Educational slide share for Post Graduate students , Fellows, Researchers in Paediatrics and Neonatology

1. Breast milk is the best feed to fulfill the growth and developmental needs
of the baby

2. Dr Isha Deshmukh
Assistant Professor
Pediatrics
BJGMC & Sassoon General Hospitals
Pune, Maharashtra , India

3. NUTRITION IN PRETERM INFANTS

4. RISKS FACTORS OF PRETERM BIRTH
4
Multiple pregnancy
Prior preterm birth
Infection
Low or advanced maternal age
Maternal chronic medical conditions (eg. Diabetes)
Under/Overnutrition
Lifestyle:
Smoking, alcohol use
Maternal psychological
health (Eg. Depression)
Genetic
(eg. Family history)
March of Dimes 2012, Plunkett 2008, Muglia 2010, Blondel 2006, Gravett 2010, Martin 2011

5. PRETERM INFANTS FACE SPECIFIC HEALTH RISKS DUE TO
ORGAN AND FUNCTIONAL IMMATURITY
5
Brain injury
NEC (Necrotizing
Enterocolitis)
Feeding difficulties and
metabolic disturbances
Respiratory Distress
Syndrome
Retinopathy of
prematurity
Jaundice and higher risk
for the brain
Anemia of prematurity
Infections
Morbidity is inversely
related to gestational age
March of Dimes 2012

6. INCOMPLETE ANATOMIC DEVELOPMENT
IN PRETERM INFANTS
6 Neu 2007 and 2008, Premji 1998, Harding 2004, Colin 2010, Fraser 2004, Tissières 2012, Melville 2013, Carmody 2013, Blackburn 2013
Gastro-intestinal (GI) system
Respiratory system
Immune system
Renal system

7. PRETERM INFANTS HAVE IMMATURE PHYSIOLOGICAL FUNCTIONS
(1)
A. Gastrointestinal system
7 Neu 2007, 2008, Blackburn 2013, Omari 2011, Premji 1998
Immature gut barrier
Inefficient digestion and
absorption
Immature gastrointestinal
motor functions
Infection, allergy, necrotizing
enterocolitis
• Feeding difficulties
• Risk of insufficient nutrient intakes
Feeding intolerance

8. PRETERM INFANTS HAVE IMMATURE PHYSIOLOGICAL FUNCTIONS
(2)
B. Immature lungs and insufficient surfactant amounts
8
Alveoli in the lung are not sufficiently developed
• Makes breathing difficult and highly inefficient
Limited amounts of surfactant (a liquid coating the
lungs and helping them to open during breathing).
• Without enough surfactant, the lungs collapse and
breathing becomes difficult.
Harding 2004, Colin 2010, Fraser 2004
Preterm infants may thus:
• Require mechanical ventilation
• Be at increased risk to develop lung diseases (eg. Respiratory distress, pneumonia, respiratory tract
infections)

9. PRETERM INFANTS HAVE IMMATURE PHYSIOLOGICAL
FUNCTIONS (3)
C. Immature immune system
• Higher risk of infection, e.g. sepsis
D. Immature kidney function
• Increased risk for renal insufficiency and renal failure
E. Immature skin barrier
• Leading to water/nutrients losses and thermal instability
9 Behrman 2007, Blackburn 2012, Tissières, 2012, Melville 2013, Carmody 2013, Darmstadt 2000, Visscher, 2014

10. SPECIFIC HEALTH RISKS OF PRETERM INFANTS (1)
10 March of Dimes, 2012, Kumar 2011,Gregory 2011, Behrman 2007, Fraser 2004
RISKS
Hypoglycemia:
• due to lack of glucose reserves
• immaturity of glucose metabolism
Severe infections and related
high risk of mortality:
i.e. Sepsis
Respiratory Distress Syndrome:
caused by immature lungs and lack
of surfactant
Necrotizing Enterocolitis:
• severe GI disease with high
mortality risk
• incidence highest in the smallest
preterm babies

11. SPECIFIC HEALTH RISKS OF PRETERM INFANTS (2)
11 Ballabh 2010, Higgins 2012, Behrman 2007
RISKS
Retinopathy of prematurity:
• Due to abnormal structure of the eye blood vessels
• May lead to sight problems including blindness
Brain injury:
eg. Hypoxia and intraventricular
hemorrhage
Anemia of prematurity:
• Due to suppressed hematopoiesis and a
greater need of red blood cells for growth
• Requiring red blood cell transfusion

