CME ORGANISED BY SIROY LIFE SCIENCES

Dr Pankaj Garg
Senior Consultant, Department of Neonatology
Institute of Child Health, Sir Ganga Ram Hospital
pankajgarg69@gmail.com, +91-9810146581
23rd June 2016, Hindu Rao Hospital
DELHI, INDIA.
www.siroylifesciences.com

Respiratory
immaturity

Infection

Poor
nutrition
stores

High risk of
multiorgan
failure

Baby Amelia smallest surviving micropremie baby

21 wks 6days weighing 260 gms born on 24th oct 2006

24 weeks; 520 gms

Stayed in NICU for 4
months; photographed at
1.5 years

Preterm survivals are

increasing

AAP: As that of fetus

Weight gain: 18-20 gms/kg/day
Length: 0.9-1.0cm/week
Head Size: 0.9-1.0 cm/week

EUGR is a real challenge to tackle

Clark. 124 American NICUs for 23-34 weeks
28% for weight
34% for length
16% for head circumference

Clark RH. EUGR remains a serious problem in

prematurely born neonates. Pediatrics 111:986990

More rapid weight gain associated with earlier age of enteral feeds and
an earlier age at achievement of full enteral feedings

Ehrenkranz RA et al. Pediatrics 2006; 117(4):1253-1261

Morbidities
Sepsis, NEC, BPD

Poor nutrition
Emotional deprivation
Lack of stimulation

Aggressive >>>>>>> Optimal Nutrition

Parentral nutrition. (Senterre T, Rigo J. J Pediatr

Gastro Nutr 2011; 53: 536-542)

Enteral nutrition. (Ehrenkranz)

Decrease the incidence of Sepsis

PN usage Sepsis
Centralized pharmacy >> Laminar flow usage >> Isolated
designated place of preparation under aseptic conditions
Use of on line filters ?????

EN usage decreases sepsis

 Preterm babies survival should

be matched with optimum

growth and nutrition is a key
issue there.

Hemodynamically Stable preterm <1250 gms,

<30 weeks
Bridging PN + MEN >>> Total EN

Hemodynamically stable >1250 gms, >30

weeks
Total EN

Hemodynamically unstable/ NEC/Abdominal

surgical anomalies
TPN
Look out for TPN associated complications

Calories: 90-110 Kcal/kg/d

Glucose: 8-12 mg/kg/mt (higher glucose leads to hepatic steatosis);
Insulin use associated with hypoglycemia and associated morbidity;
blood sugar once a shift
AA: start 3gms/kg/d >>> 3.5-4.0gm/kg/d; no routine tests
Lipid: start 2gms/kg/d >>> 3-4gm/kg/d; trigyceride biweekly
Use High Omega 3 containing preparation
Less Cholestasis, Less sepsis, Less BPD
Multivitamin: Adult MVI: 1cc/kg
Trace elements: usually after 2 weeks of TPN
Electrolytes: Na/K: 2-3meq/kg/d; monitor more frequently
Calcium / Glycerophosphate

Solutions are always hypertonic and hyperosmolar

Extravasation

Usually peripheral suffice

Can administer fluids with upper limit of osmolarity 800-

1200 mosm/l >>> till 12.5% gucose with AA or 15 %

glucose alone. (low quality evidence)
Addition of lipids reduce the associated phlebitis

Positive nitrogen balance>>> High quality

evidence
Weight gain >>> High quality evidence
Neurocognitive benefits>>>> low quality
evidence

For PN: no routine monitoring; principles

same
MEN

Milk volume up to 24ml/kg/day introduced

before 96 hours and continued for at least 7
days; n = 754
NEC RR 1.07 (0.67-1.7), not affected feeding
intolerance or growth rates

Cochrane Database Syst Rev. 2013 Mar 28;3:CD000504.

Early trophic feeding versus enteral fasting for very preterm or
very low birth weight infants.
Morgan J1, Bombell S, McGuire W.

Likely to have had mesenteric ischemia in utero.

Have an increased risk of Confirmed NEC (6.9, 95% CI

2.3-20)

ADEPT trial : Preterm infants <35 wks, SGA with abn

doppler flows fed on Day 2 of life achieved full feeds
earlier (18 vs 21 days) than those commenced on Day
6, with no difference in the incidence of NEC (8%) or
sepsis

Leaf. 2012. Pediatrics 129:e 1260-e1268.

