Human Milk Fortification

– Why, When, and How?

Mahendra Tri Arif Sampurna,
Neonatology Division, Department of Pediatrics,
Faculty of Medicine Airlangga University RSUD Dr. Soetomo
AGA 27 week : How do we
Nourish this Baby?
 NICU vs. Fetal Weight Gain

Reference
fetus

28-29wk

26-27wk

24-25wk

Ehrenkranz et al Pediatrics 1999

 Early Aggressive Nutrition is Key

Aggressive PN reduces ex-utero growth retardation (EUGR, <10%

weight at discharge ) (Senterre & Rigo 2013, Morgan C et al 2014).

EUGR is associated with long-term growth failure and motor and

cognitive impairment (Dusick AM et al 2003 Hack M et al 1991).
 Anti
Infectious

Non Nutritive
Components Trophic
Hormones
of Human Factors
Milk

Cells
Sumber Adamkin DH, 2009. Enteral feeding guideline practicum. Dalam : Adamkin DH, Editor: Nutritional
strategies for the very low birth weight infant. Cambridge University press; New York: 107-15 6
Brain Development through
Term Gestation
 Questions: AGA 27 week
APGARS 3 and 5,
UA and UV catheters in place,
On mechanical ventilation and parasetamol for ductus

• Can we feed this baby

using the GI tract?
• What are the
consequences of not
feeding this baby?
• How do we feed this
baby?
Liver after 7days of TPN vs.
Enteral Feeding in Piglets

H&E

ORO fat Staining

Diastase glycogen
staining

Wang, H. et al. J..of Nutrition,2006

Question :You are on call at 2am. Nurse reports that
this baby who is being fed 2 ml breast milk every 3
hours is having 2 cc gastric residuals. What do you
do?
• Tell the nurse not to
bother you at 2am?
• Stop all feedings?
• Ask about the physical
exam and perhaps
examine baby yourself?
Checking or Not Checking
Gastric Residuals
Table 2. Specific Outcomes Measured. (Mean ± SD)

Outcomes Check GR No Check GR P-value

(N=30) (N=31)

Enteral intake 2 weeks after birth 106.73±53.74 112.20±42.81 0.66

Enteral intake 3 weeks after birth 134.20±39.44 141.00±29.29 0.41

Day of life of full enteral intake at 120 ml/kg/d 16.8±12.4 14.3±12.5 0.29

Day of life of full enteral intake at 150 ml/kg/d 28.1±3.9 22.3±11.7 0.19

Percentage of Change of Growth Parameters:

Weight at 3 weeks 23.8±19 23.6±21 0.98

Length at 3 weeks 7.1±5 6.4±5.5 0.58
Head circumference at 3 weeks 8.6±5.9 7.8±3.9 0.51

Day of life when PN was discontinued 15.1±11 13.8±5.9 0.57

Day of life when central access was discontinued 21.3±20.7 15.6±5.9 0.17

Murgas Torrazzo, R., J. Perinatology, 2014

 Checking or Not Checking
Gastric Residuals

Table 2. Clinical Complications Measured. (%)

Outcomes Check GR No Check P-

(N=30) GR value
(N=31)
PNALD 4/30 (13.3) 4/31 (12.9) 1.00

SEPSIS 11/30 9/31 (29) 0.59

(36.7)
NEC 3/30 (10) 1/30 (3.2) 0.35

Murgas Torrazzo, R., et al. J. Perinatology, 2014

 Importance of Enteral Nutrition
Suboptimal nutrition during the first few weeks of life is
associated with significant adverse effects on the long-
term growth and neurodevelopment of preterm infants.

Enteral feeds are The resultant

GIT immaturity puts
often withheld in suboptimal nutrition
preterm infants at
the first few weeks is associated with
high risk for feed
due to feed EUGR in extreme
intolerance
intolerance LBW preterm infants

The increasing acceptance of early aggressive enteral nutrition

to achieve intrauterine growth rates has led to significant changes
in clinical practice in recent year.
 Why promote breastfeeding
and human milk feeding?
Own mothers’ milk(OMM) should be the primary diet, but if OMM
not available in sufficient quantity, pasteurised donor hm obtained
from a recognised human milk bank should be used (WHO, and more
recently, Human milk in feeding premature infants: consensus statement. JPGN Sept
2015)

Benefits of breastfeeding
less infections, less NEC, less
obesity, improved bonding and
improved neurodevelopment.
(Corpeleijn 2012, Patel AL 2013,
Kramer2008, Sisk 2007,
Meinzen-Derr 2009, Vohr 2006, Rønnestad
2005, Arenz 2004, More 2015)
 Enhancing Lactation After Preterm Birth
The initiative of supporting early, regular expression
is the most important component of an NICU
breastfeeding policy

Early skin-to-skin
care with non-
nutritive sucking
should be strongly
encouraged

