THE KEY TO SUCCESS FEEDING OF

PRETERM INFANTS

Ruurd van Elburg, Professor of Early Life Nutrition

Emma Children’s Hospital Amsterdam UMC Amsterdam
Danone Nutricia Research Utrecht, The Netherlands
1
Bali Indonesia June 27th 2019
PUBLIC DISCLOSURE

Employee of Danone Nutricia Research

Utrecht The Netherlands
EARLY LIFE NUTRITION FOR
HEALTH IN LATER LIFE
-9m to 24m
Critical window of
opportunity to
support health
later life
HEALTH

Altered growth Obesity

and development Coronary heart
Stunting disease
Allergy Diabetes DISEASE
Cognitive decline

CONCEPTION TODDLERHOOD ADULTHOOD

THE KEY TO SUCCESS ….

… is to recognize that preterm birth is a

nutritional emergency
… requiring attention from birth onwards:

- Why?
- What?
- How?

Su et al Pediatr Neonatol 2014, Corpeleijn et al Ann Nutr Metab 2011

Focus on Cardio-respiratory care
Who is discussing nutrition?
Courtesy of Nick Embleton Newcastle UK
THE KEY TO SUCCESS ….

Why is preterm birth a nutritional emergency?

EXTREMELY OR VERY
PRETERM BIRTH

Will my baby
survive?
HOW WILL IT SURVIVE?

Preterm brain Term brain

LONG TERM NEURODEVELOPMENTAL
OUTCOME OF PRETERM BIRTH
• Average IQ 12.9 point lower in very preterm infants vs
term infants (Twilhaar et al JAMA Pediatrics 2018)
• No change in IQ difference between 1990-2008
• Average scores on arithmitic (-0.71SD), spelling (-
0.44SD) and reading (-0.52SD) in preterm vs term
born children at school age (Twilhaar et al Arch Dis Child FN ed
2017)

• BPD is main predictor of outcome in both meta-

analyses
ACADEMIC PERFORMANCE IN PRIMARY
SCHOOL OF PRETERM BORN CHILDREN
- Academic performances for arithmic
(A), reading comprehension (B) and
spelling (C) show persisting
differences between term and
6 7 8 9 10 11 yrs preterm born children in primary
school (6-11 year).

- But, they showed similar

progression compared to full-term
children, suggesting intact learning
abilities.
6 7 8 9 10 11 yrs
- This provides opportunities for early
(nutritional) intervention.

Term in green Preterm in purple

6 7 8 9 10 11 yrs Adapted fromTwilhaar et al Arch Dis Child FN ed 2018

INFLUENCE OF WEIGHT GAIN ON LATER COGNITION
SYSTEMATIC REVIEW

• Observational studies reported consistent positive associations

between postnatal weight or head growth and neurocognitive
outcomes;
• Interventional studies show limited evidence for this association.

Interpretation:
Appropriate weight gain is important for brain development.

Ong et al Acta Paediatr 2015

 THE KEY TO SUCCESS FEEDING OF
PRETERM INFANTS

The goal is to achieve adequate growth (weight, length &

head circumference) to optimally support organ growth and
development/maturation for the best short time outcome
(mortality & morbidity) and long term health (such as
neurodevelopment, cardiovascular/metabolic).

Based on Cormack et al Pediatr Res 2016

WHAT ARE THE KEY FACTORS TO ACHIEVE
THIS GOAL?

• Dedicated and well-trained team!

• Parenteral nutrition
• Enteral nutrition & What kind of
enteral nutrition?
• Start and advance enteral feeds
• Feeding (in)tolerance?

Based on Corpeleijn et al Ann Nutr Metabol 2011

WHAT ARE THE KEY FACTORS TO ACHIEVE
THIS GOAL?

Dedicated and well-trained team!

• Neonatologists
• Nursing staff
• (If available) Neonatal dietician
• Lactation nurse
• (Hospital) Pharmacist
• Special lactation room

Based on Corpeleijn et al Ann Nutr Metabol 2011

WHAT ARE THE KEY FACTORS TO ACHIEVE
THIS GOAL?
Parenteral nutrition
• Needs to start in very preterm infants on day of birth
• Sufficient proteins and lipids from start onwards
• Not to be confused with the results of the PEPaNIC
multicentre, randomised controlled trial (Lancet Respir Med. 2017) in
pediatric patients (not preterm)
• Few long term follow-up studies performed
• New guidelines from ESPGHAN expected end 2020
WHAT ARE THE KEY FACTORS TO ACHIEVE
THIS GOAL?