Antenatal visit by lactation consultant

Oropharyngeal colostrum
EBM expression with in one hour
Total feeds on D1: 80ml/kg/d
Orogastric; intermittent bolus over 15 minutes 3
hourly feeds
Preferably EBM; once 25 ml EBM available add HMF
Upper acceptable osmolarity 400 mosm/l
Increase feeds by 30 ml/kg/day till 150-180 ml/kg/day
Monitor growth
KMC

Systematic review of ten randomized controlled

trials (more than 600 infants with birth weight
less than 1850 g)
Small but statistically significant short-term

improvements in weight gain (+2.33 g/kg/d; 95%CI

1.73, 2.93), linear growth (+0.12 cm/week; 95%CI 0.07,
0.18), and head growth (+0.12 cm/week; 95%CI 0.07,
0.16)

Kuschel CA, Harding JE. Multicomponent fortified human milk for promoting
growth in preterm infants (Cochrane Review). Cochrane Library 2004;3

KMC as soon as possible, at least 2 hours / day

33-34 weeks>> transition to direct breast feeds

If direct breast fed: stop HMF; add Ca/P; Vit D

800IU/d, Iron, DHA, Zinc

If breast milk fed: Continue HMF; Vit D 400 IU/d,

DHA

Different protocols in different units

1800-2200 gm
Discharge
Depending on PMA

<33 weeks>> Fenton 2013, neonatal

anthropometric data, 40 lac preterm
neonates, sex and age specific, 22-50 weeks
>33 weeks>> Intergrowth 21st Century charts,
prescriptive, separate sex

Early stimulation from NICU

Humanized NICU care
Regular check up with Developmental
Pediatrician
DASII

Nutrient

ESPGHAN 2010 (/KG/D)

KOLETZKO 2014 (/KG/D)

<1800 GMS

<1500 GMS0

FLUIDS

135-200

135-200

PROTEIN

4-4.5G (<1KG); 3.5-4 G (1-1.8)

3.5-4.5

DHA

12-30 mg

55-60mg

POTASSIUM

66-132mg

78-195mg

CALCIUM

120-140 mg

120-200 mg

PHOSPHATE

60-90 mg

60-140 mg

IRON

2-3 MG

2-3 mg

ZINC

1.1-2 mg

1.4-2.5mg

VIT D

800-1000 IU

400-1000 IU

An Essential fatty acid

Linoleic acid (LA) 18 carbon: 2 n-6
Linoleic acid (ALA) 18 carbon: 3 n-3
Desaturation & chain elongation in liver
LCPUFA

Docosahexaenoic acid( DHA)

Arachidonic acid(AA)

22 carbon: 6 n-3

20 carbon: 4 n-6

Eicosapentaenoic acid (EPA)

20 carbon: 5 n-3

EFA & LC-PUFA Sources

Omega-6
Class FA

Plant seeds
Meat, eggs

Soybean, canola
oil, Walnuts
Omega-3
Class FA

Fish, sea foods

Omega 3 fatty acids

Fish / Fish oil

Rapeseed or canola
Peanut
Olive
Perilla
Walnut
Soya
Green leafy vegetables, dry fruits
Flaxseed or linseed

Omega 6 fatty acids

Sunflower
Safflower
Sesame
Palmolive
Corn
Primrose
Borage
Invisible fats

Source

Saturates Mono Poly N6

N3

Chol.
mg

Milk fat

62.5

28.8

3.75 26

1.6

274

Dalda

25

45

26

1.6

Corn

13

24

59

58

Sunflower

10

19

66

66

Soya

15

43

38

35

2.6

Olive

14

74

0.6

Canola

59

30

20

Mustard

12

60

21

15

9.3
6

Ideal diet

5-10:1

Indian Diet

30-70:1

USA

12:1

Japan

2:1

Goyens et at : ALA>> DHA 0.013%

Goyens PL, Spilker ME, Zock PL, Katan MB, Mensink RP. Compartmental modeling to quantify
alpha-linolenic acid conversion after longer term intake of multiple tracer boluses. J Lipid

Res. 2005;46:147483

Hussein et al: ALA>> DHA 0.01%

Hussein N, Ah-Sing E, Wilkinson P, Leach C, Griffin BA, Millward DJ. Long-chain conversion of
[13C]linoleic acid and alpha-linolenic acid in response to marked changes in their dietary intake in
men. J Lipid Res. 2005;46:26980.