Each NICU should have a strong breastfeeding

policy to promote such practices
 Human Milk: Question
• The average protein content of term donor
human milk is:
a. The same as preterm baby’s own mothers milk.
b. Adequate for optimal growth of the ELBW infant.
c. Approximately 2.2 grams/dL
d. Approximately 0.9 grams/dL
 Protein Requirement
• Accretion rates of
reference fetus
estimated at 3.5-4.0
g/kg/d.
• ELBW infant would
require 330 ml/kg/d
of term donor
human milk to meet
this requirement.
Nutrient Requirements of Preterm Infants and
the Need for Fortification
Nutrients should be provided to all preterm infants to
optimise both velocity and body composition

ESPGHAN Recommendations in Preterm Infants

Weight <1000 g Weight 1000–
1800 g

Protein 4.0–4.5 3.5–4.0

(g/kg/day)
Energy 110–135
(kcal/kg/day)

Nutrient requirements cannot be met by milk alone which

provides 1-2 g/100 mL protein and 70 kcal/100mL energy.
 Benefits and risks of HM fortification
(VLBW &/or <32 weeks GA)
• Better meet nutritional recommendation of 100-135 kcal/kg/d
& 4-4.5g/kg/d protein
• Increased growth (weight, length and head circumference) in
the short term and associated with better neurodevelopmental
outcomes (Ehrenkranz 2006)
• A Cochrane review (14 trials and 1071 infants) demonstrated
increased in-hospital growth rates in preterm infants (mean age:
30 weeks) fed with fortified human milk (Brown J et al 2016)
HOWEVER

• Increased osmolality, feed intolerance, NEC

• Cows milk protein present in many fortifiers may be a trigger for
intestinal inflammation and contribute to the risk of NEC
(Abdelhamid et al 2013).
 Timing of Human Milk
Fortification

Fortifiers are commonly added once tolerating

100-150 mL/kg/day of human milk

Discontinued when the infant reaches a

weight of 2 kg or discharge

There is no evidence to support continued fortification

of human milk after discharge and such practice may
interfere with lactation
.
 Importance of Osmolality of
Fortified Human Milk
Enzymes in human milk will begin to digest
nutrients which may increase osmolality

Osmolality should be checked intermittently if feeds

are fortified 12–24 h before feeding
aim to ensure osmolality remains < 450 mOsm/kg

Feeds with osmolalities Care in prescribing

>500 mOsm may be associated enteral medications
with NEC as many >2000 mOsm

.
 Medications and Additives:
Osmolality
• AAP recommended limit is 400mOsm/Kg
• Adding 3 or 4 of the following to human milk may
markedly increase osmolality to near or over
1000mOsm/Kg.
– Multivitamins
– Spironolactone and Chlorthiazide
– Dexamethasone
– Caffeine Citrate

Radmacher and Adamkin, JPGN 2012

Breastfeeding and The Use of Human Milk

• The 6 months of breastfeeding are to be

continued ‘‘for one year or longer’’ while
complementary foods are introduced
• No specific duration of breastfeeding beyond 1
year was recommended

Ø High-risk very low birth weight ( < 1,500 g)

• Reduction in the frequency and severity of
necrotizing enterocolitis
• Improved long term neurodevelopment
Eidelman, pediatrics 2012
What’s the demand of Donor Milk?
• Hierarchy : FOMM, MM, Donor Milk, RTF,
Powdered Formula
• NEC is much less in babies fed donor milk –
improved health outcomes and huge cost savi
ngs in NICUs
• Donor milk is commonly used in preterm popu
lations
Neurodevelopment Improvement
Changes in Composition of Human
Milk Over Time
• Protein levels decrease in human milk over
the first 4 to 6 weeks or more of life regardless
of timing of delivery
• Human milk protein concentration is not
affected by maternal diet
 Composition of Preterm Human
3
Protein Content (g/dL) Milk
2.5 Makers of HMF assume 1.4-1.6 g/dL – and do
2
not account for the decrease in protein over
time
í
1.5

1
- - Donor milk - - - - - - - - - - - - - - - - - - - - - - - - - - - - - --
0.5

0
1 2 3 4 5 6 7 8 9 10 11 12

Weeks of lactation
• Macronutrient composition of preterm milk for week 1
(colostrum) and weeks 2–8 of lactation (mature milk)
• Fortified preterm milk feeds are unlikely to have an
adequate PER, potentially compromising adequate
growth
• Human milk should be supplemented (fortified) with
the nutrients in short supply, particularly with protein,
calcium, and phosphate to meet high requirements of
this group of tiny preterm infants

Boyce, C et al.2016
 Donor milk being not exactly like
mother’s milk emerges
• Different cytokine profile, different HMO profile
• Different macronutrient composition (mostly
lower protein)
• Lower concentration of LC-PUFAs
• Use may result in growth compromise compared to M
M, although not universally
• “Lacto-engineering” can help –
fortification to help growth
 Human Milk Fortification
• Multicomponent fortification of human milk
is associated with short-term improvements
in weight gain, linear, and head growth in
preterm infants
• Multi-nutrient fortifiers can be added to
breast milk to increase nutrient content by
about 10%.