Enteral nutrition
• Needs to start in very preterm infants on day of birth
• Preferably fresh own mother’s milk otherwise banked own
mother’s milk
• Aim to achieve full enteral feeding within 7-14 days in
extremely preterm & very preterm infants respectively

Kumar et al Front Nutr 2017, Dutta et al Nutrients 2015

 Human milk is the optimal nutrition for
all infants especially those born
preterm

Breastfeeding Own Mother's milk Donor Human milk Preterm

Nursing from the breast expressed milk expressed milk Formula

“Every effort, including use of preterm formula, is justified to

protect the preterm infant from growth failure and the
neurodevelopmental impairment it engenders” (E.E. Ziegler 2015)

ESPGHAN J Pediatr Gastroenterol Nutr 2010;50:85-91 / Ziegler.J Pediatr Gastroenterol Nutr 2015.
WHAT ARE THE KEY FACTORS TO ACHIEVE
THIS GOAL?

Own mother’s milk: practices for optimal support

• Kangaroo care & skin-to-skin contact

• Simultaneous expression from both breasts (electric pump)
• Peer support (in hospital & community)
• Multidisciplinary, Skilled, professional support
GROWTH IN UTERO AND AT THE NICU

Based on: Ehrenkranz et al. Pediatrics 1999; 104:280-289

Senterre et al. J Pediatr Gastroenterol Nutr 2011;53:536-42
EXTRAUTERINE GROWTH RESTRICTION
IN THE NICU
EUGR = growth (mostly weight) < p10 at discharge or PCA
40wks/TEA
• France moderate preterm infants 24% (Iacobelli BMC Pediatrics 2015)
• USA preterm infants GA<31wks 32% (Stevens Am J Perinatol 2016)
• China preterm infants GA < 34 wks 41% (Cao Zhongguo Dang Dai Er Ke
Za Zhi 2015, de Waard JPEN 2018)

• Japan preterm infants GA < 32 wks 57% (Sakurai Pediatr Int 2008)
WHAT ARE THE KEY FACTORS TO ACHIEVE
THIS GOAL?

Enteral nutrition
• Possibility for cohospitalisation of the mother, donor human
milk banks and lactation support improve use of human milk
and time to full enteral feeding (de Waard 2018)
• Human milk fortification is important to support growth (Brown
2016, Arslanoglu 2019)
META-ANALYSIS ON HMF FOR
PRETERM INFANTS
Quality of
Anticipated effects of HMF (95%CI) Nb of infants (studies)
evidence

Weight gain (g/kg/d) + 1.81 (+1.23 to +2.4) 635 (10) Low

Length gain (cm/wk) + 0.12 (+ 0.07 to +0.17) 555 (8) Low

Head growth (cm/wk) + 0.08 (+0.04 to +0.12) 555 (8) Moderate

MDI at 18 months + 2.2 ( -3.35 to +7.75) 245 (1) Moderate

PDI at 18 months + 2.4 (-1.9 to +6.7) 245 (1) Moderate

NEC RR: 1.57 (0.76-3.23) 882 (11) Low

Conclusions:
Although available trial data show that multi-nutrient fortification increases growth rates of preterm
infants during their initial hospital admission, they do not provide consistent evidence on effects on
longer-term growth or development.
Additional trials are needed to resolve this issue.
Brown, Cochrane Database of Systematic Reviews 2016
CLASSICAL POWDER HMF (+1G PROTEIN/100 ML)
OFTEN DOES NOT MEET ELBW INFANTS NEEDS
Required Required Human milk* Fortified HM§
per kg/d per 100 kcal per 100 kcal per 100 kcal
Energy, kcal 108
Protein, g 4.0 3.8 1.8 2.75
Ca, mg 184 170 37 156
P, mg 126 116 21 94
Mg, mg 6.9 6.4 4.8 6.6
Na, mmol 3.3 3.0 1.8 2.4
K, mmol 2.4 2.2 1.9 2.6
Cl, mmol 2.8 2.6 2.4 2.9
Fe, mg 2.0 1.85 0.13 1.9
Zn, mg 1.5 1.4 0.54 1.5
Cu, mg 120 111 56 102
* 4 weeks after delivery; § classical powder HMF adding 1.0 g of protein per 100 ml of milk Ziegler, WRND 2014