12. EARLY MALNUTRITION IN PRETERM INFANTS HAS
LONG-TERM CONSEQUENCES
Consequences:
• Neurodevelopmental
impairment
• Impaired growth on the
long-term
• Elevated risk for insulin
resistance and
cardiovascular disease in
later life
12 Ehrenkranz 1999, Laptook 2005, Cooke 2003, Hack 2006, Euser 2008, Lapillonne 2013, Saigal 2008
Longitudinal growth of hospitalized very
low birth weight infants
Weight
(g)
Postmenstrual age (weeks)
50th 10th
Intrauterine growth (10th and 50th)
24-25 weeks
26-27 weeks
28-29 weeks
Postnatal growth failure, occurs in 60-100% of preterm infants

13. PRETERM BIRTH HAS LONG-TERM CONSEQUENCES (1)
Physical effects:
• Visual impairment
• Hearing impairment
• Chronic lung disease
• Non-communicable diseases
• Growth failure in infancy
Neurodevelopmental effects:
• Cerebral palsy, as well as learning, cognitive, and motor impairment
• Attention deficit hyperactivity disorder
• Increased anxiety and depression
13 Behrman 2007, O‘Connor 2007, Greenough 2013, Lapillonne 2013, Mathai 2013, Sices 2007

14. PRETERM BIRTH HAS LONG-TERM CONSEQUENCES (2)
High impact on family:
14
High impact on health services and
economy:
• Annual total societal economic costs of
preterm births in the US: $26.2 billion
• On average $51’600 per preterm baby/ year
(costs highest for the smallest babies)
• Preterm birth is highly associated to:
⬆ Rates of disability, economic assistance,
persistent illness
⬇ Education degree and salary
Family and societal effects
Psychosocial
Emotional
Economic
Behrman 2007
Family

15. EARLY PROPER NUTRITION IS ESSENTIAL
Nutrition of preterm infants during early life contributes to:
• Immediate neonatal survival and better quality of life of those who survive
• Recovery from neonatal diseases and early discharge from the nursery
• Growth and mental development during infancy and later life
15
Improved growth
results in better
neurological
development
Uauy 2014
Higher growth velocity in the NICU, similar to intra-uterine growth rates
predicts better neurological outcomes at 18-22 months corrected age
Neurodevelopmentally
impaired
(%)
Weight gain (gkg-1day-1)
Cerebral
palsy
(%)

16. PRETERM INFANTS HAVE SPECIFIC NUTRITIONAL NEEDS
16
Low nutrient stores
High growth rates
Physiological, metabolic stress
At the same time:
Immature physiological functions
Feeding a preterm baby is challenging
Preterm infants have:
Schanler 2008
Medical instability
Higher nutrient requirements
than term infants

17. PRETERM INFANTS: FEEDING GOALS AND CHALLENGES
Goals of early nutritional support:
• Promote growth, body composition and nutrient accretion comparable to that of the
fetus at the same gestational age
• Minimize the risk of necrotizing enterocolitis (NEC)
• Optimize neurodevelopment and long-term health outcomes
Challenges of reaching optimal nutrition:
• Functional immaturity of the gut makes absorption and utilization of nutritional
substrates difficult
• Illnesses such as respiratory distress and sepsis not only increase nutritional
requirements but may also affect the neonate’s capacity to digest and absorb nutrients
17 Poindexter 2014, Diehl-Jones 2004

18. ENRICHED NUTRITION SHOULD CONTINUE AFTER
HOSPITAL DISCHARGE
Higher energy and protein requirements to allow for catch-up growth
Optimal amounts of Calcium and Phosphorus:
• Higher risk of poor bone mineralization and metabolic bone disease
as well as a reduced rate of skeletal growth compared to infants born
at term
Higher vitamin and mineral needs to account for nutrient deficits
18 Lapillonne 2014, Young 2012
Due to accumulated nutrient deficits and growth failure, preterm
infants still have specific nutritional needs after hospital discharge:

19. Specific Nutritional Requirements of Pre-term Infants
19

20. WHAT ARE THE SPECIFIC NUTRITIONAL NEEDS OF
PRETERM INFANTS?
Increased energy requirements
• Due to higher basal metabolic rate and high growth rate
• Needed for protein metabolism and deposition
Increased protein requirements
• Due to higher protein turnover and synthesis
• For rapid growth
• For adequate bone mineralization
20
Compared to term infants, preterm infants have:
Schanler 2008, Thureen 2007, Nzegwu 2014

21. WHAT ARE THE SPECIFIC NUTRITIONAL NEEDS OF
PRETERM INFANTS?
Increased LC-PUFAs requirements for accumulation in the growing brain and
developing retina, as these fatty acids are largely accrued in the last trimester of
pregnancy
Increased calcium and phosphorus requirements for bone formation
Higher fluid needs (15-25%) due to higher insensible water loss through immature
skin and higher ratio of surface area to body weight
Higher needs for vitamins and minerals due to limited body stores and high needs
to support growth
21
Compared to term infants, preterm infants have:
Schanler 2008, Thureen 2007, Aggarwal 2001, Fusch 2014, Koletzko 2014

