months by spoon Whole cows milk after one year Fenton growth chart to 50 weeks postconceptional age and/or WHO growth chart from term to 2 years

Feeding Progression and Growth Assessment

Based on Corrected Age (also called adjusted age) Chronological age minus prematurity Example: 4 months old - 2 months premature = 2 months corrected age Duration: use corrected age for ~1 year

Common Feeding Problems in NICU Graduates

Poor suck-swallow coordination Excessive tongue thrust Problems with gag reflex; oral aversion gastroesophageal reflux; vomiting Increased work of breathing from respiratory/cardiac disease may compromise ability to eat by decreasing feeding endurance or interest

To build a better baby, nutrition can.

Promote weight gain Create lean body mass Build strong bones Decrease infection Improve neurocognitive outcomes Support visual development

And YOU can do this by.

Encouraging breastfeeding and adequate supplies of expressed breastmilk Providing a nutrient (not just calorie) dense diet Ensuring adequate micronutrients Staying informed about advancements Being a nutrition champion

Thank you