Kuschel, The Cochrane Library 2009

 Fortification Methods
• Adjustable fortification
- To avoid both protein undernutition and overnutrition
- BUN levels as a surrogate for assessing protein adequacy
• Standard, fixed dosage fortification
- The most widely used fortification method
- To add a fixed amount of multinutrient fortifier per 100 ml of HM
to achieve the recommended nutrient intakes
• Targeted fortification
– To analyze macronutrient composition of HM Standard, fixed dosage
fortification
– Requires milk analyzer
Adjustable Fortification of Human Milk
• shown to improve protein intakes, somatic
and head growth and seems to be a practical
method to optimize HM fortification
• extra protein supplementation not only
improved weight gain but also head
circumference gain.
• were associated with both better growth and
better neurodevelopmental outcomes
Human Milk Analyzer
• Measures “true”
protein, fat, and lactose
Several brands available
one recently approved
by FDA for clinical use

• To analyze and tailor the

macronutrient content
based on real-time
analysis of HM
 Target Fortification of Human Milk
• labor intensive requiring frequent milk
sampling and precision measuring equipment.
• McLeod et al. did not find any improvement
in growth and nutrition in a group of preterm
infants born below 30 weeks of gestation
 Current Options for Human Milk
Fortification
• Bovine HMF
• Human milk-based HMF (H2MF)
• Human milk-based RTF (24/26/28 cal)
• Human milk-derived “cream” supplement
(Prolact CR)
• Liquid Protein “Fortifier”
• High Calorie Formula (such as 30 kcal/oz
preterm)
Effect of Increasing Protein Content of
HMF
• A significant reduction in the proportion of
infants less than the 10th percentile for length
at study end in the higher-protein group
• Poor length growth (stunting) in infancy and
early childhood is a strong predictor of poor
neurodevelopmental outcomes
• Weight was significantly greater in the higher
protein group

Miller, Am J Clin Nutr 2012

 Exclusive Human Milk vs Preterm Formula
• Sole-diet DBM (fortified with H2MF) vs. PTF (n=53)

• Protective due to
presence of immune
modulators or due to lac
bovine casein?
• No comparison of bovi
based HMF vs. H2MF

Cristofalo, J Pediatr 2013

 Reasonable Strategy to Optimize Enteral Feeding
Practices in ELBW and VLBW Infants
ELBW VLBW
Milk HM HM
First feeding Between 6-48 hrs Between 6-48 hrs
Initial feeding (MEF) 0.5 mL/kg/hr or 1 mL/kg/hr or
1 mL/kg q 2 hr 2 mL/kg q 2 hr

Duration of MEF 1-4 days 1-4 days

Feeding advancement 15-25 mL/kg/d
HM fortification Before 100 mL/kg/d
Target enteral intakes -
110-135 kcal/kg/d
4-4.5 g/kg/d
20-30 mL/kg/d
Before 100 mL/kg/d
110-135 kcal/kg/d
3.5-4 g/kg/d

Senterre, Nutritional Care of Preterm Infants, 3rd Ed

 Approach to Fortification
of Human Milk

• Fortification with HMF to 24 kcal/oz recipe at 75

mL/kg/d per standardized feeding protocol
• Once on full volume feedings, increase to 6 packets
HMF/100 mL (27 kcal/oz) with suboptimal growth (add
3 mL liquid protein if mostly donor milk or if length
faltering)
• If 30 kcal/oz recipe needed, add preterm formula or
transition to preterm formula (stop donor milk at 30
days per feeding protocol)
 Postdischarge Fortification - What is
the Evidence?
• Multinutrient fortification of human milk
– 2 trials with 246 preterm infants

– Overall, no significant difference in weight or HC between infants fed

HM with multinutrients compared with infants fed unfortified HM
post-discharge; small increase in length at 12 months

– Fortification did not adversely affect duration or exclusivity of

breastfeeding

– no effect on neurodevelopment at 18 mos CA; improved visual

acuity at 6 mos in one study

Young, Cochrane Database Syst Rev 2013

 Transition to Breastfeeding
• Depending on number of feedings at the breast, caloric
density of supplemental bottle/gavage feedings may
vary
– Fortified breast milk with HMF or postdischarge formula powder
• As breastfeeding sessions increase, may actually
increase caloric density to compensate for lower caloric
density of direct breastfeeding
– If growth faltering noted, can introduce 10-15 mL of “booster”
• feedings with 30 kcal/oz RTF preterm formula
• Frequent weight checks, lactation support, partnership with
pediatrician
 Summary Considerations
• Increase efforts to encourage provision of
maternal milk
• Standardized feeding protocol with “early”
fortification of human milk and consider separate
strategies for donor milk
• Point-of-care analysis of pooled milk as a less
labor-intensive alternative to target-fortification
• Additional studies on growth and body
composition with new fortification strategies
(including postdischarge management)
 TERIMAKASIH

Good Nutritions does

not save lives, It
saves Brains