Additional protein supplementation is required

 OPTIMIZATION OF HMF FOR PRETERM
INFANTS (EMBA RECOMMENDATION)
Unfortified (own)
mother’s milk
Standard fortification Adjustable fortification
• Fixed amount of fortifier • Protein adequacy
added to fixed volume monitored by BUN 2x/wk
• Used in most neonatal • Cut-off levels BUN 10-
units 16mg/dl; if <10mg/dl
• Often not sufficient for additional protein is added
adequate growth • Practical: no expensive
equipment needed
Individualized
fortification
Targeted fortification
• Macronutrients measured
and protein+/-fat added
based on results
(reference population data)
• Bedside HM analyzer
needed,
• May be labor intensive
Based on: Arslanoglu et al Front Pediatr 2019
OPTIMIZATION OF HMF FOR PRETERM
INFANTS (EMBA RECOMMENDATION)
• All preterm infants with BW < 1800g need fortification
• Fortification can be started at milk volume 50-
80ml/kg/day
• Optimization of HM fortification is required,
inidividualized fortification is recommended
(adjustable or targeted)
• Too little data on human-milk based fortifiers (O’Connor
AJCN 2018)

Arslanoglu et al Front Pediatr 2019

OPTIMIZATION OF HMF FOR PRETERM
INFANTS (EMBA RECOMMENDATION)
Fortification after discharge
• No consensus, few studies
• Seems best practice to mirror transition from
nutrient dense milk to lower density milk
• Fortification should be based on individual growth
trajectory

Arslanoglu et al Front Pediatr 2019

 OTHER KEY FACTORS TO SUCCESS
FEEDING OF PRETERM INFANTS
Donor Human Milk vs Own Mother’s Milk
• Lower protein, Ca & P
• Less bioactive components (eg bile-salt stimulated
lipase, alkaline phosphatase)
• No live microbes
• No IgM
• Less growth with individualized fortification (de
Halleux Nutrients 2019)

Neu Breastfeeding Med 2019

OTHER KEY TO SUCCESS FEEDING OF
PRETERM INFANTS
Donor Human Milk
• AAP advises donor human milk if own mothers
milk is not available (AAP Pediatrics 2012)
• ESPGHAN gives similar advise but limited
evidence for benefits (JPGN 2013)
• Specific attention to handling and administration of
donor milk (Steele Front Nutr 2018)
OTHER KEY TO SUCCESS FEEDING OF
PRETERM INFANTS
Donor Human Milk vs Own Mother’s Milk
• Own Mother’s Milk is preferred over Donor Human Milk
• Limited number of high quality studies on potential
benefits
• Many questions remain related to storage, type of
processing and administration (Wesolovska Nutrients 2019,
Moro Front Pediatr 2019)
• Specific requirements for setting up Donor Milk Banks
(Weaver Front Pediatr 2019)
• Specific attention to Muslim perception of DHM (Coulthier
Can J Diet Pract Res 2019, Alnakshabandi Paediatr Int Child Health
2016, Khalil Acta Paeditr 2016)
KEY TO SUCCESS FEEDING OF PRETERM INFANTS
CONCLUSIONS

• Preterm birth is a nutritional emergency and warrants

attention from birth onwards

• Human milk is the nutrition of first choice but needs to be

fortified for preterm infants with a birthweight < 1800g

• Successful own mother’s milk feeding is a team effort

KEY TO SUCCESS FEEDING OF PRETERM INFANTS
CONCLUSIONS

• Donor human milk is second nutritional choice if OMM is not

(sufficiently) available but needs specific attention with
regard to growth, handling, storage and processing

• Under specific conditions, DHM is also possible in a Muslim

community

• If own mother’s milk & donor human milk are not avaible a
specific preterm formula should be used
 Thank you for your attention! !

Any questions? !

© Oliver Wyman