Part of phospholipid membrane of

Brain cells; Signal transduction,

neurotransmission and neurogenesis

Retina

Anti inflammatory
Role in atopy, asthma, allergy disorders

Fetal life: uterine accretion of 42-75mg/day; 80%

absorbed in the intestine = 65mg/day = 1-1.5
wt:wt% of Fas in human milk or formula
Brain development
Retina development

Preterm
Neurodevelopment
BPD / NEC/ ROP

Term
Brain function
Atopy prevention and treatment

Adapted from
Martinez M. J
Pediatr.
1992;120(suppl):S1
29-S138.

12000
10000
8000

Diet and
Synthesis

Placenta

Omega-3 LCPUFA (mcmol in forebrain)

DHA

DHA
DPA
EPA

DHA

6000
4000
2000

DPA
0

EPA
-3.5

12
Age (months)

18

24

DHA in Pregnancy & Lactation

Conclusions & Recommendations
Demand for DHA is increased during pregnancy
& lactation
Increased supply of DHA
beneficial effect on fetus

Consensus recommendation
-Pregnant & lactating women should aim to
achieve an avarage intake of at least
200 mg DHA per day
Koletzko B, et al. World Association of Perinatal Medicine Dietary Guidelines Working
Group. J Perinat Med. 2008;36(1):5-14.

During pregnancy and lactation

At least 2.6 gms of Omega 3 LCPUFA
100-300 mg DHA/Day

Mean (standard deviation ) intake of total fat LA ,ALA and DHA intake in
pregnant and lactating women

Countries
DHA Intake (MG)

Group

total fat Intake (% E)

Recommended FAO(2010)

Bangladesh (Yakes 2010)

30(10-50)mg

20-35%E

Lactating Women

India (N=Muthayya et al.2009a)

11(4-19)mg
(3rd trimester)

2-3%E

7.6(4.4-11.8)%E

Pregnant women

LA Intake (%E)

24.3%E

ALA Intake (%E)

>0.5%E

200mg

1.9(0.9-3.5)%E

0.3(0.1-0.5)%E

6.1(4.7-8.11)%E

0.24(0.2-0.3)%E

Reference

Cross sectional studies India

(Muthayya et al.2009a)

676

Supplementation to mothers

Functional measurements:

outcomes

birth weight

No significant

comments

fish consumption

association between

above the

DHA status of mother

median was 9g

with birth weight .

Day .

Women not consuming

fish had a higher risk of
LBW infant compared to
women consuming >median
in third trimester

Reference

Location

Supplementation to mothers

Period

Cross sectional studies Cuba

56

Dose day

amount of EFA in

Functional measurements:

outcomes

comments

age at assessment

visual acuity:2months

no associations

breast milk(ALA=0.92%

between infant or

and DHA=0.43%)

maternal FA status

and

visual acuity.

Tinoco et al.2009

Brazil

37
infants)

(pre-term until 6 months

of gestational

Height (cm)

Totaln-3 PUFA
weight (g) and
was positively

associated
age

head circumference(cm)

with weight gain

(p=0.05)
height(P+0.04) and body
mass index of children
(P=0.05)

LC-PUFA in Preterm Infant Formula

Study

Type and
number

Intervention/
Control

Outcome and Results

Intervention vs Placebo

O'Connor DL, et al. Ross Preterm

Lipid Study. Pediatrics. 2001
;108:359-71

470 prematures
750-1800gr

AA+DHA vs. control

0.26%/ 0.16%

MacArthur Communicative Development, visual

acuity, Bayley motor development were better
Bayley Mental Development Index at 12 mo was
not different

Innis SM, et al. J Pediatr. 2002

May;140(5):547-54.

DBPC
194 prematures

0.15% energy DHA, or

0.14% DHA + 0.27%
ARA or control 28 days

No effect on subsequent visual acuity

Enhances weight gain

Koletzko B, et al. Eur J Nutr. 2003

Oct;42(5):243-53.

49 prematures

DHA vs breast milk

Growth and milk tolerance not different

Clandinin MT, et al. J Pediatr.

2005;146:461-8.

361 preterm infants

DHA vs control for 96

weeks

Supplemented groups had higher Bayley mental and

psychomotor development scores at 118 weeks and
better growth

Smithers LG, et al. Prostaglandins

Leuk EFA 2008;79:141-6. DINO
trial

DBPC
preterm

1% DHA vs 0.3% DHA

high-DHA group exhibited an acuity that was higher

than the control group

Makrides M, et al. JAMA.

2009;301:175-82.