22. PRETERM INFANTS HAVE HIGH ENERGY REQUIREMENTS
Energy excreted: energy excreted through faeces and urea
Energy stored: metabolizable energy incorporated into lean body mass, fat, and glycogen
Energy expended: Energy used for the maintenance of body functions, for
thermoregulation, in physical activity and for the synthesis of new tissues
22
Basis of recommendations:
Energy
Koletzko
2014
ESPGHAN 2010 LSRO 2002
Tsang 2005
<1000g 1000-1500g
kcal/kg/d 110-130 110-135 110-135 130-150 110-130
kcal/ 100ml
of Ready to Feed formula or fortified Human Milk
- - 67-94 - -
Main recommendations:
Energy intake = energy excreted + energy stored + energy expended
Koletzko 2014, Agostoni 2010, Tsang 2005, Klein 2002

23. PROTEINS ARE THE DRIVING SOURCE FOR GROWTH
Sufficient energy
and other nutrients
needed to allow
protein to be used for
tissue building
23
Functional and
structural component
of all cells in the body
Essential for growth
Adequate protein
intake results in better
overall development
If energy availability is
limited, protein is used
as energy source
Kashyap 1994, Van Goudoever 2014, Brown 2014
PROTEIN

24. DIETARY FATS ARE OF CRITICAL IMPORTANCE
FOR PRETERM INFANTS
Total dietary fats
• Are a major source of energy for the preterm infant
• Provide high-quality fatty acids that are of great importance (eg. Essential
fatty acids)
Long-chain polyunsaturated fatty acids (LC-PUFAs; eg. DHA and ARA)
are crucial for:
• The normal development of the central nervous system
• The retina and visual cortical maturation
• And have a potential impact on developmental processes affecting growth,
body composition and immune responses
24 Lapillonne 2013 and 2014, Agostoni 2010

25. MEDIUM CHAIN TRIGLYCERIDES (MCTs)
Definition: Glycerol esters of medium chain fatty acids (MCFAs) having 6 to 12 carbon chain
length
Current, but especially older scientific opinions:
• MCTs are better digested and absorbed than long-chain triglycerides (LCTs)
• High amounts should be used in preterm formulas
However, recent research shows that high MCTs levels:
• Are not better absorbed and digested than LCTs
• Do not improve:
- intragastric lipolysis
- fat absorption and energy balance
- growth rates
- gastrointestinal tolerance
- risk of NEC
• Decrease glucose oxidation and increase lipogenesis
25
Sulkers 1992 and 1993, Roman 2007, Wu 1993, Hamosh 1989 and 1991, Aggett 1991, Tsang 2005

26. MEDIUM CHAIN TRIGLYCERIDES (MCTs)
High MCTs levels might:
• Negatively alter metabolism of essential fatty acids
• Affect long-term metabolic health
Human milk contains no MCTs, but medium chain fatty acids MCFAs,
representing up to 10% of total fatty acids
26 Radonjic 2009, Uthaya 2005, Tucci 2011, Genzel-Boroviczény 1997, Tsang 2005, Agostoni 2010
Conclusion: Preterm nutrition products would benefit
from a moderate reduction in MCTs levels

27. BENEFITS OF FEEDING HUMAN MILK TO PRETERM
INFANTS
27
Benefits of
human
milk in
preterm
infants
NEC reduction
Enhanced digestion and
absorption of nutrients
Supports emotional
bonding
Allergy prevention
Better neuro-developmental
outcomes
Better feeding
tolerance
Lower risk for severe
Retinopathy of Prematurity
Lower risk for
non-communicable diseases
Protection against sepsis and
other infections
Enhanced gut
maturation

28. PRETERM AND TERM HUMAN MILK ARE DIFFERENT
Compared to term human milk, preterm human milk
is higher in:
… energy
… protein, total nitrogen and amino acids
… fat and fatty acids (eg. DHA and ARA)
… carbohydrates
… some vitamins and minerals
… some immune factors
28 Bauer 2011, Bokor 2007, Molto-Puigmarti 2011, Castellote 2011