RDBP
657 Prematures less
33 weeks

1% DHA vs 0.3% DHA

Bayley MDI was higher in girls

Bayley MDI was higher also in infants born
weighing less than 1250 g but NS

Smithers LG, et al. Am J Clin

Nutr. 2010;91:628-34.

DINO trial

1% DHA vs 0.3% DHA

3 times the standard amount of DHA did not result in any

clinically meaningful change to language development
or behavior at 3 to 5 years

Countries
DHA Intake (MG)

Age Group

IOM (Institute of Medicine )2005

FAO 2010
4yrs)

Bangladesh (Yakes 2010)

Gambia(Prentice & Paul)

108mg

total fat Intake (% E)

1-3yrs

LA Intake (%E)

30-40%

ALA Intake (%E)

5-10%E

4-18yrs

25-35%

5-10%

0.6-12%E

6-24 months

At least 35%

3-4.5%E

0.4-0.6%E

19.5(10.5-30.1)%E

3.5(1.7-6.3)%E

Breastfed (24-35months)

Non Breastfed (24-35months)

12.7(6.2-21.5)%E

Non Breastfed ( 36-48 months)

15.6(7.8-26.9)%E

0-6 months

2.9(1.3-5.2)%E
3.1(1.3-5.8)%E

46.2%E

0.6-12%E

100mg(age2-

0.39(0.19-0.68)%E 40(10-80)mg

0.42(0.12-0.74)%E 10(0-30)mg
0.41(0.18-0.76)%E

6.0%E

20(10-30)mg

0.38%E

7-12 months

34.4%E

5.4%E

0.28%E

87mg

12-17 months

27.5%E

5.1%E

0.23%E

75mg

Reference
comments

Location

Subject

Supplementation to mothers
period

Cross sectional studies

China
significant
mixed feeding

245

Randomized controlled

Dose (% of total fatty acids )

Term Infant
6 months

Trials (Ben et al.2004)

Functional measurements:

Birth until

outcomes

age at assessment

F1:0.18% AA+0.18% DHA

F2:no LCPUFA

BSID:3-6months

no

differences for

breast milk+

F3: Breast milk

growth between

supplemented

F4: Breast Milk +F1

the four feeding

formula group

groups.
Showed best
growth in the

first 3
months

(EL-Khayat et al 2007)
correlations

Pakistan

42+15

PEM infants

8 weeks

PUFA supplemented

control healthy

Mental development

index (MDI), PDI

Positive
between

plasma
children

of BSID-II

AA and DHA

levels
and both MDI and
PDI

Unay et al 2004

Turkey

80

Healthy Infants

Birth to 16wks

DHA

BERA

Positive : more

2-6 weeks of age.

2-3 mg/kg/day

AAP guidelines / ESPGHAN guidelines

References

A.LSRO 2002.
B. Tsang et al 2005.
C. ESPGHAN 2010.
D. Koletzko, Pointdexter, Uauy 2014.

Postnatal
Growth failure
Inadequate
nutrition

Impaired
neurocognitive
development
Ziegler J Ped Gastro/Nutr 2007

Aggressive

nutrition saves
preterm babies
and their brain

Dr Pankaj Garg
Senior Consultant, Department of Neonatology
Institute of Child Health
Sir Ganga Ram Hospital
pankajgarg69@gmail.com, 9810146581

Parentral nutrition

Central pharmacy vs NICU preparation

Laminar flow
Designated PN nurse
100 ml vs 500 ml bags
Dextrose solutions: 5%, 10%, 25%
Amino acid solutions
6% vs 10%

Lipid solutions
10% PLR vs 20%
Intralipid vs SMOF
Amber colored tubings

Pediatric MVI vs Adult MVI

Trace elements
Glycophoshates

Enteral nutrition
Human milk
MOM (Mothers own milk)
Donor milk
Preterm formula
P / D/ S
Term formula

Soya based formula

Enteral nutrition
Human milk fortifiers
0.4g/100 ml Fortifiers: L
1g/100 ml fortifiers: H

HIJAM-HMF

Enteral nutrition
Iron drops
Ferrous sulphate vs Ferrous ascrobate vs Colloidal iron
Drops vs Syrup
Strength
Acceptability

Enteral nutrition
Vitamin D
400 IU vs 800 IU vs 2000 IU drops
Sachet
Multivitamin drops

Enteral nutrition
Calcium preparations
Ca/Phosphate ratio
Interaction with milk or food or iron