29. HOWEVER, BREAST MILK ALONE DOES NOT MEET THE
SPECIFIC NUTRITIONAL NEEDS OF PRETERM INFANTS
29
Compared to the high nutritional requirements of preterm infants, unfortified human milk
…provides insufficient amounts of: …leading to…
• Protein  decreased growth and neurodevelopment
• Calcium and Phosphorous  impaired bone mineralization
• Sodium  (possibly) hyponatremia
• Energy  large volume of fluid needed to meet energy needs
Ziegler 2001, 2014, Reis 2000,O‘Connor 2003, Kuschel 2009, Martins 2009. Agostoni, 2010
Human
milk
composition
/
ESPGHAN
2010
and
Koletzko
2014
guidelines
(minimum
values)
per
100kcal
in
%
Feeding unsupplemented human milk leads to slower growth in preterm infants
Human milk contribution to the preterm infant’s nutritional needs
Protein Iron Calcium Phosphorus Zinc Vitamin A

30. HUMAN MILK MULTINUTRIENT FORTIFICATION SUPPORTS
GROWTH OF PRETERM INFANTS
30
Martins 2009
Better weight gain Better linear growth Better head growth
Weight
gain
(g/d)
Human milk Fortified Human Milk Human milk Fortified Human Milk
Human milk Fortified Human Milk
Lenght
gain
(cm/week)
Head
circ.
(cm/week)

31. GLOBAL NUTRITIONAL RECOMMENDATIONS FOR ENTERAL
FEEDING* IN PRETERM INFANTS
Koletzko, 2014
Nutritional Care of Preterm
Infants – Scientific Basis and
Practical Guidelines; World
Review of Nutrition and
Dietetics, vol 110, 2014
31
*Ready-to-feed Fortified Human Milk and Preterm Infant Formulas
Koletzko 2014, Agostoni 2010, Tsang 2005, Klein 2002
ESPGHAN, 2010
Enteral Nutrient Supply for
Preterm Infants:
Commentary from the
European Society for
Pediatric Gastroenterology,
Hepatology, and Nutrition
Committee on Nutrition;
JPGN, 2010
Tsang, 2005
Nutrition of the Preterm
Infant, Scientific Basis and
Practical Guidelines, 2nd
Edition, 2005
LSRO, 2002
Nutrient Requirements
for Preterm Infant
Formulas, J Nutr., 2002

32. Case, Baby of MI 28 wks, BW 1280 gms
DAYS NUTRITION
DAY 1 TPN (1.5 gms amino acids; 1.5 gms lipids)
DAY 2 minimal enteral feeding
DAY 2-8 grading up of feeds
HMF started
DAY 9-30 fortified milk- full feeds
DAY 33-34 sodium supplementation
DAY 5- 35 transition oral feeds- discharge
Weight gain: Day 9 –30 - 10 gms / day

33. Initial birth weight: 1280 gms
· Birth weight regained on day
34 of life: 1290 grams

34. Nutritional Requirements of SGA Infants
Requirements not specified for SGA/IUGR infants
Same principle of AGA infants except
• Assume reduced body fat content in these infants
• Lower weight loss during the first 5 days of life as compared with AGA
- Alparslan TONBUL et al.Tur J Med Sci 2010:40(2):185-190

35. Promotion of faster weight gain in SGA
infants: is there an adverse effect on later BP ?
153 SGA infants
Standard formula
Nutrient enriched formula (28% more protein)
Faster weight gain - higher diastolic BP at 6 – 8 yrs
Over nutrition in Infancy” increases cardiovascular risk !
Singhal et al Circulation 2007

36. Clinical practice shows protein deficits in 1st week esp in the immature preterms
(ESPGHAN 2009)
Preterm Formulae : Proteins
Protein intake atleast 3 g / kg / day
Wt gain rates linearly related to protein intakes till
4.5 g / kg / day
Recommendation: < 1 kg 4 – 4.5 g / kg /day
1 – 1.8 kg 3.5 – 4 g / kg /day
Range : 3.5 – 4.5 g / kg / day

37. Preterm Formulae
Essential fatty acids
Formula containing arachidonic acid (AA) and DHA
beneficial effects on visual system, cognitive development and immune function
AA and DHA to be added to preterm formula
AA 18 – 42 mg / kg / day
DHA 12 – 30 mg / kg / day
Ratio 1 – 2 : 1
(ESPGHAN 2009)
Recommendation:
Fat Intake : Range 4.8 – 6.6 g / kg / day

38. PRETERM FORMULAE
Per kg / d Per 100 kcal DSC LDX LBW
Per100 kcal Per 100 kcal
Proteins g
< 1 kg
1 – 1.8 kg
4 – 4.5
3.5 – 4
3.6 – 4.1
3.2 – 3.6
2.48 – 2.75 2.5
CHO gm 11.6 – 13.2 10.5 – 12 11.03 11.1
FAT gm 4.8 – 6.6 4.4 – 6 5.14 5
Ca mg 120 – 140 110 – 130 165.16 160
PO4 mg 60 – 90 55 – 80 82.58 80
ESPGHAN 2009 AVAILABLE FORMULAE

39. THANK YOU
39